• Daniele Pastori, Danilo Menichelli, Francesco Del Sole, Pasquale Pignatelli, Francesco Violi, and ATHERO-AF study group.
• I Clinica Medica, Atherothrombosis Center, Department of Clinical, Internal, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy.
• Mayo Clin. Proc. 2021 Mar 1; 96 (3): 658-665.

ObjectiveTo determine the association between direct oral anticoagulant (DOAC) use and risk of major adverse cardiac events (MACEs) in patients with atrial fibrillation (AF).Patients And MethodsThis study is a single-center prospective observational cohort study including 2366 outpatients with non-valvular AF on treatment with DOACs or vitamin K antagonists (VKAs) from February 2008 for patients on VKA and September 2013 for patients on novel oral anticoagulants. The primary endpoint was the incidence of MACE including fatal and non-fatal myocardial infarction (MI), cardiac revascularization, and cardiovascular death.ResultsThe mean age was 75.1±9.0 years; 44.7% were women. During a mean follow-up of 33.3±21.9 months (6567 patients/years) 133 MACEs occurred (2.03%/year): 79 MI/cardiac revascularization and 54 cardiovascular deaths. Of these, 101 were on VKAs (2.42%/year) and 32 on DOACs (1.34%/year; log-rank test P=.040). This difference was evident also considering MI alone (1.53%/year and 0.63%/year in the VKA and DOAC group, respectively, log-rank test P=.009). At multivariable Cox proportional hazard regression analysis, use of DOACs was associated with a lower risk of MACE (hazard ratio, 0.636; 95% CI, 0.417 to 0.970; P=.036) and MI (hazard ratio, 0.497; 95% CI, 0.276 to 0.896; p=.020). Sensitivity analysis showed that this association was consistent in younger patients (<75 years), in patients with anemia, and in those without chronic obstructive pulmonary disease and heart failure. We also found that both dabigatran and apixaban/rivaroxaban were associated with a lower rate of MACE, with similar efficacy between full and low doses.ConclusionDOACs are associated with a lower risk of MACE in patients with AF independently from dosage.Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

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