Trials 2020 15924853714931203

Randomised
Randomised trials
trials 2020
2020
May 2020
May 2020
Orsiro ®
DES Interventional
Interventionalcardiology
cardiology2015-2020
2015-2020
BIOSTEMI trial: Superiority in STEMI
EDITORS:
EDITORS:Pim
cardiology 2015-2020
Interventional cardiology 2015-2020
PimJ.J.dedeFeyter,
Feyter,Robert
RobertByrne
Byrne
Known to be effective. Proven to be superior.¹
2020 Interventional
41%
trials 2020
“With Orsiro, we incrementally
improve care for STEMI patients◊”
Randomised trials
Lower risk*
of TLF with
Dr. Juan F. Iglesias, Geneva, Switzerland
Co-Principal Investigator BIOSTEMI trial Orsiro in STEMI
Randomised
inincollaboration
collaborationwith
with
1. Compared to Xience in STEMI. *BIOTRONIK data on file, based on the Rate Ratio of 0.59.
◊
Based on author’s interpretation of the BIOSTEMI results EuroIntervention
EuroIntervention
Source: lglesias J et al. Biodegradable polymer sirolimus-eluting stents versus durable polymer
everolimus-eluting stents in patients with ST-segment elevation myocardial infarction (BIOSTEMI):
www.eurointervention.com
a single-blind, prospective, randomised superiority trial. Lancet, September, 2019. For indications please
see Instructions For Use.
Orsiro is a trademark or registered trademark of the BIOTRONIK Group of Companies. Xience is a
trademark or registered trademark of the Abbott Group of Companies. www.orsiro.com
Orsiro Mission DES ®
Ultrathin struts.1 Ultrathin struts.1

Outstanding patient outcomes.2 Outstanding patient outcomes.2
Next level of deliverability.3 Next level of deliverability.3
NEW NEW
57% 57%
More flexible More flexible
shaft shaft
Better Push3 for high track Better Push3 for high track
+57% NEW +57% NEW

Deep Deep
embedding embedding
for high cross for high cross
0 10 20 30 40 50 0 10 20 30 40 50
Force transmitted (%) Force transmitted (%)
30% 30%
Better Track 3 Better Track 3
-30% -30%
0 0.2 0.4 0.6 0.8 0 0.2 0.4 0.6 0.8

Resistance (N) Resistance (N)
75% 75%
Better Cross 3 Better Cross 3
-75% -75%
0 0.05 0.10 0.15 0.20 0.25 0.30 0 0.05 0.10 0.15 0.20 0.25 0.30
Orsiro Mission Syngery Orsiro Mission Syngery

Resolute Onyx Xience Sierra Resolute Onyx Xience Sierra
www.orsiro-mission.com www.orsiro-mission.com
1. As characterized with respect to strut thickness in Bangalore et 1. As characterized with respect to strut thickness in Bangalore et
al. Meta-analysis; 2. Based on investigator’s interpretation of NEW al. Meta-analysis; 2. Based on investigator’s interpretation of NEW
BIOFLOW-V primary endpoint result; 3. In comparison to Xience BIOFLOW-V primary endpoint result; 3. In comparison to Xience
Sierra, Resolute Onyx and Synergy for bench tests on pushability, Ergonomic hub Sierra, Resolute Onyx and Synergy for bench tests on pushability, Ergonomic hub
trackability and crossability, BIOTRONIK data on file. with kink resistance trackability and crossability, BIOTRONIK data on file. with kink resistance
Clinical data conducted with Orsiro, Orsiro Mission’s predecessor Clinical data conducted with Orsiro, Orsiro Mission’s predecessor
device can be used to illustrate Orsiro Mission clinical data. device can be used to illustrate Orsiro Mission clinical data.
Orsiro is a trademark or registered trademark of the BIOTRONIK Orsiro is a trademark or registered trademark of the BIOTRONIK
Group of Companies. Synergy is a trademark or registered trademark Group of Companies. Synergy is a trademark or registered trademark
of the Boston Scientific group of companies. Resolute Onyx is a of the Boston Scientific group of companies. Resolute Onyx is a
trademark or registered trademark of the Medtronic group of trademark or registered trademark of the Medtronic group of
companies. Xience Sierra is a trademark or registered trademark of companies. Xience Sierra is a trademark or registered trademark of
the Abbott group of companies. the Abbott group of companies.
Randomised trials 2020
in collaboration with
EuroIntervention
Pim J. de Feyter
Robert Byrne
EuroIntervention
Preface
Dear readers,
We are very pleased to present the 20th updated edition of Randomised Trials
2020. The book is a compilation of one-page summaries of published randomised
trials in the field of interventional cardiology.
Each summary has a common structure composed of (i) title and citation;
(ii) objectives, study design, patient population and primary endpoint; (iii) patient
flow and treatment allocation; (iv) results of the primary endpoint analysis and
conclusions.
The selection criteria for consideration for inclusion remain the same as the last
version: randomized trial design, clinical outcome as a primary endpoint, and
publication in one of ten high-ranking medical journals. In a small number of
cases, we also included randomized trial with surrogate outcome measures as
primary endpoint. We decided to exclude meta-analyses as the focus of the book is
on the primary results of individual clinical trials. Moreover, in order to keep the
book concise as well as up-to-date, we restrict inclusion to trials with a print
publication date within the last 5 years.
The medical journals that we selected for screening are New England Journal of
Medicine, Lancet, JAMA, bmj, European Heart Journal, Journal of the American
College of Cardiology, Circulation, Annals of Internal Medicine, EuroIntervention,
JACC Cardiovascular Interventions and Circulation Cardiovascular Interventions.
The dynamic nature of the development of interventional cardiology means that
the scope of the included trials continues to evolve. However, the central areas of
focus are interventions for coronary artery disease, antithrombotic therapies after
myocardial revascularization, procedural aspects of PCI, and interventions for
structural heart disease and hypertension.
This trial book is also available as a free online resource at https://eurointervention.
pcronline.com/trials.
We hope that the book” will be of value as a quick reference for the busy
cardiologist to support evidence based clinical decision-making.
Pim J. de Feyter MD Robert A. Byrne MB, BCh, PhD
On behalf of the Trials Book Team

May 2020
Randomised trials 2020 3

Randomised trials 2020 Graphisme et mise en page :
Interventional cardiology Groupe Composer : 2, impasse du Ramier des Catalans
2015-2020 CS 38503 - 31685 Toulouse Cedex 6 - France
Directeur de la publication Editeur

Marc Doncieux Frédéric Doncieux
Président: Marc Doncieux.
Coordination éditoriale Principal actionnaire :
Sylvie Lhoste FINANCIERE MF DONCIEUX.
Amy McDowell
Devia Bijkerk ISBN: 978-2-37274-017-3
Veronique Deltort Dépôt légal à parution
Sonia Morcuende
Le contenu de EuroIntervention ne peut être reproduit sans
Coordination digitale autorisation écrite de l’éditeur.
Ronnie Lassiaille
Gregori Despeaux
Coralie Massonnié EuroIntervention est édité par la Société Europa Group,
Davy Bonnafous
SAS au capital de 1 000 000 euros,
Florence Petit
siège social : 19, allées Jean-Jaurès,
Sarah Françoise
31000 Toulouse, France ;
Copyright © Europa Group 2020 RCS Toulouse 342 066 727, APE 8230 Z.
4 Randomised trials 2020

EuroIntervention
Table of contents
Page
1 Drug-eluting and bare metal stents. . . . . . . . . . . . . . . . . . . . . . . . . . 7

2 PCI for STEMI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
3 Stents for left main stem and bifurcation lesions . . . . . . . . . . . . . . . 79
4 Bioresorbable vascular scaffolds. . . . . . . . . . . . . . . . . . . . . . . . . . . 89
5 Drug-coated balloons. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
6 Technical approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
7 Revascularisation strategy: PCI vs CABG. . . . . . . . . . . . . . . . . . . . 111
8 Early invasive vs early conservative strategy ACS . . . . . . . . . . . . . . 127
9 Intravascular imaging-guided PCI . . . . . . . . . . . . . . . . . . . . . . . . . 137
10 Lesion haemodynamic assessment and PCI. . . . . . . . . . . . . . . . . . 143
11 Antithrombotic therapies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
12 Cardiogenic shock and cardiac arrest . . . . . . . . . . . . . . . . . . . . . . 189
13 Percutaneous treatment for structural heart disease. . . . . . . . . . . . 195
14 Renal denervation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229

1· Drug-eluting and bare metal stents
Page
Drug-eluting stents vs bare metal stents .................................................8
Comparisons drug-eluting stents ..........................................................15

1 Drug-eluting stents vs bare metal stents
BES VS EES VS BMS:

BASKET-PROVE II - 2 years
Objective to compare the 2-year clinical outcomes of biodegradable polymer biolimus-A9

(BP-DES) vs second-generation EES (DP-DES) vs thin-stent silicon-carbide-
coated BMS
Study multicentre, randomised, non-inferiority trial (margin 3.8%)
Population patients with chronic or acute CAD requiring PCI
Endpoints combined cardiac death, MI and TVR within 2 years
BP-DES 765
Patients Complete follow-up 2 years

DP-DES 765
2,291 97.7%
BMS 761
Primary endpoint 2 years
Non-inferior (BP-DES vs DP-DES) Superior (BP-DES vs BMS)

% p=0.042 p=0.0011
15
10 12.7
5
7.6 6.8
0
BP-DES DP-DES BMS
Conclusion Treatment with BP-DES appeared non-inferior to DP-DES but superior than
BMS at 2-year follow-up
Kaiser et al. Circulation 2015;131:74-81

Drug-eluting stents vs bare metal stents 1
ZES vs BMS in uncertain DES candidates:

ZEUS
Objective to compare the clinical outcome of second-generation ZES (Medtronic) with

thin-strut (<100 μm) BMS under similar DAPT duration in uncertain DES
indications
Study multicentre, multinational, randomised study
Population patients with stable or unstable symptoms who were at high risk of bleeding/
thrombosis or low risk instent restenosis. Median DAPT duration 32 days
Endpoints MACE: all-cause death, MI or TVR at 1 year
BMS 804
Patients 1:1 Follow-up

1,606 1 year
ZES 802
MACE 1 year
HR 0.76 (95% CI 0.61-0.95)
% p=0.011
25
20
15
22.1
17.5
10
5
0
BMS ZES
Conclusion ZES implantation compared with BMS in patients with uncertain DES
indication is associated with lower MACE rate at 1 year taken into account
a short (1 month) tailored DAPT regimen
Valgimigli et al. J Am Coll Cardiol 2015;65:805-15

1 Drug-eluting and bare metal stents
Titanium-nitride-oxide coated stents vs ZES:

TIDE - 5 years
Objective to compare the 5-year clinical outcomes of treatment with TiNO stent vs ZES
(Endeavor) for coronary revascularisation
Study multicentre, noninferiority, randomised trial
Population patients with stable and unstable angina
Endpoints MACE as cardiac death, MI, clinically-indicated TLR at 5 years
TINO 152
Patients
302
ZES 150
MACE at 5 years
RR 1.13 (95% CI: 0.72-1.75)
%
30
p=0.60
20 27.6 25.3
10
0
TINO ZES
Conclusion there were no differences in clinical adverse events between TiNO and ZES
treatment at 5 years but clinically driven-TVR was increased with these early-
generation stents
Pilgrim et al. EuroIntervention 2015;10:1284-7

Drug-eluting and bare metal stents 1
Polymer-free drug coated coronary stents for patients

at high risk of bleeding: LEADERS FREE
Objective to evaluate the safety and effectiveness of polymer-free umirolimus-coated

stents (transfers biolimus A9 into vessel wall) (Biofreedom stent) as compared
to a bare metal stent (Gazelle stent) in patients with high bleeding risk
Study double blind, multicentre, randomised trial non-inferiority (margin 3.2%) and
superiority
Population patients with perceived high bleeding risk (1 month DAPT)
Endpoints safety endpoint:composite cardiac death, MI or stent thrombosis at 390 days.
Primary efficacy: clinically driven target-lesion revascularisation
Biofreedom stent 1,221
Patients 1:1 Follow-up 390 days:

2,466 98.1% complete
BMS stent 1,211
Safety endpoint 390 days

HR 0.71 (95% CI: 0.56-0.91). p<0.001 non inferiority
% p=0.005 superiority
15
10
12.9
5 9.4
0
Biofreedom BMS
%
Efficacy endpoint 390 days
15 HR 0.50 (95% CI: 0.37-0.69) p<0.001
10
5
9.8
0
5.1
Biofreedom BMS
Conclusion the polymer-free umirolimus-coated stent is superior to BMS in patients at

high-bleeding risk, when used with 1 month dual antiplatelet therapy
Urban et al. NEJM 2015;373:2038-47

1 Drug-eluting and bare metal stents
High bleeding risk patients after polymer-free DES:

LEADERS FREE 2 years
Objective to analyse 2-year outcomes in patients treated with polymer-free DES vs BMS
Study multicentre, double-blind RCT
Population patients with high-bleeding risk undergoing PCI
Endpoints primary safety endpoint was composite of cardiac death, MI, stent thrombosis;
primary efficacy was clinically driven TLR
Polymer-free DES (BioFreedom)

1,211
HBR patients
2,466
BMS
1,211
Safety p=0.039 Efficacy p<0.0001

20
15.3
15 12.0
15 12.6
10
6.8
10
5
5
0 0
PF-DES BMS PF-DES BMS
Conclusion in high bleeding risk patients undergoing PCI, polymer-free DES remained
safer and more effective than BMS at 2 years
Garot et al. J Am Coll Cardiol 2017;69:162-71

Drug-eluting stents vs bare metal stents 1
Drug-eluting stents in elderly patients with coronary artery disease:

SENIOR
Objective to compare the outcome of elderly patients treated with drug-eluting stents vs
bare metal stents
Study single-blind, multicentre, randomised trial
Population patients aged 75 or older, PCI for stable coronary artery disease or acute
coronary syndrome
Endpoints to compare major adverse cardiac and cerebrovascular events between groups
at 1 year
DES 596
Patients
1,200
BMS 694
Primary endpoint 1 year

RR 0.71 (95% CI 0.52-0.94)
p=0.02
%
20
16
12
10
0
DES BMS
Conclusion among elderly patients who have PCI, a DES and a short duration of DAPT are
better than BMS and a similar duration of DAPT with respect to the occurence
of all-cause mortality, myocardial infarction, stroke and ischemia- driven target
lesion revascularisation
Varenne et al. Lancet. 2018;391:41-50

1 Drug-eluting stents vs bare metal stents
Drug-eluting or bare-metal stents in all-comer patients with

coronary artery disease: NORSTENT
Objective to assess the long-term effects of contemporary drug-eluting stents versus

contemporary bare-mental stents on rates of death, myocardial infarction,
repeat revascularisation and stent thrombosis and on quality of life
Study multicentre, open-label, assessor-blinded, randomised controlled trial
Population patients with stable or unstable coronary artery disease
Endpoints composite of death from any cause and nonfatal spontaneous myocardial
infarction after a median of 5 years of follow-up
Drug-eluting stents 4,504

Patients
9,013
Bare-metal stents 4,509
Primary endpoint at 5 years

HR 0.98 (95% CI 0.88-1.09)
P=0.66
%
20 16.6 17.1
15
10
0
DES BMS
Conclusion No significant differences between patients receiving DES and those receiving
BMS in the composite outcome of death from any cause and nonfatal
spontaneous MI. Rates of repeat revascularisation were lower in the group
receiving DES
Bonaa et al. N Engl J Med 2016;375:1242-52

Comparisons drug-eluting stents 1
Everolimus vs paclitaxel-eluting stents:

COMPARE 5 years
Objective to report the 5-year clinical outcomes of revascularisation with everolimus-

eluting stents (EES) compared with paclitaxel-eluting stents (PES)
Study prospective single centre randomised trial
Population all-comers
Endpoints composite death, MI or TVR at 5 years
EES 897
Patients Follow-up 5 years:
PES 903
MACE: 5 years
RR 0.73 (95% CI: 0.61-0.87)
% p=0.0005
35
30
25
20
15
25.1
10 18.4
5
0
EES PES
5 years EES vs PES RR (95% CI) p-value

Mortality % 9.0 10.3 0.88 (0.66-1.16) 0.36
MI % 7.0 11.5 0.61 (0.45-0.82) 0.001
TVR % 6.7 10.7 0.62 (0.46-0.85) 0.003
Def./prob. ST % 3.12 5.9 0.53 (0.34-0.83) 0.005
Conclusion at 5-year follow-up EES remained superior to PES for revascularisation of

coronary stenosis in all-comers
Smits et al. JACC. Cardiovasc. Interv. 2015;8:1157-65

1 Comparisons drug-eluting stents
Biodegradable Polymer BES vs Durable EES:

COMPARE II 5 years
Objective to report the 5 year clinical outcome of the biodegradable polymer biolimus-
eluting stent (BES) with durable polymer everolimus-eluting stent (EES)
Study prospective, multicentre randomised non-inferiority trial (2:1)
Endpoints MACE: cardiac death, MI, or TVR at 5 years
BES
1,795
Patients 2:1 Follow-up complete
2,707 98% at 5 years
EES
912
MACE 5 years
RR: 1.11 (95% CI 0.92-1.33)
p=0.26
%
20
17.3 15.6
15
10
0
BES EES
Conclusion The clinical outcome after 5 year follow-up of BES implantation was
non-inferior compared to EES implantation
Vlachojannis et al. J Am Coll Cardiol Intv. 2017;10:1215-21

Stenting of totally occluded arteries:

PRISON III 3 years
Objective to compare the clinical outcomes of stent implantation for totally occluded
nature arteries with sirolimus-eluting (SES) vs zotarolimus-eluting (Endeavor or
Resolute) ZES stents
Study multicentre, randomised trial
Population patients treated for total coronary occlusions
Endpoints MACE: all-cause death, MI or ischemic-driven TLR at 3 years
SES 51 SES 103
Patients Patients
97 207
Endeavor 46 Resolute 104
MACE 3 years MACE 3 years

% p=0.68 % p=0.84
20 15
19.6
10
11.9
10 14.3 10
5
0 0
SES Endeavor SES Resolute
Conclusion there were no significant differences at 3 years between SES and Endeavor or SES
and Resolute for stent treatment of totally occluded vessels. However, study is
underpowered
Teeuwen et al. EuroIntervention 2015;10:1272-5

Zotarolimus vs everolimus-eluting coronary stents:

RESOLUTE all-comers: 5 years
Objective to report the final 5-year follow-up clinical outcomes of coronary stenosis
treatment with zotarolimus (ZES) compared to everolimus-eluting stents (EES)
Study prospective, multicentre, randomised trial (non inferiority)
Population patients with stable CAD or acute coronary syndromes including STEMI or
NSTEMI
Endpoints device oriented: cardiac death, MI and TLR; patient oriented: all cause death,
MI any revascularisation. MACE: all-cause death, MI, emerg. CABG or TLR
ZES 1,140 Evaluable 5 years:

1,123 (ZES)
Patients
2,292
EES stent 1,211 1,133 (EES)
5-year composite outcome ZES% vs EES% p-value p-value

Device oriented 17.0 16.2 0.61 0.36
Patient oriented 35.3 32.0 0.11 0.001
MACE 21.9 21.6 0.88 0.003
Definite/probable ST 2.8 1.8 0.12 0.005
Conclusion at 5-year follow-up EES remained superior to PES for revascularisation of

coronary stenosis in all-comers
Smits et al. JACC. Cardiovasc. Interv. 2015;8:1157-65

Sirolimus vs. paclitaxel-eluting stents:

SORT OUT II: 10 years
Objective to report the 10-year clinical outcomes of first generation drug-eluting stents
(sirolimus and paclitaxel stents)
Study randomised, controlled trial
Endpoints MACE: cardiac death, MI and TVR
SES 1,065
Patients Alive after
2,098 10 years: 73.1%
PES 1,033
MACE 10 years
HR 0.96 (95% CI: 0.83-1.11)
p=0.60
%
32.5 33.1
35
30
25
20
15
10
5
0
SES PES
MACE rate after first year: 2.6% annual
Conclusion there are no apparent differences in MACE rates between SES and PES
implantation during 10-year follow up
Galløe et al. J Am Coll Cardiol 2017;69:616-24

Everolimus vs Sirolimus-eluting stents:

SORT-OUT IV: 5 years
Objective to report the 5-year safety and efficacy of everolimus vs sirolimus-eluting stents
in patients treated for all-comers
Study multicentre non inferiority randomised trial
Endpoints MACE as cardiac death, MI, TVR and definite stent thrombosis
EES 1,390
Patients Follow-up
2,774 5 years complete
99.9%
SES 1,384
5 years MACE
HR 0.80 (95% CI: 0.66-0.97)
%
p=0.02
20
15
17.4
10 14.0
5
0
EES SES
very late ST: EES 0.2% vs SES 1.4%

HR 0.16 (95% CI: 0.05-0.53)
Conclusion MACE at 5 years was lower with EES – compared SES – treated patients
Jensen et al. J Am Coll Cardiol 2016;67:751-62

Biodegradable polymer BES vs durable polymer SES:

SORT-OUT V 5 years
Objective to report the 5-year safety and efficacy of the biodegradable polymer-coated
biolimus-eluting NOBORI stent compared to the durable polymer-coated
sirolimus-eluting CYPHER stent
Study open-label, multicentre, non-inferiority randomised trial
Endpoints composite of safety: cardiac death, MI, definite stent thrombosis and efficacy-
target vessel revascularisation at 5 years
NOBORI
1,229
Patients
Complete follow-up : 100%
2,468
CYPHER
1,239
Composite endpoint 5 years

OR 0.93% (95% CI: 0.75- 1.16)
p=0.53
%
20
14.8 15.8
10
0
NOBORI CYPHER
Conclusion the 5-year safety and efficacy of implantation of the NOBORI stent was similar
to implantation of the CYPHER stent for treatment of all-comers
Jakobsen et al. EuroIntervention. 2017;13:1337-45

Zotarolimus vs biolimus-eluting stents:

SORT-OUT VI
Objective to investigate the safety and efficacy of biocompatible durable-polymer-coated

zotarolimus eluting stents (ZES) compared with biodegradable-polymer coated
biolimus-eluting stents (BES)
Study multicenter, open-label randomised trial. Non-inferiority trial (margin 0.025)
Population all-comers with stable angina or ACS (Including MI)
Endpoints safety: cardiac death or MI within 12 months and
efficacy: clinically indicated TLR within 12 months
ZES 1,502
Patients 1:1
2,999 Follow-up: 12 months
BES 1,497
Cardiac death/MI/TLR 12 months

p=0.004 (non-inferiority)
risk difference 0.3% (–1.3 to 1.9) p=0.72
%
8
4 5.3 5.0
2
0
ZES BES
Conclusion the ZES-stent is non-inferior to the BES-stent in all-comers within 1-year

follow-up
Raungaard et al. Lancet 2015;385:1527-35

Zotarolimus vs biolimus eluting stents:

SORT-OUT VI: 3 years
Objective to compare the 3 year safety and efficacy of biocompatible durable-polymer

ZES with biodegradable-polymer BES
Study multicentre, randomised, non-inferiority trial
Population patients with chronic CAD and ACS
Endpoints MACE: cardiac death, MI and TLR at 36 months
ZES 1,507
Patients Complete data
2,999 99.7% at 3 years
BES 1,497
MACE at 3 years
HR 0.90 (95% CI: 0.71-1.14)
p=0.36
%
10 8.6 9.6
0
BES ZES
Conclusion implantation of BES compared to ZES is associated with similar clinical

outcome at 3 years
Raungaard et al. J Am Coll Cardiol Intv 2017;10:255-64

Sirolimus- versus biolimus-eluting stents:

SORT-OUT VII trial
Objective to compare safety and efficacy of 2 third generation DES’s: a biodegradable

polymer ultrathin strut sirolimus eluting stent (ORSIRO) versus a biodegradable
polymer biolimus-eluting stent (NOBORI)
Study multicentre randomised non-inferiority study (margin 3%)
Endpoints target lesion failure as a composite of cardiac death, MI or target lesion
revascularisation at 1 year
ORSIRO 1,261
Patients Complete follow-up
2,525 99.9%
NOBORI 1,264
Target lesion failure 1 year

Risk difference –0.78%
%
p <0.0001 1-sided non inferiority
10
6
3.8 4.6
4
0
ORSIRO NOBORI
Conclusion the sirolimus-eluting OSIRO stent was non-inferior to the biolimus-eluting

NOBORI stent at 1-year follow-up
Okkels-Jensen et al. Circ. Cardiovasc. Interv. 2016;9:e003610

Everolimus-eluting vs biolimus-eluting stents with biodegradable

polymers: SORT-OUT VIII Trial
Objective to compare the clinical efficacy of a thin-strut biodegradable polymer

everolimus-eluting platinum-chromium stent (EES) with a bio-degradable-
polymer biolimus-eluting stainless-steel stent (SES)
Study multicentre randomised non-inferiority trial (margin of 3% risk at 12 months)
Endpoints target lesion failure as a composite of safety (cardiac death and MI) and
efficacy (target lesion revascularisation) at 12 months
EES 1,385
Patients
2,764
BES 1,379
Target lesion failure 12 months

Absolute risk difference 0.4%
% p<0.001
5 4.4
4.0
4
0
EES BES
Conclusion EES was non-inferior to BES in terms of major adverse events at

1 year
Maeng et al. J Am Coll Cardiol Intv. 2019;12:624-33

5-year outcomes after implantation of ZES or EES:

TWENTE
Objective to compare 5-year results with durable polymer ZES versus EES
Study multicentre, patient-blinded RCT
Population patients with stable CAD or NSTE-ACS with no limit on lesion complexity or
disease burden
Endpoints target vessel failure (cardiac death, target vessel MI or TVR)
ZES 697
Patients
1,391
EES 694
TVF p=0.36
20 18.1
16.1
15
10
0
ZES EES
Conclusion long-term outcomes in patients treated with either durable polymer ZES or EES
were broadly similar
Von Birgelen et al. JAMA Cardiol. 2017;2:268-76

Zotarolimus-eluting versus everolimus-eluting stents DUTCH PEERS:

TWENTE II 5 years
Objective to report the 5 years clinical outcomes of zotarolimus-eluting (Resolute

Integrity) as compared to Everolimus-eluting (Promus Element) coronary
stenting in all-comers
Study multicentre, patient-blinded randomised trial
Population all-comers giving informed consent
Endpoints TVF as a composite of cardiac death, target-vessel MI or clinically-indicated
TVR at 5 years
ZES 906
Patients Clinical follow-up:
1,181 99.3% at 5 years
EES 905
Target vessel failure at 5 years

HR 0.94 (95% CI 0.73 to 1.21)
p=0.62
%
15 13.2 14.2
10
0
ZES EES
Conclusion at 5 years there were no significant differences of adverse clinical events

between stenting with zotarolimus-eluting as compared to everolimus-eluting
stents used in all-comers
Zocca et al. J Am Coll Cardiol Interv. 2018;11:462-9

Randomised trial of durable polymer zotarolimus-eluting versus

biodegradable polymer sirolimus-eluting stents: BIONYX
Objective to compare ZES with durable polymer versus SES with biodegradable polymer
Study randomised, multicentre, non-inferiority trial
Population all-comer population at 7 centres in Belgium, Netherlands, Israel
Endpoints target vessel failure at 12 months
ZES (Resolute Onyx)

1,243
All-comer patients
2,516
SES (Osiro)
1,245
Target vessel failure

Pnon inferiority=0.0005
% 4.5 4.7
5
0
ZES SES
Conclusion ZES was non-inferior to SES for clinical outcomes at 1 year
Von Birgelen et al. Lancet. 2018;392:1235-45

Biodegradable polymer everolimus-eluting and sirolimus-eluting

stents vs durable polymer zotarolimus-eluting stents: BIO-RESORT
Objective to investigate in all-comers the safety and efficacy of three stents eluting either
everolimus, sirolimus or zotarolimus
Study investigator-initiated, multicentre, double-blind, randomised non-inferiority trial
Population all-comer patients aged 18 years or older
Endpoints composite safety: cardiac death or target vessel-related myocardial infarcation
and efficacy: target vessel revascularisation at 12 months
1,172 everolimus-eluting stent

(synergy)
Patients 1,173 zotarolimus-eluting stent

3,545 (resolute)
1,169 sirolimus-eluting stent

(orsiro)
P non inferiority for EES and SES <0,001

%
10
6 5 5 5
4
0
everolimus-eluting sirolimus-eluting zotarolimus-eluting
Conclusion at 12 months, biodegradable polymer everolimus-eluting and sirolimus-eluting

stents were non-inferior to durable polymer zotarolimus-eluting stents
Von Birgelen et al. Lancet 2016;388:2607-17

ISAR-TEST 4:
5-year outcome
Objective to report the final 5-year clinical outcomes of biodegradable polymer SES
(Yukon Choice PC) versus permanent polymer EES (Xience) versus permanent
polymer SES (Cypher)
Study randomised clinical trial
Population real world patients undergoing PCI
Endpoints composite cardiac death, MI or TLR at 5 years
Biodegradable
(YUKON) 1,299
Patients 5-year follow-up
2,603 XIENCE 652
Permanent polymer 91.2%
1,304
CYPHER 652
Primary endpoint 5 years Primary endpoint 5 years

HR 1.04 (95% CI 0.84 to 1.29) HR 1.21 (95% CI 0.95 to 1.53)
p=0.71 p=0.12
% % 23.5
25 20.5 19.5 25 19.5
20 20
15 15
10 10
5 5
0 0
YUKON XIENCE CYPHER XIENCE
YUKON XIENCE CYPHER

Stent thrombosis % 1.2 1.4 2.4 n.s.
Conclusion YUKON, XIENCE and CYPHER stent implantation was associated with
comparable 5-year clinical outcome
Kufner et al. EuroIntervention 2016;1372-8

BP-SES vs. PP-EES vs. PP-SES:

10-year follow-up ISAR-TEST 4
Objective to compare the efficacy and safety of biodegradable polymer based sirolimus-
eluting stents (BP-SES, YOKON CHOICE) vs. permanent polymer-based
everolimus-eluting stents (PP-EES, XIENCE) vs. early generation permanent
polymer-based sirolimus-eluting stents (PP-SES, CYPHER) during 10-year
follow-up
Study 2 centre, prospective randomised trial
Population – patients with ischemic symptoms and ≥50% de novo stenosis
– excluded: left main and cardiogenic shock
Endpoints MACE as death, MI or target lesion revascularisation at 10 years
BP-SES 1,299
Patients
2,603 PP-EES 652 Follow-up available: 83%
PP-SES 652
MACE at 10 years
HR: BP-SES vs. PP-SES 0.82 (98.3% CI 0.69-0.96)
HR: PP-EES vs. PP-SES 0.79 (98.3% CI 0.65-0.96)
HR: PP-SES vs. PP-EES 1.04 (98.3% CI 0.87-1.24)
%
54.9
60 47.7 46.0
30
0
BP-SES PP-EES PP-SES
Conclusion BP-SES and PP-EES showed comparable clinical outcomes at 10 years.

