Three, six, or twelve months of dual antiplatelet therapy after DES implantation in patients with or without acute coronary syndromes: an individual patient data pairwise and network meta-analysis of six randomized trials and 11 473 patients.

Abstract

We sought to determine whether the optimal dual antiplatelet therapy (DAPT) duration after drug-eluting stent (DES) placement varies according to clinical presentation. We performed an individual patient data pairwise and network meta-analysis comparing short-term (≤6-months) versus long-term (1-year) DAPT as well as 3-month vs. 6-month vs 1-year DAPT. The primary study outcome was the 1-year composite risk of myocardial infarction (MI) or definite/probable stent thrombosis (ST). Six trials were included in which DAPT after DES consisted of aspirin and clopidogrel. Among 11 473 randomized patients 6714 (58.5%) had stable CAD and 4758 (41.5%) presented with acute coronary syndrome (ACS), the majority of whom (67.0%) had unstable angina. In ACS patients, ≤6-month DAPT was associated with non-significantly higher 1-year rates of MI or ST compared with 1-year DAPT (Hazard Ratio (HR) 1.48, 95% Confidence interval (CI) 0.98-2.22; P = 0.059), whereas in stable patients rates of MI and ST were similar between the two DAPT strategies (HR 0.93, 95%CI 0.65-1.35; P = 0.71; Pinteraction = 0.09). By network meta-analysis, 3-month DAPT, but not 6-month DAPT, was associated with higher rates of MI or ST in ACS, whereas no significant differences were apparent in stable patients. Short DAPT was associated with lower rates of major bleeding compared with 1-year DAPT, irrespective of clinical presentation. All-cause mortality was not significantly different with short vs. long DAPT in both patients with stable CAD and ACS. Optimal DAPT duration after DES differs according to clinical presentation. In the present meta-analysis, despite the fact that most enrolled ACS patients were relatively low risk, 3-month DAPT was associated with increased ischaemic risk, whereas 3-month DAPT appeared safe in stable CAD. Prolonged DAPT increases bleeding regardless of clinical presentation. Further study is required to identify the optimal duration of DAPT after DES in individual patients based on their relative ischaemic and bleeding risks.