Antiplatelet

Therapy for Acute

Coronary
Syndrome

Death is inevitable but

premature death is not.
- Sir Richard Doll

 Antiplatelet and anticoagulant drugs are a cornerstone of the

medical treatment of acute coronary syndrome (ACS), reducing
the rates of both morbidity and death 1-4
A key distinction when treating ACS is whether the
electrocardiogram shows ST segment elevation or non ST
elevation
In ST-elevation myocardial infarction, another distinction is how
perfusion is to be restored, ie, with primary percutaneous
coronary intervention or with thrombolysis
In cases of non-ST-elevation ACS (ie, unstable angina or nonStelevation myocardial infarction), a second key question is
whether the initial strategy will be invasive (with angiography
performed urgently) or conservative (with angiography
performed later).
1.
2.
3.
4.

J Am Coll Cardiol 2011; 57:e215

e367
J Am Coll Cardiol 2012; 60:645
681
Lancet 1996; 348:13291339
Circulation 1994; 89:8188

Milestones For Aspirin

5th century BC

Hippocrates

1897 AD

Felix Hoffman/Friedrich Bayer

1900 present
1971

Most widely used drug in

world
Sir John Vane

the

Benefits of Aspirin on Risk of

Stroke
In 158 trials, there were 3,522 nonfatal and
1,424 fatal strokes after randomization.
Antiplatelet therapy, principally with aspirin,
reduced stroke by about 25%, regardless of
whether the patient entered the trial with prior
MI, stroke, TIA, or other high-risk conditions.
Antiplatelet therapy, principally with aspirin,
increases the absolute risk of hemorrhagic
stroke by 3 per 10,000 treated patients. The
upper bound of the 95% confidence interval is
less than 1 per 1000 treated patients.
AntiThrombotic Trialists Collaboration. Lancet, 2002

Second International Study of

Infarct Survival

ISIS-2 Collaborative Croup Lancet. 1988 Aug 13;332: 349-60 .

Duration of Dual
Anti-Platelet
Therapy

European and US Guidelines

PCI-CURE
CV Death or MI

CHARISMA
Instantaneous Hazard for Moderate or Severe Bleeding

CHARISMA
Primary End Point

TRILOGY-ACS
Primary Efficacy End Point to 30 Months (Age < 75 years)

DAPT Trial
Total Enrollment

DES vs BMS

DAPT Trials
Unanswered Questions

OPTIMIZE
Second-generation DES
Effect of Short- and Long-term DAPT

New Trials With Ticagrelor

y
gistr
e
R
S
PARI

PARIS Registry
Patterns of Non-Adherence to
Anti-Platelet Regimens In Stented
Patients: An Observational
Single Arm Study

Medication Usage

tr
egis
R
S
I
PAR

3582
(71.1%)

2014
(40.0%)

991
(19.7%)

1894
(37.6%)

47 (0.9%)

5012
(99.6%)

5031
(100%)

1177
(23.4%)

5012
(99.6%)

311 (6.2%)

Procedural Information

tr
egis
R
S
I
PAR

Stents by Type

tr
egis
R
S
I
PAR

Total # of stents used: 8434 (1.68 stents/pt)

Thienopyridine at Discharge

tr
egis
R
S
I
PAR

Rates of Non-Adherence
(Patient-level)

tr
egis
R
S
I
PAR

Incidence of Non-Adherence
tr
egis
R
S
I
PAR

Any Non-Adherence
Variable
Any Non-adherence
Disruption, n (%)

Patients Episodes
104 (2.1)

147

72 (69)

102 (70)

Interruption, n (%) 20 (19)

27 (18)

Discontinuation, n
12 (12)
(%)

18 (12)

Incidence of NonAdherence
(Cont.)

tr
egis
R
S
I
PAR

Non Adherence to Thienopyridine:

Variable

Patients Episodes

Any Non-adherence,
n (%)

66 (1.3)

69

Disruption, n (%)

43 (65)

46 (67)

Interruption, n (%) 12 (18)

12 (17)

Discontinuation, n
11 (17)
(%)

11 (16)

Incidence of NonAdherence
(Cont.)

tr
egis
R
S
I
PAR

Non Adherence to Aspirin:

Variable

Patients Episodes

Any Non-adherence,
n (%)

70 (1.4)

78

Disruption, n (%)

51 (73)

56 (72)

Interruption, n (%) 12 (17)

15 (19)

Discontinuation, n
(%)

7 (10)

7 (9)

Reasons for Disruption

tr
egis
R
S
I
PAR

Bleeding
ASA
Thienopyridine

18
14

NonCompliance
34
30

Other
4
2

Reasons for Interruption

tr
egis
R
S
I
PAR

Surger
y
ASA
5
Thienopyridi
5
ne

Other Medical
Procedure
(epidural, catheter removal, GI
Scope)