PP-SES was associated with higher adverse event rate at 10 years
Kufner et al. Circulation. 2019;139:325-33

Sirolimus- and probucol-eluting versus zotarolimus-eluting stents:

ISAR-TEST-5 Trial 5 years
Objective to evaluate the 5-year clinical outcome of polymer-free SES and probucol
stents compared to durable polymer-based ZES-stent
Study multicentre non-inferiority randomised trial (2:1)
Population symptomatic patients with signs of ischemia. L main excluded
Endpoints composite of cardiac death, MI or TLR at 5 years
SE/probucol 2,002
Patients 2:1 Follow-up 5 years
3,002 complete 89.8%
ZES 1,000

HR 0.98 (95% CI 0.84-1.15)
p=0.80
% 23.8 24.2
25
20
15
10
0
SES/probucol ZES
5 years definite or probable ST% 1.3 versus 1.6 (p=0.64)
Conclusion 5-year clinical outcomes were similar for treatment with SES/probucol stent
and ZES stents
Kufner et al. JACC Cardiovasc Interv 2016;9:784-92

Bioresorbable polymer SES vs permanent polymer EES:

CENTURY II 5 years
Objective to report the 5-year clinical outcomes of bioresorbable polymer SES (BP-SES;
Ultimaster) compared to permanent polymer EES (PP-EES; Xience)
Study prospective, single-blind multicentre, non-inferiority randomised trial
Endpoints freedom of target lesion failure: cardiac death, TU-MI and target lesion
revascularisation at 5 years
BP-SES
551
Patients
Complete follow-up: 95.9%
1,101
PP-EES
550
Freedom target lesion failure at 5 years

p=0.54
% 90.0 91.1
100
50
0
BP-SES PP-EES
Conclusion the BP-SES stent was non-inferior to PP-EES stent in terms of freedom
of target lesion failure at 5 years
Wijns et al. EuroIntervention. 2018;14:e343-51

ORSIRO stent vs Xience prime / Xpedition stent:

BIOSCIENCE 5 years
Objective to report the 5 year clinical outcomes of an ultra thin cobalt-chromium

biodegradable-polymer sirolimus-eluting stent (ORSIRO) compared to a thin-
strut, durable-polymer everolimus-eluting stent (Xience prime)
Study single blind, multicenter randomised non-inferiority trial (margin 3.5%)
Endpoints target-vessel failure as cardiac death, MI and clinically indicated TLR
at 5 years
ORSIRO
1,063
Patients
Complete follow-up: 95% at 5 years
2,119
Xience
1,056
Target vessel failure at 5 years

RR 1.07 (95% CI: 0.88 to –1.31)
p=0.487
%
25 20.2 18.8
0
ORSIRO Xience
There was no difference in rate of definite stent thrombosis

at 5 years between the two groups
Conclusion the 5 year target vessel failure rate is similar for ultra thin strut biodegradable
SES and thin strut durable polymer EES for PCI among all-comers
Pilgrim et al. Lancet. 2018;392:737-46

Bioresorbable polymer-coated everolimus-eluting stent:

EVOLVE II
Objective to determine the safety and efficacy of the Synergy stent (bioresorbable
polymer-coated everolimus-eluting stent), compared to Promus stent
(everolimus eluting stent)
Population patients with non-ST-segment elevation ACS or stable CAD
Endpoints target lesion-failure at 12 months- a composite of any ischaemia driven
revascularisation of target lesion, MI related to target vessel or any cardiac
death
Synergy 846 Follow-up 98.2%

Patients 1:1
1,684
Promus 838 Follow-up 96.2%

% p=0.0003 for non-inferiority
10
8
6
4
6.7 6.5
2
0
Synergy Promus
Conclusion The 1-year target lesion failure rate of the Synergy bioabsorbable polymer
everolimus-eluting stent was non-inferior to Promus element everolimus-eluting
stents
Kereiakes et al. Circ Cardiovasc. Interv. 2015;8:e002372

Thin-strut, bioresorbable polymer-coated EES:

EVOLVE II – 5 years
Objective to report the 5-year clinical adverse event rate of the Synergy stent (thin-strut,
bioresorbable polymer-coated everolimus-eluting stents) compared to Promus
Element Plus stent
Population patients with stable angina or non STEMI
Endpoints 5-year target lesion failure: cardiac death, MI or ischaemia driven TLR
Synergy 846
Patients
1,684
Promus 838
5-year target lesion failure

%
p=0.91
20
14.3 14.2
0
Synergy Promus
Conclusion Synergy stent implantation was non-inferior compared to Promus stent

implantation with respect to 5-year major adverse event rate in patients with
stable CAD or non STEMI patients
Kereiakes et al. Circulation Cardiovasc Interv. 2019;12:e008152

Nobori drug eluting stent vs Taxus stent:

NOBORI 1 trial 5 years
Objective to report the 5-year clinical outcome of the Nobori DES (Biolimus A9) as
compared to TAXUS DES (Express/Liberte)
Study multicentre, randomised trial (2:1 ratio)
Population patients needing PCI with up to two de novo lesions
Endpoints composite of any death, any MI or revascularisation at 5 years
NOBORI 238
Patients 2:1 Follow-up 5 years:

363 96% complete
TAXUS 125
Composite endpoint 5 years

p=1.00
%
30
27.3 27.2
20
10
0
NOBORI TAXUS
Conclusion this relatively small sized study showed no difference in adverse events at
5 years between Nobori DES and TAXUS DES
Chevalier et al. EuroIntervention 2015;11:549-554

Nobori BES versus EES (Xience/Promus):

NEXT 5 years
Objective to report the 5-year clinical outcome of a biolimus-eluting (BES) versus

everolimus-eluting (EES) stent implantation
Study prospective, multicentre, randomised non-inferiority trial (margin hazard ratio
1.38)
Population stable angina and unstable patients (17%)
Endpoints any target vessel lesion revascularisation (TLR) and safety composite: death or
MI
Eligible
for 5 year BES 1,283
Complete follow-up
Patients FU substudy 2,408
3,241 2,568 (93.8%) at 5 years
EES 1,285
TLR at 5 years Death/MI at 5 years

HR 1.04 (95% CI 0.8-1.34) HR 0.91 (95% CI 0.75-1.11)
P non inferiority=0.01 P non inferiority <0.0001
% 9.8 9.3 %
10 20
15.1 16.5
15
5 10
5
0 0
BES EES BES EES
Conclusion at 5 years the clinical outcome of a BES-stent is non-inferior to an EES-stent

implantation
Natsuaki et al. EuroIntervention 2018;14:815-8

Paclitaxel vs Everolimus-eluting stents in Diabetes:

TUXEDO
Objective to compare the clinical outcomes of paclitaxel-eluting stents (TAXUS) versus

everolimus-eluting stents (Xience) in patients with Diabetes
Study multicentre, randomised non-inferiority study (margin 4% points for upper
boundary of 95% CI)
Population patients with symptomatic CAD and diabetes mellitus
Endpoints target-vessel failure defined as composite of cardiac death, target-vessel MI or
ischaemia-driven TV revascularisation at 1 year
TAXUS 914
Patients Follow-up 1 year:

XIENCE 916
Target-vessel failure at 1 year

p=0.38 non-inferiority
%
risk difference 2.7% (93% CI 0.8-4.5)
6
5.6
3
2.9
0
TAXUS XIENCE
1 year TAXUS vs Xience p-value

TVF 5.6% vs 2.9% 0.005
MI 3.2% vs 1.2% 0.004
ST 2.1% vs 0.4% 0.002
TVR 3.4% vs 1.2% 0.002
Conclusion in symptomatic CAD patients with diabetes paclitaxel stents were not non-
inferior compared to everolimus stents, with higher MACE with paclitaxel
at 1 year
Kaul et al. NEJM 2015;373:1709-19

Excel versus BuMA stents:

PANDA III trial
Objective to determine whether BuMA SES (PGLA polymer-based sirolimus-eluting stent)

is non inferior or superior to the Excel (PLA polymer-based sirolimus-eluting
stent)
Study multicentre randomised controlled inferiority trial (margin 3.5%)
Endpoints TLF as composite cardiac death, target vessel MI or ischemia driven TLR at
1 year
BuMA SES 1,174 Follow-up 99.6%

Patients
2,348
Excel SES 1,174 Follow-up 99.1%
TLF at 1 year
difference 0.06% (95% CI - 1.93 to 2.04)
p=0.0003 (non-inferiority)
% p superiority=0.95
10
8 6.4 6.4
6
0
BuMA - SES Excel - SES
Conclusion The 1-year target lesion failure of BuMA-SES was non-inferior compared to
Excel-SES for treatment of all-comers
Xu et al. J Am Coll Cardiol 2016;67:2249-58

Comparison between two biodegradable polymer stents:

PANDA III 2 years
Objective to compare 2-year outcomes with BP-SES (BUMA) vs BP-SES (EXCEL)

Study multicentre, non-inferiority, RCT
Population all comers, no exclusion criteria for lesion complexity or disease burden
Endpoints TLF
BP-SES (BUMA)
1,174
Patients
2,348
BP-SES (EXCEL)
1,174
TLF p=0.67
15
10 7.4 6.9
5
0
BUMA EXCEL
Conclusion two years rates of TLF were similar with both types of BP-SES
Wang et al. EuroIntervention 2018;14:e1029-37

Everolimus-Eluting Stents:
PLATINUM-Trial 5 years
Objective to report the final 5-year clinical outcome of platinum-chromium everolimus

eluting stent (PtCr-EES) compared to cobalt chromium everolimus eluting stent
(CoCr-EES)
Study multicentre open-label non inferiority randomised trial
Population patients with stable and unstable angina (excluded CTO)
Endpoints target lesion failure: cardiac death, T-V-MI or ischemia-driven target lesion
revascularisation
PtCr-EES 768 Completed follow-up: 94.6%

Patients
1,530
CoCr-EES 762 Completed follow-up: 93.5%
Target lesion failure 5 years

HR 0.97 (95% CI 0.69-1.37)
p=0.87
%
10 9.1 9.3
0
PtCr-EES CoCr-EES
Conclusion the 5-year clinical outcome of PtCr-EES is comparable to that of CoCr-EES
Kelly et al. J Am Coll Cardiol Intv. 2017;10:2392-400

Randomised Comparison of Ridaforolimus-and Zotarolimus-Eluting

Coronary Stents in Patients with Coronary Artery Disease: BIONICS
Objective to evaluate in a non-inferiority design the relative safety and efficacy of

ridaforolimus-eluting stents (RESs) and slow-release zotarolimus-eluting stents
Study multicentre, randomised controlled trial, non-inferiority design
Population stable coronary artery disease and ACS (not STEMI) patients
Endpoints target lesion failure (composite of cardiac death, target vessel-related
myocardial infarction, and target lesion revascularisation) at 1 year
RES 975
Patients 1:1
1,919
ZES 969
Primary endpoint at 1 year

p=0.001
%
6 5.4 5.4
0
ZES RES
Conclusion novel RESs met the prespecified criteria for non-inferiority compared with
zotarolimus-eluting stents for the primary end point of target lesion failure at
12 months
Kandzari et al. Circulation. 2017;136:1304-14

Sirolimus-bioabsorbable polymer-coated stent vs. everolimus durable

polymer stent after PCI: DESSOLVE III
Objective to investigate the clinical outcomes of implantation of a sirolimus-

bioabsorbable polymer-coated stent (MiStent) versus everolimus-eluting
durable polymer stent (Xience)
Study single-blind, multicentre, phase 3 non-inferiority randomised trial (phase 3
study; margin of 4.0%)
Endpoints composite of cardiac death, target-vessel MI or clinically indicated T-L
revascularisation at 1-year
MiStent 697 (6 no procedure) 1 year: 653

Patients
1,398
Xience 690 (5 no procedure) 1 year: 666

absolute difference –0.8% (95% CI –3.3 to 1.8)
Pnon-inf.=0.0001
%
10
8 6.5
5.8
6
0
MiStent Xience
Conclusion the sirolimus-eluting bioabsorbable polymer stent was non-inferior to the

everolimus-eluting durable polymer stent during 1 year follow-up
de Winter et al. Lancet. 2018;391:431-40

Bioresorbable polymer SES vs durable polymer EES:

BIOFLOW V
Objective to examine the clinical outcomes of an ultrathin bioresorbable polymer

sirolimus-eluting stent (Biotronik) compared with a durable polymer
everolimus-eluting stent (Xience)
Study prospective, multicentre, randomized (2:1) trial
Population patients with stable and unstable CAD and non-STEMI / unstable angina
Endpoints target lesion failure as a composite of cardiovascular death, target-vessel MI or
ischemia-driven target lesion revascularisation at 12 months
Biotronik 12 months
884 833
Patients 2:1
1,334
Xience 12 months
450 427

95% CI: –6.84 to –0.29
p=0.0399
%
12 10.0
6.0
6
0
Biotronik Xience
Conclusion the implantation of an ultra-thin bioresorbable polymer sirolimus-eluting stent

was associated with less adverse events at 12 months compared with a durable
polymer everolimus-eluting stent for treatment of patients with stable angina
and ACS
Kandzari et al. Lancet. 2017;390:1843-52

Biodegradable Polymer SES vs durable polymer EES:

BIOFLOW-II 5 years
Objective to compare the 5-year clinical outcomes of biodegradable polymer sirolimus-

eluting stent O-SES with a durable polymer everolimus-eluting stent X-EES
Study multicentre 2:1 non-inferiority randomised trial
Population patients with stable angina
Endpoints TLF as a composite cardiac death, target vessel MI and clinically driven TLR
at 5 years
O-SES
298
Patients 2:1
Complete follow-up: 96.9%
452
X-EES
154
TLF at 5 years
HR 0.81 (95% CI 0.46-1.44)
p=0.473
%
15 12.7
10.4
0
O-SES X-EES
Conclusion the biodegradable polymer SES was associated with similar 5-year adverse
events compared to durable polymer EES
Lefevre et al. J Am Coll Cardiol Intv. 2018;11:995-1002

Permanent polymer zotarolimus vs. polymer-free amphilimus stent:

ReCre8
Objective to compare the clinical safety and efficacy of polymer-free amphilimus-eluting

stents (PF-AES) with permanent-polymer zotarolimus-eluting stents (PP-ZES)
Study physician-initiated, prospective multicentre, randomised non-inferiority trial
(1:1; margin 3.5%)
Endpoints target lesion failure as cardiac death, target-vessel MI or target-lesion
revascularisation at 12 months
PF-AES
747
Patients 1,491
Follow-up 100%
1,502 stented
PP-ZES
744
Primary endpoint 12 months

Risk-difference 0.5%
upper-limited 1-sided 95% CI 2.6%
Pnon-inf =0.0086
%
10
6.2 5.6
5
0
PF-AES PP-ZES
Conclusion PF-AES is non-inferior to PP-ZES in treating all-comers at 12 months
Rozemeijer et al. Circulation. 2019;139:67-77

Platinum-chromium vs Cobalt-chromium EES:

PLATINUM-PLUS
Objective to compare the safety and efficacy of platinum chromium based everolimus-
eluting stents (EES) with a cobalt-chromium EES
Study prospective, multicentre, single-blind, non-inferiority randomized 2:
1 trial (absolute difference <3.0%)
Population all-comers with stable and unstable CAD (33%)
Endpoints TVF as composite of target vessel death, MI or ischemia-driven TVR
at 12 months
Platinum EES
1,952
Patients 2:1
Completed follow-up: 96%
2,980
Cobalt EES
1,028
Primary endpoint 12 months (intention to treat)

Absolute difference 1.4%
(95% CI: –0.1 to –2.9)
%
10
4.6
5 3.2
0
Platinum EES Cobalt EES
Conclusion Platinum-chromium EES is non-inferior to Cobalt-chromium EES at 1 year

after implantation in all-comers
Fajadet et al. EuroIntervention. 2017;12:1595-604

FIREHAWK stent vs Xience Stent:

TARGET ALL COMERS
Objective to investigate the clinical outcomes of a localised abluminal groove low-dose

sirolimus-eluting biodegradable polymer coronary stent (Firehawk) compared to
a durable polymer everolimus-eluting stent (Xience)
Study prospective, multicentre open-label non-inferior randomized trial (non-inferiority
margin 3.5%)
Population all-comers (stable angina 47%)
Endpoints target lesion failure: cardiovascular death, target-vessel MI and ischemia-driven
target lesion revascularisation at 12 months
FIREHAWK
Excluded 758
Patients 131
Follow-up: 96%
1,653
Xience.
764

difference 0.2% (95% CI: –1.9 to 2.2)
P non-inferiority 0.004
%
10
6.1 5.9
5
0
Firehawk Xience
Conclusion the clinical outcome of the FIREHAWK stent implantation was non-inferior
to the Xience stent implantation at 12 months in all-comers
Lansky et al. Lancet. 2018;392:1117-26

Sirolimus-eluting coronary stent with ultra-thin struts (Supraflex):

TALENT
Objective to compare the clinical outcome of the Supraflex stent with Xience stent
(everolimus-eluting stent)
Study prospective, randomised, single-blind, multicentre, non inferiority study
(margin 4.0%)
Endpoints composite of cardiac death, target-vessel MI or clinically indicated target-lesion
Supraflex 720
Patients
1,436
XIENCE 715
Primary end point 1 year

absolute difference 0.3%
% P non inferiority <0.0001
10
4.9 5.3
5
0
Supraflex XIENCE
Conclusion the Supraflex stent was non-inferior compared to Xience stent at 12 months in
all-comer population
Zaman et al. Lancet 2019;393:987-97

First-generation SES vs new-generation EES:

RESET 7 years
Objective to compare the 7 year clinical outcomes of a first generation sirolimus-eluting

stent (SES) with a new generation everolimus-eluting stent (EES)
Study prospective multicentre randomised trial (non-inferiority)
Endpoints any target lesion revascularisation at 7 years
EES 1,335
Patients 7 year patients Completed 91.5%
3,197 2,667
SES 1,332
Target lesion revascularisation 7 years

HR 0.87 (95% CI: 0.68-1.10) p=0.24
%
20
10.2 11.7
10
0
EES SES
7-year cardiac death or MI:
EES 20.6% vs BES 23.6%
HR 0.85 (95% CI: 0.72-1.005) p=0.06
Conclusion the need for target lesion revascularisation was, during a follow-up duration of
7 years, not different with new generation EES compared to first generation
SES
Shiomi et al. J Am Coll Cardiol Intv. 2019;12:637-47

Sirolimus-eluting vs Everolimus-eluting stents for STEMI:

BIOSTEMI
Objective to investigate the safety and clinical efficacy of ultra thin strut biodegradable
polymer SES compared to thin strut durable-polymer EES in patients with
STEMI
Study multicentre, prospective, single blind randomised trial
Population patients with STEMI referred for primary PCI
Endpoints target lesion failure as cardiac death, target vessel MI, clinical indicated TL
revascularisation during 12 month follow-up
SES 649 (Orsiro)

Patients Complete follow-up 95%
1,300
EES 651 (Xience Xpedition)

RR 0.59 (95% bayesian Crl)
(0.37-0.94)
%
10 Posterior probability superiority 0.986
6
5 4
0
SES EES
Conclusion biodegradable polymer SES treatment was superior to durable polymer EES
treatment in patients with STEMI
Iglesias et al. Lancet. 2019;394:1243-53

Bioresorbable polymer SES

vs durable polymer EES: BioFlow IV
Objective to compare safety and efficacy of a new third-generation sirolimus-eluting stent

system with bioresorbable polymer (Orsiro) compared with an everolimus-
eluting stent system with permanent polymer (XIENCE)
Study prospective, international, multicentre, 2:1 randomised, non-inferiority tria
Population patients with stable CAD or ACS (not STEMI) and de novo lesions in ≤2 vessels
Endpoints target vessel failure
ORSIRO SES
385
Patients with CAD
575
XIENCE EES
190
Difference −2.27% (2.29%)

% p non-inf <0.001
10
7.5
5.5
5
0
SES EES
Conclusion Orsiro SES was non-inferior to XIENCE EES
Saito et al. EuroIntervention. 2019;15:e1006-13

Polymer-based vs Polymer-free stents

in patients at high bleeding risk: ONYX ONE
Objective to compare polymer-based zotarolimus-eluting stents with polymer-free

biolimus-coated stents in patients at high bleeding risk
Study prospective, multicentre, non-inferiority randomised trial
Population patients undergoing PCI classified as being at high bleeding risk
Endpoints composite of death from cardiac causes, myocardial infarction, or stent
thrombosis at 1 year
Polymer-based ZES + 1 month DAPT

1,003
Patients
1,996
Polymer-free BES + 1 month DAPT
993
Cardiac Death, MI or Stent Thrombosis

Diff 0.2% (97.5% CI: 3.5%)
p non inf =0.01
%
20 17.1 16.9
10
0
Polymer ZES Polymer-Free BES
Conclusion among patients at high bleeding risk who received 1 month DAPT after
PCI, use of polymer-based zotarolimus-eluting stents was noninferior to use of
polymer-free drug-coated stents with regard to safety
Windecker et al. N. Eng J Med. 2020; 382:1208-18

2 ∙ PCI for STEMI
Page
Fibrinolysis .........................................................................................56
Stent comparison ................................................................................58
Culprit vs total revascularisation ...........................................................63
Aspiration thrombectomy .....................................................................70
Miscellaneous.....................................................................................72

2 Fibrinolysis
Primary PCI vs Fibrinolysis

in STEMI: DANAMI 2 – 16 years
Objective to investigate the 16-year cardiovascular outcomes in patients with STEMI

treated with primary PCI vs fibrinolysis
Study national, multicentre, randomized controlled enrolling patients at both invasive
and referral centres between December 1997 to October 2001
Population age ≥18 with STEMI (≥30 mins ≤12 hours from pain onset) (and estimated
transfer time ≤3 hours to cath lab if applicable)
Endpoints composite of death or rehospitalisation for myocardial infarction (MI)
Primary PCI
790
Patients with STEMI
1,572
Fibrinolysis
782
Death or rehospitalisation for MI

% HR 0.86 (0.76-0.98)
62.3
80
58.7
60
40
20
0
Primary PCI Fibrinolysis
Conclusion in patients with STEMI the benefit of primary PCI (with or without interhospital
transfer) over fibrinolysis was maintained at 16-year follow-up
Thrane et al. Eur Heart J. 2019;0:1-8

Fibrinolysis 2
Low Dose Intracoronary Alteplase during Primary PCI in patients

with Acute Myocardial Infarction: T-TIME
Objective to determine whether low dose intracoronary fibrinolysis reduces microvascular

dysfunction after primary PCI
Study placebo-controlled, multicentre, randomised controlled trial
Population patients with STEMI <6 hours from onset + occlusion of a major coronary
artery
Endpoints microvascular obstruction (MVO) as % of LV mass at MRI at 2-7 days
Alteplase 20 mg
(n=145)
Patients Alteplase 10 mg
440 with STEMI (n=141)
Placebo
(n=151)
p=0.32
p=0.74
4 3.5
3 2.5 2.3
2
0
20 mg 10 mg Placebo
Conclusion intracoronary alteplase does not reduce microvascular obstruction in patients

undergoing primary PCI
McCartney et al. JAMA. 2019;321:56-68

2 Stent comparison
Everolimus eluting stents vs BMS for STEMI:

EXAMINATION 5 years
Objective to report the 5-year safety and efficacy outcomes of everolimus-eluting stents
(EES) compared with BMS (Multilink Vision) for primary stenting of STEMI
Study multicentre, single blind randomised trial
Population patients with STEMI undergoing PCI within 48 hours of onset of symptoms
Endpoints composite all-cause death MI or revascularisation at 5 years
EES 751
Patients 1:1 Follow-up 5 years:

