Interventional Cardiology

Duration of Dual Antiplatelet Therapy After Percutaneous

Coronary Intervention: Is Less More?
Rik Rozemeijer, MD, PharmD, Wijnand P van Bezouwen, MD, Michiel Voskuil, MD, PhD, and Pieter R Stella, MD, PhD

Department of Cardiology, University Medical Centre Utrecht, Utrecht, the Netherlands

Abstract
The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) using the latest-generation drug-eluting
stents remains a matter of debate. Evidence suggests short regimens of DAPT are favorable for patients with a low ischemic risk, while those
at a high risk of ischemia may benefit from taking DAPT for a long duration. An individually assessed risk profile is pivotal in guiding DAPT
duration. Risk scores may aid individual patient DAPT decisions, but the value they add to clinical outcomes still needs to be established in
a prospective randomized trial. This review aims to provide an overview on DAPT, evaluate the available evidence on DAPT duration with
a description of common pitfalls of trial interpretation, and assess available tools for individual risk assessment in patients scheduled for
PCI with the latest-generation DES.

Keywords
Coronary artery disease, ischemic heart disease, percutaneous coronary intervention, drug-eluting stent, dual antiplatelet therapy

Disclosure: The authors have no conflicts of interest to declare.

Submitted: June 29, 2018 Accepted: October 24, 2018 Citation: US Cardiology Review 2018;12(2):91–7. DOI: https://doi.org/10.15420/usc.2018.4.2
Correspondence: Pieter R Stella, University Medical Center Utrecht, Department of Cardiology, Heidelberglaan 100, Room E.04.201, 3584 CX, Utrecht, the Netherlands.
E: p.stella@umcutrecht.nl

Dual antiplatelet therapy (DAPT) consisting of aspirin and a P2Y12 inhibitor
is prescribed in the treatment of acute coronary syndrome (ACS) or
following percutaneous coronary intervention (PCI) for drug-eluting
stent (DES) implantation. An important misconception remains that
DAPT should be prescribed to prevent stent thrombosis. Although this
may seem obvious, it should be emphasized that the incidence of stent
thrombosis is below 1.0  % in second-generation DES and recurrent
adverse events are equally attributable to culprit lesions or non-culprit
lesions which can also be prevented by DAPT.1,2
Current guidelines recommend at least 12 months of DAPT for patients
with ACS who have a low bleeding risk (class 1, level A).3,4 It is advised
to treat patients with a low bleeding risk for at least 6 months for stable
coronary artery disease (class 1, level A). Optimal DAPT duration remains
a matter of debate. Risk assessment is key in this decision, and the
higher bleeding risk with longer DAPT duration must be balanced with
the benefits of prolonged DAPT duration for patients with increased
ischemic risk.3-5
The authors therefore aimed to evaluate current evidence regarding
antiplatelet agents, DAPT duration and risk assessment of patients
scheduled for PCI with implantation of a latest-generation DES.
adhesion, activation and aggregation are considered key elements in the
formation of arterial thrombi, and are targets of antiplatelet therapy in the
treatment of ACS or DES implantation.7,8
At present, several distinct antiplatelet agents are used in routine practice:
aspirin; clopidogrel; prasugrel and ticagrelor.9–11 Aspirin irreversibly
inhibits the cyclooxygenase (COX-1) enzyme, reducing the formation of
thromboxane A2 and prostaglandins from arachidonic acid, which leads
to decreased platelet activation. Several trials have demonstrated that
aspirin reduces cardiovascular events.12 However, blocking COX-1 with
aspirin also leads to a dose-dependent increased risk of bleeding, mainly
in the upper gastrointestinal tract.13
Clopidogrel is the only agent of the purigernic G-protein-coupled P2Y12
receptor inhibitors that is currently recommended for stable coronary
artery disease, and is one of the most widely investigated antiplatelet
agents. A synergistic effect of clopidogrel on top of aspirin has been
established.14 As a prodrug, this thienopyridine requires a two-step
oxidation process that contributes to the non-uniform inter-individual
clopidogrel response,which has led to high-on platelet reactivity in
30–40 % of patients; this has prompted further research into other potent
P2Y12 inhibitors.15

Antiplatelet therapy In contrast to clopidogrel, prasugrel requires single-step oxidation by

Thrombocytes, or platelets, are anucleate cell fragments that are the hepatic cytochrome P450 iso-enzyme family, leading to a rapid-
essential for primary hemostasis and repair of the endothelium.6 Platelet onset, highly potent antiplatelet effect with less variability between

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Table 1: Characteristics of Major Studies Investigating Short Dual Antiplatelet Therapy

Study (year) Size S-DAPT L-DAPT Design Non-inferiority Time of ACS Primary endpoint Bleeding
(n) (months) (months) margin (%) randomization (%) criteria
RESET (2012)25 2,117 3 12 NI 4.0 At time of index 54 Cardiovascular death, MI, ST, TIMI
TVR, major or minor bleeding
OPTIMIZE (2013)27 3,119 3 12 NI 2.7 At time of index 32 All-cause death, MI, stroke, Modified
major bleeding REPLACE–2
and GUSTO
EXCELLENT (2012)24 1,443 6 12 NI 4.0 At time of index 51 Cardiac death, MI, TVR TIMI
SECURITY (2015)23 1,399 6 12 NI 2.0 At time of index 38 Cardiac death, MI, stroke, ST, BARC
major bleeding
ISAR-SAFE (2015)22 4,005 6 12 NI 2.0 6 months after PCI 40 All-cause death, MI, ST, stroke, TIMI
major bleeding
I-LOVE-IT 2 (2016)21 1,829 6 12 NI 3.7 At time of index 81 Cardiac death, TV–MI, TLR BARC
IVUS-XPL (2016) 26
1,400 6 12 S N/A At time of index 49 Cardiac death, MI, stroke, TIMI
major bleeding
SMART-DATE (2018)20 2,712 6 12 NI 2.0 At time of index 100 All-cause death, MI, stroke BARC
NIPPON (2017) 35
3,773 6 18 NI 2.0 At time of index 28 All-cause death, MI, stroke, BARC
major bleeding
PRODIGY (2012)34 2,013 6 24 S N/A 30 days after PCI 74 All-cause death, MI, stroke BARC
ITALIC (2017)36 1,850 6 24 NI 2.0 At time of index 43 All-cause death, MI, TVR, TIMI
stroke, major bleeding

