Optimal Duration of Dual Antiplatelet Therapy after Drug-Eluting Stents: Meta-Analysis of Randomized Trials

Introduction: The optimal duration of dual antiplatelet therapy (DAPT) after drug-eluting stent implantation (DES) is not certain. The AHA/ACC guidelines recommend 12 months of DAPT based on observational trials. Recently, several large randomized controlled trials (RCT) suggested a noninferiority of shorter duration of DAPT and other trials showed a benefit from extended duration of DAPT after 12 months of DES implantation. Methods: PubMed databases were searched for RCTs comparing the continued use of DAPT to shorter duration of DAPT (aspirin alone) for variable durations beyond 3 months of DES implantation. Our analysis was limited to trials with clinical outcomes. Odds ratio (OR) and 95% confidence intervals (CI) were calculated using fixed and random-effects models. Subgroup analyses were performed for second generation DES and for trials comparing 12 months of DAPT vs. earlier interruption or longer duration of DAPT. Results: We identified 10 RCTs including 32,136 subjects randomized to continued use of DAPT vs. aspirin alone for variable durations after 3 months of DES implantation. There was no significant heterogeneity among studies (Q test P > 0.1). Compared to shorter DAPT, longer DAPT resulted in a significant reduction in stent thrombosis (0.3% vs. 0.7%, P < 0.01) and myocardial infarction (1.3% vs. 2%, P < 0.01), and a significant increase in major bleeding (0.8% vs. 0.4%, P < 0.01). There was no difference in cardiac deaths or stroke. All-cause deaths were slightly lower with shorter DAPT compared to longer DAPT (OR 0.8, 95% CI 0.7 to 0.99, P = 0.04). A small number of subjects were included between 3 and 6 months after DES implantation. Conclusion: DAPT continued beyond 6 months after second generation DES implantation decreases stent thrombosis and myocardial infarction, but increases major bleeding and all-causes mortality compared to shorter DAPT (aspirin alone). There was no difference in cardiac mortality or stroke.