BMS 747

HR 0.80 (95% CI: 0.65-0.98)
p=0.033
%
26
21 26
16 21
11
1
EES BMS
5 years EES BMS p-value

all-cause mortality 9.0% 12% 0.047
Conclusion at 5-year follow-up EES treatment for STEMI is superior to BMS treatment
mainly driven by reduction of all cause-death
Sabaté et al. Lancet. 2016;387:357-66

Stent comparison 2
Biodegradable polymer DES versus bare metal stents in patients

with STEMI: COMFORTABLE AMI 5-year results
Objective to compare long-term follow-up of BP-DES versus BMS in acute STEMI

Study multicentre, assessor-blind, RCT
Population patients with STEMI undergoing primary PCI
Endpoints MACE defined as cardiac death, target vessel re-infarction or ischaemia-driven,
TLR
BES 575
Patients with STEMI
1,161
BMS 582
p=0.001
MACE 14.9
15
10 8.6
0
BP-BES BMS
Conclusion in patients undergoing primary PCI, MACE at 5 years was significantly lower
with BP-DES compared with BMS
Räber et al. Eur Heart J. 2019;40:1909-19

2 Stent comparison
EES vs SES for primary PCI of acute MI:

XAMI - 3 years
Objective to report the 3-year clinical outcomes of primary PCI for acute MI with second-
generation everolimus-eluting stents compared to first-generation sirolimus
eluting stents
Study multicentre, randomised trial (2:1)
Population patients with acute myocardial infarction
Endpoints MACE as cardiac death, re-MI or TVR at 3 years
EES 400
Patients 2:1
620
SES 220
MACE at 3 years
p=0.30
%
15
10
10.5
5 8.0
0
EES SES
3-year definite/probable stent thrombosis EES 2.3% vs SES 3.2%

p=0.60
Conclusion there were no significant differences in clinical outcome between EES or SES
for stent treatment of patients with acute myocardial infarction
Hofma et al. EuroIntervention 2015;10:1280-3

Stent comparison 2
MGuard implantation for STEMI:

MASTER 1 year
Objective to evaluate the 1-year clinical and angiographic outcomes of MGuard (a BMS
covered with polymer mesh to reduce distal embolisation) stenting compared to
BMS for STEMI treatment (40% DES)
Study prospective, multicentre randomised trial
Population patients with STEMI <12 hours duration prior to PPCI
Endpoints MACCE: all-cause death, re MI, stroke, TLR at 1 year
MGuard 217 Follow-up: 94.9%
Patients 1:1
443
BMS 216 Follow-up: 98.6%
MACCE 1 year
% p=0.04
12
10
8 10.0
6
4
2
4.7
0
MGuard BMS
Stroke at 1 year thrombectomy 1.2% vs PCI alone 0.7% (p=0.015)
Conclusion MGuard stenting for STEMI is associated with higher MACCE rate
(predominantly higher TLR) compared to BMS (40% DES) at 1 year
Dudek et al. Circ Cardiovasc. Interv. 2015;8:e001484

2 Stent comparison
Biodegradable polymer SES in STEMI:

MASTER study
Objective to compare the safety and efficacy of a new biodegradable polymer sirolimus-
eluting stent (ultimaster stent) BP-SES with a bare-metal stent (BMS) for the
treatment of STEMI
Study prospective single blind multicentre non-inferiority randomised trial (3:1)
(margin 3%)
Population patients undergoing primary PCI for STEMI
Endpoints TVF defined as cardiac death, MI or clinically driven TVR at 12 months
BP-SES 375
Patients 3:1
Complete follow-up 98.4%
500
BMS 125
Target vessel failure at 12 months

Pnon-inferiority=0.0004
% 14.4
15
10
6.1
5
0
BP-SES BMS
Conclusion BP-SES was clinically non-inferior to BMS for PCI treatment of STEMI
Valdes-Chavarri et al. EuroIntervention. 2019;14:e1836-42

Culprit vs total revascularisation 2
Complete vs culprit-only revascularisation for PCI STEMI:

CvLPRIT
Objective to test feasibility, safety and benefit of complete revascularisation vs culprit-

revascularisation in STEMI
Study multicentre, randomised study
Population patients with STEMI and multivessel disease undergoing primary PCI
Endpoints composite all-cause death, re-MI, heart failure and ischemia-driven
revascularisation within 12 months
Complete revascularisation 150
Patients 1:1
296
Culprit revascularisation 146
MACE at 12 months
%
HR 0.45 (95% CI 0.24-0.84)
25 p=0.009
20
15
21.2
10
5 10
0
Complete Culprit
revascularisation revascularisation
Complete revascularisation was associated with non-significant

reduction in death, MI, heart failure or repeat-revascularisation
Conclusion in patients with STEMI and multivessel disease complete revascularisation is

associated with reduced MACE at 12 months as compared to culprit-only
revascularisation
Gershlick et al. J Am Coll Cardiol 2015;65:963-72

2 Culprit vs total revascularisation
Compare vs Culprit lesion-only PCI in STEMI:

CvLPRIT 5 years
Objective to report the 5-year clinical outcomes of Complete revascularisation compared

to Culprit-lesion only in patients with STEMI and multivessel disease
Study multicentre randomised trial
Population patients with STEMI and multivessel disease undergoing primary PCI
Endpoints MACE as composite of all-cause death, MI, ischemia-driven revascularisation
and heart failure at 5-years
Complete 150
Patients median follow-up achieved
296 in >90% of patients
Culprit 146
MACE at 5 years
HR 0.57 (95% CI: 0.37 to 0.87)
p=0.0079
%
40
37.7
24.0
20
0
Complete Culprit-only
Conclusion 5-year follow-up complete vs culprit-only lesion PCI treatment of patient with
STEMI and multivessel disease demonstrated that complete revascularisation
was associated with lower rate of MACE
Gershlick et al. J Am Coll Cardiol. 2019;74:3083-94

STEMI: complete revascularisation vs culprit lesion only:

DANAMI-3 – PRIMULTI
Objective to evaluate the clinical outcome of complete revascularisation using an FFR-

guided approach compared to culprit vessel treatment only for patient with
STEMI and multivessel disease
Study open label, randomised controlled trial
Population patients with STEMI less than 12 hrs duration and having multivessel disease
Endpoints composite all-cause death, re MI, ischaemia-driven revascularisation of lesions
in non-infarct related arteries at follow-up 27 months median
infarct vessel only 313
Patients
627
complete revascularisation 314 (2 days after PPCI)
Primary endpoint median 27 months

%
HR 0.56 (95% CI: 0.38-0.83)
25 p=0.004
20
15
22.0
10
13.0
5
0
infarct vessel only complete
revascularisation
No differences in all-cause death or re-MI. Ischaemia-driven revascularisation
culprit only 17% vs complete revascularisation 5%.
Conclusion FFR-guided complete revascularisation in STEMI with multivessel disease

reduces ischaemia driven revascularisation compared to culprit lesion
treatment only, but there was no difference of all-cause death or re-MI
Engstrom et al. Lancet. 2015;386:665-71

Deferred vs. Conventional stent implantation in STEMI patients:

DANAMI 3 – DEFER
Objective to report the 2-year clinical outcomes of deferred stent implantation compared
with standard PPCI in STEMI patients
Study open label, multicenter randomised trial
Population STEMI patients within 12 hours onset of symptoms. Deferred stent
implantation was done after stabilisation infarct related artery with balloon
dilatation (TIMI2,3)
Endpoints composite all-cause death, hospital admission, heart failure, re-MI or
unplanned revascularisation of TL within 2-year follow-up
Standard PCI 612
Patients median follow-up

1,215 42 months
Deferred PCI 612

HR 0.99 (95% CI 0.76-1.29)
% p=0.92
20
15 18 17
10
0
Standard PCI Deferred PCI
Conclusion deferred stent implantation does not reduce death, heart failure, MI or
revascularisation in patients with PCI for STEMI
Kelbaek et al. Lancet 2016;387:2199-206

Complete revascularisation with MV-PCI for MI:

COMPLETE Trial
Objective does staged complete revascularisation with PCI for STEMI (non-culprit)
reduce adverse events compared to PCI of culprit-lesion only in acute MI with
MV-Disease
Study multinational randomised trial
Population STEMI patients with MV-Disease staged non-culprit lesion PCI performed
either during or after index hospitalisation
Endpoints first composite cardiovascular death or MI. Second composite cardiovascular
death, MI or ischemia-driven revascularisation at median follow-up of 3 years
Complete revascularisation
2,016
Patients
4,041
Culprit-lesion only
2,025
Cardiovasc death/MI: 3 years Cardiovasc death /MI/

HR 0.74 (95% CI: 0.60-0.91) revascularisation: 3 years
P=0.004 HR 0.51 (95% CI: 0.43-0.61)
P<0.001
% %
20 20
16.7
10.5
7.8 8.9
10 10
0 0
Complete Culprit-only Complete Culprit-only
revascularisation revascularisation
Conclusion complete revascularisation (staged) PCI was superior to culprit-lesion only PCI
in patients with STEMI and multivessel disease to reduce adverse events
Mehta et al. N Engl J Med. 2019;381:1411-21

Fractional flow reserve-guided multivessel angioplasty in myocardial

infarction: COMPARE-ACUTE
Objective to compare FFR guided complete revascularisation with infarct-related artery

only revascularisation in STEMI
Study multicentre, randomised, investigator-initiated; 1:2 ratio
Population patients with STEMI and multivessel disease who had undergone primary PCI
of an infarct-related coronary artery
Endpoints composite all-cause death, nonfatal myocardial infarction, revascularisation
and cerebrovascular events at 12 months
FFR guided
Complete revascularisation 295
Patients
885
Infarct-related artery only PCI 590
MACE 12 months
HR 0.35 (95% CI: 0.22-0.55)
p<0.001
%
25 20.5
20
15
10 7.8
5
0
FFR guided IRA only
Conclusion FFR-guided complete revascularisation of non-infarct-related arteries in the

acute setting resulted in a risk of a composite cardiovascular outcome that was
lower than the risk among those who were treated for the infarct-related artery
only
Smits et al. N Engl J Med. 2017;376:1234-1244

Angiography vs stress-echo guided complete revascularisation in

STEMI and MV- disease: CROSS-AMI
Objective to assess the clinical outcome of complete angiographically-guided

revascularisation versus stress-echo guided revascularisation in patients with
STEMI
Population patients with STEMI and multi-vessel disease
Endpoints composite cardiac death, Re MI, revascularisation or admission for heart failure
at 12 months
Angiography
154
Patients
306
Echocardiography
152
Composite end point 12 months

HR 0.95 (95% CI: 0.52-1.72)
p=0.85
%
20
15
14.0 14.0
10
0
Angiography Echocardiography
The trial was prematurely stopped after inclusion of 77% of planned study population
Conclusion angiography-guided compared to stress echocardiography guided complete

revascularisation in patients with STEMI and MV-D the rate of MACE was not
different at 12 months
Calvino-Santos et al. Circ Cardiovasc Interv. 2019;12:e007924

2 Aspiration thrombectomy
Thrombectomy prior to primary PCI for STEMI:

TOTAL trial
Objective to report the clinical outcome of manual thrombectomy prior to PPCI compared
to no thrombectomy before PPCI
Study multicentre, prospective, randomised trial
Population patients referred for primary PCI within 12 hrs after onset of symptoms
Endpoints composite cardiovascular death, re-MI, cardiogenic shock or NYHA class IV
heart failure within 180 days
Thrombectomy 5,033
Patients
10,063
No thrombectomy 5,030
Primary endpoint 180 days

HR 0.99 (95% CI 0.85-1.15)
% p=0.86
15
10
5
6.9 7.0
0
Thrombectomy No thrombectomy
Stroke within 30 days: Thrombectomy 7% vs no thrombectomy 0.3%

p=0.02
No significant difference in cardiovascular death, re-MI or target-vessel revascularisation
Conclusion thrombectomy before primary PCI for STEMI patients does not reduce adverse
cardiovascular events within 180 days but is associated with higher risk of
stroke within 30 days
Jolly et al. N Engl J Med 2015;372:1389-98

Aspiration thrombectomy 2
Thrombus aspiration for PCI for STEMI:

TOTAL trial 1 year
Objective to report the 1-year clinical outcome of thrombus-aspiration during primary PCI
for STEMI
Study prospective, multicentre, randomised trial
Population patients with STEMI referred for PCI within 12 hours of onset of symptoms.
Aspiration started before crossing lesion
Endpoints composite cardiovascular death, MI, cardiogenic shock or heart failure at
1 year
Final study population

Thrombectomy 5,372
5,035
Patients 1:1
10,732
Final study population
PCI alone 5,360
5,029
Composite endpoint 1 year

HR 1.0 (95% CI 0.87-1.15)
%
p=0.99
10
6
8.0 8.0
4
0
Thrombectomy PCI alone
Stroke at 1 year thrombectomy 1.2% vs PCI alone 0.7% (p=0.015)
Conclusion routine thrombectomy during PCI for STEMI does not reduce adverse events at
1 year
Jolly et al. Lancet. 2016;387:127-35

2 Miscellaneous
Pre-treatment PCI
Cyclosporine before PCI in patients with STEMI:

CIRCUS
Objective to test whether cyclosporine, administered before primary PCI in patients with
acute anterior STEMI would improve clinical outcomes and prevent left
ventricular remodeling
Study multicentre, double-blind randomised trial
Population patients with anterior STEMI and occluded culprit coronary artery before
primary PCI
Endpoints composite all-cause death, worsening heart failure or rehospitalisation for heart
failure or adverse LV-remodeling at 1 year
i.v. cyclosporine (2.5 mg/kg body weight) 395

Patients Available
970 for study
Placebo 396
Composite endpoint 1 year

odds ratio 1.04 (95% CI: 0.78-1.39)
% p=0.77
60
50
59 58.1
40
30
20
10
0
cyclosporine placebo
No significant differences of the separate components of the endpoint

were observed between the two groups.
Conclusion cyclosporine given before primary PCI for acute anterior STEMI, did not reduce
clinical outcomes or prevent adverse left ventricular remodeling
Cung et al. NEJM. 2015;373:1021-31

Miscellaneous 2
Early iv beta-blockers in STEMI before PPCI:

EARLY BAMI study
Objective to report the safety and efficacy of iv. beta blockers before PPCI compared with
no beta-blockers before PPCI (placebo)
Study placebo controlled, multicenter, randomised study
Population patients with STEMI with symptoms >30 minutes and <12 hours
Endpoints MACE : cardiac death, non-fatal re-MI and TVR at 30 days
Metoprolol 336
Patients Follow-up 30 days
683
Placebo 346
MACE 30 days
% p=0.72
10
6
6.2 6.9
4
0
Metoprolol Placebo
MRI endpoint mean infarct size metoprolol 15.3%

vs. placebo 14.9% p=0.62
Conclusion early beta blockers before PPCI in STEMI patients does not reduce adverse
clinical events at 30 days
Roolvink et al. J Am Coll Cardiol. 2016;67:2705-15

2 Miscellaneous
Early i.v. beta-blockers in STEMI before PPCI:

EARLY-BAMI
Objective to report the effect of i.v. beta-blockers administration before PCI on the
adverse event rate at 1 year in patients with STEMI
Study double-blind placebo controlled randomised trial
Population patients with STEMI undergoing PPCI
Endpoints composite death, non-fatal MI or revascularisation
Metoprolol 336 One-year follow-up: 92%

Patients
683
Placebo 347
MACE at 1 year
OR 1.07 (95% CI 0.59-1.93)
p=0.835
%
10 7.7 7.3
0
Metoprolol Placebo
Conclusion i.v. metoprolol administration early before PPCI for STEMI does not reduce
clinical adverse events at 1 year
Roolvink et al. EuroIntervention 2018;14:688-91

Miscellaneous 2
Atorvastatin prior to PCI in acute coronary syndromes:

SECURE-PCI
Objective to study the effect of loading doses of atorvastatin (2×80 mg) versus placebo
on clinical outcomes prior to planned PCI for patients with ACS. All patients
received 30 mg atorvastatin after 24 hours
Study double-blind multicentre randomised trial
Population patients with ACS and planned invasive management: 65% PCI, 8% CABG,
27% medical treatment
Endpoints composite of all-cause death, MI, stroke and unplanned revascularisation
through 30 days
Atorvastatin: 2,087
Patients 99.3% completed follow-up
4,191
Placebo: 2,104
Composite MACE at 30 days

Absolute difference 0.85% (95% CI –0.7 to 2.4)
HR 0.88 (95% CI 0.69 to 1.11)
p=0.27
%
10
6.2 7.1
0
atorvastatin placebo
Conclusion Atorvastatin prior to planned PCI for patients with ACS did not reduce major
adverse events at 30 days
Berwanger et al. JAMA. 2018;3:1113-18

2 Miscellaneous
Oxygen therapy in STEMI:

DETO2X-AMI
Objective to determine whether oxygen supply (oxygen 6 L/min for 6-12h) in patients
with PCI for STEMI reduces MACE or procedural adverse events compared
to ambient air
Study open-label multicentre randomised trial
Population patients with suspected AMI who are normoxemic
Endpoints composite of all-cause death, rehospitalisation with MI, cardiogenic shock
or stent thrombosis at 1 year
Oxygen
1,361
Patients
2,807
Ambient Air
1,446

HR 0.85 (95% CI 0.64 -1.13)
p=0.27
%
10
7.5
6.3
0
Oxygen Ambient Air
Conclusion supplemental oxygen in patients with PCI for STEMI does not significantly
reduce 1 year major adverse events
Hofmann et al. Eur Heart J. 2018;39:2730-39

Miscellaneous 2
Remote ischaemic conditioning in acute myocardial infarction:

CONDI-2/ERIC-PCI trial
Objective to report the clinical efficacy of remote ischaemic conditioning as compared to

standard treatment in patients with STEMI undergoing primary PCI
Study international, single-blind, multicentre randomised trial
Population patients with STEMI and primary PCI
Endpoints combined endpoint of cardiac death or hospitalisation for heart failure at
12 months
Control 2,569
(132 excluded)
Patients
5,401
Remote ischaemic conditioning 2,546
(154 excluded)
Cardiac death/heart failure 12 months

HR 1.10 (95% CI: 0.91 to 1.32)
p=0.32
%
9.4
10 8.6
0
Control Remote ischaemic
conditioning
Remote ischaemic conditioning: ischaemia and reperfusion applied to the arm

with 4 cycles of 5 min. inflation and 5 min. deflation of an automated cuff device
Conclusion remote ischaemic conditioning in patients with STEMI and primary PCI does
not reduce cardiac death or heart failure
Hausenloy et al. Lancet. 2019;394:1415-24

3 ∙ Stents for left main stem and bifurcation lesions
Page
Stents for left main and bifurcation lesions ...........................................80

3 Stents for left main and bifurcation lesions
Treatment of coronary bifurcations

DKCRUSH-II 5 years
Objective to report the clinical outcome of double kissing crush (DK-crush) versus
provisional stenting (PS) of coronary bifurcation lesions
Study multicentre, randomised trials
Population symptomatic patients with Medina 1,1,1 or 0,1,1 bifurcation lesions
Endpoints MACE as cardiac death, MI and TVI
DK-crush 185
Patients 4 patients lost to
350 follow-up at 5 years
PS 185
MACE at 5 years
HR 1.67 (95% CI: 0.99-2.83)
P=0.051
% 23.8
25
20
15.7
15
10
0
PS DK-crush
Conclusion the DK-crush technique is associated with a lower 5-year MACE rate as
compared to provisional stenting for the treatment of bifurcation lesions
Chen et al. Circ Cardiovasc Interv 2017;10:e 004497

Stents for left main and bifurcation lesions 3
DK Crush vs culotte stenting for distal left main bifurcations:

DKCRUSH-III: 3 years
Objective to report the differences in clinical outcomes of treatment of distal left main
bifurcation lesions with double kissing crush vs culotte stenting technique
Study prospective multicentre randomised study
Population patients with distal left main bifurcation Medina 1,1,1 or 0,1,1
Endpoints MACE as composite of cardiac death, MI or TVR at 3 years
DK crush 210
Patients Completed follow-up
419 3 years: 99.5%
Culotte 209
MACE: 3 years
%
p<0.001
25
20
23.7
15
10
5
8.2
0
DK crush Culotte
3-year outcome DK crush Culotte p-value

Death % 1.4 2.9 0.34
MI % 3.4 8.2 0.037
TVR % 5.8 18.8 <0.001
Definite ST % 0 3.4 0.007
Conclusion DK crush stenting for distal left main bifurcation lesions is associated with
better 3-year clinical outcome than culotte stenting
Chen et al. JACC. Cardiovasc. Interv 2015;8:1335-42

Double Kissing Crush vs. provisional stenting for left main

bifurcations: DKCRUSH-V
Objective to determine whether DK (double kissing) crush – 2 stent technique is superior

to provisional stenting (PS) for treatment of distal LM bifurcation lesions
Study prospective, randomised, international multi-centre trial
Population symptomatic patients (stable, unstable, AMI >24 h) with LM bifurcation lesion
(Medina 1,1,1 or 0,1,1)
Endpoints target lesion failure: cardiac death, TV-MI or clinical target lesion
DK CRUSH 240 Follow-up complete in all patients

Patients
482
PS 242

HR 0.42 (95% CI 0.21-0.85)
p=0.02
10.7
%
10
5.0
5
0
DK-CRUSH PS
Conclusion a planned double kissing crush 2 stent technique was superior to provisional
stenting for the treatment of left main bifurcation lesions
Chen et al. J Am Coll Cardiol. 2017;70:2605-17

Double Kissing Crush vs. provisional

stenting for left main stenosis: DKCRUSH-V: 3 years
Objective to report the 3-year clinical outcome of double kissing crush stenting versus
provisional stenting (PS) for unprotected left main distal bifurcation lesions
(UPLMb)
Population patients with ischaemic symptoms or myocardial ischaemia and Medina
1,1,1 or 0,1,1 de novo UPLMb lesions
Endpoints TLF as composite of cardiac death, target vessel MI or clinically driven TLR
at 3 years
DK crush 100% complete

240 follow-up
Patients
482
Provisional
242

HR 0.47 (95% CI: 0.28-0.81)
p=0.006
16.9
%
20
15
10 8.3
0
DK crusk PS
Conclusion provisional stenting for unprotected left main distal bifurcation lesions was
associated with increased MACE rate at 3 years as compared to double kissing
crush treatment
Chen et al. JACC Cardiovasc Interv. 2019;12:1927-37

Bifurcation stent vs provisional stenting for bifurcation lesions:

TRYTON
Objective to compare the outcome of a dedicated bifurcation stent (TRYTON Medical)

with side-branch balloon angioplasty with DES for treatment of left main
bifurcation lesions
Study single-blind, multicentre, randomised trial – non-inferiority with margin 5.5%
Population patients with de novo true left main bifurcation lesion
Endpoints target vessel failure (TVF): cardiac death, MI, clinical driven TVR (MB or SB) at
9 months
TRYTON 355 Clinical follow-up 97%
Patients
704
Provisional 349 Angiographic follow-up 87%
TVF 9 months SB in-segment diameter restenosis

pnon-inferiority: 0.42 (not within 5.5% margin) 9 months
p=0.11 p=0.002
% %
20 40
38.6
17.4 31.6
10
12.8 20
0 0
TRYTON Provisional TRYTON Provisional
Conclusion provisional stenting is preferred strategy for treatment of true left main
bifurcation lesions
Généreux et al. J Am Coll Cardiol 2015;65:533-43

Provisional T-stenting vs routine T-stenting:

BBK-1 5 years
Objective to compare the 5-year clinical outcome of treatment of de novo-bifurcation

lesions with provisional T-stenting as compared with routine T-stenting
Population patients with de novo bifurcation lesion
Endpoints incidence of target lesion revascularisation at 5 years
Provisional T-stenting 101
Patients Follow-up 5 years:

202 100% complete
Routine T-stenting 101
TLR 5 years
p=0.97
%
20
15
16.2 16.3
10
0
Provisional T-stenting Routine T-stenting
Conclusion the 5-year TLR rate was similar using provisional T-stenting compared to
routine T-stenting for treatment of de novo bifurcational lesions
Ferenc et al. EuroIntervention 2015;11:856-59

Bifurcation lesions:
SMART-STRATEGY 3 years
Objective to report the 3-year clinical outcome of a conservative strategy compared to

aggressive strategies for provisional side branch (SB) intervention
Study non blinded, single centre, randomised trial
Population patients with stable angina or NON-STEMI and large de novo bifurcation lesion
Endpoints TVF as composite cardiac death, MI or TVR at 3 years
Conservative 128
Patients
258 Follow-up 1 year
Aggressive 130
TVF 3 years
%
p=0.049
25 20.8
20
15 11.7
10
0
Conservative Agressive
Conclusion a conservative strategy for provisional SB intervention is associated with better

3-year outcome compared to an agressive strategy
Song et al. J Am Coll Cardiol 2016;9:517-26

Bifurcation lesion treatment:

EBC Two Study
Objective to compare a provisional strategy with a systematic 2-stent technique for

percutaneous treatment of true bifurcation lesions with significant large sized
ostial disease length side branches
Study multicentre, randomised controlled study
Population symptomatic patients with true bifurcation lesions: SB diameter ≥2.5mm,
ostial disease length ≥5 mm
Endpoints composite of death, MI and TVR at 12 months
Provisioned
103 (16% underwent T-stenting)
Patients
200
2-stents
97

HR 1.02 (95% CI 0.78-1.34)
p=0.53
%
12
10.3
10
7.7
8
0
provisional 2-stent technique
Conclusion the composite death, MI and TVR at 12 months is not different between
provisional stenting and 2-stent technique for treatment of true bifurcation
lesions
Hildick-Smith et al. Circ Cardiovasc Interv 2016;9:e003643

4 ∙ Bioresorbable vascular scaffolds
Page
Bioresorbable vascular scaffolds...........................................................90

4 Bioresorbable vascular scaffolds
Bioresorbable everolimus-eluting scaffold vs Everolimus-eluting

stents: ABSORB II
Objective to report secondary endpoints for clinical and procedural outcomes of 1-year of
treatment with EES scaffold (Absorb) compared to EES (Xience)
Study single-blind, multicentre, randomised trial (2:1)
Population stable patients with evidence of myocardial ischemia
Endpoints secondary endpoints: composite death, MI, revascularisation and anginal status
at 1 year
Follow-up 98%
Absorb 335 complete at 1 year
Patients 2:1
501
Follow-up 99%
Xience 166 complete at 1 year
Secondary endpoint 1 year

% p=0.28
10
5
5
3
0
Absorb Xience
Anginal status by Seattle Angina Questionnaire demonstrated that 74% of patients in both groups
were angina-free
Conclusion at 1 year there was no apparent difference between Absorb and Xience in terms
of MACE and angina
Serruys et al. Lancet 2015;385:43-54

Bioresorbable vascular scaffolds 4
Everolimus-eluting bioresorbable scaffolds vs everolimus-eluting

metallic stents: primary results of ABSORB II 3 years
Objective to assess vasomotion and late loss at 3 years

Study single-blind, prospective, active-controlled, multicentre randomised trial
Population patients aged 18-85 years with evidence of myocardial ischaemia and one or
two de novo native lesions
Endpoints primary endpoint: superiority of bioresorbable vascular scaffold (BVS) versus
metallic stent (EES) in angiographic vasomotor reactivity. Co- primary endpoint:
non-inferiority of angiographic late luminal loss
Absorb BVS 335

