Duration of dual antiplatelet therapy and outcome in patients with acute coronary syndrome undergoing percutaneous revascularization: A meta-analysis of 11 randomized trials

BACKGROUND: Acute coronary syndromes (ACS) represent a context of higher thrombotic risk, where larger advantages have been achieved by the administration of dual antiplatelet therapy (DAPT). However, the indication of 1 year DAPT after coronary angioplasty for ACS has been supported by an outdated randomized trial (PCI-CURE). In addition, the initial fear of late thrombotic events emerged with first generation drug-eluting stents (DES), that suggested the need of a prolonged DAPT prescription, has been completely overcome by the recent technological evolution of DES, that have shown faster re-endothelization and lower rates of late thrombotic complications. By keeping in mind the balance between thrombotic and bleeding complications, and due to the paucity of dedicated randomized trials, the identification of the optimal duration of DAPT after ACS is still matter of debate, and is therefore the aim of the present meta-analysis. METHODS: Literature and main scientific session abstracts were searched. The primary efficacy endpoint was mortality, primary safety endpoint was the occurrence of major bleedings. A pre-specified analysis was conducted according to the DAPT strategy allocation (<12 vs standard 12 months duration and 6-12 months vs extended DAPT). RESULTS: We included 3 RCTs and subanalyses from 8 RCTs, with a total of 17,941 patients. No difference in mortality was observed between shorter vs longer DAPT (OR[95%CI] = 1.11[0.90,1.36], p = 0.33; phet = 0.76). A shorter DAPT duration significantly reduced the rate of major bleeding events (1.5%, vs 1.9%, OR [95%CI] = 0.75 [0.60, 0.94], p = 0.01; phet = 0.43). The reduction in bleeding events was more significant in trials evaluating extended DAPT duration (OR[95%CI] = 0.62[0.45, 0.85], p = 0.003; phet = 0.49). No difference in cardiovascular mortality, myocardial infarction and stent thrombosis was observed with shorter vs standard 12-moth DAPT, whereas a more extended treatment (beyond 1 year), was associated with a significant reduction in recurrent ischemic events. Similar results were observed at a sensitivity analysis conducted according to the type of stent, time to randomization or DAPT duration. CONCLUSIONS: Based on the current meta-analysis including 17,941 ACS patients undergoing PCI, a short duration of DAPT may be safely considered, with similar rates of recurrent thrombotic complications as compared to the standard 12 months, and similar mortality. A more extended DAPT administration (beyond 1 year) provides benefits in ischemic events, but with an excess in haemorragic complications, with overall neutral effects on mortality.