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  • Dual Versus Triple Antithrombotic Therapy for Atrial Fibrillation-ACS/PCI: One Size Does Not Fit All

    Atrial fibrillation (AF) occurs in 10–15 % of patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI)  . The theoretical need for the use of both oral anticoagulants (OAC) and dual antiplatelet therapy (DAPT) to reduce thrombotic complications in these patients poses a therapeutic dilemma, because such triple antithrombotic therapy (TAT) regimen is associated with a significant increase in bleeding  . These findings underscore the need to identify antithrombotic treatment regimens associated with reduced bleeding without compromising efficacy. In 2013, the What is the Optimal antiplatElet & Anticoagulant Therapy in Patients With Oral Anticoagulation and Coronary StenTing (WOEST) trial was the first to assess the impact of withdrawing aspirin among patients undergoing PCI concomitantly treated with an OAC. In particular, patients were randomized to either dual antithrombotic therapy (DAT) with OAC and a single antiplatelet agent (i.e., clopidogrel) or TAT with DAPT and an OAC  . Despite some limitations, such as the use of vitamin K antagonists (VKA) and use of TAT up to 12 months, this study paved the way for the design of further randomized controlled trials (RCTs) using non-VKA oral anticoagulants (NOACs) among AF patients with ACS or undergoing PCI  . Four pivotal RCTs have been conducted with the commercially available NOACs (dabigatran, rivaroxaban, apixaban and edoxaban), comparing a strategy of DAT with a P2Y 12 inhibitor (mostly clopidogrel) plus a NOAC versus TAT with aspirin and a P2Y 12 inhibitor plus VKA (average duration of 4.7 months)  . The DAT approach, in which the use of aspirin was limited to the peri-PCI period, lasting on average 1–2 days in 3 of the RCTs and 7 days in another, consistently showed a reduction in bleeding  . After the publication of these studies, both North American and European guidelines recommend that the default use of TAT should be limited up to 1 week for the majority of patients and prolonged up to 1 month in patients at high thrombotic risk if not at increased risk of bleeding  . However, none of the four RCTs were powered for major adverse cardiac events (MACE) or any of its individual components. These considerations have raised concerns on whether the above-mentioned recommendations are sufficiently evidenced-based to support the non-inferior efficacy of a DAT regimen. To this extent, meta-analyses are useful to increase the statistical power of less frequently occurring endpoints, particularly if the sample size of a given trial is limited.

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