Abbreviations: ACS = acute coronary syndrome; BARC = Bleeding Academic Research Consortium; GUSTO = Global Use of Strategies to Open Occluded Arteries; L-DAPT = long dual antiplatelet
therapy; NI = non-inferiority; REPLACE = Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events; S = superiority; S-DAPT = short dual antiplatelet therapy; ST = stent thrombosis;
TIMI = thrombolysis in myocardial infarction; TLR = target lesion revascularization; TVR = target vessel revascularization; TV-MI = target vessel myocardial infarction. Study acronyms:
EXCELLENT = the Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting; I–LOVE–IT 2 = Evaluate Safety and Effectiveness of the Tivoli DES and the Firebird DES for Treatment
of Coronary Revascularization; ISAR–SAFE = Intracoronary Stenting and Antithrombotic Regimen: Safety And EFficacy of 6 Months Dual Antiplatelet Therapy After Drug-Eluting Stenting; ITALIC
= Is There a Life for DES After Discontinuation of Clopidogrel; IVUS–XPL = Impact of Intravascular Ultra-sound Guidance on Outcomes of XIENCE PRIME Stents in Long Lesions; NIPPON = Nobori
Dual Antiplatelet Therapy as Appropriate Duration; OPTIMIZE = Optimized Duration of Clopidogrel Therapy Following Treatment With the Zotarolimus-Eluting Stent in Real-World Clinical Practice;
PRODIGY = Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study; RESET = REal Safety and Efficacy of 3–month dual antiplatelet Therapy following Endeavor
zotarolimus-eluting stent implantation; SMART–DATE = Smart Angioplasty Research Team: Safety of 6-month Duration of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in
Patients With Acute Coronary Syndromes; SECURITY = Second Generation Drug-Eluting Stent Implantation Followed by Six- Versus Twelve-Month Dual Antiplatelet Therapy.

individuals than clopidogrel.16,17 Prasugrel should be administered
only after the coronary anatomy of a patient has been established,
except for those with ST-elevation myocardial infarction (STEMI),
who will undergo primary PCI. Notably, prasugrel is associated
with significantly higher rates of TIMI (thrombolysis in MI) major
bleeding, life-threatening bleeding and fatal bleeding, and should
not be administered to those with a history of stroke or transient
ischemic attack.10
Ticagrelor, as a first-in-class cyclopentyltriazolopyrimidine, can be
administered before assessment of the coronary anatomy and acts
by reversible and direct inhibition of platelets by allostatic modulation
of the P2Y12 receptor, leading to a highly potent, rapid-onset and
more predictable antiplatelet effect compared to clopidogrel.11,18 With a
plasma half-life of 8–12 hours, ticagrelor requires administration twice
daily, which may be unattractive to patients with poor compliance. An
important adverse effect of ticagrelor is dyspnea (usually self-limiting),
which occurred in roughly 20 % of patients in major trials and accounted
for a substantial number of withdrawals.11
Ever since the introduction of DAPT, extensive research has tried to
establish the optimal duration of DAPT. This has led the adoption of two
main strategies for patients scheduled for PCI: abbreviated, or short
DAPT; and prolonged DAPT.
Evidence on Short Duration of Dual
Antiplatelet Therapy
The primary motivators to study short DAPT (S-DAPT; 3–6 months) or
ultra-short DAPT (US-DAPT; 3 months or less) are the increased risk of
major bleedings caused by DAPT and the improved safety profile of the
latest generation DES,which reduces the risks for late and very late stent
thrombosis (ST).19 To date, eight trials have investigated S-DAPT (n=6) or
US-DAPT (n=2) and compared these to 12 months of therapy (Table 1).
All trials demonstrated S-DAPT or US-DAPT to be non-inferior to 12 months
of therapy in a comparison of primary composite outcomes (Table 2).20–27
When interpreting the evidence, several aspects should be kept in mind.
First, most trials investigating S-DAPT or US-DAPT had a non-inferiority
design. Accompanying non-inferiority margins range from 2  % in three
trials to up to 4 %,which is rather wide to conclude non-inferiority.20,22–25
Second, the trials were not powered for individual endpoints like ST, but
for composite primary endpoints, which were differently composed,
complicating interpretation and compatibility. For example, three trials
did not include major bleeding in the primary endpoint.20,21,24 Patient
selection is the third and probably most important consideration when
interpreting different trials. Most trials included a variety of patient
groups or at least combined people with stable coronary artery disease
and ACS, thereby limiting translation to individual patients. Two trials
investigating S-DAPT had stricter inclusion criteria, including only patients

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Table 2: Results of Major Studies Investigating Short Dual Antiplatelet Therapy

Study (year) Effect Primary All-cause death MI ST (definite or Stroke Major bleeding
estimate endpoint probable)
RESET (2012)25 RD (95 % CI) 0.0 % (−2.5–2.5) −0.5 % (−1.4–0.4) −0.2 % (−0.7–0.3) −0.1 % (−0.5–0.3) 0.1 % (−0.1–1.0) −0.4 % (−0.9–0.1)
OPTIMIZE (2013)27 HR (95 % CI) 1.03 (0.77–1.38) 0.95 (0.63–1.45) 1.17 (0.77–1.76) 1.08 (0.49–2.36) 0.99 (0.29–3.44) 0.71 (0.32–1.60)
EXCELLENT (2012) 24
HR (95 % CI) 1.14 (0.70–1.86) 0.57 (0.17–1.95) 1.86 (0.74–4.67) 6.02 (0.72–49.96) 0.60 (0.14–2.51) 0.50 (0.09–2.73)
SECURITY (2015)23 RD (95 % CI) 0.8 % (−2.4–1.7) −0.1 % (−0.7–0.5) 0.2 % (−1.2–1.7) −0.1 % (−0.7–0.4) 0.6 % (−0.2–1.3) −0.5 (−1.4–0.4)
ISAR-SAFE (2015)22 HR (95 % CI) 0.91 (0.55–1.50) 0.66 (0.27–1.63) 0.93 (0.44–1.97) 1.25 (0.33–4.65) 1.40 (0.44–4.41) 0.80 (0.21–2.98)
I-LOVE-IT 2 (2016) 21
Cumulative 7.2 % versus 1.1 % versus 1.4 % 4.4 % versus 3.9 % 0.6 % versus 0.2 % 1.2 % versus 1.4 % 1.2 % versus
incidence, 6.4 % p=0.53 p=0.57 p=0.53 p=0.25 p=0.71 0.7 % p=0.21
log-rank p-value
IVUS-XPL (2016)26 HR (95 % CI) 1.07 (0.52–2.22) 0.50 (0.17–1.45) N/A 1.00 (0.14–7.11) 2.00 (0.50–7.99) 0.71 (0.23–2.25)
SMART-DATE (2018)20 HR (95 % CI) 1.13 (0.79–1.62) 0.9 (0.57–1.42) 2.41 (1.15–5.05) 1.5 (0.68–3.35) 0.92 (0.41–20.8) 0.6 (0.22–1.65)
NIPPON (2017) 35
RD (95 % CI) −0.6 % (−1.5–0.3) −0.5 (−1.2–0.0) −0.2 (−0.6–0.1) −0.1 (−0.4–0.2) −0.1 (−0.6–0.4) 0.1 % (−0.6–0.7)
PRODIGY (2012)34 HR (95 % CI) 0.98 (0.74–1.29) 1.00 (0.72–1.40) 1.06 (0.69–1.63) 1.15 (0.55–2.41) 0.60 (0.29–1.23) 0.56 (0.32–0.98)
ITALIC (2017)36 HR (95 % CI) 0.94 (0.58–1.52) 0.55 (0.26–1.15) 1.34 (0.56–3.17) 2.00 (0.50–7.98) 0.85 (0.29–2.53) N/A