Patients
501
Xience EES 166
Primary endpoint 3 years Co-primary endpoint 3 years

P superiority=0.49 P non inferiority=0.78
mm 0.056 mm 0.37
0.06 0.047 0.40
0.30 0.25
0.04
0.20
0.02
0.10
0.00 0.00
BVS EES BVS EES
Conclusion at 3 years vasomotion in the stented segment is not superior with BVS versus
EES and late loss is inferior with BVS
Serruys et al. Lancet 2016;388:2479-91

Everolimus-eluting bioresorbable scaffolds:

ABSORB III
Objective to determine the safety and effectiveness of Absorb scaffold as compared to

Xience stent (everolimus-eluting)
Study multicentre, randomised study. 2:1 design, superiority and non-inferiority
(margin 4.5 percentage points)
Population patients with stable and unstable angina undergoing PCI for one or two
coronary lesions in separate vessels
Endpoints target-lesion failure as composite of cardiac death, MI or ischemia-driven
TL-revascularisation at 1-year
Scaffold 1,322
Patients 2:1 Follow-up: 99.1%

2,008 complete
XIENCE 686

Difference 1.7% (95% CI-0.5-3.9)
p=0.16 superiority
%
8
5 7.8
6.1
3
0
Scaffold XIENCE
1 year Absorb Xience p-value
cardiac death 0.6% 0.1% 0.29
TV-MI 6.0% 4.6% 0.18
TL-revascularisation 3.0% 2.5% 0.50
device thrombosis 1.5% 0.7% 0.13
Conclusion the everolimus-eluting bioresorbable scaffold was non inferior within the 4.5%
margin of non inferiority as compared to the everolimus-eluting cobalt
chromium stent at 1 year follow-up
Ellis et al. NEJM 2015;373:1905-15

Everolimus-eluting Bioresorbable Coronary Scaffolds:

ABSORB III 3 years
Objective to report the 3-year clinical outcome of everolimus-eluting bioresorbable

coronary scaffolds (ABSORB) compared to everolimus-eluting cobalt chromium
stent (Xience)
Study multicentre randomised non-inferiority trial (2:1 design)
Population patients with stable and unstable angina with 1 or 2 de novo lesions
Endpoints target lesion failure as cardiac death, target vessel MI or ischemia driven target
lesion revascularisation through 3 years following stent implantation
ABSORB 1,322 Completed follow-up: 96.5%

Patients 2:1
2,008
Xience 686 Completed follow-up: 96.4%

HR 1.31 (95% CI 0.99-1.73)
p=0.06
%
15 13.4
10.4
10
0
ABSORB XIENCE
device thromosis Absorb 2.3% vs. Xience 0.7% p=0.01
Conclusion the 3 year adverse event rates were higher with Absorb than with Xience stent
implantation
Kereiakes et al. J Am Coll Cardiol. 2017;70:2852-62

Everolimus-eluting Absorb bioresorbable scaffold vs EES:

ABSORB-JAPAN
Objective to report the 1-year clinical outcome of Absorb BVS compared with cobalt-
chromium everolimus-eluting stents (CoCr-EES). (XIENCE Prime)
Study prospective, multicentre, single-blind randomised trial (2:1 ratio). Non
inferiority (8.6% vs 9.0% assumed event-rate)
Population patients with evidence of ischemia (stable and unstable angina)
Endpoints composite of cardiac death, TV-MI or ischemia driven TLR of 1 year
Absorb BVS 266

2:1
Patients Follow-up: 99%
400 complete
CoCr-EES 134
Composite adverse events 1 year

Difference 0.39%. p <0.0001 for non-inferiority
%
5
4.2
3
3.8
BVS CoCr-EES
The stent thrombosis rate was 1.5% with both devices
Conclusion the Absorb BVS is comparable to CoCr-EES in terms of MACE at 1 year
Kimura et al. Eur Heart J 2015;36:3332-42

Bioresorbable scaffolds vs metallic stents: AIDA
Objective to compare the clinical outcome of an everolimus-eluting bioresorbable scaffold

with everolimus-eluting metallic stent in context of routine clinical practice
Study multicentre non-inferiority randomised trial (margin 4.5%)
Population patients undergoing PCI with lesion (s) suitable for drug-eluting stent
implantation
Endpoints target vessel failure as composite of death, MI or target-vessel revascularization
Vascular scaffold
924
Patients Median follow-up
1,845 707 days
Metallic stent
921
Target-vessel failure Definitive/probable

2-year cumulative event rate stent thrombosis
HR 1.12 (95% CI 0.85-1.48) HR 3.87 (95% CI 1.78-8.42)
%
P=0.43 %
p˂0.001
15 11.7 10.7 5
3.5
10
5
0.9
0 0
Vascular scaffold Metallic stent Scaffold Stent
Early reporting because of safety concerns
Conclusion there was no statistical difference in the rate of target-vessel-failure between

scaffold or metallic stent implantation. The scaffold-implantation is associated
with a higher rate of stent thrombosis
Wykrzykowska et al. N Engl J Med. 2017;376:2319-28

Absorb bioresorbable scaffold vs. Xience DES:

AIDA 2 years
Objective to report the 2-year clinical outcomes of implantation of Absorb BV Scaffold

compared to Xience EES
Study single-blind multicentre non-inferiority (1:1) randomised clinical trial (margin
3.3%)
Population patients undergoing PCI and lesion suitable for either BVS or EES implantation
Endpoints TVF as a composite cardiac death, MI and target vessel revascularisation at
2 years
Absorb BVS 924

Patients 2:1 Complete follow-up: 96.9%
1,845
Xience EES 921
Target vessel failure 2 years

HR 1.12 (95% CI 0.94-1.49)
p sup=0.436
p non.inf=0.003
%
15
11.0
9.9
0
Absorb BVS Xience EES
Kaplan-Meier estimates of thrombosis (definite or probable) were:

Absorb BVS 3.3% vs Xience EES 0.9% (p<0.001)
Conclusion At 2 years there is no statistically difference in target vessel failure between

Absorb BVS and Xience EES. The thrombosis rate is higher with Absorb BVS
Tyssen et al. EuroIntervention. 2018;14:e426-33

ABSORB-IV: 30-day and 1-year results from a randomised trial

of BVS versus conventional DES
Objective to compare outcomes of patients treated with bioresorbable vascular scaffolds

(BVS) vs everolimus-eluting stents (EES)
Study active-controlled, blinded, multicentre, randomised trial
Population patients with stable CAD or ACS aged 18 years or older
Endpoints target-lesion failure = cardiac death, target vessel myocardial infarction,
or ischemia-driven target lesion revascularisation
BVS
1,296
Patients with SCAD or ACS
2,604
EES
1,308
Target Lesion Failure 30 days Target Lesion Failure 1 year

Pnon-inferiority=0.0244 Pnon-inferiority=0.0006
% %
10 10
7.8
6.4
5.0
5 3.7 5
0 0
BVS EES BVS EES
Conclusion target lesion failure rates were numerically higher with BVS vs EES
at 30 days and 1 year though criteria for non-inferiority were met
Stone et al. Lancet. 2018;392:1530-40

5 ∙ Drug-coated balloons
Page
Drug-coated balloons.........................................................................100

5 Drug-coated balloons
Drug-coated balloons for treatment of small CAD:

BASKET SMALL 2
Objective to investigate the clinical outcomes of drug-coated balloons compared to

second generation DES (Xience or paclitaxel-eluting Taxus element stent)
Study prospective, open-label, multicenter randomised non-inferiority trial
(margin 4.0%)
Population all-comers with de novo lesion in arteries <3 mm
Endpoints MACE as composite of cardiac death, non-fatal MI and TVR at 12 months
drug-coated balloon
Predilation
382
Patients
successful Completed follow-up: 96%
883
758 DES
376
MACE at 12 months
HR 0.97 (95% CI: 0.58 -1.64)
p=0.918
absolute difference –3.83 to 3.93% p.non inf –0.918
%
10
7.3 7.5
0
drug-coated balloon DES
Target vessel revascularization did not differ

between the two groups (3.4% vs 4.5%; p=0.438)
Conclusion the 12 month adverse event rate of drug-coated balloons is non-inferior to DES
for treatment of coronary artery lesions in small vessels in all-comers
Jeger et al. Lancet. 2018;392:849-56

Drug-coated balloons 5
Drug-coated balloon treatment in patients with high-bleeding risk:

DEBUT
Objective to investigate whether drug coated balloon-only treatment (with possibility to

bailout stenting) was safe and effective compared to PCI with bare metal stents
Study investigator-initiated randomised single blind multicentre non-inferiority trial
(margin 3% difference)
Population risk factors for bleeding: use oral anticoagulants, age >80 years, anaemia,
thrombocytopenia, malignancy, previous stroke or bleeding, severe renal
dysfunction, hepatic failure, planned surgery, substantial frailty, previous
significant bleeding included patients with stable angina or ACS with expected
simple PCI procedure
Endpoints MACE at 9 months
Drug coated balloon 102

Patients recruited Patients studied
220 208
Bare metal stent 106
MACE 9 months
RR 0.07. (95% CI: 0.01-0.52) non-inferiority p<0.00001
superiority p=0.00034
%
20
14.0
10
1.0
0
DCB BMS
Conclusion treatment of simple coronary lesions with drug-coated balloon was superior to
bare metal stents in patients at a high-bleeding risk
Rissanen et al. Lancet. 2019;394:230-9

5 Drug-coated balloons
BMS or DES vs Drug-coated balloon

in NSTEMI: PEPCAD NSTEMI
Objective to investigate the clinical outcomes of patients with NSTEMI treated with drug-
coated balloon as compared to BMS or DES stent implantation
Study multicentre, randomised non-inferiority trial
Population patients with NSTEMI
Endpoints TLF as combined death, re-infarction and TL revascularisation at 9 months
DCB
104
Patients
210
Stent
106
TLF at 9 months
non-inferiority level −0.07
(90% CI: 0.032-0.09)
% P<0.003
10
6.6
5
3.8
0
DCB Stent
Conclusion Conclusion:treatment of patients with NSTEMI with drug-coated balloons was

non-inferior to treatment with BMS or DES
Scheller et al. EuroIntervention 2020;15:1527-33

6 ∙ Technical approaches
Page
Radial vs femoral ..............................................................................104
Surveillance angiography ...................................................................108
CTO .................................................................................................109

6 Radial vs femoral
Radial vs femoral access in ACS:

MATRIX Access
Objective to assess whether radial access is superior to femoral access in patients with
ACS undergoing coronary angiography and PCI
Study multicentre, superiority randomised trial
Population patients with ACS (including STEMI) about to undergo invasive management
by interventionalist with expertise in both femoral or radial access
Endpoints MACE: death, MI, stroke at 30 days. Net adverse clinical events (NACE):
MACE or BARC major bleeding at 30 days
Radial 4,197
access (94%)
Patients 1:1 Follow-up 30 days
8,404 ±99% complete
Femoral 4,207
access (97%)
MACE: 30 days NACE: 30 days

RR 0.85 (95% CI: 0.74-0.99) RR 0.83 (95% CI: 0.73-0.96)
% p=0.031 %
p=0.009
15 15
10 10
10.3 11.7
8.8 9.8
5 5
0 0
Radial Femoral Radial Femoral
radial vs femoral RR 95% CI p-value

BARC bleeding % 1.6 2.3 0.67 (0.49-0.92) 0.013
All-cause mortality % 1.6 2.2 0.72 (0.53-0.99) 0.045
Conclusion radial access compared to femoral access in patients with ACS undergoing
invasive management reduces net adverse clinical events
Valgimigli et al. Lancet. 2015;385:2465-76

Radial vs femoral 6
Radial versus femoral access of PCI for ACS:

MATRIX 1 year
Objective to report the 1-year adverse event rate of radial access compared to femoral
access for treatment of CAD in patients with ACS
Study multicentre, open-label superiority trial (two-nested trial)
Population patients with ACS
Endpoints MACE as composite of all-cause death, MI or stroke at 1 year. NACE (net
adverse clinical events): major bleeding or MACE
Radial 4,197
Patients Complete follow-up: 99.8%
8,404
Femoral 4,207
MACE 1 year NACE 1 year

RR 0.89 (95% CI: 0.80-1.0) RR 0.87 (95% 0.78-0.97)
p=0.0526 p=0.0128
% %
20 20 17.2
14.2 15.7 15.2
10 10
0 0
Radial Femoral Radial Femoral
Conclusion the major adverse 1-year event rate was not different between radial and
femoral access, but the 1-year net adverse clinical event rate was lower with
radial access compared to femoral access

6 Radial vs femoral
Standard vs ultrasound-guided radial or femoral access:

SURF
Objective to compare the outcomes of cardiac catheterisation vs transradial or trans

femoral access and standard vs ultrasound guided arterial access
Study prospective single-centre, randomised trial: 2×2 factorial (radial vs femoral and
standard vs ultrasound)
Population unselected patients : angiography only (77.4% vs 72.9%) and PCI (22.5% vs
27.1%)
Endpoints composite of ACUITY: major bleeding and MACE (death, stroke, MI, urgent
TLR) and vascular complications at 30 days
Transfemoral 688
1,388
Transradial 700
ACUITY at 30 days
RR 0.37 (95% CI: 0.17-0.81)
%
5
p=0.013
3.5
1.3
0
Transfemoral Transradial
There was no difference between standard and ultrasound

guidance: p=0.76
Conclusion transradial access was associated with a significant reduction in complications

compared to the femoral access
Nguyen et al. EuroIntervention. 2019;15:e522-3

Radial vs femoral 6
Femoral vs Radial Access in STEMI:

SAFARI-STEMI trial
Objective to determine if radial access is associated with better clinical outcome

compared to standard femoral access in patients undergoing primary PCI
Study investigator-driven, multicentre, open-label randomised trial
Population patients with STEMI referred for primary PCI
Endpoints all-cause mortality at 30 days
Radial access 1,136

Patients available patients 99.6%
2,292
Femoral access 1,156
30 day mortality
RR 1.15 (95% CI: 0.58-2.30)
%
5
p=0.69
4
3
1.3
2 1.5
1
0
Radial access Femoral access
The trial was terminated following a DSMB requested futility analysis

which resulted in a futility index of 0.83
Conclusion the 30-day all-cause mortality rate is not different between radial access and
femoral access for the treatment of STEMI with primary PCI
Le May et al. JAMA-Cardiology. 2020;5:126-34

6 Surveillance angiography
Routine coronary angiography after PCI:

ReACT Trial
Objective to evaluate the impact of routine follow up coronary angiography after PCI on
clinical outcome as compared to no angiography
Population all-comers who underwent successful PCI
Endpoints composite death, MI, stroke, emergency ACS or hospitalisation for heart failure
during median 4.6 years
Angiography 349
Patients
700
No angiography 351
MACE median 4.6 years

HR 0.94 (95% CI: 0.67-1.31)
p=0.70
% 24.7
25 22.4
20
15
10
0
Angiography No angiography
Conclusion follow-up routine angiography after PCI is not associated with increased clinical
benefit
Shiomi et al. J Am Coll Cardiol Intv 2017;10:109-17

CTO 6
PCI for Chronic Total Occlusion:

DECISION-CTO trial
Objective to establish the clinical benefit of PCI of CTO compared to no PCI of CTO with
the option for PCI of obstructive non-CTO lesions and medical treatment
Study open-label multicentre, randomised non-inferiority trial
Population patients with silent ischaemia, stable angina or acute coronary syndrome and
a denovo CTO (3 months)
Endpoints composite of death, MI, stroke or any revascularisation during a mean follow-
up 4.0 years
CTO-PCI 417 Success rate 90.6%

Planned no. of Enrolled
patients 834
1,284
No CTO-PCI 398 19.6% cross-over to PCI
Primary endpoint median 4 years

HR 1.03 (95% CI: 0.77 to 1.37)
p=0.86
%
30
22.3 22.4
20
10
0
CTO-PCI No CTO-PCI
Problems: trial stopped before completion of 1248 planned enrollments.

Cross-over of No CTO-PCI to PCI: 20%
Conclusion there was no difference in the incidence of major cardiac adverse events with
CTO-PCI as compared to no CTO-PCI at a median follow-up of 4 years
Lee et al. Circulation. 2019;139:1674-83

7 ∙ Revascularisation strategy: PCI vs CABG
Page
PCI vs CABG.....................................................................................112
Revascularisation vs medical .............................................................122
Miscellaneous...................................................................................126

7 PCI vs CABG
Hybrid Coronary Revascularization in M-VD - HYBRID
Objective to investigate the 5-year clinical outcomes of hybrid coronary revascularization

(HCR) as compared to conventional CABG
Study single-centre randomised trial
Population patients with M-VD involving LAD and at least 1 other critical (>70%) lesion
Endpoints all cause mortality at 5 years
HCR 94
Patients
191
CABG 97
Mortality at 5 years
p=0.69
%
10
9.2
6.4
5
0
HCR CABG
Conclusion HCR has similar 5-year mortality when compared to conventional CABG
Tajstra et al. JACC Cardiovascular Interventions. 2018;11:847-52

PCI vs CABG 7
SES vs minimal invasive CABG for LAD stenosis:

7 years
Objective to assess the 7-year clinical events of PCI with sirolimus-eluting stent (SES)
compared to minimal invasive direct CABG (MIDCAB) for treatment of isolated
left anterior descendens stenosis
Study prospective, multicentre, randomised study
Population symptomatic patients with ischaemia and isolated LAD stenosis
Endpoints freedom of MACE defined as cardiac death, MI and need for repeat TVR of
7 years
SES 65
1:1 Follow-up
Patients 7 years
130
Complete 99.3%
MIDCAB 65
MACE at 7 years
% p=0.17
30
20
22
10
12
0
SES MIDCAB
TVR: PCI 20% vs MIDCAB 1.5% - p < 0.001
Conclusion there was no statistical difference in combined cardiac death, MI or TVR

between SES and MIDCAB at 7 years
Blazek et al. JACC Cardiovasc Interv 2015;8:30-8

7 PCI vs CABG
Everolimus-eluting stents vs bypass Surgery for multivessel disease:

BEST
Objective to compare the clinical outcomes of EES treatment vs bypass surgery for
patients with multivessel disease
Study multicentre, randomised, noninferiority study (margin 4%)
Population patients with multivessel disease considered eligible for either PCI or CABG
Endpoints composite death, MI, TVR at 2 years
PCI 438
1:1 Early termination study due to

Patients slow enrollment (estimated
880 1,776 patients)
CABG 442
MACE at 2 years MACE at median 4.6 years

p=0.32 non-inferiority HR 1.47 (95% CI 1.01-2.13)
(95% CI 0.8 to 6.9) p=0.04
% %
15 20
11 15
10
15.3
10
5 7.9 10.6
5
0 0
PCI CABG PCI CABG
Conclusion the rate of MACE is higher in patients with multivessel diease undergoing EES
treatment compared to bypass surgery
Park et al. N Engl J Med 2015;372:1204-12

PCI vs CABG 7
Stent vs CABG for left main CAD:

PRECOMBAT-study 5 years
Objective to determine the 5-year outcomes of PCI compared with CABG for the
treatment of LM-CAD
Study multicentre, randomised trial (1:1)
Population newly diagnosed LM-stenosis (>50%) in candidates suitable for either PCI or
CABG
Endpoints composite of all-cause death, MI, stroke or ischaemia-driven TVR at 5 years
PCI 300 (SES)

Patients 1:1 Completed follow-up:
600 PCI 93%
CABG 92%
CABG 300
MACCE at 5 years
HR 1.27 (95% CI: 0.84-1.90)
% p=0.26
20
15
17.5
10 14.3
5
PCI CABG
There were no significant differences of all-cause death, MI or stroke between

PCI and CABG. TVR occurred more frequently in PCI group (11.4% vs 5.5%).
p=0.012.
Conclusion at 5 years there was not a significant difference in clinical outcome between
PCI and CABG for treatment of LM-CAD
Ahn et al. JACC. 2015;65:2198-206

7 PCI vs CABG
PCI vs CABG in treatment of unprotected left main stenosis:

NOBLE
Objective to compare percutaneous coronary intervention and coronary-artery bypass

grafting for treatment of left main coronary artery disease
Study prospective, randomised, open-label, non-inferiority trial
Population patients with stable angina pectoris or non-ST-elevation myocardial infarction
Endpoints major adverse cardiac or cerebrovascular events (MACCE), a composite of all-
cause mortality, non-procedural myocardial infarction, any repeat coronary
revascularisation and stroke
PCI 598
Patients
1,201
CABG 603
Kaplan-Meier 5-year estimates of MACCE

HR 1.48 (95% CI 1.11-1.96)
P superiority=0.0066
%
40
29
30
19
20
10
0
PCI CABG
Conclusion CABG is superior to PCI for treatment of left main disease in terms of major
cardiac or cerebrovascular events
Mäkikallio et al Lancet 2016; 388:2743-52

PCI vs CABG 7
PCI vs CABG for left main stenosis:

NOBLE trial 5 years
Objective to report the 5 year clinical outcomes PCI versus CABG for the treatment of left
main stenosis
Study prospective, open-label randomised non-inferiority trial
Population stable angina and acute coronary syndrome (except STEMI) with
>50% diameter stenosis or FFR ≤0.80 in left main artery
Endpoints MACCE: comprising all-cause death, MI, repeat revascularisation or stroke at
5 years (median 4.9 years)
PCI 598 complete 5-year follow- up: 550

Patients
1,201
CABG 609 complete 5-year follow- up: 543
Kaplan-Meier 5 year MACCE

HR 1.58 (95% CI: 1.24-2.01)
p=0.0002
exceeding limit non-inferiority (1.35)
%
30
28
19
20
10
0
PCI CABG
Primary 5-year composite endpoint: CABG was superior to PCI: p=0.0002
Conclusion PCI was inferior to CABG for treatment of left main coronary stenosis at 5 year
follow-up in terms of major cardiac and cerebrovascular events
Holm et al. Lancet. 2020;395:191-9

7 PCI vs CABG
Everolimus-eluting stents or bypass surgery for left main coronary

artery disease: EXCEL
Objective to compare percutaneous coronary intervention and coronary-artery bypass

grafting for treatment of left main coronary disease
Study prospective, randomised, open-label, non-inferiority trial
Population patients with left main coronary artery disease of low or intermediate
anatomical complexity
Endpoints composite of death from any cause, stroke or myocardial infarction at 3 years
PCI 948
Patients
1,905
CABG 957

P non inferiority=0.02
P superiority=0.98
%
20
15.4 14.7
15
10
0
PCI CABG
Conclusion in patients with left main coronary disease and low or intermediate anatomical
complexity, PCI was noninferior to CABG for the composite end point of death,
stroke or MI at 3 years
Stone et al. N Engl J Med 2016;375:2223-35

PCI vs CABG 7
5-year outcomes after PCI or CABG for left main disease:

EXCEL 5 years
Objective to report the five-year outcomes of PCI as compared with CABG for treatment
of patients with left main disease
Study international, open-label, multicentre randomised trial
Population patients with 70% or more stenosis of left main artery or 50% to less than
70% that is hemodynamically significant and eligible for either PCI or CABG
(low or intermediate complexity lesions)
Endpoints composite of all cause death, stroke or MI at 5 years
PCI 948 5 years follow-up: 93.2%

Patients
1,905
CABG 957 5 years follow-up: 90.1%

Difference 2.8 percentage points
95% CI –0.9 to 6.5; p=0.13
%
25 22.0
19.2
0
PCI CABG
Conclusion there was no significant difference in the composite rate of death, stroke or MI
at 5 years between PCI and CABG for treatment of low or intermediate complex
left main coronary artery disease
Stone et al. N Eng J Med. 2019;381:1820-30

7 PCI vs CABG
PCI vs CABG in patients with LM or 3-VD:

10 year follow-up SYNTAXES trial
Objective to report the 10-year all cause death of treatment with PCI or CABG in patients
3-VD or left main disease
Study multicentre, randomised non-inferiority trial
Population patients with 3-VD or left main disease eligible for either PCI or CABG
Endpoints all-cause death at 10 years
PCI 903
Patients Vital status information
1,800 complete in 94% of patients
CABG 897
All-cause death 10 years

HR 1.17 (95% CI: 0.97-1.41)
p=0.092
27.0
%
30
24.0
20
10
0
PCI CABG
3-VD patients PCI 28% vs CABG 21%

HR 1.41 (95% CI: 1.10-1.80)
L main patients PCI 26% vs CABG 28%
HR 0.90 (95% CI: 0.68-1.20)
Conclusion there is no significant difference in all-cause death between PCI and CABG at
10 years. CABG is associated with lower 10-year mortality in patients with
3-vessel disease
Thuijs et al. Lancet. 2019;394:1324-34

PCI vs CABG 7
PCI versus CABG for treatment of diabetics:

FREEDOM Follow-On study
Objective to report the long-term survival of DM patients with multivessel disease who
underwent PCI or CABG
Population Freedom trial 1,900 patients. Of these 943 participated in Freedom follow-up
trial
Endpoints all-cause mortality after median follow-up of 7.5 years
PCI 478
Freedom
Freedom trials
follow-up
1,900 patients
943 patients
CABG 465
Freedom follow-on All-patients FREEDOM 1,900

Long term all-cause mortality all-cause mortality
(median follow-up 7.5 years) (median follow-up 8 years)
HR 1.32 (95% CI 0.97 to 1.78) HR 1.36 (95% CI 1.07 to 1.74)
p=0.076 p=0.01
% %
30 30
23.7 24.3
18.7 18.3
20 20
10 10
0 0
PCI-DES CABG PCI-DES CABG
Conclusion coronary revascularisation with CABG in patients with DM and MVD is

associated with long term lower all-cause mortality than PCI
Farkouh et al. J Am Coll Cardiol 2019;73:629-38

7 Revascularisation vs medical
PCI for chronic total occlusion compared to optimal medical

treatment: EURO-CTO
Objective to investigate the clinical outcome of PCI for chronic total occlusion and
optimal medical treatment (OMT) as compared with optimal medical treatment
alone in terms of symptomatic improvement in patients with stable angina
Study prospective, multicentre, open-label randomised trial (2:1)
Population patients with single and multivessel disease. Patients with M-VD received first
treatment of any significant non-CTO lesion >4 weeks before randomisation
Endpoints change in health status as assessed with SAQ between treatment groups from
baseline to 12 months (SAQ = Seattle angina questionnaire)
PCI+DES+OMT 259
1980 Patients Follow-up completed 100%
Screened 396
OMT 137
12 months improvement subscales SAQ

PCI compared to OMT
Physical limitation p=0.02
Angina frequency p=0.003
Quality of life p=0.007
Anginal stability p=0.89
Treatment satisfaction p=0.47
At 12 months MACE were comparable between two groups
Conclusion PCI for CTO is associated with an improvement of health status compared to
optimal medical treatment in patients with stable angina
Werner et al. Eur Heart J. 2018;39:2484-93

Revascularisation vs medical 7
PCI in stable angina:

ORBITA
Objective to assess the effect of PCI versus Placebo procedure on exercise time in
patients with stable angina
Study double-blind, multicentre, randomised trial (placebo controlled)
Population patients with stable angina and at least one angiographically significant lesion
(≥70%)
Endpoints difference in exercise time increment between the two groups
PCI 105
Patients treated
230 200
Placebo 95
Difference exercise time increment

