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

Abstract

Aims: Recent trials have examined the effect of prolonged dual antiplatelet therapy (DAPT) in a variety of patient populations, with heterogeneous results regarding benefit and safety, specifically with regard to cardiovascular and non-cardiovascular mortality. We performed a meta-analysis of randomized trials comparing more than a year of DAPT with aspirin alone in high-risk patients with a history of prior myocardial infarction (MI).

Methods and results: A total of 33 435 patients were followed over a mean 31 months among one trial of patients with prior MI (63.3% of total) and five trials with a subgroup of patients that presented with, or had a history of, a prior MI (36.7% of total). Extended DAPT decreased the risk of major adverse cardiovascular events compared with aspirin alone (6.4 vs. 7.5%; risk ratio, RR 0.78, 95% confidence intervals, CI, 0.67-0.90; P = 0.001) and reduced cardiovascular death (2.3 vs. 2.6%; RR 0.85, 95% CI 0.74-0.98; P = 0.03), with no increase in non-cardiovascular death (RR 1.03, 95% CI 0.86-1.23; P = 0.76). The resultant effect on all-cause mortality was an RR of 0.92 (95% CI 0.83-1.03; P = 0.13). Extended DAPT also reduced MI (RR 0.70, 95% CI 0.55-0.88; P = 0.003), stroke (RR 0.81, 95% CI 0.68-0.97; P = 0.02), and stent thrombosis (RR 0.50, 95% CI 0.28-0.89; P = 0.02). There was an increased risk of major bleeding (1.85 vs. 1.09%; RR 1.73, 95% CI 1.19-2.50; P = 0.004) but not fatal bleeding (0.14 vs. 0.17%; RR 0.91, 95% CI 0.53-1.58; P = 0.75).

Conclusion: Compared with aspirin alone, DAPT beyond 1 year among stabilized high-risk patients with prior MI decreases ischaemic events, including significant reductions in the individual endpoints of cardiovascular death, recurrent MI, and stroke. Dual antiplatelet therapy beyond 1 year increases major bleeding, but not fatal bleeding or non-cardiovascular death.

Keywords: Clopidogrel; Dual antiplatelet therapy; Myocardial infarction; Prasugrel; Stable coronary heart disease; Ticagrelor.