Abbreviations: N/A = not available; RD = risk difference; ST = stent thrombosis. Study acronyms: EXCELLENT = Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting;
I–LOVE–IT 2 = Evaluate Safety and Effectiveness of the Tivoli DES and the Firebird DES for Treatment of Coronary Revascularization; ISAR–SAFE = Intracoronary Stenting and Antithrombotic Regimen:
Safety And EFficacy of 6 Months Dual Antiplatelet Therapy After Drug-Eluting Stenting; ITALIC = Is There a Life for DES After Discontinuation of Clopidogrel; IVUS–XPL = Impact of Intravascular Ultra-
sound Guidance on Outcomes of XIENCE PRIME Stents in Long Lesions; NIPPON = Nobori Dual Antiplatelet Therapy as Appropriate Duration; OPTIMIZE = Optimized Duration of Clopidogrel Therapy
Following Treatment With the Zotarolimus-Eluting Stent in Real-World Clinical Practice; PRODIGY = Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study;
RESET = REal Safety and Efficacy of 3–month dual antiplatelet Therapy following Endeavor zotarolimus-eluting stent implantation; SMART–DATE = Smart Angioplasty Research Team: Safety of 6–
month Duration of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With Acute Coronary Syndromes; SECURITY = Second Generation Drug-Eluting Stent Implantation
Followed by Six- Versus Twelve-Month Dual Antiplatelet Therapy.

with stable angina, silent ischemia or unstable angina or studied only
those with biomarker positive ACS.20,23 Overall, mostly patients with a
relatively low ischemic risk (stable coronary artery disease or biomarker
negative ACS) were included in the majority of these trials. Finally, trials
used homogeneous and different bleeding endpoint criteria, which
complicates the interpretation of results.
Multiple meta-analyses have attempted to compare the outcomes of
trials investigating S-DAPT.28–33 The results of these meta-analyses are
consistent and none of them show a difference in mortality. Importantly,
the risks for ST, MI and stroke were not increased in the S-DAPT arm,
while an increased risk for major bleeding events was observed with
12 months’ treatment.
Three trials compared S-DAPT to prolonged DAPT (>12 months
of treatment).34–36 Two trials concluded S-DAPT to be non-inferior
to prolonged DAPT, and one trial noted a trend of more complications in
the arm who were treated for 24 months.35,36 The only trial powered for
superiority did not find 24 months of therapy to be superior to S-DAPT,
but did notice a significant increase in BARC 3 or 5 bleeding events
(HR 0.56, 95 % CI [0.32–0.98], p=0.037).34
It seems likely that S-DAPT may be beneficial to selected patients
with a high risk of bleeding. Major bleeding events are an important
complication because of the association between major bleedis and a
poor prognosis,in addition to the negative impact these events have
on a patient’s quality of life.37 Notably, a recent individual patient data
meta-analysis found an association between bleeding-related deaths and
DAPT duration after PCI.38 More specifically, S-DAPT was associated with
a reduction of bleeding-related deaths compared to long DAPT (L-DAPT;
12 months of treatment) and prolonged DAPT. When interpreting these
results, it is important to address the definition used for bleeding-related
death, where death was considered to be possibly bleeding related if
occurring within 1 year of the bleeding episode, which is a rather liberal
definition, leading to an overestimated result. On the other hand, most
patients were treated with clopidogrel. With the availability of more
potent P2Y12 inhibitors in current practice, the effects on bleeding events
or even mortality in these trials may be underestimated. Of course,
causality cannot be established, but the impact of bleeding should not be
underestimated. More studies have found bleedings associated with an
increased risk of recurrent bleeding and all-cause mortality.39,40
Evidence on Prolonged Duration of Dual
Antiplatelet Therapy
To date, four trials compared prolonged DAPT (>12 months of treatment)
to a standard regimen of DAPT (12 months of treatment).41–44 The trials’
characteristics are shown in Table 3, and the main results are summarized
in Table 4. The Dual Antiplatelet Trial (DAPT) is the largest study and
was powered for superiority for the primary endpoints of definite
or probable ST and a composite endpoint of death, MI and stroke.41
For both ST (definite and probable) and the composite primary endpoint,
a significant decrease was found when prolonging DAPT (ST: HR 0.29,
95 % CI [0.17–0.48], p<0.001, composite endpoint: HR 0.71, 95 % CI [0.59–
0.85], p<0.001). Notably, all-cause deaths were higher in the prolonged
DAPT arm (HR 1.36, 95  % CI [1.00–1.85], p=0.05), as a result of to the
larger occurrence of non-cardiovascular deaths in the prolonged DAPT
arm (HR 2.23, 95 % CI [1.32–3.78], p=0.002). This difference in mortality
was explained by a between-group imbalance of patients diagnosed with
cancer. Not surprisingly, prolonged DAPT caused an increase in bleeding
complications (HR 1.61, 95 % CI [1.21–2.16], p=0.001). In their individual
patient data analysis, Palmerini et al.38 observed numerically more
bleeding-related deaths in the DAPT trial.

