Antithrombotic therapy in patients with atrial fibrillation after percutaneous coronary intervention: a systematic review and individual patient data network meta-analysis

Background Atrial fibrillation (AFib) and coronary artery disease frequently coexist: around 10% of patients with AFib require percutaneous coronary intervention (PCI). Although randomized trials demonstrated direct oral anticoagulants (DOAC) and a P2Y12 inhibitor are the best antithrombotic combination in this setting, important gaps in knowledge remain, limiting certainty and generalizability of these findings. Purpose To conduct a patient-level meta-analysis of randomized trials evaluating antithrombotic strategies in patients with AFib undergoing PCI: 6 trials (10,634 patients) comparing 1.DOAC plus P2Y12 inhibitor (4,083), 2.vitamin K antagonist (VKA) plus single antiplatelet therapy (SAPT, 1,247), 3.VKA plus dual antiplatelet therapy (DAPT, 3,715), and 4.DOAC plus DAPT (1,589) were included (Figure 1). Methods The primary efficacy outcome was the composite of cardiovascular death, myocardial infarction, and stroke. The primary safety outcome was TIMI major or minor bleeding. Results At 1-year follow-up no differences were found in the risk of the primary efficacy outcome among the strategies. DOAC plus P2Y12 inhibitor reduced the risk of the primary safety outcome compared with VKA plus DAPT (HR, 0.59, 95%CI, 0.50 – 0.70) or DOAC plus DAPT (HR 0.73, 95%CI 0.57 – 0.95), while the risk was similar compared to VKA plus SAPT. Consistent findings were observed using BARC and ISTH bleeding definitions. The risk of intracranial bleeding was reduced with DOAC plus P2Y12 inhibitor compared with VKA plus DAPT. The risk of stent thrombosis did not differ among the antithrombotic strategies (Figure 2). Subgroup analyses showed consistent findings, except for enhanced reduction of bleeding in patients younger than 65 years old with DOAC plus P2Y12 (pinteraction: 0.042). When assessing the impact of aspirin cessation timing on the risk of MI and definite or probable ST, no significant interaction between randomized antithrombotic strategy and timing of aspirin cessation was observed (pinteraction MI = 0.59, definite or probable ST =0.084). Consistently, when the duration of aspirin therapy was analyzed as a continuous variable, the risk of MI (HR 1.00, 95% CI 0.99-1.01) and definite or probable ST (HR 1.00, 95% CI 0.98-1.02) was not affected in patients randomized to DOAC or VKA plus P2Y12 inhibitor, while the risk of definite or probable ST was marginally reduced for each additional day of aspirin therapy in patients randomized to triple antithrombotic therapy (HR 0.99, 95% CI 0.98-1.00). Conclusion In patients with AFib undergoing PCI, the risk of cardiovascular death, myocardial infarction, and stroke was similar regardless of whether patients received DOAC or VKA, or SAPT versus DAPT. Omission of a second antiplatelet agent reduced the risk of bleeding across all severity grades, including intracranial haemorrhage. These findings were consistent across subgroups assessed and independent of the duration of aspirin therapy.Figure 1Figure 2