Duration of dual antiplatelet therapy and stability of coronary heart disease: a 60 000-patient meta-analysis of randomised controlled trials

Abstract

Background Dual antiplatelet therapy (DAPT) has important implications for clinical outcomes in coronary disease. However, the optimal DAPT duration remains uncertain.Methods and results We searched four major databases for randomised controlled trials comparing long-term (≥12 months) with short-term (≤6 months) or shorter (≤3 months) DAPT in patients with coronary syndromes. The primary outcome was all-cause mortality. Secondary outcomes were any bleeding and major bleeding (safety), cardiac death, myocardial infarction, stent thrombosis, revascularisation and stroke (efficacy). Nineteen randomised controlled trials (n=60 111) satisfied inclusion criteria, 8 assessed ≤3 months DAPT. Compared with long-term (≥12 months), short-term DAPT (≤6 months) was associated with a trend towards reduced all-cause mortality (RR: 0.90, 95% CI: 0.80 to 1.01) and significant bleeding reduction (RR: 0.68, 95% CI: 0.55 to 0.83 and RR: 0.66, 95% CI: 0.56 to 0.77 for major and any bleeding, respectively). There were no significant differences in efficacy outcomes. These associations persisted in sensitivity analysis comparing shorter duration DAPT (≤3 months) to long-term DAPT (≥12 months) for all-cause mortality (RR: 0.91, 95% CI: 0.79 to 1.05). In subgroup analysis, short-term DAPT was associated with lower risk of bleeding in patients with acute or chronic coronary syndromes (RR: 0.66, 95% CI: 0.54 to 0.81 and RR: 0.53, 95% CI: 0.33 to 0.65, respectively), but higher risk of stent thrombosis in acute coronary syndrome (RR: 1.49, 95% CI: 1.02 to 2.17 vs RR: 1.25, 95% CI 0.44 to 3.58).Conclusion Our meta-analysis suggests that short (≤6 months) and shorter (≤3 months) durations DAPT are associated with lower risk of bleeding, equivalent efficacy and a trend towards lower all-cause mortality irrespective of coronary artery disease stability.