Optimal duration of dual antiplatelet therapy after percutaneous coronary intervention with drug eluting stents: meta-analysis of randomised controlled trials

ObjeCtive To assess the benefits and risks of short term (<12 months) or extended (>12 months) dual antiplatelet therapy (DAPT) versus standard 12 month therapy, following percutaneous coronary intervention with drug eluting stents. Design Meta-analysis of randomised controlled trials. Data sOurCes PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, Scopus, Web of Science, Cochrane Library, and major congress proceedings, searched from 1 January 2002 to 16 February 2015. review methODs Trials comparing short term (<12 months) or extended (>12 months) DAPT regimens with standard 12 month duration of therapy. Primary outcomes were cardiovascular mortality, myocardial infarction, stent thrombosis, major bleeding, and all cause mortality. results 10 randomised controlled trials (n=32 287) were included. Compared to 12 month DAPT, a short term course of therapy was associated with a significant reduction in major bleeding (odds ratio 0.58 (95% confidence interval 0.36 to 0.92); P=0.02) with no significant differences in ischaemic or thrombotic outcomes. Extended versus 12 month DAPT yielded a significant reduction in the odds of myocardial infarction (0.53 (0.42 to 0.66); P<0.001) and stent thrombosis (0.33 (0.21 to 0.51); P<0.001), but more major bleeding (1.62 (1.26 to 2.09); P<0.001). All cause but not cardiovascular death was also significantly increased (1.30 (1.02 to 1.66); P=0.03). COnClusiOns Compared with a standard 12 month duration, short term DAPT (<12 months) after drug eluting stent implementation yields reduced bleeding with no apparent increase in ischaemic complications, and could be considered for most patients. In selected patients with low bleeding risk and very high ischaemic risk, extended DAPT (>12 months) could be considered. The increase in all cause but not cardiovascular death with extended DAPT requires further investigation. Introduction Drug eluting stents have consistently improved the safety and efficacy of percutaneous coronary intervention as compared with bare metal stents.1-4 While drug eluting stents have reduced in-stent restenosis, uncertainty has arisen regarding the risk of associated late and very late stent thrombosis. Dual antiplatelet therapy consisting of aspirin plus a P2Y12 receptor antagonist is recommended after drug eluting stent implantation for at least 12 months by the American College of Cardiology/American Heart Association and for six to 12 months by European guidelines,5 6 followed by aspirin monotherapy. Current recommendations, however, are based largely on observational data with few randomised controlled trials. The most recent trials and meta-analyses have suggested comparable efficacy of short term dual antiplatelet therapy versus therapy of at least 12 months, especially with newer generation drug eluting stents,7-9 but these studies are underpowered to draw definitive conclusions. On the other hand, very late stent thrombosis still occurs with drug eluting stents, especially after first generation devices, raising the question of whether prolongation of dual antiplatelet therapy offers clinical benefit. One randomised controlled trial recently showed a significant reduction of stent thrombosis with dual antiplatelet therapy extended beyond 12 months at the price of increased bleeding.10 Thus, the optimal duration of dual antiplatelet therapy is debated, with short term and extended protocols not yet compared to standard 12 month treatment within the same trial. We aimed to perform a meta-analysis of randomised controlled trials to compare the efficacy and safety of short term and extended dual antiplatelet therapy with standard 12 month therapy. Methods Data sources and search strategy Established methods were used in compliance with the Preferred Reporting Items for Systematic reviews and WhAT IS AlReAdy knoWn on ThIS TopIC Dual antiplatelet therapy is currently recommended after the implantation of drug eluting stents, but the optimal duration is a matter of debate The currently recommended 12 month duration is of uncertain value WhAT ThIS STudy AddS Compared with a 12 month duration, short term (<12 months) dual antiplatelet therapy yields reduced bleeding without increasing ischaemic complications Dual antiplatelet therapy extended beyond 12 months reduces ischaemic and thrombotic events compared with a 12 month regimen, but at the price of greater risk of major bleeding and all cause death The increase in all cause but not cardiovascular death seen with extended therapy requires further investigation