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Table 3: Characteristics of Major Studies Investigating Long Dual Antiplatelet Therapy

Study (year) Size (n) Standard L–DAPT Design Time of ACS Primary endpoint Bleeding criteria
DAPT (months) (months) randomisation (%)
ARCTIC (2014)43 2440 12 18–30 Superiority 12 months after index 26 All-cause death, MI, ST, stroke, STEEPLE
revascularization
DAPT (2014)41 9961 12 30 Superiority 12 months after index 42 ST and death, MI, stroke BARC and GUSTO
DESLATE (2014) 42
5045 12 36 Superiority 12 months after index 61 Cardiac death, MI, stroke TIMI
OPTIDUAL (2016)44 1799 12 48 Superiority 12 months after index 27 All-cause death, MI, stroke ISTH
major bleeding

ACS = acute coronary syndrome; BARC = Bleeding Academic Research Consortium; GUSTO = Global Use of Strategies to Open Occluded Arteries; ISTH = International Society
on Thrombosis and Haemostasis; L–DAPT = long dual antiplatelet therapy; S–DAPT = short dual antiplatelet therapy; ST = stent thrombosis; STEEPLE = Safety and Efficacy of Enoxaparin in
Percutaneous Coronary Intervention Patients: an International Randomized Evaluation; TIMI = Thrombolysis In MI. Study acronyms: ARCTIC = Assessment by a double Randomisation of a
Conventional antiplatelet strategy versus a monitoring-guided strategy for drug-eluting stent implantation and, of Treatment Interruption versus Continuation 1 year after stenting;
DAPT = Dual Antiplatelet Therapy; DES–LATE = Optimal Duration of Clopidogrel Therapy With DES to Reduce Late Coronary Arterial Thrombotic Event; OPTIDUAL = OPTImal DUAL
Antiplatelet Therapy.

Table 4: Results of Major Studies Investigating Long Dual Antiplatelet Therapy

Study (year) Effect estimate Primary All-cause death MI ST (definite or Stroke Major bleeding
endpoint probable)
ARCTIC (2014)43 HR (95 % CI) 0.94 (0.66–1.35) 0.71 (0.45–1.10) 1.43 (0.80–2.58) 1.59 (0.61–4.09) 1.01 (0.55–1.85) 0.71 (0.42–1.20)
DAPT (2014) 41
HR (95 % CI) 0.71 (0.59–0.85) 1.36 (1.00–1.85) 0.47 (0.37–0.61) 0.29 (0.17–0.48) 0.68 (0.40–1.17) *RD 1.0 % (0.4–1.5)
DESLATE (2014)42 HR (95 % CI) 1.17 (0.68–2.03) 1.32 (0.49–3.55) 1.04 (0.41–2.62) N/A 0.69 (0.19–2.44) 0.15 (0.02–1.20)
OPTIDUAL (2016)44 HR (95 % CI) 0.75 (0.50–1.28) 0.65 (0.34–1.22) 0.67 (0.31–2.18) 2.97 (0.31–28.53) 0.69 (0.22–2.18) 0.98 (0.47–2.05)

*Major bleedings reported as risk difference. N/A = not available; RD = risk difference; ST = stent thrombosis. Study acronyms: ARCTIC = Assessment by a double Randomisation of a Conventional
antiplatelet strategy versus a monitoring-guided strategy for drug-eluting stent implantation and, of Treatment Interruption versus Continuation 1 year after stenting; DAPT = Dual Antiplatelet
Therapy; DES–LATE = Optimal Duration of Clopidogrel Therapy With DES to Reduce Late Coronary Arterial Thrombotic Event; OPTIDUAL = OPTImal DUAL Antiplatelet Therapy.

The Assessment by a double Randomization of a Conventional Patient-tailored Duration of Dual

antiplatelet strategy versus a monitoring-guided strategy for drug-
eluting stent implantation and of Treatment Interruption versus
Continuation 1 year after stenting (ARCTIC)-Interruption trial did not find
a difference in the composite primary endpoint (death, MI, ST, stroke
or transient ischemic attack, and urgent revascularization).43 However,
it should be emphasized that this study was prematurely terminated,
and the event rates were lower than anticipated. The prolonged DAPT
arm did, however, show a significant increase in STEEPLE (Safety
and Efficacy of Enoxaparin in Percutaneous Coronary Intervention
Patients: An International Randomized Evaluation) bleeding (HR 0.26,
95 % CI [0.07–0.91], p=0.04). Therefore, the ARCTIC-Interruption authors
concluded that prolonging DAPT has no apparent benefit and could
harm patients. Both the Optimal Duration of Clopidogrel Therapy with
DES to Reduce Late Coronary Arterial Thrombotic Event (DES-LATE)
trial and the OPTImal DUAL Antiplatelet Therapy (OPTIDUAL) trial did
not observe any potential harm from prolonging DAPT nor a beneficial
effect.42,44 This is explained by the fact that these studies were powered
to detect major differences only.
Several meta-analyses have combined these trials. The results
for all-cause death and cardiac death are conflicting. 29,30,32,33,45
One showed prolonged DAPT reduced cardiac death,while another
indicated non-cardiac death to be increased by prolonged DAPT.29,45
Evidence also showed prolonged DAPT reduced ischemic events at the
cost of more major bleedings.29,30,32,33,45 Patients with a high ischemic
burden are most likely to benefit from prolonged DAPT or maybe even
life-long DAPT.
Antiplatelet Therapy
The European Society of Cardiology’s focused update on DAPT3 states that
the use of risk scores to guide DAPT duration may be considered (class
IIB recommendation). Multiple risk scores to assess a patient’s ischemic
or bleeding risk have been proposed: the DAPT score,the PARIS registry
risk scores, PRECISE-DAPT, and CREDO-Kyoto (Tables 5–7 and Figure 1).46–49
The first risk assessment tool was the DAPT score,which was derived
from the DAPT trial to aid clinical decision-making regarding DAPT
duration.46 This score aims to predict who would benefit from prolonged
DAPT at 12 months after PCI after an event-free period of 12 months.
Including eight variables (age, smoking, diabetes, MI at presentation, prior
PCI or MI, paclitaxel-eluting stent, stent diameter, chronic heart failure
and vein graft stent), the score ranges from −2 to 10. Any score below 2
is associated with a bleeding risk that exceeds ischemic risk, indicating
DAPT cessation at 12 months. High scores (≥2) are associated with an
increased ischemic risk, leading to an increased net clinical benefit from
continuing DAPT treatment. Important limitations of the DAPT score are:
a limited external validity because it is derived from the DAPT study
cohort, which included ischemic patients and those who were bleeding
event free after 12 months; and the reduced effect when correcting for
paclitaxel-eluting stents, which are no longer used.
The PARIS registry risk scores are two scores to predict bleeding and
ischemic risk after PCI.47 The ischemic score is composed solely of clinical
characteristics (diabetes, ACS type, smoking, creatinine clearance, prior
PCI, and prior coronary artery bypass graft), although procedural and

