Effectiveness, Safety, and Major Adverse Limb Events in Atrial Fibrillation Patients with Concomitant Diabetes Mellitus Treated with Non-Vitamin K Antagonist Oral Anticoagulants

Abstract Background: Evidence of adverse clinical outcomes for non-vitamin K antagonist oral anticoagulant (NOACs) and warfarin in patients with atrial fibrillation (AF) and diabetes mellitus are limited. We investigated the effectiveness, safety, and major adverse limb events for NOACs versus warfarin among diabetic AF patients. Methods: In this nationwide retrospective cohort study collected from Taiwan National Health Insurance Research Database, we identified a total of 20,967 and 5,812 consecutive AF patients with diabetes taking NOACs and warfarin from June 1, 2012, to December 31, 2017, respectively. We used propensity-score stabilized weighting to balance covariates across study groups. Results: NOAC was associated with a lower risk of major adverse cardiovascular events (MACE) (adjusted hazard ratio (aHR):0.88; [95% confidential interval (CI):0.78-0.99]; P =0.0283), major adverse limb events (aHR:0.72;[95%CI:0.57-0.92]; P =0.0083), and major bleeding (aHR:0.67;[95%CI:0.59-0.76]; P <.0001) compared to warfarin. NOACs decreased MACE in patients of 75 but not in those aged <75 years ( P interaction=0.01), and in patients with ischemic heart disease (IHD) compared to those without IHD ( P interaction<0.01). For major adverse limb events, the advantage of risk reduction for NOAC over warfarin persisted in high risk subgroups including age 75 years, chronic kidney disease, IHD, peripheral artery disease, or use of concomitant antiplatelet drugs. Conclusion: NOACs were associated with a lower risk of effectiveness, safety, and major adverse limb events than warfarin among diabetic AF patients. Thromboprophylaxis with NOACs should be considered in the diabetic AF population with a high atherosclerotic burden.