Difference 16.8 sec (95% CI –8.9 to 42.0)
p=0.200
sec 28.4
30
20
11.8
10
0
PCI Placebo
Conclusion in patients with guide-line directed optimum medical therapy PCI did not
increase exercise time compared to patients with optimal medical therapy
undergoing a placebo procedure
Al-Lamee et al. Lancet 2018;391:31-40

7 Revascularisation vs medical
Coronary Disease in Patients with Advanced Kidney Disease:

ISCHEMIA CKD
Objective to compare an invasive strategy (angiography +/- revascularisation + OMT)

versus a conservative strategy (OMT) in patients with advanced chronic kidney
disease
Study prospective, multicentre, assessor-blinded, randomised trial
Population patients with advanced CKD + moderate-to-severe- ischaemia
Endpoints composite of death or nonfatal myocardial infarction
Invasive strategy (n=388)

Patients with CKD
+ ischaemia
(n=777)
Conservative strategy (n=389)
HR 1.01 (95% CI: 0.79-1.29; p=0.95)

Death/MI
40 36.4 36.7
30
20
10
0
Invasive Conservative
Conclusion In patients with stable CAD, advanced CKD and moderate or severe
ischaemia an invasive strategy was not superior to a conservative
strategy
Bangalore et al. N Eng J Med. 2020;382:1608-18

Revascularisation vs medical 7
Initial Invasive or Conservative Strategy

for Stable Coronary Disease: ISCHEMIA
Objective to compare an invasive strategy (angiography +/- revascularisation + OMT)

versus a conservative strategy (OMT)
Study prospective, multicentre, assessor-blinded, randomised trial
Population patients with stable CAD + moderate-to-severe ischaemia
Endpoints composite of death from cardiovascular causes, MI, or hospitalisation for
unstable angina, heart failure, or resuscitate cardiac arrest
Invasive strategy (n=2,588)

Patients with CAD
+ ischaemia
(n=5,179)
Conservative strategy (n=2,591)
Difference −1.8% (95% CI: −4.7-1.0)
18.4
16.4
Primary endpoint
20
15
10
0
Conclusion Invasive strategy comprising angiography and revascularisation

and OMT was not superior to OMT alone in reducing adverse outcome events
OMT to 5 years
Maron et al. N Eng J Med. 2020; 382: 1395-407

7 Miscellaneous
Ranolazine after incomplete PCI revascularisation:

RIVER-PCI
Objective does adjunctive anti-ischemic therapy with ranolazine in patients with

incomplete revascularisation after PCI improve prognosis
Study multicentre, double-blind placebo controlled randomised study
Population patients with history of angina with incomplete (one or more lesions >50%
stenosis) revascularisation after PCI
Endpoints rate of ischemia-driven revascularisation or ischemia-driven revascularisation
without revascularisation at follow-up
Ranolazine 1,332
twice-daily 1,000 mg
Patients Median follow-up : 643 days
2,561 Complete 98%
Placebo 1,319
Composite endpoint
HR 0.95 (95% CI: 0.82-1.10)
% p=0.48
30
28
26
15
0
Ranolazine Placebo
Conclusion ranolazine did not reduce the composite rate of ischaemia-driven

revascularisation or hospitalisation with revascularisation in patients with
angina pectoris and incomplete post-PCI revascularisation
Weisz et al. Lancet 2016;387:136-45

8 ∙ Early invasive vs early conservative strategy ACS
Page
Early invasive vs early conservative strategy ACS..................................128

8 Early invasive vs early conservative strategy ACS
Routine invasive vs selective invasive strategy N-STEMI:

RITA – 3: 10 years
Objective to report 10-year follow-up outcomes of a routine invasive strategy compared to

selective invasive strategy to treat N-STEMI patients
Study open multicentre, randomised controlled trial
Population patients randomised within 48 hrs of an index episode of ischeamia if chest
pain at rest and evidence of CAD
Endpoints 10-year all-cause mortality
Routine invasive 895
Patients
1,810
Selective invasive 915
10-year all-cause mortality

% p=0.94 (95% CI: 4.2-3.8)
30
20 25.1 25.4
10
0
routine invasive (RI) selective invasive (SI)
10-year cardiovascular deaths: RI 15.1% vs SI 16.1%: p=0.65
Risk stratification (modified Grace score): all-cause mortality

RI group SI group
Low risk (< 90) % 12.6 14.2
Medium risk (90-107) % 38.0 37.0
High risk (>107) % 57.8 58.1
Conclusion patients with N-STEMI managed with routine invasive strategy have
comparable 10-year total mortality and cardiovascular mortality rates when
compared with selective invasive strategy
Henderson et al. JACC. 2015;66:511-20

Early invasive vs early conservative strategy ACS 8
Invasive vs. conservative strategy non-STEMI in elderly:

AFTER Eighty Study
Objective to demonstrate whether patients aged 80 or older would benefit from an early
invasive strategy vs. a conservative strategy for treatment of non-STEMI
patients
Study open label multicentre controlled trial
Population patients 80 or older undergoing invasive strategy (early angiography with
immediate treatment assessment : PCI, CABG or medical) or conservative:
optimum medical treatment only
Endpoints composite of death, MI, stroke and need urgent revascularisation
Invasive 229
Patients Median follow-up

457 1.53 years
Conservative 228
Primary endpoint 1.53 years

HR 0.53 (95% CI: 0.41-0.69)
% p=0.0001
60
45
61.4
30 40.6
15
0
The hazards rates were better for MI and need
urgent revascularisation with invasive strategy
The hazards rates were better for MI and need urgent revascularisation with invasive strategy
Conclusion an invasive strategy for treatment of non-STEMI in patients aged 80 years or

older is superior to a conservative strategy
Tegn et al. Lancet 2016;387:1057-65

Single-staged vs multi-staged PCI in MV-D NSTEMI:

SMILE
Objective to report the 1-year clinical outcome of single-staged PCI compared to multi-
staged PCI in NSTEMI patients with multivessel disease
Study 2-centre randomised trial
Population NSTEMI patients with MV-Disease. Second-stage procedure was performed
between 3 to 7 days after index procedure
Endpoints MACCE : death, cardiac death, MI, rehosp. UA, TVR and stroke at 1 year
1-stage 264
Patients 15 patients lost to

542 follow-up at 1 year
Multi-stage 263
MACCE at 1 year
HR 0.55 (95% CI: 0.36-0.82)
% p=0.004
25
20 23.2
15
10 13.6
5
0
1-stage Multi-stage
The difference driven by 1 year TVR rate:

1-stage : 8.4% vs multi-stage 15.2% (p=0.01)
Conclusion 1-stage complete revascularisation is superior to multi-stage complete

revascularisation in NSTEMI patients with multi-vessel disease. This was
mainly driven by the unexplained beneficial TVR- rate in the 1-stage approach
Sardella et al. J Am Coll Cardiol 2016;67:264-72

Non-STEMI patients: immediate versus delayed intervention:

RIDDLE-NSTEMI study
Objective to compare the clinical outcome of immediate versus delayed invasive

intervention in patients with NSTEMI
Study single centre, open label randomised
Population patients with NSTEMI: chest pain <24 hours
Endpoints composite of death or new MI at 30 days
Immediate 162
Patients
323
Delayed 160
(1 patient died before randomisation)

HR 0.32 (95% CI 0.13-0.74)
p=0.008
%
15
13.0
10
5
4.3
Immediate Delayed
(1.4 hours) (61.0 hours)
Conclusion immediate invasive strategy in NSTEMI is associated with superior outcome at

30 days compared to a delayed invasive strategy
Milosevic et al. JACC Cardiovasc Interv 2016;9:541-9

Early invasive vs non-invasive treatment for non-STEMI patients

FRISC-II: 15 years
Objective to report the very long term clinical outcome (15-17 years) of early invasive to
a non-invasive treatment of patients with non-STEMI
Study prospective, randomised multicentre trial
Population patients with suspected non-ST-elevation ACS
Endpoints composite of death or MI at a minimum of 15 years follow-up outcomes were
compared as average postponement of next event
Invasive
1,222 Survival data and death complete for 99%
Patients
2,457
Non-invasive
1,235 Other events: 89% complete
Overall group: the mean gain by invasive strategy compared to non-invasive

strategy
Days 549 95% CI 204-888 days p=0.0020
Effect was larger in non smokers, elevated troponin T levels, high growth
differentiation factor –15
The difference was mainly driven by postponement of new myocardial infarction
Revascularisation non-invasive strategy:

– During hospital 14%
– After 2 years 46%
– After 15 years 58%
Conclusion an early invasive strategy in patients with non-ST-elevation postpones the

occurrence of death or next MI by an average of 18 months compared to a non-
invasive strategy
Wallentin et al. Lancet 2016;388:1903-11

Early invasive vs Selective strategy for NSTEMI: ICTUS 10 years
Objective to report the 10-year clinical outcomes of an early invasive strategy versus
selective invasive strategy in patients with acute coronary syndrome
Population patients with non ST-segment elevation acute coronary syndrome and elevated
cardiac troponin T
Endpoints composite death or spontaneous MI
Early invasive
604
Patients Vital status known at 10 years:
1,200 96%
Selective invasive
596
10 year death / spontaneous MI

HR 1.12 (95% CI : 0.97-1.46)
p=0.11
% 33.8
40 29
30
20
10
0
Early invasive Selective invasive
Revascularization: 82.6% early invasive and 60.5% selective invasive strategy
Conclusion an early invasive strategy in patients with non ST-segment elevation ACS has
no benefit in terms of 10 year death and spontaneous MI compared to
a selective invasive strategy
Hoedemaker et al. J Am Coll Cardiol. 2017;69:1883-93

Timing revascularisation in patients with transient ST-segment

elevation: Transient-STEMI
Objective to assess the effect of an immediate vs. delayed invasive strategy on infarct
size measured by cardiac magnetic resonance imaging
Study investigator-initiated prospective multicentre randomised trial
Population clinical presentation STEMI with complete relief of symptoms and
normalisation of ST-segments. Immediate strategy: 0.3 h vs. delayed strategy:
22.7 h
Endpoints infarct size as percentage of left ventricular mass at day four
Immediate
70
Patients
142
Delayed 72 (4 patients [5.6%]
urgent intervention)
Infarct size CMR (% LV mass)

% p=0.48
5
1.3 1.5
Immediate (60) Delayed (63)
Conclusion overall, in patients with transient MI the infarct size is small, and there is no
difference in infarct size in an immediate or delayed invasive strategy
Lemkes et al. European Heart J. 2019;40:283-91

Early versus standard care invasive strategy for non-STEMI patients:

VERDICT
Objective to investigate the clinical efficacy of a strategy of very early angiography and
PCI within 12 hours compared to standard invasive therapy within 48 to
72 hours
Study prospectively 2 centre randomised trial
Population patients with Non-STEMI ACS
Endpoints combined all-cause death, re MI, hospital admission for refractory ischemia or
hospital admission for heart failure
Very early invasive

(Angio: median 4.7 hours - PCI: 88.4%)
1,075
Patients
2,147
Standard invasive
(Angio: 61.6 hours - PCI: 83.1%)
1,072
Primary endpoint (follow-up 4.3 years)

HR 0.92 (95% CI 0.78-1.08)
p=0.29
%
27,5 29,5
30
20
10
0
Very early Standard
Conclusion a strategy of very early invasive coronary angiography does not improve
longterm clinical outcome compared to a standard strategy of invasive coronary
angiography
Kofoed et al. Circulation. 2018;138:2741-50

9 ∙ Intravascular imaging-guided PCI
Page
IVUS-guided PCI...............................................................................138

9 IVUS-guided PCI
IVUS vs angio-guided CTO treatment:

CTO-IVUS study
Objective to report the 1-year clinical outcomes of IVUS-guided stent (DES) treatment of
CTO compared with angio-guided stent (DES) treatment
Study prospective, multicentre randomised study
Population patients with CTO studied after successful crossing with guide-wire
Endpoints primary endpoint: 1-year cardiac death, secondary endpoint: cardiac death, MI,
TVR at 12 months
IVUS-guided 201
Patients
402
Angio-guided 201
% Cardiac death 1 year

5 no difference
4
3
2
1 0.0
0 1.0
IVUS Angio
MACE: 1 year
% HR 0.35 (95% CI 0.13-0.97)
10 p=0.035
5 7.1
0
2.6
IVUS Angio
Conclusion IVUS guided CTO DES treatment did not reduce cardiac death at 1 year but it
reduced MACE at 1 year compared with angio-guided CTO DES treatment
Kim et al. Circ. Cardiovasc. Interv. 2015;8:e002592

IVUS-guided PCI 9
Ultrasound-guided vs Angiography-guided DES

for long lesions: IVUS-XPL
Objective to determine the 1-year clinical outcome of IVUS-guided DES implantation

compared with angiography-guided DES implantation for treatment of long
coronary lesions
Population patients with chest pain (or ischemia) and lesion ≥ 28mm length, receiving an
everolimus-drug eluting stent
Endpoints MACE composite of cardiac death, TLR-MI or ischemia driven TLR at 1 year
IVUS-guided 700
Patients 1:1 Follow-up 1 year:

Angiography-guided 700
MACE 1 year
HR 0.48 (95% CI 0.28-0.83) p=0.007
%
6
5.8
4
2 2.9
0
IVUS-guided Angiography-guided
No difference between cardiac death and TLR-MI
Conclusion IVUS-guided everolimus-drug eluting stenting of long lesion (≥28 mm) is

superior to angiography-guided stenting with lower MACE at 1 year
Hong et al. Jama 2015;314:2155-63

9 IVUS-guided PCI
Ultra sound-guided vs angiography guided DES for long lesions:

IVUS-XPL 5 years
Objective to report the 5 year clinical outcomes of IVUS-guided compared to

angiography-guided PCI with an everolimus-eluting stent in patients with long
lesions
Population patients with typical chest pain or evidence of myocardial ischemia and long
coronary lesion (≥28 mm length)
Endpoints MACE as cardiac death, TL-MI, ischemia-driven TL-revascularisation at 5 years
IVUS guided 700

Patients Follow-up completed in
1,400 85% patients (1,183 patients)
Angiography-guided 700
MACE at 5 years
HR 0.50 (95% CI: 0.34 to 0.75)
p=0.001
%
15
10.7
10
5.6
5
0
IVUS guided Angiography
guided
Conclusion IVUS-guided DES implantation is associated with significant lower MACE rate
at 5 years as compared to angiography-guided DES implantation
Hong et al. J Am Coll Cardiol Intv. 2020;13:62-71

IVUS-guided PCI 9
Ultrasound versus angiography-guided DES implantation:

ULTIMATE
Objective to determine the clinical benefits of IVUS guidance compared to angiography

guidance during DES implantation
Study prospective multicentre randomised study
Endpoints target vessel failure: cardiac death, TV-MI and clinically driven target-vessel
IVUS 724
Patients
1,448 Follow-up complete 99.7%
Angio 724
Target vessel failure 12 months

HR 0.53 (95% CI: 0.31-0.90)
p=0.019
%
6
5.4
4 2.9
2
0
IVUS Angio
Conclusion IVUS-guided DES implantation improved clinical outcome at 12 months

compared with angiography guided DES implantation
Zhang et al. J Am Coll Cardiol. 2018;72:3126-37

10. Lesion haemodynamic assessment and PCI
Page
FFR and PCI.....................................................................................144

10 FFR and PCI
Deferral vs performance of PCI of functionally non-significant

stenosis: DEFER 15 years
Objective to report the 15-year clinical outcome of deferral PCI of functionally non-
significant coronary lesion as compared to PCI treatment of this lesion
Study multicentre, international randomised trial
Population patients referred for elective PCI of single de novo lesion (>50% visual
assessment) and no conclusive evidence of reversible ischaemia
Endpoints death, MI or repeat revascularisation at 15 years
Deferral PCI 91 Complete follow-up 81
Patients
FFR ≥0.75 15 years (92%)
325
Performance PCI 90 Complete follow-up 84
Mortality 15 years MI 15 years

p=0.79 p=0.033
% %
40 10
8 10.0
30
33.0 31.1 6
20
4
10 2
0
2.2
0
Deferral Performance Deferral Performance
Note: the DEFER study was not powered for 15-year clinical outcomes follow-up
Conclusion Deferral of PCI of a functionally non-significant coronary stenosis is safe,

associated with favourable 15-year outcome without evidence of catch-up
phenomenon
Zimmermann, et al. Eur Heart J 2015;36:3182-88

FFR and PCI 10
Fractional flow reserve vs angiography guided PCI:

FAME 5 years
Objective to investigate whether the favourable initial clinical outcome of FFR guided PCI
in patients with MV-disease persisted over 5-year follow up
Population symptomatic patients with a stenosis of >50% in at least 2 major arteries
Endpoints MACE as composite of death, MI and any repeat revascularisation at 5 years
Angiography 446 At 5 years 429
Patients
1,005
FFR 509 At 5 years 436
MACE at 5 years
RR 0.91 (95% CI 0.75-1.10) p=0.31
%
32
28
31
24 28
20
16
12
0
Angiography FFR
Number stents per patient angiography 2.7 vs FFR 1.9 p<0.0001
Conclusion long-term safety of FFR-guided PCI persisted during 5 years. The absolute
difference of MACE with FFR guidance persists at 5 years but is no longer
significant because of the smaller number of patients at risk beyond 2 years at
which time MACE was significantly different
van Nunen et al. Lancet 2015;386:1853-60

10 FFR and PCI
PCI guided FFR:

FAME 2 5 years
Objective to report the 5-year clinical outcomes of FFR guided PCI and medical
treatment in patients with stable CAD compared to an initial medical treatment
Population patients with stable angina or documented silent ischemia and
a haemodynamically significant stenosis (FFR ≤0.80)
Endpoints composite of death, MI or urgent revascularisation
PCI 447 Completed follow-up 93.9%

Patients with
Patients
FFR ≤0.80
1,220
888
Medical 441 Completed follow-up 93.1%
Primary endpoint 5 years Urgent revascularisation 5 years

HR 0.46 (95% CI: 0.34 to 0.63) HR 0.27 (95% CI: 0.18-0.41)
%
p<0.001 %
p<0.001
30 27.0 30
21.1
13.9
6.3
0 0
PCI Medical PCI Medical
There were no differences in the rate of death (5.1% and 5.2%) and myocardial
infarction (8.1 and 12.0%) between the PCI group and medical therapy group
Conclusion an initial PCI-guided treatment was associated with a lower 5-year adverse
event rate compared to an initial medical treatment in patients with stable
CAD. The difference was mainly caused by increase in urgent revascularisation
rate in the medical treatment group.
Xaplanteris et al. NEJM. 2018;379:250-9

FFR and PCI 10
FFR vs angiographic guiding for NSTEMI:

FAMOUS-NSTEMI
Objective to assess the management and outcomes of NSTEMI patients treated with
FFR-guided vs angiographic-guided management
Study prospective, multicentre, randomised study (1:1)
Population patients with recent NSTEMI, at least one risk factor with urgent invasive
management (within 72 hrs) was planned or if history of recurrent ischaemia
within 5 days
Endpoints between-group difference in the proportion of patients allocated to medical
management
FFR-guided 176
Patients 1:1
350
Angiographic-guided 174
Primary outcome: initial medical management

% p=0.022
30
20
22.7
10
13.2
0
FFR-guided Angiographic-guided
FFR
Change in treatment between medical Rx, PCI or CABG in 21.6%
Study not powered for difference in clinical outcomes
Conclusion in NSTEMI patients FFR-guided management was associated with higher initial
medical treatment
Layland et al. Eur Heart J 2015;36:100-11

10 FFR and PCI
Instantaneous wave-free ratio vs fractional flow reserve to guide

PCI: iFR-SWEDEHEART
Objective to evaluate whether iFR is non-inferior to FFR with respect to the rate of
subsequent major adverse cardiac events
Study multicentre, randomised, controlled, open-label, non-inferiority, registry-based
Population patients with intermediate coronary stenosis
Endpoints composite all cause death, nonfatal myocardial infarction or unplanned
revascularisation within 12 months
iFR 1,019
Patients
2,037
FFR 1,018
MACE 12 months
%
8
6.7
7 6.1
6
5
4
3
2
1
0
iFR FFR
Conclusion an iFR-guided revascularisation strategy was non-inferior to an FFR-guided

revascularisation strategy with respect to the rate of major adverse cardiac
events at 12 months
Götberg et al. N Engl J Med. 2017;376:1813-23

FFR and PCI 10
Use of the instantaneous wave-free ratio or fractional flow reserve

in PCI: DEFINE-FLAIR
Objective to compare adenosine-free instantaneous wave-free ratio (iFR) with

conventional fractional-flow reserve (FFR) for PCI guidance
Study multicentre, randomised, blinded, non-inferiority
Population patients with intermediate coronary stenosis
Endpoints composite all cause death, nonfatal myocardial infarction or unplanned
iFR guided PCI 1,242

Patients
2,492
FFR guided PCI 1,250
MACE 1 year
p<0.001 non-inferiority
%
8
6.8 7.0
7
6
5
4
3
2
1
0
iFR FFR
Conclusion coronary revascularisation guided by iFR was non-inferior to revascularisation

guided by FFR with respect to the risk of major adverse cardiac events at 1 year
Davies et al. N Engl J Med. 2017;376:1824-34

11 ∙ Antithrombotic therapies
Page
Duration dual antiplatelet treatment ...................................................152
P2Y12 inhibitors ................................................................................162
Platelet reactivity / genotyping ...........................................................174
Antiplatelet therapy in OAC................................................................177
Bivalirudin........................................................................................183
Dual pathway inhibition .....................................................................187

11 Duration dual antiplatelet treatment
Antiplatelet duration following BMS implantation:

DAPT
Objective to compare the rates of stent thrombosis and MACCE after 30-month vs
12-month thienopyridine in patients treated with BMS taking aspirin
Study international, multicentre, randomised, double-blinded placebo-controlled trial
Population patients with BMS stent who were free of MI, stroke, repeat revascularisation,
stent thrombosis or moderate/severe bleeding at 12 months thieropyridine
treatment
Endpoints definite/probable stent thrombosis (ST-ARC) at 12-30 months.
MACCE: death, MI, stroke at 12 to 30 months
Continued
thienopyridine 842
Patients with BMS 12 months

1,687
Placebo 845
Stent thrombosis: 12-30 months MACCE: 12-30 months

HR 0.49 (95% CI 0.15-1.64) HR 0.92 (95% CI 0.57-1.47)
% p=0.24 % p=0.72
2 10
1 5
1.11
4.04 4.69
0.5
0 0
thienopyridine placebo thienopyridine placebo
Conclusion in patients treated with BMS and tolerance of 12-month post-stent

thienopyridine, continued thienopyridine for another 18 months did not reduce
stent thrombosis or MACCE
Kereiakes et al. JAMA 2015;313:1113-21

Duration dual antiplatelet treatment 11
6-month versus 12-month dual-antiplatelet treatment:

IVUS-XPL
Objective to investigate whether a 6-month DAPT duration was comparable to

a 12-month DAPT duration following implantation of a long everolimus-eluting
stent (>28 mm)
Population patients with typical chest pain or evidence of myocardial ischemia
Endpoints composite of cardiac death, MI, stroke or TIMI major bleeding at 1 year
DAPT 6 months: 699

1,400
DAPT 12 months: 701

HR 1.07 (95% CI 0.52-2.22)
p=0.854
%
6
4
2.2 2.1
2
DAPT 6 months DAPT 12 months
Conclusion the composite adverse event rate at 1 year was comparable with 6-month DAPT
duration compared to 12-month DAPT duration
Hong et al. JACC Cardiovasc Interv. 2016;9:1438-46

DAPT 6 – versus 24 month therapy after DES in non-resistant

aspirin patients: ITALIC – Final Results
Objective to report the 2-year follow-up results of 6 vs 24 months DAPT after DES
implantation
Study prospective open-label multicentre randomised non-inferiority trial (margin 2%)
Population patients were aspirin responders
Endpoints composite death, MI, urgent TVR, stroke and major bleeding at 24 months
6 month DAPT
Randomised 926
Patients 1,850 Follow-up
1,894 94%
24 month DAPT
924
Composite endpoint: 24 months

HR 0.939 (95% CI 0.58-1.52)
p=0.799
% 3.5 3.7
4
0
6 month 24 month
DAPT DAPT
Caution: the trial was prematurely stopped at recruitment of 2,031 patients (initially planned 2,475)
Conclusion 6 month DAPT is non inferior to 24 month DAPT after implantation of DES
in patients with good aspirin response
Didier et al. JACC Cardiovasc Interv. 2017;10:1202-10

DAPT: 6 vs 18 months therapy

NIPPON-STUDY
Objective to compare 6 month versus 18 month DAPT outcome of patients after

biodegradable polymer DES implantation
Study prospective multicentre randomised non-inferiority trial with margin 2.0%
Endpoints NACCE: all-cause death, Q wave or non-Q wave MI, cerebrovascular events,
major bleeding at 6 to18 months after DES implantation
18 month DAPT
1,887
Patients
3,772
6 month DAPT
1,886
NACCE 6-18 months

0.6% difference (95% CI:1.5-0.3)
%
p=0.24
4
2.1
1.5
2
0
6 months 18 months
DAPT DAPT
Caution: Rather wide non-inferiority margin of 2.0%
Conclusion 6 month of DAPT was non inferior to 18 month of DAPT after DES
implantation with biodegradable coating
Nakamura et al. JACC Cardiovasc Interv. 2017;10:1189-98

Six versus twelve months DAPT after DES

for STEMI: DAPT-STEMI
Objective to compare six months DAPT versus 12 months DAPT

Study multicentre, open-label, non-inferiority randomised controlled trial
Population patients treated with zoterolimus eluting stents for STEMI + event free at
6 months
Endpoints death, any myocardial infarction, any revascularisation, stroke, major bleeding
at 2 years
Aspirin only 433

(6 months DAPT)
Patients
870
DAPT 437
(12 months DAPT)
STEMI patients event free at 6 months

% p=0.004
10
6.6
5 4.8
0
6 months DAPT 12 months DAPT
Conclusion 6 months DAPT was not inferior to 12 months DAPT
Kedhi et al. BMJ 2018;363:k3793

6-month vs 12 month or longer DAPT in ACS:

SMART-DATE
Objective to investigate whether a reduced 6 month duration of DAPT would be

non-inferior to the conventional 12 month or longer duration of DAPT
in patients with ACS
Study multicentre, open-label non-inferiority randomised trial (margin 2.0%)
Population patients with unstable angina, non-STEMI and STEMI
Endpoints composite of all-cause death, MI or stroke at 18 months
6 month DAPT
1,357
Patients
Follow-up completed: 97.5%
2,712
12 month of longer DAPT
1,355
Composite end point 18 months

HR 1.13 (95% CI 0.97-1.62)
P non-inferiority=0.03
4.7
4.2
%
5
0
6 months 12 months or longer
The rates of death, stroke, stent thrombosis and bleeding

was not significantly different between the groups
MI rate: 6 month 1.8% vs 12 month 0.7%. p=0.02
Conclusion prolonged DAPT in patients with ACS should remain standard of care
Hahn et al. Lancet. 2018;391:1274-84

6 versus 12 months dual antiplatelet therapy after biodegradable

polymer DES: I-LOVE IT 2
Objective to compare 6 versus 12 months DAPT in patients treated with BP-DES

Study multicentre, assessor-blind, non-inferiority RCT
Population patients with stable CAD or ACS
Endpoints TLR at 12 months
BP-DES 6-month DAPT 909