2
3

Coumad
GI Upset Allergy
in
3
3
2
0
4
0

Non-Adherence guided by
healthcare professionals

tr
egis
R
S
I
PAR

Total episodes of Recommended DAPT non-adherence: 82

Baseline Characteristics

tr
egis
R
S
I
PAR

Variable

Adherent
n=4929

Age, years

63.94 [11.33]

Male, n (%)
Acute coronary syndrome, n
(%)
Diabetes Mellitus, n (%)
Dyslipidemia, n (%)
Hypertension, n (%)
Peripheral Vascular
Disease, n (%)
Prior coronary artery
disease, n (%)
Prior MI, n (%)

Nonadherent
n=104

3676 (74.6)
1987 (40.5)

64.83
[11.31]
74 (71.2)
60 (58.3)

1627
3744
3944
387

36
66
76
9

(33.0)
(76.0)
(80.0)
(7.9)

(34.6)
(63.5)
(73.1)
(8.7)

p-value
0.42
0.43
<0.0001
0.73
0.003
0.08
0.76

1987 (40.5)

60 (58.3)

<0.0001

1201 (24.4)

19 (18.3)

0.15

Rates of 30-Day nonadherence

in Similar Registries

tr
egis
R
S
I
PAR

Timeframe

Population

DAPT
Discontinuation
at 30 days (%)

Airoldi et al1

2002 2004

PCI with DES

3021

2.4%

PREMIER
Registry2

2003 2004

DES for MI

500

13.6%

MATRIX
Registry3

2004-2006

PCI with SES

1504

5.8%

E-Five Registry4

2005-2007

PCI with ZES

7988

2.1%

E-SELECT
Registry5

2006-2008

PCI with SES

14,365

2%

Study

1.
2.
3.
4.
5.

Airoldi F et al. Circulation. 2007 Aug 14;116(7):745-54.

Spertus J et al. Circulation 2006 June 20; 113(24):2803-9.
Claessen B et al. Am J Cardiol 2011;107:528-534.
Lotan C et al. J Am Coll Cardiol Interv 2009; 2(12), 1227-1235.
Urban P et al J Am Coll Cardiol 2011;57:1445-54.

Adverse Event Rates

Total

tr
egis
R
S
I
PAR

Adherent Non-adherent
(n=4929)
(n=104)

Ischemic
MACE, n (%)

78 (1.5)

67 (1.4)

11 (10.6)

Death, all-cause, n(%)

17 (0.3)

15 (0.3)

2 (1.9)

Cardiac Death, n (%)

15 (0.3)

14 (0.3)

1 (1.0)

54 (1.1)

46 (0.9)

8 (7.7)

Stent Thrombosis, n (%)

26 (0.5)

23 (0.5)

3 (2.9)

TVR, n (%)

30 (0.6)

25 (0.5)

5 (4.8)

TLR, n (%)

23 (0.5)

19 (0.4)

4 (3.8)

9 (0.2)

6 (0.1)

3 (2.9)

ACUITY Major, n (%)

35 (0.7)

23 (0.5)

12 (11.5)

BARC 3, n (%)

30 (0.6)

18 (0.4)

12 (11.5)

Myocardial
(%)

Infarction, n

Bleeding
TIMI major, n (%)

BARC Bleeding Scale

BARC Classification

N (% of total population)

Type 1 (not actionable)

26 (0.5)

Type 2 (requiring medical

attention)

37 (0.7)

Type 3

30 (0.6)

3a

15 (0.3)

3b

15 (0.3)

3c

Type 4 (CABG related)

BARC Type 5 (Fatal)

1. Mehran et al. Circulation 2011 Jun 14;123(23):2736-47.

Stent Thrombosis

tr
egis
R
S
I
PAR

Stent Thrombosis
(n=26)
Probable (n=9)

Definite (n=17)
Adherent (n=14)

Non-adherent (n=3)

Disrupted ASA
(n=2)

Disrupted
Clopidogrel (n=1)

Odds Ratio (95% CI) for stent thrombosis associated with

non-adherence: 6.3 (1.9-21.4)

Relative Risk of NonAdherence on

30 Day Stent Thrombosis in
Contemporary Adhere
Registries
nt

tr
egis
R
S
I
PAR

Non-Adherent

RR

PARIS Registry

0.5%

2.9%

5.8

Airoldi et al1

0.9%

4.2%

4.7

eSELECT Registry2

0.5%

4.6%

9.2

1. Airoldi F et al. Circulation. 2007 Aug 14;116(7):745-54.

2. Urban P et al. J Am Coll Cardiol 2011;57:1445-54.

GOALS OF HEALTH CARE

PROVIDERS AND ACADEMIC
RESEARCHERS
Maximize benefit and minimize risk which is
not to be confused with avoidance of risk.
Make clinical decisions based on the totality of
evidence not dependence on particular
subgroups of particular studies.
Avoid misstatements of benefit to risk ratios
which may increase publicity, academic
promotions and grant support in the short run
but confuse colleagues and frighten patients
and make it more difficult to conduct high
quality research
( COX-2 inhibitors and glitazones)