Duration of dual antiplatelet therapy after drug-eluting stent implantation: meta-analysis of randomized controlled trials.

Abstract

PURPOSE: Patients are recommended for 6-12 months' dual antiplatelet therapy (DAPT) after drug-eluting stents (DES) implantation. The optimal duration of DAPT which could make the most of clinical benefits while diminishing related risks has always been debated. Previous meta-analyses comparing short-term (<12 months) and extended durations (>12 months) of DAPT showed no significant benefit for longer duration treatment but a significant increase in the risk of bleeding. With the latest evidence, the optimal duration of DAPT needs to be re-examined to guide clinical practice. We performed a meta-analysis of randomized controlled trials to assess the risks and benefits of diverse DAPT durations after DES implantation. METHODS: We performed literature search using MEDLINE, Scopus, EMBASE, ISI Web of Science, Cochrane Library, ClinicalTrials.gov and recent conference proceedings, and included those trials randomizing patients to receive different durations of DAPT after DES implantation and reporting frequency of cardiovascular and bleeding events. Statistical analysis was performed using RevMan 5.3.4. Heterogeneity was calculated using I2 statistics; bias in the selection or publication of studies was assessed. RESULTS: Eleven randomized controlled trials with 33520 patients were included for analysis with 4 trials comparing extended DAPT vs. 12 months' regimen and 7 trials comparing short-term DAPT vs. 12 months' regimen. Compared to 12 months' DAPT treatment, extended DAPT significantly reduced the frequency of myocardial infarctions (OR 0.54 95%CI: 0.43-0.66; p<0.00001) and stent thrombosis (OR 0.36 95%CI: 0.24-0.55; p<0.00001), but the risks of major bleeding (OR 1.54 95%CI 1.22-1.96) and all-cause mortality (OR 1.43 95%CI 1.14-1.81) were substantially increased. There was no significant difference in preventing stroke, cardiac mortality and repeat revascularization. Compared to short-term DAPT, 12-month DAPT was associated with increased major bleeds (OR 1.98 95%CI: 1.26-3.11). However, no significant difference was found in the risk of other primary outcomes. CONCLUSION: 12-month DAPT appears to be a reasonable compromise between preventing stent thrombosis and increasing bleeding risk. Our meta-analysis included both the largest DAPT trial and the most recent OPTIDUAL trial yielded new conclusions. Extending DAPT beyond 12 month shows benefits in reducing myocardial infarction and stent thrombosis, but with a concurrent increase in major bleeding and all-cause, although not cardiovascular, mortality. Discontinuation of DAPT before 12 months decreases the number of major bleeds with no apparent difference in other primary endpoints. In practice, this means that patients vulnerable to bleeding can have a short duration of DAPT but for those who are not at risk of bleeding, extended DAPT beyond 12 months can be considered.