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Table 5: Duration of Dual Antiplatelet Therapy Risk Score Table 6: PARIS Risk Scores

Parameter Score PARIS ischemic risk score PARIS bleeding risk score
Age (years) Parameter Score Parameter Score
   ≥75 −2 Diabetes Age (years)
   65 to <75 −1 None 0 <50 0
   <65 0 Type 2 diabetes +1 50–59 +1
Cigarette smoking 1 Type 1 diabetes +3 60–69 +2
Diabetes 1 Acute coronary syndrome 70–79 +3
MI at presentation 1 No 0 ≥80 +4
Prior PCI or prior MI 1 Yes, troponin negative +1 BMI, kg/m2
Paclitaxel-eluting stent 1 Yes, troponin positive +2 <25 +2
Stent diameter <3 mm 1 Current smoking 25–34.9 0
CHF or LVEF <30 % 2 No 0 ≥35 +2
Vein graft stent 2 Yes +1 Current smoking
Total score range: −2–10 CrCl <60ml/min No 0

CHF = congestive heart failure; LVEF = left ventricular ejection fraction; PCI = percutaneous Absent 0 Yes +2
coronary intervention.
Present +2 Anemia
Prior PCI Absent 0
angiographic characteristics also influence patients’ ischemic risk.50
No 0 Present +3
The bleeding score includes age, BMI, smoking, anemia, creatinine
Yes +2 CrCl <60ml/min
clearance and triple therapy. Smoking and reduced creatinine increase
Prior CABG Absent 0
a patient’s ischemic risk as well as bleeding risk, according to the
No 0 Present +2
derivation cohort. Retrospective validation of the PARIS risk scores using
data from the platelet reactivity and clinical outcomes after coronary Yes +2 Triple therapy on discharge

artery implantation of DES (ADAPT-DES) registry resulted in moderate No 0

discrimination of both the thrombotic and bleeding risk scores. Yes +2
Total score range: 0–12 Total score range: 0–15
The PRECISE-DAPT score was developed as a standardized tool to weight
CrCl = creatinine clearance; CABG = coronary artery bypass grafting; PCI = percutaneous
bleeding risk before selecting DAPT treatment duration and aims to coronary intervention.
predict out-of-hospital bleeding events with a five-item score. The external
validation in two validation cohorts (PLATelet inhibition and patient Table 7: CREDO-Kyoto Risk Scores
Outcomes [PLATO] and the BernPCI registry) indicated replicable moderate
discriminative ability. Its clinical utility is, however, lower than those of other CREDO ischemic risk score CREDO bleeding risk score
risk scores since the score is primarily based on laboratory results.48
Parameter Score Parameter Score
Severe chronic kidney disease 2 Platelet count <100/ml 2
The CREDO-Kyoto risk scores aim to assess thrombotic and bleeding risks
AF 2 Severe chronic kidney disease 2
using two scores: an eight-item ischemic risk score and a seven-item
bleeding risk score.49 Four parameters are included in both scores. This Peripheral vascular disease 2 Peripheral vascular disease 2

raises questions about clinical applicability, as patients with a high ischemic Anemia 2 Heart failure 2
score are likely to have an increased bleeding score too, leaving the Age ≥75 years 1 Prior MI 1
question whether to prolong or shorten DAPT duration unanswered. Unlike Heart failure 1 Malignancy 1
other scoring systems, in CREDO-Kyoto, the procedural parameters were Diabetes 1 AF 1
tested and included chronic total occlusion in the final ischemic score.
Chronic total occlusion 1

Total score range: 0–12 Total score range: 0–11

In the first validation studies, the DAPT score was retrospectively
replicated in the PRODIGY study, but failed to discriminate the risk
on bleeding and ischemic events using data from the ISAR-SAFE
cohort.51,52 Hereafter, both the DAPT score and PARIS registry scores
were retrospectively validated and compared in a Chinese population
(n=5,709).53 Only the DAPT score showed modest accuracy for predicting
major bleedings. Both scores showed poor discriminative capacity
predicting ischemic events. Therefore, the DAPT score and risk scores
from PARIS may not be applicable in a Chinese population. In the Spanish
CardioCHUVI (Cardiologia del Complejo Hospitalario Universitario de Vigo)
cohort (n=1,926),PARIS bleeding score and PRECISE-DAPT score were
retrospectively validated.54 For major bleedings, PARIS and PRECISE-DAPT
showed a moderate discriminative power and, using decision curve
analyses, it was concluded that the PARIS bleeding score had a superior
performance. Recently, the DAPT score was successfully validated in
a pooled Japanese cohort (n=12,223).55 One year after PCI, the DAPT

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 Interventional Cardiology

Figure 1: PRECISE–DAPT Score Clinical Perspectives and Future Research

Several randomized trials have established the pivotal role of DAPT
Bleeding score following PCI for latest-generation DES implantation. Individual
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 assessment of a patient’s risk profile will be essential to optimize DAPT
Points duration. A substantial proportion of patients have stable coronary
artery disease. Especially for stable patients with a low ischemic risk
≥12.0 11.5 11.0 10.5 ≤10.0
profile, the authors believe short durations of DAPT may be beneficial,
Hemoglobin (g/dl) given the improved safety profile of currently available DES. On the
≤5 8 10 12 14 16 18 ≥20 other hand, it seems obvious that patients with a high ischemic risk
3 profile may need prolonged or even lifelong DAPT.
White blood cell count (x10 cells/µl)

