Dual Therapy Versus Triple Therapy Major Bleeding Outcomes in Patients With Atrial Fibrillation Who Developed Indications for Percutaneous Coronary Intervention: A Meta-Analysis

Introduction: Patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) poses a therapeutic dilemma for the attending physician. Standard anticoagulation with a vitamin K antagonist (VKA) plus dual antiplatelet therapy with a P2Y12 inhibitor and aspirin reduces the risk of stroke and thrombosis, but increases risk of bleeding. The effectiveness and safety of several novel oral anticoagulants are still unclear in these patients. Methods: PubMed, Cochrane and Embase databases were systematically searched for studies from 2016 until 30 November 2023. The search key terms were ‘DOACs,’ ‘atrial fibrillation,’ ‘percutaneous coronary intervention’ and ‘bleeding.’ Two independent reviewers appraised eligible studies using well-defined criteria. The main outcomes of interest were International Society on Thrombosis and Haemostasis (ISTH) major bleeding, stent thrombosis and major adverse cardiovascular events (MACE). The random-effects model was used to derive pooled estimates. Results: The search yielded four studies which were all randomized controlled trials (RCTs). There were a total of 10,963 participants. Pooled estimates showed a statistically significant difference between direct oral anticoagulants (DOAC) + P2Y12 and VKA + DAPT for ISTH major bleeding (OR 0.62, 95% CI 0.57 – 0.69, p = <0.00001). There was no statistically significant difference between DOACs + P2Y12 and VKA + DAPT for stent thrombosis (RR 1.17, 95% CI 0.79 – 1.72, p = 0.43) and MACE (RR 1.00, 95% CI 0.87 – 1.13, p = 0.07). Discussion: In patients with AF who had undergone PCI, the risk of bleeding was lower among those who received dual therapy with DOAC + P2Y12 than among those who received triple therapy with warfarin, a P2Y12 inhibitor and aspirin. However, dual therapy was noninferior to triple therapy with respect to the risk of stent thrombosis and MACE. Keywords: Dual oral anticoagulation; atrial fibrillation; percutaneous coronary intervention; major bleeding; stent thrombosis; major adverse cardiovascular events