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

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.