1,829 12-month DAPT 920
Patients
2,737
DP-DES
908
TLF
10
6.8 5.9
5
0
6-month DAPT 12-month DAPT
Conclusion 6-month dual antiplatelet therapy was non-inferior to 12 months in terms of

TLF in patients treated with BP-DES
Han et al. Circ. Cardiovasc. Interv. 2018;9:e003145

6- vs 12-month clopidogrel treatment post PCI:

ISAR-SAFE
Objective to test the hypothesis that 6-month clopidogrel is non-inferior to 12-month

clopidogrel in patients undergoing DES implantation
Study multicentre, randomised, double-blinded placebo controlled non-inferiority trial
(margin +2%). Patients were randomised 6 months after DES implantation to
either 6 months placebo or additional 6 months of clopidogrel
Population patients with DES implantation for stable CAD and ACS
Endpoints composite death, MI, stent thrombosis, stroke and TIMI major bleeding
9 months after randomisation
Placebo 1,997
Patients 1:1
4,000
Clopidogrel 2,003
The trial was stopped prematurely due to slow recruitment

% p<0.001 for non-inferiority
3
1.5 1.6
0
Placebo Clopidogrel
Conclusion there was no significant difference in clinical outcome between 6 and

12 months of clopidogrel treatment after DES-implantation
Schulz-Schüpke et al. Eur Heart J 2015;36:1252-63

Stopping or continuing clopidogrel 12 months after DES: OPTIDUAL
Objective to demonstrate that continuation of clopidogrel (for 36 additional months)

treatment after 12 month DES implantation is superior than stopping
clopidogrel at 12 months (but remaining on aspirin)
Study multicentre, open-label randomised trial
Population all-comers with DES implantation who had remained free of MACCE or major
bleeding within 12 ± 3 months after index treatment
Endpoints net adverse clinical events as death, MI, stroke or major bleeding at a median
follow-up of 33.4 months
Extended DAPT 695

Patients planned Patients recruited
1,966 1,385
Aspirin 690
The study was prematurely stopped due to slow recruitment
Net adverse clinical event rate 33.4 months

HR 0.75 (95% CI: 0.50-1.28)
%
10 p=0.17
8
6
4
5.8 7.5
2
0
Extended DAPT Aspirin
Conclusion extended DAPT was not superior to stopping clopidogrel at 12 months. The
study was stopped prematurely
Helft et al. Eur Heart J 2016;37:365-74

Short term DAPT in patients with ACS:

REDUCE trial
Objective to investigate whether treatment with DAPT for 3 months is non-inferior to

standard 12 month DAPT in patients with ACS
Study prospective, open-label multicentre, non-inferiority randomised study
(margin 5%)
Population patients with ACS treated with COMBO stent
Endpoints composite all-cause death, MI, stent thrombosis, stroke TUR and bleeding at
12 months
DAPT 3 months 751

Patients
1,496
DAPT 12 months 745
Primary endpoint at 12 months

Risk difference −0.022
Upper limit 95% CI: 0.027
HR 0.97 (0.68-1.39)
p<0.001
%
10
8.2 8.4
0
DAPT 3 months DAPT 12 months
Conclusion 3 month DAPT is non-inferior to 12 month DAPT in patients with ACS

receiving a COMBO stent
de Luca et al. EuroIntervention. 2019;15:e990-98

11 P2Y12 inhibitors
1-Year Outcomes of Patients Undergoing Primary Angioplasty

for Myocardial Infarction Treated with Prasugrel Versus Tricagrelor:
PRAGUE-18
Objective to compare efficacy and safety between prasugrel and tricagrelor in patients
with AMI undergoing PCI
Study open-Label, multicentre, superiority randomized trial
Population patients with AMI treated with Primary PCI
Endpoints combined endpoint: cardiovascular death, MI or stroke at 1 year
Prasugrel 634
Patients
1,230
Tricagrelor 596
CV DEATH / MI / STROKE
p=0.503
%
8
6.6
6
5.7
0
Prasugrel Ticagrelor
Conclusion Prasugrel and Tricagrelor are similarly effective during the first year after MI
Motovska et al. JACC. 2018;71:371-81

P2Y12 inhibitors 11
Reduced-dose Prasugrel vs. standard Clopidogrel in elderly patients:

Elderly ACS-2 study
Objective to compare the clinical outcomes of a low maintenance dose of 5 mg prasugrel

with standard clopidogrel 75 mg in elderly patients following PCI
Study multicentre, open-label, blinded end point, randomised trial
Population elderly patients >74 years with acute coronary syndrome
Endpoints composite all-cause death, MI, disabling stroke and rehospitalisation for
cardiovascular causes or bleeding at 1 year
Prasugrel 713
Expected to enroll 2,000 patients,
Patients premature termination because of
1,443 futility of efficacy
Clopidogrel 730

HR 1.01 (95% CI: 0.78-1.30)
p=0.96
%
20
17.0 16.6
0
Prasugrel PFO
Conclusion low dose 5 mg Prasugrel did not reduce adverse events compared to standard
75 mg Clopidogrel in elderly patients undergoing PCI for acute coronary
syndrome
Savonitto et al. Circulation. 2018;137:2435-45

11 P2Y12 inhibitors
Double dose clopidogrel or plus cilostazol vs. standard dual

antiplatelet clopidogrel: Post PCI-CREATIVE
Objective to study the safety and effectiveness of intensified antiplatelet therapies double
dose clopidogrel (DOUBLE) vs. DOUBLE plus cilostazol (TRIPLE) vs.
conventional clopidogrel (STANDARD) after PCI
Study single centre, randomised controlled trial
Population patients with low responsiveness to clopidogrel measured with thrombo
elastography
Endpoints MACCE as composite of all-cause death, MI,TVR or stroke at 18 months
DOUBLE 359
Patients Low responders

TRIPLE 355
9,741 1,078
STANDARD 362
MACCE at 18 months
Standard vs. Double HR 0.72 (95% CI: 0.47-1.09)
Standard vs. Triple HR 0.55 (95% CI: 0.35-0.87)
%
15
14.4
10.6
8.5
0
STANDARD DOUBLE TRIPLE
Major bleeding (BARC): no significant differences
Conclusion in patients with low responsiveness to clopidogrel a double dose of clopidogrel

plus cilostazol improved clinical outcomes without increasing major bleeding
rates
Tang et al. Circulation. 2018;137:2231-45

P2Y12 inhibitors 11
Antiplatelet therapy with ticagrelor, aspirin or both

after bypass surgery: DACAB
Objective to compare saphenous vein graft patency after ticagrelor, aspirin or both
Study multicentre, open-label, randomised controlled trial
Population patients within 24 hours of elective CABG without any indication for DAPT or
high bleeding risk
Endpoints saphenous vein graft patency at 1 year
Ticagrelor+Aspirin
(n=168)
Patients Ticagrelor
500 post-CABG (n=166)
Aspirin
(n=166)
p<0.001
p=0.10
Graft patency
88.7
82.8
100
76.5
0
Ticagrelor+Aspirin Ticagrelor Aspirin
Conclusion Ticagrelor plus aspirin significantly improved graft patency at 1 year compared
with aspirin alone. The study was not powered to detect differences in MACE or
major bleeding
Zhao et al. JAMA 2018;319:1677-86

11 P2Y12 inhibitors
Randomised trial of ticagrelor vs. aspirin in patients

after coronary artery bypass grafting: TiCAB
Objective to compare the efficacy of ticagrelor and aspirin after CABG surgery
Study prospective, multicentre, placebo-controlled, randomised trial
Population patients age >18 with ACS or stable CAD scheduled for CABG surgery
Endpoints composite of cardiovascular death, myocardial infarction (MI), repeat
revascularisation, and stroke 12 months after CABG
Ticagrelor
946
Patients post CABG 1:1
1,859 (of 3,850 planned)
Aspirin
947
CV death, MI, revascularisation or stroke

HR 1.19 (0.87-1.62)
p=0.28
% 9.7
10
8.2
0
Ticagrelor Aspirin
Conclusion no significant difference in major cardiovascular events or major bleeding could

be demonstrated though the trial was prematurely terminated and
underpowered
Schunkert et al. Eur Heart J. 2019;40;2432-40

P2Y12 inhibitors 11
Ticagrelor plus aspirin for 1 month, followed by ticagrelor alone for

23 months compared to 12 months standard DAPT followed by
12 months aspirin alone: GLOBAL LEADERS
Objective to report the clinical 2-year outcome of a combination of ticagrelor and aspirin
for 1 month, followed by ticagrelor for 23 months compared to standard DAPT
for 12 months (aspirin plus clopidogrel or ticagrelor) followed by another
12 months aspirin alone
Study randomised, open-label, multicentre superiority trial
Population patients with stable CAD or ACS
Endpoints composite of all-cause death or new Qwave MI at 24 months; secondary safety
endpoint: bleeding BARC grade 3 to 5
Experimental 7,980
Patients Vital status complete in 99.9%
15,968 ECG’s analyzable: 92.7%
Control 7,988

RR 0.87 (95% CI: 0.75 to –1.01)
% p=0.073
10
3.81 4.37
0
Experimental Control
Bleeding grade 3-5: experimental 2.04% vs control 2.12%
RR 0.97 (95% CI 0.78-1.20) p=0.77
Conclusion treatment with ticagrelor plus aspirin (1 month) followed by ticagrelor for
23 months was not superior to standard DAPT (12 months) followed by another
12 months of aspirin treatment
Vrankx et al. Lancet. 2018;392:940-9

11 P2Y12 inhibitors
Ticagrelor with or without Aspirin

in High-Rish Patients after PCI: TWILIGHT
Objective to examine effect of Ticagrelor alone vs Ticagrelor + Aspirin regarding clinically

relevant bleeding
Study prospective, multicentre, placebo-controlled, randomised trial
Population patients who were at high risk for bleeding or ischemic event and undergone
PCI
Endpoints Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding
Ticagrelor
3,555
Patients
7,119
Ticagrelor + Aspirin
3,564
BARC 2, 3 or 5 Bleeding
HR 0.56 (0.45-0.68)
p<0.001
%
10
7.1
5 4.0
0
Ticagrelor Ticagrelor + Aspirin
Conclusion ticagrelor monotherapy was associated with a lower incidence of

clinically relevant bleeding than ticagrelor plus aspirin
Mehran et al. N Engl J Med. 2019;381:2032-42

P2Y12 inhibitors 11
P2Y12 inhibitor monotherapy vs DAPT after PCI:

SMART-CHOICE TRIAL
Objective to determine whether P2Y12 inhibitor monotherapy 3 months after PCI is

non-inferior to 12 month DAPT following PCI
Study open-label multicentre non-inferiority randomised trial (margin 1.8%)
Population patients undergoing PCI without contra-indication to aspirin, clopidogrel,
prasugrel, ticagrelor, everolimus, sirolimus and no active pathological bleeding
Endpoints composite all-cause death, MI or stroke at 12 months after PCI
P2Y12 monotherapy 1,495 97.3% completed the trial

3 months
Patients
2,993
DAPT 12 months 1,498
Composite endpoint 12 months

Difference 0.4% (1-sided 95% CI: 0.0-1.3)
%
5
Pnon-inferiority: 0.007
2.9 2.5
0
P2Y12 mono DAPT
Bleeding rate (BARC 2-5):

P2Y12 2.0% vs DAPT 3.4% HR 0.58 (95% CI: 0.36-0.92) P=0.02
Conclusion P2Y12 monotherapy for 3 months was non-inferior to 12 month DAPT after PCI
in terms of major cardiac cerebrovascular events
Hahn et al. JAMA. 2019;321:2428-37

11 P2Y12 inhibitors
1 month DAPT followed by clopidogrel vs 12 month DAPT:

STOPDAPT-2 trial
Objective to compare the adverse clinical events of 1 month dual antiplatelet (DAPT-1)
therapy followed by clopidogrel with 12-month dual antiplatelet therapy (DAPT-12)
Study open-label multicentre randomised inferiority trial (margin 2.3%)
Population patients with successful PCI with CoCR-EES stent without in-hospital MACE
(except periprocedural MI)
Endpoints composite of cardiovascular and bleeding events: cardiovascular death, MI,
definite stent thrombosis, stroke or TIMI major or minor bleeding
DAPT – 1 month
1,500
Clopidogrel 12 months
Patients 99% Completed trial
3,009
DAPT – 12 months
1,509
Primary endpoint
HR 0.64 (95% CI: 0.42-0.98)
% non-inferiority p<0.001
5
4
3.70
3 2.36
2
0
DAPT 1 month DAPT 12 months
secondary MACE (cardiovascular death, MI, stent thrombosis, stroke)
1.96% vs 2.51% HR 0.79 (95% CI: 0.49-1.29) p=0.34
non inferiority p=0.005
secondary major bleeding: 0.41% vs 1.54% HR 0.26 (95% CI: 0.11-0.64)
Conclusion 1 month DAPT followed by clopidogrel (monotherapy) compared to 12 month

DAPT (aspirin and clopidogrel) was associated with lower cardiovascular MACE
and bleeding
Watanabe et al. JAMA. 2019;321:2414-27

P2Y12 inhibitors 11
Ticagrelor in patients with diabetes and stable CAD

and previous PCI: THEMIS-PCI
Objective to investigate the clinical efficacy of ticagrelor vs placebo in addition to aspirin

in stable CAD patients with type 2 diabetes and history of previous PCI
Study prespecified subgroup analysis of the THEMIS trial which is a phase 3, double-
blinded, multicentre randomised trial (58% of overall THEMIS)
Population patients with history of PCI and DM type 2 and previous PCI: median time
since recent PCI 3.3 years
Endpoints composite cardiovascular death, MI or stroke during median follow-up
3.3 years
Ticagrelor
5,558
Patients
11,154
Placebo
5,596
Cardiovascular death, MI, stroke 3.3 years

HR 0.85 (95% CI: 0.74-0.97)
p=0.013
%
10 8.6
7.3
0
Ticagrelor Placebo
TIMI major bleeding: ticagrelor 2% vs placebo 1.1%
HR 2.03 (95% CI: 1.48-2.76) p<0.0001
Conclusion ticagrelor treatment in patients with diabetes, stable CAD and previous PCI
reduced cardiovascular death, myocardial and stroke compared with placebo,
but this was associated with increased bleeding
Bhatt et al. Lancet. 2019;394:1118-20

11 P2Y12 inhibitors
Ticagrelor or prasugrel in patients with ACS:

ISAR-REACT 5
Objective to compare the efficacy and safety of the use of ticagrelor or prasugrel in
patients with acute coronary syndromes planned for PCI
Study multicentre open label randomised trial
Population patients with STEMI (41%) or UA (13%) or NSTEMI (46%) undergoing PCI
(84%)
Endpoints composite of death, MI or stroke at 1 year
Ticagrelor 2,012
4,018
Prasugrel 2,006
Death/MI/Stroke 1 year
HR 1.36 (95% CI: 1.90-1.70)
p=0.006
%
10 9.3
6.9
0
Ticagrelor Prasugrel
Major bleeding: ticagrelor 5.4% vs prasugrel 4.8%
HR 1.12 (95% CI: 0.83-1.51) p=0.46
Conclusion the incidence at 1 year of death, MI or stroke was significantly lower with
prasugrel compared to ticagrelor for treatment of patients with ACS with
planned PCI while the incidence of bleeding was not different
Schüpke et al. N Engl J Med. 2019;381:1524-34

P2Y12 inhibitors 11
Ticagrelor versus Clopidogrel in ACS

and invasive management: TICAKOREA
Objective to compare the safety and efficacy of ticagrelor with clopidogrel in patients
with ACS
Population patients with ACS (with or without ST-Elevation) and intended invasive
R x (85%)
Endpoints clinically significant bleeding (composite of major or minor bleeding according
to PLATO) at 12 months
Ticagrelor
400
180 mg loading dose
90 mg twice daily
Patients
16 patients lost to follow up
800
Clopidogrel
400
600 mg loading dose
75 mg daily
Significant bleeding 12 months

HR 2.26 (95% CI: 1.34-3.79)
p=0.002
%
15
11.7
10
5.3
5
0
Ticagrelor Clopidrogel
Conclusion ticagrelor was associated with a significant higher bleeding rate than
clopidogrel in patients with ACS and intended invasive management
Park et al. Circulation. 2019;140:1865-77

11 Platelet reactivity / genotyping
Platelet function monitoring to adjust antiplatelet therapy:

ANTARCTIC
Objective to establish whether platelet function monitoring to adjust prasugrel treatment

would improve clinical outcome
Study multicentre, open-label, blinded endpoint, randomised controlled trial
Population patients aged 75 years or older who underwent coronary stenting for treatment
of acute coronary syndrome
Endpoints composite cardiovascular death, MI, stroke, stent thrombosis urgent
revascularisation and BARC-bleeding (types 2,3 or 5) at 12 months
Monitoring 442 Platelet function testing was done

Patients 14 days after randomisation and
877 repeated 14 days after treatment
Conventional 435 adjustment
Primary endpoint at 12 months

HR 1.003 (95% CI 0.78-1.29)
p=0.98
% 28 28
30
25
20
15
10
0
monitoring conventional
Conclusion platelet function monitoring with treatment adjustment of prasugrel in elderly

patients who underwent stenting for ACS did not improve 12 month clinical
outcome
Cayla et al. Lancet 2016;388:2015-22

Platelet reactivity / genotyping 11
Guided de-escalation of antiplatelet treatment in patients with acute

coronary syndrome undergoing percutaneous coronary intervention:
TROPICAL-ACS
Objective to investigate the safety and efficacy of early de-escalation of antiplatelet

treatment from prasugrel to clopidogrel guided by platelet function testing
(PFT)
Study investigator-initiated, open-label, assessor-blinded, multicentre randomised
trial
Population patients with acute coronary syndrome with PCI
Endpoints net clinical benefit (cardiovascular death, myocardial infarction, stroke or
bleeding grade 2 or higher according to BARC criteria) at 1 year
Guided de-escalation 1,304

Patients
2,610
Control/Standard treatment 1,306

Psuperiority=0.12
%
10 9%
7%
0
De-escalation Control
Conclusion guided de-escalation of antiplatelet treatment was non-inferior to standard

treatment with prasugrel at 1 year after PCI in terms of net clinical benefit
Sibbing et al. Lancet. 2017;390:1747-57

11 Platelet reactivity / genotyping
Genotype-guided strategy for P2Y12 inhibitors during PPCI:

POPULAR Trial
Objective to determine whether CYP2C19 genotype guided antiplatelet therapy for

selection or oral P2Y12 inhibitors does reduce adverse events during PPCI
Study open-label, assessor-blinded randomised trial (non-inferiority )
Population patients undergoing PPCI. In genotype guided arm carriers of loss-of function
alleles (CYP2C19 *2 or *3) received ticagrelor or prasugrel, non-carriers
received clopidogrel. Standard treatment : prasugrel or ticagrelor
Endpoints net adverse clinical events: all-cause death, MI, Stent thrombosis, stroke or
major bleeding (PLATO criteria) at 12 months or PLATO major/minor bleeding
at 12 months
Genotype-guided
1,242
Patients
2,488
Intention-to-treat analysis
Standard 1,246
Net adverse clinical events PLATO bleeding 12 months

12 months HR 0.78 (95% CI: 0.61-0.98)
Difference 0.7 (95% CI: 2.0-0.7) P=0.04
% Pnon-inferiority<0.001 %
15 15
12.5
9.8
5.1 5.9
0 0
Genotype Standard Genotype Standard
Conclusion CYP2C19 genotype guided strategy for selection of oral P2Y12 inhibitor was
non-inferior to standard treatment at 12 months and was associated with
a lower bleeding incidence in patients undergoing primary PCI
Claassens et al. N Engl J Med. 2019;381:1621-31

Antiplatelet therapy in OAC 11
Triple therapy in patients requiring oral anticoagulation after DES:

ISAR-Triple
Objective to evaluate whether 6-week duration of clopidogrel in addition to aspirin/oral

anticogulation (OAC) is superior compared to 6-month clopidogrel in addition
to aspirin/OAC
Study open-label multicentre randomised trial
Population patients undergoing DES implantation who require oral anticogulation
Endpoints composite death, MI, definite ST, stroke, or major bleeding (TIMI) at 9 months
6-week clopidogrel 307
Patients 1:1
614
6-month clopidogrel 307

HR 1.14 (95% CI: 0.68-0.91)
%
15 p=0.63
10
9.8 8.8
5
0
6 weeks clopidogrel 6 months clopidogrel
Conclusion 6-week triple treatment in post-DES implantation patient is not superior to

6-month triple treatment
Fiedler et al. JACC. 2015;65:1619-29

11 Antiplatelet therapy in OAC
Rivaroxaban versus standard treatment in patients with atrial

fibrillation undergoing PCI: PIONEER AF-PCI
Objective to explore prevention of bleeding of two treatment strategies of rivaroxaban

versus oral vitamin K antagonist treatment in patients with atrial fibrillation
undergoing PCI
Study multicentre open-label randomised trial
Population patients with paroxysmal, persistent or permanent nonvalvular atrial fibrillation
who had just received a stent
Endpoints occurrence of clinically significant bleeding as a composite of major and minor
bleeding according to TIMI
Low dose Rivaroxaban (15 mg daily) for 12 months

+P2Y12 inhibitor Group 1: 709
Patients 1:1:1 Very low dose Rivaroxaban (2.5 mg twice daily)

2,236 Group 2: 709
+DAPT for 1,6 or 12 months
Vit K antagonist (once daily)

Group 3: 706
+DAPT for 1, 6 or 12 months
Clinically significant bleeding

Group 1 vs group 3 HR 0.59 (95% CI 0.47 to 0.76) p˂0.001
Group 2 vs group 3 HR 0.63 (95% CI 0.50 to 0.80) p<0.001
%
30 26.7
20 16.8 18.0
10
0
Group 1 Group 2 Group 3
Conclusion a treatment strategy of low dose rivaroxaban+P2Y12 inhibitor or very low dose of
rivaroxaban+DAPT was associated with a lower bleeding rate compared to
standard treatment with vitamin K antagonists
Gibson et al. N. Engl J Med. 2016;375:2423-34

Dabigatran versus vitamin K antagonists in patients with atrial

fibrillation and PCI: RE-DUAL PCI
Objective to compare the use of two regimens of dual antithrombotic therapy including
dabigatran with the use of triple antithrombotic therapy using warfarin in
patients with atrial fibrillation who had undergone PCI
Study open-label multicentre randomised non-inferiority trial (margin 1.38)
Population patients with non-valvular paroxysmal, persistent or permanent atrial fibrillation
Endpoints major or clinically relevant non-major bleeding according to ISTH criteria
Dual therapy dabigatran 110 mg (twice daily)

plus P2Y12 (clopidogrel or ticagrelor) 981
Patients Dual therapy dabigatran 150 mg (twice daily)

2,725 763
plus P2Y12 (clopidogrel or ticagrelor)
Triple therapy with warfarin plus aspirin

and P2Y12 (clopidogrel or ticagrelor) 981
Bleeding major or clinical significant non-major

dual 110 vs. triple HR 0.52 (95% CI 0.42 to 0.63) p˂0.001
dual 150 vs. triple HR 0.72 (95% CI 0.58 to 0.88) p<0.001
%
30 26.9 25.7
20.2
20 15.4
10
0
dual 110 mg dual 150 mg triple warfarin
dabigatran dabigatran
Conclusion the risk of bleeding was lower in the dabigatran treatment strategy compared to
warfarin strategies in patients with atrial fibrillation after PCI
Cannon et al. N. Engl J Med. 2017;377:1513-24

Oral anticoagulation with and without single antiplatelet therapy in patients

with atrial fibrillation beyond 1 year after coronary stenting: OAC-ALONE
Objective to compare OAC alone versus OAC + single antiplatelet therapy (APT)
Study prospective, multicentre, open-label, noninferiority trial
Population patients with atrial fibrillation beyond 1-year after stenting
Endpoints composite of all-cause death, myocardial infarction, stroke, or systemic
embolism
OAC alone
344
Patients with A. Fib
*696 (of 2,000 planned)
OAC + APT
* 6 patients withdrew 346
Death, MI, Stroke, Embolism

HR 1.16 (0.79-1.72)
p non-inferiority <0.020
%
20
15.7
15 13.6
10
0
OAC + alone OAC + APT
Conclusion non-inferiority of OAC alone compared to OAC + single antiplatelet therapy was
not established. Due to premature termination of enrolment the trial was
underpowered and non-conclusive
Matsumura-Nakano et al. Circulation. 2019;139:604-16

Edoxaban vs Vit K antagonist anti thrombotic treatment in patients

with AF and PCI: ENTRUST-AF PCI
Objective to assess the incidence of clinically relevant non-major or major bleeding

during treatment with Edoxaban compared to Vit K antagonists in patients with
atrial fibrillation undergoing PCI
Study multicentre, open-label phase 3b non-inferiority randomised study (margin
1.20)
Population patients with atrial fibrillation requiring oral anticoagulation who had
successful PCI in all-comers
Endpoints composite of major or clinically relevant non-major (CRNM) bleeding (ISTH
criteria) during 12-month follow-up
Edoxaban 60 mg
+P2Y12 inhibitor 12 months 751
Patients
1,506
Vit KA +
P2Y12 inhibitor /aspirin (1-12 months) 755
Major or CRNM bleeding 12 months

HR 0.83 (95% CI: 0.65-1.05)
% 20.0
20
17.0
10
0
Edoxaban VKA
Conclusion in patients with atrial fibrillation and successful PCI edoxaban regimen was
non-inferior to Vit K antagonist regimen with respect to bleeding
Vranckx et al. Lancet. 2019;394:1335-43

Antithrombotic therapy after ACS or PCI in Atrial Fibrillation:

AUGUSTUS
Objective to compare antithrombotic regimens for patients with atrial fibrillation after
ACS or PCI
Study prospective, multicentre, randomised sham-controlled, two-by-two factorial
design
Population patients with atrial fibrillation who were planning to take P2Y12 inhibitor after
ACS or PCI
Endpoints the primary outcome was major or clinically relevant nonmajor bleeding
Apixiban Aspirin
2,306 2,307
Patients
4,614
Vitamin K antagonist Placebo
2,308 2,307
Bleeding P<0.001
20
16.1
14.7
15
10.5
9.0
10
0
Apixiban VKA Aspirin Placebo
Conclusion in patients treated with P2Y12 inhibitor with atrial fibrillation and ACS or PCI,
Apixaban instead of vitamin K antagonist and placebo instead of aspirin
resulted in less bleeding
Lopes et al. N Engl J Med. 2019;380:1509-24

Bivalirudin 11
Bivalirudin vs unfractioned heparin in ACS:

MATRIX
Objective to report the 30 days safety and efficacy of bivalirudin compared to

unfractioned heparin administered to patients with ACS scheduled for PCI
(bivalirudin vs heparin and post-infusion bivalirudin vs no infusion bivalirudin)
Study multicentre, open-label superiority two nested trials
Population patients with NSTEMI and STEMI
Endpoints bivalirudin vs heparin: MACE – death, MI or stroke and net adverse events:
major bleeding or MACE. Post-PCI bivalirudin infusion vs no infusion:
composite urgent TVR, definite ST or net adverse events
Heparin 3,603
Patients Post PCI bivalirudin 1,799
7,213
Bivalirudin 3,610
No post PCI bivalirudin 1,811
30 days Bivalirudin vs heparin RR (95% CI) p-value