≤50 60 70 80 ≥90 Regarding the currently available risk scores, any clinical value
Age (years) they add needs to be determined in a prospective randomized trial.
Although the authors believe risk scores are likely to improve in aiding
≥100 80 60 40 20 0
individual patient-tailored DAPT, physicians should acknowledge
Creatinine clearance (ml/min)
the limitations of existing risk scores, and fully assess the patient’s
No Yes risk profile and coronary angiographic characteristics. Since optimal
Previous bleed durations of DAPT have been investigated for more than a decade,
many clinicians believe simplification may be required regarding
score successfully stratified ischemic and bleeding risks. However, the pharmacotherapy after PCI.
investigators observed low ischemic event rates in patients with a high
DAPT score. Therefore, questions remain over the clinical utility of the Future research may examine de-escalation of DAPT. For example,
score and the benefit of prolonging DAPT treatment. Last, in a nationwide the ongoing Ticagrelor With Aspirin or Alone in High-Risk Patients
Swedish registry (n=41,101) the DAPT score had poor discriminative After Coronary Intervention (TWILIGHT) study (NCT02270242)
capacity for ischemic events and did not discriminate bleeding risk.35 challenges the concept of DAPT as ticagrelor monotherapy for
long-term platelet inhibition in a broad population of patients
Results of these validation studies are conflicting, but differences undergoing PCI with DES. As the latest-generation DES with enhanced
between the validation cohorts need to be taken into account. Cohort safety profiles are likely to reduce adverse events even further, a
size and geographical background in particular may differ substantially paradigm shift to de-escalation of DAPT should be evaluated in future
between derivation cohorts. dedicated trials.

1.  almerini T, Biondi-Zoccai G, Della Riva D, et al. Stent thrombosis

P clopidogrel in patients with acute coronary syndromes. N Engl J
with drug-eluting and bare-metal stents: evidence from a
comprehensive network meta-analysis. Lancet 2012;379:1393–
402. https://doi.org/10.1016/S0140-6736(12)60324-9; PMID:
22445239.
2. Stone GW, Maehara A, Lansky AJ, et al. A prospective
natural-history study of coronary atherosclerosis. N Engl J Med
2011;364:226–35. https://doi.org/10.1056/NEJMoa1002358;
PMID: 21247313.
3. Valgimigli M, Bueno H, Byrne RA, et al. 2017 ESC focused
update on dual antiplatelet therapy in coronary artery disease
developed in collaboration with EACTS: the Task Force for dual
antiplatelet therapy in coronary artery disease of the European
Society of Cardiology (ESC) and of the European Association
for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2017;39:213–60.
https://doi.org/10.1093/eurheartj/ehx419; PMID: 28886622.
4. Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA guideline
focused update on duration of dual antiplatelet therapy in
patients with coronary artery disease: a report of the American
College of Cardiology/American Heart Association Task Force
on Clinical Practice Guidelines. J Am Coll Cardiol 2016;68:1082–115.
https://doi.org/10.1016/j.jacc.2016.03.513; PMID: 27036918.
5. Bonaca MP, Bhatt DL, Cohen M, et al. Long-term use of
ticagrelor in patients with prior myocardial infarction. N Engl J Med
2015;372:1791–800. https://doi.org/10.1056/NEJMoa1500857;
PMID: 25773268.
6. Cuisset T, Verheugt FWA, Mauri L. Update on antithrombotic
therapy after percutaneous coronary revascularisation. Lancet
2017;390:810–20. https://doi.org/10.1016/S0140-6736(17)31936-
0; PMID: 28831996.
7. Libby P. Mechanisms of acute coronary syndromes and their
implications for therapy. N Engl J Med 2013;368:2004–13. https://
doi.org/10.1056/NEJMra1216063; PMID: 23697515.
8. Davi G, Patrono C. Platelet activation and atherothrombosis.
N Engl J Med 2007;357:2482–94. https://doi.org/10.1056/
NEJMra071014; PMID: 18077812.
9. Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in
addition to aspirin in patients with acute coronary syndromes
without ST-segment elevation. N Engl J Med 2001;345:494–502.
https://doi.org/10.1056/NEJMoa010746; PMID: 11519503.
10. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus
Med 2007;357:2001–15. https://doi.org/10.1056/NEJMoa0706482;
PMID: 17982182.
11. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus
clopidogrel in patients with acute coronary syndromes. N Engl J
Med. 2009;361:1045–57. https://doi.org/10.1056/NEJMoa0904327;
PMID: 19717846.
12. Antithrombotic Trialists’ Collaboration. Collaborative meta-
analysis of randomised trials of antiplatelet therapy for
prevention of death, myocardial infarction, and stroke in high
risk patients. BMJ 2002;324:71–86. https://doi.org/10.1136/
bmj.324.7329.71; PMID: 11786451.
13. CURRENT-OASIS 7 Investigators, Mehta SR, Bassand JP, et
al. Dose comparisons of clopidogrel and aspirin in acute
coronary syndromes. N Engl J Med 2010;363:930–42. https://doi.
org/10.1056/NEJMoa0909475; PMID: 20818903.
14. Schomig A, Neumann FJ, Kastrati A, et al. A randomized
comparison of antiplatelet and anticoagulant therapy after the
placement of coronary-artery stents. N Engl J Med 1996;334:1084–
9. https://doi.org/10.1056/NEJM199604253341702; PMID:
8598866.
15. Stone GW, Witzenbichler B, Weisz G, et al. Platelet reactivity and
clinical outcomes after coronary artery implantation of drug-
eluting stents (ADAPT–DES): a prospective multicentre registry
study. Lancet 2013;382:614–23. https://doi.org/10.1016/S0140-
6736(13)61170-8; PMID: 23890998.
16. Ferreiro JL, Angiolillo DJ. New directions in antiplatelet therapy.
Circ Cardiovasc Interv 2012;5:433–45. https://doi.org/10.1161/
CIRCINTERVENTIONS.111.966176; PMID: 22715450.
17. Wiviott SD, Trenk D, Frelinger AL, et al. Prasugrel compared with
high loading- and maintenance-dose clopidogrel in patients
with planned percutaneous coronary intervention: the Prasugrel
in Comparison to Clopidogrel for Inhibition of Platelet Activation
and Aggregation-Thrombolysis in Myocardial Infarction 44
trial. Circulation 2007;116:2923–32. https://doi.org/10.1161/
CIRCULATIONAHA.107.740324; PMID: 18056526.
18. Gurbel PA, Bliden KP, Butler K, et al. Randomized double-blind
assessment of the ONSET and OFFSET of the antiplatelet
effects of ticagrelor versus clopidogrel in patients with
stable coronary artery disease: the ONSET/OFFSET study.
Circulation 2009;120:2577–85. https://doi.org/10.1161/
CIRCULATIONAHA.109.912550; PMID: 19923168.
19. D angas GD, Serruys PW, Kereiakes DJ, et al. Meta-analysis of
everolimus-eluting versus paclitaxel-eluting stents in coronary
artery disease: final 3–year results of the SPIRIT clinical trials
program (Clinical Evaluation of the Xience V Everolimus Eluting
Coronary Stent System in the Treatment of Patients With De
Novo Native Coronary Artery Lesions). JACC Cardiovasc Interv
2013;6:914–22. https://doi.org/10.1016/j.jcin.2013.05.005; PMID:
2405085.
20. Hahn J-Y, Song YB, Oh J-H, et al. 6–month versus 12–month or
longer dual antiplatelet therapy after percutaneous coronary
intervention in patients with acute coronary syndrome
(SMART–DATE): a randomised, open-label, non-inferiority
trial. Lancet 2018;391:1274–84. https://doi.org/10.1016/S0140-
6736(18)30493-8
21. Han Y, Xu B, Xu K, et al. Six versus 12 months of dual
antiplatelet therapy after implantation of biodegradable
polymer sirolimus-eluting stent: randomized substudy of the
I–LOVE–IT 2 Trial. Circ Cardiovasc Interv 2016;9:e003145. https://doi.
org/10.1161/CIRCINTERVENTIONS.115.003145; PMID: 26858080.
22. Schulz-Schupke S, Byrne RA, Ten Berg JM, et al. ISAR–SAFE:
a randomized, double-blind, placebo-controlled trial of 6 vs.
12 months of clopidogrel therapy after drug-eluting stenting.
Eur Heart J 2015;36:1252–63. https://doi.org/10.1093/eurheartj/
ehu523; PMID: 25616646.
23. Colombo A, Chieffo A, Frasheri A, et al. Second–generation
drug–eluting stent implantation followed by 6– versus 12–
month dual antiplatelet therapy: the SECURITY randomized
clinical trial. J Am Coll Cardiol 2014;64:2086–97. https://doi.
org/10.1016/j.jacc.2014.09.008; PMID: 25236346.
24. Gwon HC, Hahn JY, Park KW, et al. Six-month versus 12–month
dual antiplatelet therapy after implantation of drug-eluting
stents: the Efficacy of Xience/Promus Versus Cypher to Reduce
Late Loss After Stenting (EXCELLENT) randomized, multicenter
study. Circulation 2012;125:505–13. https://doi.org/10.1161/
CIRCULATIONAHA.111.059022; PMID: 22179532.
25. Kim BK, Hong MK, Shin DH, et al. A new strategy for
discontinuation of dual antiplatelet therapy: the RESET Trial
(REal Safety and Efficacy of 3–month dual antiplatelet Therapy
following Endeavor zotarolimus-eluting stent implantation).
J Am Coll Cardiol 2012;60:1340–8. https://doi.org/10.1016/j.

