A Report of the American College of Cardiology/American Heart Association
Task Force on Clinical Practice Guidelines
The optimal duration of dual antiplatelet therapy (DAPT) after implantation of newer-
generation drug-eluting stents (DES) remains uncertain. Similarly, questions remain about the role of DAPT in long-term therapy of stable post–myocardial infarction (MI) patients.
Our objective was to compare the incidence of death, major hemorrhage, MI, stent thrombosis, and
major adverse cardiac events in patients randomized to prolonged or short-course DAPT after
implantation of newer-generation DES and in secondary prevention after MI.
We used traditional frequentist statistical and Bayesian approaches to address the following
questions: Q1) What is the minimum duration of DAPT required after DES implantation? Q2) What is the
clinical benefit of prolonging DAPT up to 18 to 48 months? Q3) What is the clinical effect of DAPT in
stable patients who are >1 year past an MI?
We reviewed evidence from 11 randomized controlled trials (RCTs) that enrolled 33,051
patients who received predominantly newer-generation DES to answer: A1) Use of DAPT for 12 months,
as compared with use for 3 to 6 months, resulted in no significant differences in incidence of death (odds
ratio [OR]: 1.17; 95% confidence interval [CI]: 0.85 to 1.63), major hemorrhage (OR: 1.65; 95% CI: 0.97
to 2.82), MI (OR: 0.87; 95% CI: 0.65 to 1.18), or stent thrombosis (OR: 0.87; 95% CI: 0.49 to 1.55).
Bayesian models confirmed the primary analysis. A2) Use of DAPT for 18 to 48 months, compared with
use for 6 to 12 months, was associated with no difference in incidence of all-cause death (OR: 1.14; 95%
CI: 0.92 to 1.42) but was associated with increased major hemorrhage (OR: 1.58; 95% CI: 1.20 to 2.09),
decreased MI (OR: 0.67; 95% CI: 0.47 to 0.95), and decreased stent thrombosis (OR: 0.42; 95% CI: 0.24
to 0.74). A risk-benefit analysis found 3 fewer stent thromboses (95% CI: 2 to 5) and 6 fewer MIs (95%
CI: 2 to 11) but 5 more major bleeds (95% CI: 3 to 9) per 1,000 patients treated with prolonged DAPT per
year. Post hoc analyses provided weak evidence of increased mortality rate with prolonged DAPT. We
reviewed evidence from 1 RCT of 21,162 patients and a post hoc analysis of 1 RCT of 15,603 patients to
answer: A3): Use of DAPT >1 year after MI reduced the composite risk of cardiovascular death, MI, or
stroke (hazard ratio: 0.84; 95% CI: 0.74 to 0.95) but increased major bleeding (hazard ratio: 2.32; 95%
CI: 1.68 to 3.21). A meta-analysis and a post hoc analysis of an RCT in patients with stable
cardiovascular disease produced similar findings.
The primary analysis provides moderately strong evidence that prolonged DAPT after
implantation of newer-generation DES entails a tradeoff between reductions in stent thrombosis and MI
and increases in major hemorrhage. Secondary analyses provide weak evidence of increased mortality
with prolonged DAPT after DES implantation. In patients whose coronary thrombotic risk was defined by
a prior MI rather than by DES implantation, the primary analysis provided moderately strong evidence of
reduced cardiovascular events at the expense of increased bleeding.
Circulation. 2016;133: DOI: 10.1161/CIR.0000000000000405.
A cura di Calogero Calcullo