Extended Duration Dual Antiplatelet Therapy in Patients with Myocardial Infarction: a study-level meta-analysis of controlled randomized trials

Abstract Background Whether dual antiplatelet therapy (DAPT) is beneficial beyond one year after myocardial infarction (MI) is not demonstrated; in particular, available studies may be individually underpowered for end-points at low incidence, i.e. major and fatal bleeding or mortality. We thus assessed the effectiveness and safety of prolonged DAPT after MI over the long-term. Methods We conducted a systematic search to identify randomized trials on the topic; three studies and 21,534 post-MI patients receiving placebo or aspirin plus P2Y12 inhibition for ≥2 years were included. Incidence of the following outcome measures was evaluated: major adverse cardiac events (MACE), major bleeding, fatal bleeding, cardiovascular and non-cardiovascular death. Results Occurrence of MACE was lower in patients treated with prolonged DAPT: 6.3% vs 7.9% in those without prolonged DAPT (OR 0.74, 95% CI 0.60-0.91, P=0.005); in the former there was also a significant 16% reduction in cardiovascular mortality. Increase in major bleeding with extended duration DAPT was not significant in the overall analysis (1.5% vs 1.0%; P=0.10), but became significant in the analysis restricted to patients receiving ticagrelor or prasugrel as second antiplatelet agent (OR 2.16, 95% CI 1.63-2.86); prolonged use of DAPT did not raise rates of fatal bleeding or non-cardiovascular mortality. Conclusion Prolonged DAPT after MI reduces MACE and cardiovascular mortality over the long-term; this was paralleled by higher risk of non-fatal major bleeding mainly with the newer, more potent P2Y12 antagonists. Tailoring duration of DAPT after MI on the comparative evaluation of both ischemic and bleeding risk is mandatory in this setting.