96 US CARDIOLOGY REVIEW

USC_Stella_vFINAL.indd 96 04/12/2018 19:31


jacc.2012.06.043; PMID: 22999717.
26. H ong SJ, Shin DH, Kim JS, et al. 6–month versus 12–month
dual-antiplatelet therapy following long everolimus-eluting
stent implantation: the IVUS–XPL randomized clinical trial.
JACC Cardiovasc Interv 2016;9:1438–46. https://doi.org/10.1016/j.
jcin.2016.04.036; PMID: 27212028.
27. Feres F, Costa RA, Abizaid A, et al. Three vs twelve months of
dual antiplatelet therapy after zotarolimus-eluting stents: the
OPTIMIZE randomized trial. JAMA 2013;310:2510–22. https://doi.
org/10.1001/jama.2013.282183, PMID: 24177257.
28. Palmerini T, Della Riva D, Benedetto U, et al. Three, six, or twelve
months of dual antiplatelet therapy after DES implantation
in patients with or without acute coronary syndromes: an
individual patient data pairwise and network meta-analysis
of six randomized trials and 11 473 patients. Eur Heart J
2017;38:1034–43. https://doi.org/10.1093/eurheartj/ehw627;
PMID: 28110296.
29. Palmerini T, Benedetto U, Bacchi-Reggiani L, et al. Mortality
in patients treated with extended duration dual antiplatelet
therapy after drug-eluting stent implantation: a pairwise
and Bayesian network meta-analysis of randomised trials.
Lancet 2015;385:2371–82. https://doi.org/10.1016/S0140-
6736(15)60263-X; PMID: 25777667.
30. D’Ascenzo F, Moretti C, Bianco M, et al. Meta-analysis
of the duration of dual antiplatelet therapy in patients
treated with second-generation drug-eluting stents. Am
J Cardiol 2016;117:1714–23. https://doi.org/10.1016/j.
amjcard.2016.03.005; PMID: 27134057.
31. Rozemeijer R, Voskuil M, Greving JP, et al. Short versus long
duration of dual antiplatelet therapy following drug-eluting
stents: a meta-analysis of randomised trials. Neth Heart J
2018;26:242–51. https://doi.org/10.1007/s12471-018-1104-6;
PMID: 29541996.
32. Giustino G, Baber U, Sartori S, et al. Duration of dual antiplatelet
therapy after drug-eluting stent implantation: a systematic
review and meta-analysis of randomized controlled trials. J
Am Coll Cardiol 2015;65:1298–310. https://doi.org/10.1016/j.
jacc.2015.01.039; PMID: 25681754.
33. Navarese EP, Andreotti F, Schulze V, et al. Optimal duration
of dual antiplatelet therapy after percutaneous coronary
intervention with drug eluting stents: meta-analysis of
randomised controlled trials. BMJ 2015;350:h1618. https://doi.
org/10.1136/bmj.h1618; PMID: 25883067.
34. Valgimigli M, Campo G, Monti M, et al. Short- versus long-term
duration of dual-antiplatelet therapy after coronary stenting:
a randomized multicenter trial. Circulation 2012;125:2015–26.
https://doi.org/10.1161/CIRCULATIONAHA.111.071589; PMID:
22438530.
35. Nakamura M, Iijima R, Ako J, et al. Dual antiplatelet therapy
for 6 versus 18 months after biodegradable polymer
US CARDIOLOGY REVIEW
USC_Stella_vFINAL.indd 97
Towards Tailored Dual Antiplatelet Therapy
drug-eluting stent implantation. JACC Cardiovasc Interv
2017;10:1189–98. https://doi.org/10.1016/j.jcin.2017.04.019;
PMID: 28641838.
36. Didier R, Morice MC, Barragan P, et al. 6– versus 24–month dual
antiplatelet therapy after implantation of drug-eluting stents in
patients nonresistant to aspirin: final results of the ITALIC Trial
(Is There a Life for DES After Discontinuation of Clopidogrel).
JACC Cardiovasc Interv 2017;10:1202–10. https://doi.org/10.1016/j.
jcin.2017.03.049; PMID: 28641840.
37. Genereux P, Giustino G, Witzenbichler B, et al. Incidence,
predictors, and impact of post-discharge bleeding after
percutaneous coronary intervention. J Am Coll Cardiol
2015;66:1036–45. https://doi.org/10.1016/j.jacc.2015.06.1323;
PMID: 26314532.
38. Palmerini T, Bacchi Reggiani L, Della Riva D, et al. bleeding-
related deaths in relation to the duration of dual-antiplatelet
therapy after coronary stenting. J Am Coll Cardiol 2017;69:2011–22.
https://doi.org/10.1016/j.jacc.2017.02.029; PMID: 28427576.
39. Rao SV, Dai D, Subherwal S, et al. Association between
periprocedural bleeding and long-term outcomes following
percutaneous coronary intervention in older patients. JACC
Cardiovasc Interv 2012;5:958–65. https://doi.org/10.1016/j.
jcin.2012.05.010; PMID: 22995883.
40. Kwok CS, Khan MA, Rao SV, et al. Access and non-access
site bleeding after percutaneous coronary intervention
and risk of subsequent mortality and major adverse