MACE % 10.3 10.9 0.94 (0.81-1.09) 0.44
Net adverse events % 11.2 12.4 0.89 (0.78-1.03) 0.12
Post PCI vs no
infusion infusion
Urgent TVR or definite ST 0.34
11.0 11.9 0.91 (0.74-1.11)
or net adverse events %
Conclusion The safety and efficacy of bivalirudin compared to heparin is similar in patients
with ACS scheduled to undergo PCI
Valgimigli et al. NEJM. 2015;373:977-1009

11 Bivalirudin
Bivalirudin versus unfractionated heparin in ACS:

MATRIX 1 year
Objective to report the 1-year safety and efficacy of bivalirudin compared to

unfractionated heparin given to patients with ACS scheduled for PCI
Study open-label multicentre superiority two-nested randomised trial
Population patients with ACS
Endpoints MACE: all-cause death, MI or stroke (heparin vs. bivalirudin). NACE: all-cause
death, MI, stroke or major bleeding
Bivalirudin 3,610
Patients Complete follow-up 99.9%
7,213
Unfr.heparin 3,603
MACE 1 year NACE 1 year

RR 0.94 (95% CI: 0.83-1.05) RR 0.91 (95% CI: 0.81-1.02)
p=0.28 p=0.10
% %
20
16.8 20
17.0 18.4
15.8
10 10
0 0
Bivalirudin Heparin Bivalirudin Heparin
Conclusion bivalirudin was not associated with lower MACE or NACE at 1 year compared to
unfractionated heparin for ACS patients undergoing PCI

Bivalirudin 11
Bivalirudin vs heparin alone or heparin and tirofiban

during PPCI BRIGHT
Objective to determine the clinical outcome of bivalirudin with 3 hrs post-PCI infusion –
1.75 mg/kg/h compared to heparin alone or heparin plus tirofiban
Study multicentre- open label randomised trial (superiority bivalirudin)
Population patients with AMI (including STEMI) within 12 hrs symptom onset or within 12
to 24 hrs within ongoing chest-pain, ST-elevation or new LBBB and NSTEMI
with emergency PCI (clinically induced)
Endpoints composite MACE (all-cause death, re-MI, ischaemia driven TVR or stroke) or
bleeding at 30 days
Bivalirudin 735
Patients 1:1 Follow-up 30 days

2,194 Heparin alone 729 100% complete
Heparin plus tirofiban 730
30-day endpoint MACCE+bleeding

RR: 0.67 (95% CI: 0.5-0.9) RR: 0.52 (95% CI: 0.4-0.7)
% p=0.008 p<0.001
20
15
17.0
10 13.2
5 8.8
0
bivalirudin heparin heparin plus tirofiban
30-day bleeding rates: bivalirudin 4.1%

heparin 7.5% p<0.001
heparin plus tirofiban 12.3%
There were no significant differences of MACCE between the 3 groups.
Conclusion bivalirudin is superior to heparin alone or heparin plus tirofiban at 30 days

undergoing primary PCI for AMI. This was mainly due to reduced bleeding rate
with bivalirudin
Han et al. JAMA. 2015;313:1336-46

11 Bivalirudin
Bivalirudin vs Heparin in acute myocardial infarction:

VALIDATE-SWEDEHEART
Objective to investigate whether the use of bivalirudin would result in a lower rate
of adverse events than heparin treatment among patients with acute MI
undergoing PCI
Study registry-based, multicentre open-label randomised trial
Population patients with STEMI (3005) and NSTEMI (3001) undergoing PCI using radial
access in 90.3% and P2Y12 inhibitor in all patients
Endpoints composite of all-cause death, MI or major bleeding during 180 days
of follow-up
Bivalirudin
3,004
Patients
6,006
Heparin
3,002

HR 0.89 (CI% 0.74-1.07)
p=0.21
%
7.2 8.0
10
0
Bivalirudin Heparin
Conclusion the rate of adverse cardiac events was not lower using bivalirudin as compared
to heparin among patients with acute myocardial infarction undergoing PCI
Erlinge et al. N Engl J Med. 2017;377:1132-42

Dual pathway inhibition 11
Rivaroxaban in Peripheral Artery Disease after Revascularisation:

VOYAGER-PAD
Objective to assess efficacy and safety of rivaroxaban in addition to aspirin in patients

with PAD and recent revascularisation
Study multicentre, double-blind, randomised trial
Population patients with peripheral artery disease who had undergone revascularisation
Endpoints primary efficacy outcome was a composite of acute limb ischemia, major
amputation for vascular causes, MI, ischemic stroke, or death from
cardiovascular causes. The principle safety outcome was major bleeding.
Rivaroxaban 2.5 mg (n=3,286)

Patients with PAD
(n=6,594)
Placebo (n=3,278)
Efficacy Safety
HR 0.85 (95% CI: 0.76-0.96) HR 1.43 (95% CI: 0.97-2.10)
p=0.009 p=0.07
% 19.9 %
20 17.3 10
6
10
4 2.65
1.87
2
0 0
RIVA PLACEBO RIVA PLACEBO
Conclusion Rivaroxaban lowered the risk of major vascular complications compared with
placebo without a significant increase in TIMI major bleeding
Bonaca et al. N Eng J Med. 2020; March, 28

12 ∙ Cardiogenic shock and cardiac arrest
Page
Cardiogenic shock and cardiac arrest ..................................................190

12 Cardiogenic shock and cardiac arrest
PCI Strategies in patients with acute myocardial infarction and

cardiogenic shock: CULPRIT-SHOCK
Objective to compare culprit only (±Staged) PCI with immediate multi-vessel PCI in
patients with myocardial infarction and shock
Population patients who had multi-vessel disease, acute myocardial infarction, and
cardiogenic shock
Endpoints composite of death or severe renal failure leading to renal- replacement therapy
within 30 days after randomisation
CULPRIT only PCI±Staged: 344

Patients
706
Immediate multivessel: 341
Primary endpoint at 30 days

RR 0.83 (95% CI 0.71-0.96)
p=0.01
%
60 55.4
45.9
40
20
0
CULPRIT only Multivessel PCI
Conclusion the 30-day risk of a composite death or severe renal failure leading to renal-
replacement therapy was lower among those who initially underwent PCI of the
culprit lesion only than among those who underwent immediate multi-vessel
PCI
Thiele et al. N Engl J Med. 2017;377:2419-32

Cardiogenic shock and cardiac arrest 12
CULPRIT SHOCK (Late Outcomes):

One-Year Outcomes after PCI Strategies in Cardiogenic Shock
Objective to compare outcomes of patients in cardiogenic shock treated with culprit

only PCI versus multivessel PCI
Study multicentre, assessor-blind, randomised controlled trial
Population patients with cardiogenic shock and multivessel coronary disease
Endpoints prespecified end points at 1 year included death from any cause, recurrent MI
Culprit Only PCI

351
Patients with cardiogenic shock
706
Multivessel PCI
355
Death at 1 year Recurrent MI at 1 year

RR 0.88 (95% CI: 0.76 to 1.01) RR 0.85 (95% 0.29 to 2.50)
p=0.01 p=0.01
%
60 50 56.9 %
5
4
40
3 2.1
2
1.7
20
1
0 0
Culprit only Multivessel PCI Culprit only Multivessel PCI
Conclusion mortality and recurrent myocardial infarction at 1 year was comparable in both
treatments groups. There was no clear evidence of delayed benefit
with multivessel PCI
Thiele et al. N Eng J Med. 2018;379:1699-1710

12 Cardiogenic shock and cardiac arrest
Intra-aortic balloon pump in cardiogenic shock and MI:

IABP-Shock 6 years
Objective to report the 6-year clinical outcome of the impact of IABP in cardiogenic
shock as compared to a control group in patients with acute myocardial
infarction
Study an open-label, prospective, multicentre study
Population patients with cardiogenic shock and planned early revascularisation preferably
by PCI
Endpoints all-cause mortality at 6.2 years
IABP 301
Patients Follow-up complete 98.5%
600
Control 299
All-cause mortality at 6.2 years

RR 0.99; 95% CI 0.88-1.11
p=0.98
%
80
66.3 67.0
60
40
20
0
IABP Control
Conclusion IABP has no beneficial effect on the longterm all-cause mortality in patients
with acute MI complicated by cardiogenic shock
Thiele et al. Circulation. 2019;139:395-403

Cardiogenic shock and cardiac arrest 12
Coronary Angiography after Cardiac Arrest (non-STEMI):

COACT
Objective to report the survival rate of patients with sudden cardiac arrest who underwent
immediate coronary angiography or angiography that was delayed until
neurologic recovery
Population patients with out-of-hospital cardiac arrest, successfully resuscitated and
without signs of STEMI
Endpoints survival at 90 days
Immediate
angiography 273
Patients
552
Delayed angiography
265
Overall survival at 90 days

OR 0.89 (95% CI 0.62 to 1.27)
% p=0.51
100
64.5 67.2
50
0
Immediate Delayed
angiography angiography
Conclusion in patients successfully resuscitated after out-of-hospital cardiac arrest (no

signs of STEMI) a strategy of immediate versus delayed angiography was not
better with respect to survival at 90 days
Lemkes et al. N Engl J Med. 2019;380:1397-407

13 ∙ Percutaneous treatment for structural heart disease
Page
TAVI .................................................................................................196
Mitral clip ........................................................................................212
Closure foramen ovale .......................................................................215

13 TAVI
Balloon expandable vs self-expandable valves for TAVI:

CHOICE - 1 year
Objective to report the clinical outcomes of balloon expandable Edwards Sapien Valve
compared to self-expandable Medtronic Corevalve for treatment of severe aortic
stenosis
Study multicentre, randomised controlled trial
Population patients with symptomatic severe aortic stenosis at high surgical risk
undergoing TAVR through transfemoral route
Endpoints 1-year rates of all-cause death, cardiovascular death, stroke and repeat
hospitalisation for heart failure
Balloon-expandable 121 Device success 95.9%
Patients
241
Self-expandable 120 Device success 77.5%
Clinical outcomes 1 year Balloon-exp. Self-exp. RR (95% CI) p-value

All-cause death % 17.4 12.8 1.35 (0.73-2.5) 0.37
Cardiovascular death % 12.4 9.4 1.32 (0.63-2.75) 0.54
Stroke % 9.1 3.4 2.66 (0.87-8.12) 0.11
Hosp. heart failure % 7.4 12.8 0.58 (0.26-1.27) 0.19
≥moderate AR % 1.1 12.1 0.005
New pacemaker % 23.4 38.0 0.02
Conclusion Despite higher balloon expandable device success rate and taken into account
the limited statistical power of the study, there were no statistically significant
differences of 1-year clinical outcomes in patients treated with balloon-
expandable or self-expandable valves
Abdel-Wahab et al. JACC. 2015;66:791-800

TAVI 13
Surgical versus transcatheter aortic valve replacement in high-risk

patients: US CORE VALVE HIGH-RISK 3 years
Objective to report the 3-year clinical outcomes of TAVR vs. SAVR for the treatment of
aortic valve stenosis of patients with high surgical risk profile
Study prospective, multicenter, randomized non-inferiority study
Population patients with aortic stenosis: aortic valve area <0.8 cm2 or index <0.5 cm2/m2
and either mean gradient >40 mmHg or peak velocity jet >4 m/s
Endpoints MACCE as all cause death, MI, any stroke or re-intervention; all-cause mortality
or stroke
TAVR 391 median follow-up 35.8 months
Patients
750 complete follow-up 93%
Surgery 359
median follow-up 34.6 months
3-year outcomes TAVR vs. SAVR p value

All cause death % 32.9 39.1 0.006
Any stroke % 12.6 19.0 0.034
All cause death or major stroke % 35.0 41.6 0.046
MACCE % 40.2 47.9 0.025
Conclusion patients with severe aortic stenosis at increased surgical risk had improved
3-year adverse clinical outcomes after TAVR compared to SAVR
Deeb et al. J Am Coll Cardiol 2016;67:2565-74

13 TAVI
TAVR vs standard care for inoperable aortic stenosis:

PARTNER IB 5 years
Objective to report the 5-year all-cause mortality of TAVR compared to standard

treatment in patient with inoperable aortic stenosis
Study multicentre controlled randomised trial
Population patients with severe aortic stenosis were not candidate for surgical valve
replacement
Endpoints all-cause mortality at 5 years
TAVR 179 (Sapien)
Screened Enrolled
3,015 358
Standard 179
All-cause mortality 5 years

HR 0.50 (95% CI: 0.39-0.65)
p<0.0001
%
100
75 93.6
50 71.8
25
0
TAVR Standard
Conclusion TAVR is more favourable than standard treatment for inoperable aortic stenosis
Kapadia et al. Lancet. 2015;385:2485-91

TAVI 13
TAVR vs SAVR:
PARTNER IA 5 years
Objective to report the mortality rate at 5 years of TAVR with balloon expandable valve
(Sapien) by either femoral or apical approach compared with surgical aortic
valve replacement (SAVR)
Population surgical high-risk patients with severe aortic valve stenosis
Endpoints all-cause mortality at 5 years (intention-to-treat)
TAVR 348
Screened Enrolled
3,105 699
SAVR 351
All-cause mortality at 5 years

HR 1.04 (95% CI: 0.86-1.24)
p=0.76
%
70
60
50 67.8 62.4
40
30
20
10
0
TAVR SAVR
no valve deterioration at 5 years
TAVR=moderate or severe aortic regurgitation was associated with higher mortality
Conclusion TAVR is an alternative to surgery for patients with high surgical risk
Mack et al. Lancet. 2015;385:2477-84

13 TAVI
SAPIEN XT vs SAPIEN for TAVR of inoperable patients

PARTNER IIB
Objective to compare the 1-year clinical outcome of the next generation balloon
expandable SAPIEN XT (with lower profile delivery system) with SAPIEN valve
for inoperable aortic valve patients
Study multicentre, randomised non-inferiority study (ratio 1.35 at 1-sided alpha of
0.025)
Population inoperable (predicted probability of ≥50% of death or irreversible morbidity at
30 days) aortic valve stenosis patients
Endpoints composite of all-cause mortality, major stroke and rehospitalisation at 1 year
SAPIEN XT 284
Patients
All included at 1 year
560
SAPIEN 276
Composite 1-year endpoint

%
non-inferiority <0.002
40
30 37.7 37.2
20
10
0
SAPIEN SAPIEN XT
Overall and major vascular complication were higher at 30 days

with SAPIEN compared to SAPIEN XT (22.1% vs 15.5%; p=0.04)
Conclusion the lower-profile SAPIEN XT is non-inferior to SAPIEN for treatment of

inoperable patients with severe aortic valve stenosis
Webb et al. JACC. Cardiovasc. Interv. 2015;8:1797-806

TAVI 13
TAVR vs. SAVR in intermediate risk patients:

PARTNER IIA
Objective to report the 2-year clinical outcomes of patients with aortic stenosis at
intermediate risk of treatment with TAVR as compared to surgical aortic valve
replacement
Study parallel prospective, multicenter, randomised non-inferiority study (risk ratio
<1.20)
Population patients with aortic stenosis at intermediate surgical risk (STS risk model:
death at 30 days) treated with balloon expandable SAPIEN XT valve system
Endpoints death from any cause or disabling stroke at 2 years
TAVR 1,011
Patients
2,032
Surgery 1,021

HR 0.89 (95% CI 0.73-1.09) p=0.25
% Non inferiority: p=0.001
25
20
21.1
15 19.3
10
0
TAVR Surgery
Conclusion TAVR was similar to surgical aortic valve replacement in patients with aortic
stenosis with intermediate surgical risk profile at 2-year follow-up
Leon et al. NEJM 2016;374:1609-20

13 TAVI
Transcatheter or Surgical Aortic-valve replacement:

PARTNER-2A 5 years
Objective to report the 5-year clinical outcomes of transcatheter aortic valve replacement
(TAVR) as compared with surgical aortic valve replacement (Sapiens XT value
system)
Study prospective, multicentre, randomised non-inferiority study
Population patients with severe aortic stenosis and intermediate surgical risk (predicted
surgical mortality of 4% to 8% at 30 days)
Endpoints death from any cause or disabling stroke
TAVR data available 920 (91%)

1,011
Patients
At 5 years
2,032
Surgery
1,021 data available 831 (81.4%)
Death or disabling stroke at 5 years

HR 1.09 (95% CI: 0.95-1.25)
P=0.21
% 47.9
50 43.4
40
30
20
10
0
TAVR Surgery
Conclusion there was no significant difference of 5-year rate of death or disabling

stroke between surgery or TAVR in patients with severe aortic
stenosis at intermediate surgical risk
Makkar et al. N Eng J Med. 2020;382:799-809

TAVI 13
TAVR with balloon-expandable valve in low-risk patients:

PARTNER III
Objective to compare the clinical outcome of TAVR with surgical replacement in low-risk
patients
Study multicentre, randomised trial (1:1), non inferiority margin 6%
Population patients with aortic valve-stenosis with STS-PROM risk score less than 4.0%
Endpoints composite all-cause death, stroke or rehospitalisation at 1 year
TAVR 496 Available patients 1 year

Patients treated
1,000 950
Surgery 454 98.4%
Composite end point 1 year

non-inferiority –6.6% (95% CI –10.8 to –2.5)
P non inferiority <0.001
HR 0.54 (95% CI 0.37 to 0.79)
P sup=0.001
% 15.1
15
10 8.5
0
TAVR Surgery
Conclusion the 1-year rate of adverse events in patients with severe aortic stenosis at low
risk was significantly lower with TAVR as compared to surgery
Mack et al. N Engl J Med. 2019;380:1695-705

13 TAVI
TAVR versus SAVR for severe aortic valve stenosis:

NOTION
Objective to report the 1-year clinical outcome of transcatheter aortic valve replacement
(TAVR) compared to surgical aortic valve replacement (SAVR)
Population patients ≥70 years with severe aortic valve stenosis eligible for either TAVR or
SAVR
Endpoints composite of all-cause death, stroke or MI at 1 year
TAVR 145
Patients Follow-up at 1 year
280 complete 100%
SAVR 135

p=0.43
%
20
16.3
15 13.1
10
0
TAVR SAVR
Conclusion There was no difference in outcome at 1-year follow-up between TAVR versus
SAVR for treatment of severe aortic stenosis
Thyregod et al. J Am Coll Cardiol 2015;65:2184-94

TAVI 13
TAVR versus SAVR:

NOTION 5 years
Objective to report the 5-year clinical outcomes of TAVR compared to SAVR for the
treatment of severe aortic stenosis
Population patients with severe aortic stenosis (self expanding CoreValve prosthesis)
Endpoints composite of all-cause mortality, stroke, MI at 5 years
TAVR 142
Patients
280
Surgery 135
MACE at 5 years
Kaplan-Meier estimates log-rank p=0.86
%
50
38.0 36.3
40
30
20
10
0
TAVR Surgery
Conclusion there are no significant differences in clinical adverse outcomes between TAVR
and surgery for treatment of severe aortic stenosis at 5 years
Thyregod et al. Circulation. 2019;139:2714-23

13 TAVI
Surgical or transcatheter aortic-valve replacement in intermediate

risk patients: SURTAVI
Objective to compare outcomes of patients with severe aortic stenosis (AS) and
intermediate risk treated with TAVI or surgery
Study multicentre, randomised, non-inferiority
Population patients with symptomatic severe aortic stenosis
Endpoints composite all cause death or disabling stroke at 24 months
Treated TAVI 864

Patients 1,660
1,746
Surgical AVR 796
MACE 24 months
Bayesian analysis
Posterior probability of non-inferiority
% >0.999
16
14.0
14 12.6
12
10
8
6
4
2
0
TAVI SAVR
Conclusion TAVI was a non-inferior alternative to surgery in patients with severe aortic
stenosis at intermediate surgical risk
Reardon et al. N Engl J Med. 2017;376:1321-31

TAVI 13
Mechanically expanded vs. self-expanding TAVR – REPRISE III
Objective to compare the clinical outcome of mechanically expanded aortic valve

replacement (MEV) with self-expanding aortic valve replacement (SEV) for
treatment of severe aortic stenosis
Study multicentre, non-inferiority randomised (2:1) trial (margin 10.5%)
Population patients with severe aortic stenosis at high risk of mortality
Endpoints safety: composite all-cause mortality, stroke, major bleeding, severe kidney
injury and major vascular complications at 30 days effectiveness: composite
all-cause mortality, stroke and moderate or greater paravalvular leak at 1 year
MEV 607 Full-set analysis 1 year : 96.7%

Patients 2:1
912
SEV 305 Full-set analysis 1 year: 97.4%
Safety endpoint 30 days Effectiveness endpoint 1 year

difference 3.1% (95% CI-2.3 to 8.5) difference –10.1%(95% CI –16.2 to 3.9)
p=0.003 (non-inferiority) p˂0.001 (non-inferiority)
% %
30 30 15.4
25.5
20.3
20 17.2 20 15.4
10 10
0 0
MEV SEV MEV SEV
Superiority testing 1 year primary effectiveness endpoint:
MES vs. SEV: 15.8% vs. 26.0% difference –10.2% (–16.3 to –4.0) <0.001
Conclusion treatment for severe aortic stenosis with use of mechanically expanded vs. self
expanding TAVR did not result in inferior safety or efficacy outcomes
Feldman et al. JAMA. 2018;319:27-37

13 TAVI
Transcatheter Aortic-Valve Replacement with Self-Expanding

Valve in Low-Risk Patients: Evolut Low Risk
Objective to compare TAVI with surgical AVR in patients at low surgical risk
Study prospective, multicentre, non-blinded, non-inferiority, randomised trial
Population severe aortic steosis + predicted 30-day mortality <3%
Endpoints composite of death or disabling stroke at 24 months, using Bayesian methods
TAVI
734
Patients with AS
1,468
SAVR.
734
Death or stroke
Difference −1.4% (2.1%)
Probability of non-inferiority >0.999
%
10
6.7
5.3
5
0
TAVI SAVR
Conclusion TAVR with a self-expanding supraannular bioprosthesis was noninferior to

surgery with respect to the composite end point of death or disabling stroke at
24 months
Popma et al. N Engl J Med. 2019;380:1706-15

TAVI 13
Self expanding versus balloon expandable bioprothesis for TAVR:

SCOPE-Trial
Objective to compare the safety and efficacy of the ACURATE neo (self-expanding TAVR
prothesis) with the SAPIEN 3 TAVR prothesis (balloon expandable) for the
treatment of symptomatic severe aortic stenosis
Study investigator-initiated, multicentre non-inferiority, randomised trial
(margin 7.7%)
Population patients aged 75 or older with symptomatic severe aortic stenosis at increased
surgical risk
Endpoints all cause death, any stroke, severe bleeding, major vascular complications,
coronary artery obstruction, acute kidney injury, rehospitalisation (for valve-
related symptoms or heart failure) and valve-related dysfunction at 30 days
ACURATE: 372
Screened Enrolled Follow-up 99%
5,132 739
SAPIEN-3: 367

Risk difference 7.1%
(apper 95% CI: 12.0%)
% p=0.42
30
24.0
16.0
0
ACURATE SAPIEN-3
Conclusion the self-expanding ACURATE neo was not non-inferior compared to balloon-
expandable SAPIEN 3
Lanz et al. Lancet. 2019;394:1619-28

13 TAVI
Rivaroxaban after TAVI:

GALILEO study
Objective to compare the efficacy of rivaroxaban (10 mg daily) with aspirin (75-100 mg
daily for the first 3 months) as compared to aspirin (75-100 mg daily) with
clopidogrel (at a dose of 75 mg daily during the first 3 months) in patients with
successful TAVR
Study open label, event-driven multicentre randomised study
Population patients with successful TAVR and no established indication for long term
anticoagulation
Endpoints composite of all-cause death or thromboembolic events (stroke, MI, valve
thrombosis, embolism, deep vein thrombosis or pulmonary embolism). Safety
endpoint: composite of life threatening, disabling or major bleeding during
median 17 months
Rivaroxaban 826
Patients
Follow-up complete 96.8%
1,644
Antiplatelet 818
Death or thromboembolic event Bleeding median 17 months

median 17 months HR 1.50 (95% CI: 0.95 to 2.37)
HR 1.35 (95% CI: 1.01 to 1.81) p=0.08
p=0.04
% %
15 12.7 15
9.5
5.6
3.8
0 0
Rivaroxaban Antiplatelet Rivaroxaban Antiplatelet
Trial was terminated prematurely because of safety concerns
Conclusion a treatment strategy of anticoagulation after TAVR including rivaroxaban

(10 mg daily) was associated with higher adverse events and bleeding rates
than antiplatelet based strategy
Dangas et al. N Eng J Med. 2020;382:120-29

TAVI 13
TAVR with self-expending valve in low risk patients:

a prespecified interim analysis at 12 months
Objective to compare the safety and effectiveness of TAVR with surgical valve
replacement. A pre-specified Bayesian interim analysis was performed
12 months after the 850th patient underwent the procedure
Study multicentre, randomised non-inferiority trial (margin 6%)
Population patients with severe aortic-valve stenosis (valve area <1.0 cm2, mean gradient
40 mmHg or mean aortic-valve velocity >4.0 m/sec) and no more than
predicted 3% risk of death with surgery
Endpoints composite all-cause death or disabling stroke at 24 months using a Bayesian
method after 12 months
TAVR 725 12 months

432
Patients treated
1.468 1,403
Surgery 678 352
Estimated 24-month Bayesian analysis

probability non-inferiority >0.999
%
10
6.7
5.3
5
0
TAVR Surgery
Conclusion TAVR with self-expanding bioprothesis is non-inferior to surgery in lowrisk

patients
Popma et al. N Eng J Med. 2019; 380:1706-15

13 Mitral clip
Percutaneous repair or surgery for mitral regurgitation:

EVEREST II 5 years
Objective to evaluate the final 5-year clinical outcomes of percutaneous mitral valve (MV)
repair with MitraClip device compared with MV surgery
Study non blinded, multicentre, randomised study (2:1)
Population candidates for mitral repair or replacement surgery
Endpoints composite of freedom of death, surgery or 3+ or 4+ MR through 5 years.
Percutaneous 178 87% at 5 years
Patients 2:1
258
Surgery 80 70% at 5 years
Freedom of composite endpoint at 5 years

p=0.01
%
70
60
50 64.3
40
30 44.2
20
10
0
Percutaneous Surgical
5 years percutaneous surgical p-value

death 20.8% 26.8% 0.36
MV surgery or re-op 27.9% 8.9% 0.003
3+ or 4+ MR 12.3% 1.8% 0.02
Conclusion surgical mitral valve repair was superior to MitraClip repair due to the higher
requirement of surgery for residual MR after MitraClip repair, while 5-year
mortality was not statistically different
Feldman et al. J Am Coll Cardiol 2015;66:2844-54

Mitral clip 13
Transcatheter Mitral-Valve repair versus medical treatment for

secondary mitral regurgitation: MITRA-FR
Objective to compare whether transcatheter mitral-valve repair (TMVR) with MitraClip

improves clinical outcomes in patients with heart failure and severe functional
mitral regurgitation
Study randomised, multicentre, semi-label
Population i. severe secondary mitral regurgitation. ii. Left ventricular ejection fraction
between 15 and 40%. iii. Symptomatic heart failure
Endpoints the primary efficacy outcome was a composite of death from any cause or
unplanned hospitalisation for heart failure at 12 months
TMVR 152
304 patients
with heart failure
and MR Medical therapy control
152
Death or unplanned hospitalisation for heart failure

p=0.53
%
70
54.6
60 51.3
50
40
30
20
10
0
TMVR Control
Conclusion the rate of death or unplanned hospitalisation for heart failure at 1 year did not
differ between patients allocated to TMVR versus medical therapy alone
Obadia et al. N Eng J Med. 2018;379:2297-306