cardiovascular events: systematic review and meta-analysis.
Circ Cardiovasc Interv 2015;8: e001645. https://doi.org/10.1161/
CIRCINTERVENTIONS.114.001645; PMID: 25825007.
41. Mauri L, Kereiakes DJ, Yeh RW, et al. Twelve or 30 months of
dual antiplatelet therapy after drug-eluting stents. N Engl J Med
2014;371:2155–66. https://doi.org/10.1056/NEJMoa1409312;
PMID: 25399658.
42. Lee CW, Ahn JM, Park DW, et al. Optimal duration of dual
antiplatelet therapy after drug-eluting stent implantation: a
randomized, controlled trial. Circulation 2014;129:304–12. https://
doi.org/10.1161/CIRCULATIONAHA.113.003303; PMID: 24097439.
43. Collet J-P, Silvain J, Barthélémy O, et al. Dual-antiplatelet treatment
beyond 1 year after drug-eluting stent implantation (ARCTIC–
Interruption): a randomised trial. Lancet 2014;384:1577–85. https://
doi.org/10.1016/S0140-6736(14)60612-7; PMID: 25037988.
44. Helft G, Steg PG, Le Feuvre C, et al. Stopping or continuing
clopidogrel 12 months after drug-eluting stent placement: the
OPTIDUAL randomized trial. Eur Heart J 2016;37:365–74. https://
doi.org/10.1093/eurheartj/ehv481; PMID: 26364288.
45. Udell JA, Bonaca MP, Collet JP, et al. Long-term dual antiplatelet
therapy for secondary prevention of cardiovascular events in
the subgroup of patients with previous myocardial infarction:
a collaborative meta-analysis of randomized trials. Eur Heart J
2016;37:390–9. https://doi.org/10.1093/eurheartj/ehv443; PMID:
26324537.
46. Y eh RW, Secemsky EA, Kereiakes DJ, et al. Development and
validation of a prediction rule for benefit and harm of dual
antiplatelet therapy beyond 1 year after percutaneous coronary
intervention. JAMA 2016;315:1735–49. https://doi.org/10.1001/
jama.2016.3775; PMID: 27022822.
47. Baber U, Mehran R, Giustino G, et al. Coronary thrombosis
and major bleeding after PCI with drug-eluting stents:
risk scores from PARIS. J Am Coll Cardiol 2016;67:2224–34.
https://doi.org/10.1016/j.jacc.2016.02.064; PMID: 27079334.
48. Costa F, van Klaveren D, James S, et al. Derivation and
validation of the predicting bleeding complications in patients
undergoing stent implantation and subsequent dual antiplatelet
therapy (PRECISE–DAPT) score: a pooled analysis of individual-
patient datasets from clinical trials. Lancet. 2017;389:1025–34.
https://doi.org/10.1016/S0140-6736(17)30397-5; PMID: 28290994.
49. Natsuaki M, Morimoto T, Yamaji K, et al. Prediction of thrombotic
and bleeding events after percutaneous coronary intervention:
CREDO-Kyoto Thrombotic and Bleeding Risk Scores. J Am Heart
Assoc 2018;7:e008708. https://doi.org/10.1161/JAHA.118.008708;
PMID: 29789335.
50. Dangas GD, Claessen BE, Mehran R, et al. Development and
validation of a stent thrombosis risk score in patients with
acute coronary syndromes. JACC Cardiovasc Interv 2012;5:1097–
105. https://doi.org/10.1016/j.jcin.2012.07.012; PMID:23174632.
51. Piccolo R, Gargiulo G, Franzone A, et al. Use of the dual-
antiplatelet therapy score to guide treatment duration after
percutaneous coronary intervention. Ann Intern Med 2017;167:17–
25. https://doi.org/10.7326/M16-2389; PMID: 28605779.
52. Harada Y, Michel J, Lohaus R, et al. Validation of the DAPT score
in patients randomized to 6 or 12 months clopidogrel after
predominantly second-generation drug-eluting stents. Thromb
Haemost 2017;117:1989–99. https://doi.org/10.1160/TH17-02-
0101; PMID: 28783201.
53. Song L, Guan C, Yan H, et al. Validation of contemporary
risk scores in predicting coronary thrombotic events and
major bleeding in patients with acute coronary syndrome
after drug-eluting stent implantations. Catheter Cardiovasc Interv
2018;91(S1):573–81. https://doi.org/10.1002/ccd.27468;
PMID: 29322612.
54. Abu-Assi E, Raposeiras-Roubin S, Cobas-Paz R, et al. Assessing
the performance of the PRECISE-DAPT and PARIS risk scores
for predicting one-year out-of-hospital bleeding in acute
coronary syndrome patients. EuroIntervention 2018;13:1914–22.
https://doi.org/10.4244/EIJ-D-17-00550; PMID: 29131804.
55. Yoshikawa Y, Shiomi H, Watanabe H, et al. Validating utility
of dual antiplatelet therapy score in a large pooled cohort
from 3 Japanese percutaneous coronary intervention
studies. Circulation 2018;137:551–62. https://doi.org/10.1161/
CIRCULATIONAHA.117.028924; PMID: 28982692.
97
04/12/2018 19:31