13 Mitral clip
Transcatheter Mitral-Valve repair in patients with heart failure:

COAPT
Objective to assess the effectiveness and safety of transcatheter mitral valve repair
(TMVR) with MitraClip in patients with heart failure
Study randomised, multicentre, open-label
Population patients with heart failure and severe secondary mitral regurgitation,
symptomatic despite maximal therapy
Endpoints primary effectiveness endpoint: all heart failure hospitalisation within
24 months. Primary safety end point; freedom from device-related
complications at 12 months
TMVR 302
614 patients
with heart failure
and MR
Control group 312
Heart failure hospitalisation per year

p<0.001
% 67.9
70
60
50
40
35.8
30
20
10
0
TMVR Control group
Conclusion among patients with heart failure and mitral regurgitation who were
symptomatic despite maximal medical therapy TMVR with MitraClip was safe
and effective as reducing heart failure hospitalisation
Stone et al. N Eng J Med. 2018;379:2307-18

Closure foramen ovale 13
Patent Foramen Ovale closure or medical therapy:

RESPECT longterm
Objective does closure of a patent foramen ovale (PFO) compared to medical therapy
reduce recurrent ischemic stroke in patients with earlier cryptogenic ischemic
stroke
Population patients 18-60 years of age who had PFO and earlier cryptogenic ischemic
stroke
Endpoints recurrent ischemic stroke or early (within 30 days after randomisation) death
during median 5.9 years follow-up
PFO (Follow-up
499 3,141 patient-years)
Patients
980
Med. Rx (Follow-up
481 2,669 patient-years)
Recurrent ischemic stroke 5.9 years

HR 0.55 (95% CI 0.31-0.999)
p=0.046
%
5.8
6
3.6
4
0
PFO Med. Rx.
The original trial (median follow-up 2.1 years) did not show a statistical difference
in recurrence stroke rate
Conclusion during an extended follow-up period (median 5.9 years) PFO had a lower
recurrent stroke event rate than medical therapy in patients with earlier
cryptogenic stroke
Saver et al. N Engl J Med. 2017;377:1022-32

13 Closure foramen ovale
Patent foramen ovale closure vs anticoagulation

vs antiplatelets after stroke: CLOSE
Objective to compare the effectiveness of patent foramen ovale (PFO) closure vs

anticoagulation plus antiplatelets vs antiplatelet treatment to prevent recurrent
stroke in patients with a recent cryptogenic stroke
Study multicentre open-label randomised study 1:1:1 ratio
Population patients (16-60 years old) with recent cryptogenic stroke attributed to PFO
with associated atrial septal aneurysm or large interatrial shunt
Endpoints occurrence of stroke during 5.3±2.0 years follow-up
PFO closure Anti-coag.

groups 238 groups 187
Patients 1-2 1-3
663
Antiplatelets Antiplatelets
235 174
Stroke 5.3 years Stroke 5.3 years

group 1 vs 2 group 1 vs 3
HR 0.03 (95% CI 0-0.26) HR 0.44 (95% CI 0.11-1.48)
p˂0.001 p=n.s
n pts 14 n pts
15 15
10 10 7
5 5
3
0
0 0
PFO closure + Antiplatelets Anticoagulation Antiplatelets
antiplatelets
Conclusion the frequency of stroke recurrence was lower with PFO closure plus antiplatelet
Rx than with antiplatelet treatment alone
Mas et al. N Engl J Med. 2017;377:1011-21

Closure foramen ovale 13
Patent Foramen closure vs Medical therapy:

REDUCE
Objective to determine the efficacy of patent foramen ovale closure (PFO) with
anitplatelet treatment vs antiplatelet therapy alone to reduce recurrent stroke
in patients who had cryptogenic stroke
Study multicentre, multinational randomised study 2:1 ratio
Population patients 18-59 years of age, with earlier cryptogenic stroke within 180 days
before randomisation and PFO with right-to-left shunt
Endpoints clinical evidence of recurrent ischemic stroke or incidence of 24-month
incidence of new brain infarction detected with MRI
PFO closure
441
Patients 2:1 Follow-up median
664 3.2 years
Antiplatelet
223
Recurrent ischemic stroke 3.2 years New brain infarction 24 months

HR 0.23 (95% CI 0.09-0.62) HR 0.51 (95% CI 0.29-0.91)
p=0.002 p=0.04
% 5.4 %
6 15
11.3
4 10
5.7
1.4
2 5
0 0
PFO closure Antiplatelet PFO closure Antiplatelet
Conclusion the risk of recurrent ischemic stroke was lower with PFO closure with
antiplatelet treatment compared to antiplatelet treatment only in patients with
earlier cryptogenic stroke
Søndergaard et al. N Engl J Med. 2017;377:1033-42

13 Closure foramen ovale
High-risk patent foramen ovale: Closure vs Medical Treatment:

DEFENSE-PFO
Objective to compare the clinical outcomes of PFO closure with medical treatment
in patients with cryptogenic stroke and high risk PFO
Study multicentre, open-label randomised superiority trial
Population patients with high-risk PFO: atrical septum aneurysm, hypermobility
or PFO size ≥2 mm
Endpoints composite of stroke, vascular death or major bleeding (TIMI) during 2 years
follow-up
PFO closure
120 60 (DAPT)
Cryptogenic stroke high-risk PFO
Patients
450 Medication-only
60 (DAPT+VKA)

Logrank p=0.013
%
15 12.9
0.0
0
medication-only PFO
Conclusion PFO-closure in patients with high-risk PFO was associated with a lower rate of
adverse events compared to medication only
Lee et al. J Am Coll Cardiol. 2018;71:2335-42

14 ∙ Renal denervation
Page
Renal denervation .............................................................................220

14 Renal denervation
Renal denervation vs antihypertensive Rx for resistant

hypertension DENERHTN
Objective to compare the ambulatory blood-pressure lowering efficacy and safety of renal
denervation added to standardised stepped-care antihypertensive treatment
(SSAHT) with same SSAHT alone for resistant hypertension
Study open label randomised trial (1:1)
Population patients with resistant hypertension (treatment resistance to indapamide
1.5 mg, ramipril 10 mg (or irbesartan 300 mg) and amlodipine 10 mg daily for
4 weeks
Endpoints mean change in daytime systolic blood pressure from baseline to 6 months by
ambulatory blood pressure monitoring
Renal+SSAHT 53 +stepped AHT if ≥135/85 Hg:

1:1 spironolactone 25 mg dd
Screened Analysed biosprolol 10 mg dd
1,416 106 prazosin 5 mg dd
SSAHT alone 53 rilmenidine 1 mg dd
Change systolic blood pressure
–15,8 mgHg –9,9 mmHg p=0.0329
Renal dener+SSAHT SSAHT alone
Conclusion Renal denervation+SSAHT decreased systolic blood pressure more than SSAHT
alone after 6-month treatment
Azizi et al. Lancet 2015;385:1957-65

Renal denervation 14
Ultrasound renal denervation to treat hypertension:

RADIANCE-HTN SOLO
Objective to demonstrate that endovascular ultrasound renal denervation reduce

ambulatory blood pressure in patients with mild to moderate hypertension
while off anti-hypertensive medication
Study multicentre, single-blind sham controlled randomised study
Population patients with combined systolic-diastolic hypertension with blood
pressure ≥135/85 mmHg and <170/105 mmHg after 4 week discontinuation
of ant-hypertensive medication
Endpoints change in daytime ambulatory systolic blood pressure at 2 months
in the intention-to-treat population
Renal denervation
74
Patients 2:1
146
Renal denervation
72
Daytime ambulatory systolic blood pressure reduction:

renal denervation –8.5 mmHg SD 9.3
sham procedure –2.2 mmHg SD 10.0
Baseline adjusted difference. −6.3 mmHg (95% CI –9.4 to –3.1)

p=0.0011
Conclusion endovascular ultrasound denervation reduced ambulatory systolic pressure

at 2 months
Azizi et al. Lancet. 2018;391:2335-45

Ultrasound renal denervation or sham for hypertension

RADIANCE-HTN SOLO: 6 months
Objective to report the 6 month results after addition of a standardised stepped-care

antihypertensive treatment following ultrasound renal denervation (RDN) or
sham procedure
Study multicentre, randomised, blinded, sham controlled trial
Population patients who had a BP ≥135/85 between 2 and 5 months after initial
randomisation and blinded treatment received a standardised stepped-care
antihypertensive treatment
Endpoints change in daytime ambulatory systolic BP, medication burden and safety
RDN 69
Patients 6 months
146 140
Sham 71
1) daytime ambulatory systolic BP reduction:

RDN −18.1±12.2 vs Sham −15.6±13.2 mmHg difference
−4.3 mmHg (95% CI: −7.9 to −0.6) p=0.024
2) average number antihypertensive medications:

RDN 09±0.9 vs Sham 1.3±0.9; p=0.010
3) defined daily doses

RDN 1.4±1.5 vs Sham 2.0±1.8; p=0.018
4) No major adverse events in both groups
Conclusion the systolic BP reduction after endovascular ultrasound RDN was maintained
at 6 months while using less antihypertensive medications as compared to
Sham procedure
Azizi et al. Circulation. 2019;139:2542-53

Catheter-based radio frequency ablation renal denervation to treat

hypertension: SPYRAL HTN-OFFMED
Objective to evaluate the effect of renal denervation on blood pressure in the absence of
antihypertensive medication
Study multicentre, single-blind sham controlled randomised trial
Population patients with office systolic blood pressure ≥150 mmHg and <180 mmHg,
office diastolic blood pressure of ≥90 mmHg, and a mean 24-h ambulatory
SBP of ≥140 mmHg and <170 mmHg at a second screening
Endpoints change in 24-h blood pressure at 3 months in intention-to-treat population
Patients 2:1
80
Sham-procedure 42
Changes in 24-h blood pressure

Renal denervation Sham control
3 month 24-h SBP –5.5 (–9.1 to 2.0) p=0.00031 –0.5 (–3.1 to 2.9) p=0.76
3 month 24-h DBP –4.8 (–0.79 to 2.6) p<0.0001 –0.4 (–2.2 to 1.4) p=0.64
Changes in office blood pressure

Renal denervation Sham control
3 month office SBP –10.0 (–15.1 to –4.9). p=0.0004 –2.3 (–6.1 to 1.6) p=0.238
3 month office DBP –5.3 (–7.8 to –2.7) p=0.0002 –0.3 (–2.9 to 2.2) p=0.805
Conclusion renal denervation was associated with significant reduction in 24-h ambulatory
and office SPP and DBP at 3 months compared to sham-control
Townsend et al. Lancet. 2017;390:2160-70

Renal denervation for the blood pressure reduction:

SPYRAL HTM- ON MED
Objective to assess the safety and efficacy of catheter-based renal denervation for
treatment of moderate uncontrolled hypertension despite treatment
Study multicentre, randomised sham-controlled, blinded trial
Population patients with office systolic blood pressure between 150 and 180 mmHg, or
office diastolic pressure 90 mmHg or higher and mean 24h ambulatory systolic
blood pressure between 140 and 170 mmHg. Patients were on standard
treatment with 1, 2 or 3 antihypertensive drugs
Endpoints blood pressure change from baseline based on ambulatory blood pressure
measurements at 6 months
Screened enrolled
467 80
Sham control 42
Difference blood pressure 6 months denervation vs. sham
Office SBP: –6.8 mmHg (95% CI –12.5 to –1.1) p=0.0205
24h SBP: –7.4 mmHg (95% CI –12.5 to –2.3) p=0.0051
Office DBP: –3.5 mmHg (95% CI –7.0 to 0.0) p=0.0478
24h DBP: –4.1 mmHg (95% CI –7.8 to –0.4) p=0.0292
Conclusion renal denervation in the main renal arteries and branches reduced the blood
pressure compared to sham controlled patients
Kandzari et al. Lancet 2018;391:2346-55

Different renal denervation devices and techniques:

RADIOSOUND-HTN
Objective to compare the efficacy of the treatment of resistant hypertension with

1) Radiofrequency renal sympathetic denervation (RDN) of main renal arteries,
2) Radiofrequency RDN of main renal arteries, side branches and accessories
and 3) Endovascular ultra sound-based RDN of main renal artery
Study single-blind, single-centre 3 arm randomised trial
Population patients with resistant hypertension
Endpoints change in systolic day time ambulatory blood pressure at 3 months
RDN main renal artery 39
Patients 1:1:1
RDN main + branches 39
120
Ultrasound main renal 42
Change systolic BP 3 months

p=0.22
p=0.043 p=0.99
mmHG min
20
–13.2
–6.5 –8.3
0
Ultrasound RDN MAIN RDN MAIN+branches
Conclusion ultrasound-based ablation seems superior to radiofrequency ablation of the

main renal arteries only. The benefit of radiofrequency ablation of main renal
artery and side branches requires more study
Fengler et al. Circulation 2019;139:590-600

Renal Denervation for hypertension:

REDUCE HTN REINFORCE
Objective to investigate bipolar radio frequency renal denervation; as compared to sham-

control, in patients with hypertension not receiving medications at baseline
Study prospective, blinded, multicentre sham procedure controlled trial
Population patients with office bases systolic BP of ≥150 and ≤180 mmHg and average
24-h ambulatory SBP of ≥135 and ≤170 mmHg after 4 week medication
without
Endpoints 8 week change in 24 h ambulatory SBP
(vessel renal denervation system)
Screened Randomised
167 51
Sham control 17
8-week change ambulatory SBP:

Renal denervation: −5.3 mmHg
Sham control: −8.5 mmHg
difference 3.3 mmHg (95% CI: −2.8 to 9.3 mmHg)
p=0.30
The study was terminated for apparent futility. Anti hypertensive medications was added after
8 weeks. By 6 months decreases in SBP were greater for the denervation group.
Conclusion at 8 weeks there was no difference or decrease of SBP between renal

denervation and sham-control
Weber et al. J Am Coll Cardiol. Interv 2020;13:461-70

INDEX
A C DEBUT...................................... 101
ABSORB II ............................90, 91 CENTURY II ................................33 DECISIOR-CTO..........................109
ABSORB III ...........................92, 93 CHOICE.....................................196 DEFENSE-PFO .......................... 218
ABSORB IV ................................. 97 CIRCUS ....................................... 72 DEFER ......................................144
ABSORB-JAPAN.........................94 CLOSE....................................... 216 DEFINE-FLAIR .......................... 149
AFTER-EIGHTY.........................129 COACT ......................................193 DENERHTN ..............................220

COAPT ...................................... 214
AIDA......................................95, 96
DESSOLVE III ..............................44
COMFORTABLE AMI...................59
ANTARTIC................................. 174
DETO2X-AMI .............................. 76
COMPARE................................... 15
AUGUSTUS ..............................182
COMPARE II................................ 16 DKCRUSH II................................80
COMPARE-ACUTE ......................68 DKCRUSH III............................... 81

B
COMPLETE .................................67 DKCRUSH V .........................82, 83
BASKET PROVE II......................... 8
CONDI-2/ERIC-PCI .....................77
BASKET SMALL 2.....................100
CROSS-AMI ................................69 E
BBK-I ..........................................85
CTO-IVUS .................................138 EARLY-BAMI ......................... 73, 74
BEST ......................................... 114
CULPRIT-SHOCK ..............190, 192 EBC-TWO....................................87
BIO-RESORT ..............................29
CvLPRIT ................................63, 64
ELDERLY-ACS-2........................163
BIOFLOW II .................................46
ENTRUST-AF PCI ..................... 181
BIOFLOW IV ................................53
D
EURO-CTO................................122
BIOFLOW V .................................45 DACAB......................................165
BIONICS .....................................43 DANAMI 3 PRIMULTI .................65 EVEREST II ............................... 212
BIONYX ......................................28 DANAMI 3-DEFER ......................66 EVOLUT-Low Risk .............208, 211
BIOSCIENCE ...............................34 DANAMI-2 ..................................56 EVOLVE II ..............................35, 36
BIOSTEMI ...................................52 DAPT ........................................ 152 EXAMINATION ...........................58
BRIGHT ....................................185 DAPT-STEMI .............................156 EXCEL ............................... 118, 119

F L PARTNER II B ...........................200
FAME ........................................ 145 LEADERS FREE .................... 11, 12 PARTNER III .............................203
FAME 2 .....................................146 PCI-STEMI TOTAL ....................... 71
FAMOUS-NSTEMI .................... 147 M PEPCAD NSTEMI......................102
FREEDOM FOLLOW-ON ........... 121 MASTER ..................................... 61 PIONEER AF-PCI ...................... 178
FRISC-II ....................................132 MASTER-STUDY .........................62 PLATINUM..................................42
MATRIX............ 104, 105, 183, 184 PLATINUM PLUS........................48
G MITRA-FR................................. 213 POPULAR ................................. 176
GALILEO ................................... 210 POST-PCI CREATIVE ................164
GLOBAL LEADERS ................... 167 N PRAGUE - 18 ............................ 162
NEXT ..........................................38 PRECOMBAT ............................ 115
H NIPPON ....................................155 PRISON III................................... 17
HYBRID .................................... 112 NOBLE .............................. 116, 117
NOBORI ...................................... 37 R
I NORSTENT ................................. 14 RADIANCE-HTN SOLO .....221, 222
I LOVE IT 2 ................................158 NOTION ........................... 204, 205 RADIOSOUND-HTN .................225
IABP-SHOCK ............................192 REACT ......................................108
ICTUS .......................................133 O RECRE8 ...................................... 47
iFR-swedeheart .........................148 OAC-ALONE..............................180 REDUAL PCI ............................. 179
ISAR-REACT ............................. 172 ONYX ONE..................................54 REDUCE ........................... 161, 217
ISAR-SAFE ................................159 OPTIDUAL ................................160 REDUCE HTN REINFORCE ......226
ISAR-TEST 4 .........................30, 31 ORBITA .....................................123 REPRISE III ...............................207
ISAR-TEST 5 ...............................32 RESET......................................... 51
ISAR-TRIPLE ............................. 177 P RESOLUTE.................................. 18
ISCHEMIA .................................125 PANDA III..............................40, 41 RESPECT .................................. 215
ISCHEMIA-CKD ........................ 124 PARTNER I A ............................199 RIDDLE-NSTEMI ....................... 131
ITALIC .......................................154 PARTNER I B ............................198 RITA-3.......................................128
IVUS-XPL ..........................139, 140 PARTNER II A ...................201, 202 RIVER-PCI.................................126

S STOP-DAPT-2 ........................... 170 TWENTE .....................................26
SAFARI-STEMI .......................... 107 SURF ........................................106 TWENTE II .................................. 27
SAFE-PCI ..................................105 SURTAVI ...................................206 TWILIGHT .................................168
SCOPE ......................................209 SYNTAXES ................................120
SECURE PCI ............................... 75 U

SENIOR....................................... 13 T ULTIMATE ................................. 141
SMART-CHOICE ....................... 169 T-TIME ........................................ 57 US-CORE VALVE ....................... 197
SMART-DATE............................ 157 TALENT.......................................50
SMART-STRATEGY .....................86 TARGET ALL COMERS ...............49 V

SMILE .......................................130 THEMIS-PCI ............................. 171 VALIDATE - SWEDEHEART .......186
SORT-OUT II ............................... 19 TICAB .......................................166 VERDICT ...................................135
SORT-OUT IV ..............................20 TICAKOREA .............................. 173 VOYAGER-PAD..........................187
SORT-OUT V ............................... 21 TIDE ............................................ 10
SORT-OUT VI ........................22, 23 TOTAL ......................................... 70 X

SORT-OUT VII ............................. 24 TRANSIENT-STEMI ..................134 XAMI ...........................................60
SORT-OUT VIII ............................25 TROPICAL-ACS ......................... 175
SPYRAL HTN-OFF MED ...........223 TRYTON......................................84 Z

SPYRAL HTN-ON MED ............224 TUXEDO .....................................39 ZEUS............................................. 9
Ultrathin struts.1 Ultrathin struts.1

Outstanding patient outcomes.2 Outstanding patient outcomes.2
Next level of deliverability.3 Next level of deliverability.3
NEW NEW
57% 57%
More flexible More flexible
shaft shaft
Better Push3 for high track Better Push3 for high track
+57% NEW +57% NEW

Deep Deep
embedding embedding
for high cross for high cross
0 10 20 30 40 50 0 10 20 30 40 50
Force transmitted (%) Force transmitted (%)
30% 30%
Better Track 3 Better Track 3
-30% -30%
0 0.2 0.4 0.6 0.8 0 0.2 0.4 0.6 0.8

75% 75%
Better Cross 3 Better Cross 3
-75% -75%
0 0.05 0.10 0.15 0.20 0.25 0.30 0 0.05 0.10 0.15 0.20 0.25 0.30
Orsiro Mission Syngery Orsiro Mission Syngery

Resolute Onyx Xience Sierra Resolute Onyx Xience Sierra
www.orsiro-mission.com www.orsiro-mission.com
1. As characterized with respect to strut thickness in Bangalore et 1. As characterized with respect to strut thickness in Bangalore et
al. Meta-analysis; 2. Based on investigator’s interpretation of NEW al. Meta-analysis; 2. Based on investigator’s interpretation of NEW
BIOFLOW-V primary endpoint result; 3. In comparison to Xience BIOFLOW-V primary endpoint result; 3. In comparison to Xience
Sierra, Resolute Onyx and Synergy for bench tests on pushability, Ergonomic hub Sierra, Resolute Onyx and Synergy for bench tests on pushability, Ergonomic hub
trackability and crossability, BIOTRONIK data on file. with kink resistance trackability and crossability, BIOTRONIK data on file. with kink resistance
Clinical data conducted with Orsiro, Orsiro Mission’s predecessor Clinical data conducted with Orsiro, Orsiro Mission’s predecessor
device can be used to illustrate Orsiro Mission clinical data. device can be used to illustrate Orsiro Mission clinical data.
Orsiro is a trademark or registered trademark of the BIOTRONIK Orsiro is a trademark or registered trademark of the BIOTRONIK
Group of Companies. Synergy is a trademark or registered trademark Group of Companies. Synergy is a trademark or registered trademark
of the Boston Scientific group of companies. Resolute Onyx is a of the Boston Scientific group of companies. Resolute Onyx is a
trademark or registered trademark of the Medtronic group of trademark or registered trademark of the Medtronic group of
companies. Xience Sierra is a trademark or registered trademark of companies. Xience Sierra is a trademark or registered trademark of
the Abbott group of companies. the Abbott group of companies.
Randomised
Randomised trials
trials 2020
2020
May 2020
May 2020
Orsiro ®
DES Interventional
Interventionalcardiology
cardiology2015-2020
2015-2020
BIOSTEMI trial: Superiority in STEMI
EDITORS:
EDITORS:Pim
cardiology 2015-2020
PimJ.J.dedeFeyter,
Feyter,Robert
RobertByrne
Byrne
Known to be effective. Proven to be superior.¹
2020 Interventional
41%
trials 2020
“With Orsiro, we incrementally
improve care for STEMI patients◊”
Randomised trials
Lower risk*
of TLF with
Dr. Juan F. Iglesias, Geneva, Switzerland
Co-Principal Investigator BIOSTEMI trial Orsiro in STEMI
Randomised
inincollaboration
collaborationwith
with
1. Compared to Xience in STEMI. *BIOTRONIK data on file, based on the Rate Ratio of 0.59.
◊
Based on author’s interpretation of the BIOSTEMI results EuroIntervention
EuroIntervention
Source: lglesias J et al. Biodegradable polymer sirolimus-eluting stents versus durable polymer
everolimus-eluting stents in patients with ST-segment elevation myocardial infarction (BIOSTEMI):
a single-blind, prospective, randomised superiority trial. Lancet, September, 2019. For indications please
see Instructions For Use.
Orsiro is a trademark or registered trademark of the BIOTRONIK Group of Companies. Xience is a
trademark or registered trademark of the Abbott Group of Companies. www.orsiro.com

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Randomised

Ultrathin struts.1 Ultrathin struts.1

+57% NEW +57% NEW

0 0.2 0.4 0.6 0.8 0 0.2 0.4 0.6 0.8

Orsiro Mission Syngery Orsiro Mission Syngery

Pim J. de Feyter MD Robert A. Byrne MB, BCh, PhD

On behalf of the Trials Book Team

Randomised trials 2020 3

Directeur de la publication Editeur

4 Randomised trials 2020

1 Drug-eluting and bare metal stents. . . . . . . . . . . . . . . . . . . . . . . . . . 7

Randomised trials 2020 5

 Drug-eluting stents vs bare metal stents .................................................8

 Comparisons drug-eluting stents ..........................................................15

Randomised trials 2020 7

BES VS EES VS BMS:

Objective to compare the 2-year clinical outcomes of biodegradable polymer biolimus-A9

Patients Complete follow-up 2 years

Primary endpoint 2 years

Non-inferior (BP-DES vs DP-DES) Superior (BP-DES vs BMS)

BP-DES DP-DES BMS

Kaiser et al. Circulation 2015;131:74-81

8 Randomised trials 2020

ZES vs BMS in uncertain DES candidates:

Objective to compare the clinical outcome of second-generation ZES (Medtronic) with

Patients 1:1 Follow-up

Valgimigli et al. J Am Coll Cardiol 2015;65:805-15

Randomised trials 2020 9

Titanium-nitride-oxide coated stents vs ZES:

Pilgrim et al. EuroIntervention 2015;10:1284-7

10 Randomised trials 2020

Polymer-free drug coated coronary stents for patients

Objective to evaluate the safety and effectiveness of polymer-free umirolimus-coated

Biofreedom stent 1,221

Patients 1:1 Follow-up 390 days:

BMS stent 1,211

Safety endpoint 390 days

Conclusion the polymer-free umirolimus-coated stent is superior to BMS in patients at

Urban et al. NEJM 2015;373:2038-47

Randomised trials 2020 11

High bleeding risk patients after polymer-free DES:

Polymer-free DES (BioFreedom)

Safety p=0.039 Efficacy p<0.0001

Garot et al. J Am Coll Cardiol 2017;69:162-71

12 Randomised trials 2020

Drug-eluting stents in elderly patients with coronary artery disease:

Primary endpoint 1 year

Varenne et al. Lancet. 2018;391:41-50

Randomised trials 2020 13

Drug-eluting or bare-metal stents in all-comer patients with

Objective to assess the long-term effects of contemporary drug-eluting stents versus

Drug-eluting stents 4,504

Primary endpoint at 5 years

Bonaa et al. N Engl J Med 2016;375:1242-52

14 Randomised trials 2020

Everolimus vs paclitaxel-eluting stents:

Objective to report the 5-year clinical outcomes of revascularisation with everolimus-

5 years EES vs PES RR (95% CI) p-value

Conclusion at 5-year follow-up EES remained superior to PES for revascularisation of

Smits et al. JACC. Cardiovasc. Interv. 2015;8:1157-65

Randomised trials 2020 15

Biodegradable Polymer BES vs Durable EES:

Vlachojannis et al. J Am Coll Cardiol Intv. 2017;10:1215-21

Drug-eluting stents vs bare metal stents .................................................8

Comparisons drug-eluting stents ..........................................................15