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Non-valvular atrial fibrillation (NVAF) is often accompanied by multiple comorbid conditions, which increase the associated risks and complexity of patient management. This study evaluated the risk of stroke/systemic embolism (SE) and major bleeding (MB) among multimorbid patients with NVAF who were prescribed non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin.


A retrospective study of patients with NVAF and high multimorbidity who initiated apixaban, dabigatran, rivaroxaban, or warfarin from 1 January 2013 to 30 September 2015 was conducted using five insurance claims databases. Multimorbidity was defined as six or more comorbid conditions, and 1:1 propensity score matching (PSM) was conducted between the NOAC-warfarin and NOAC-NOAC cohorts. Cox proportional hazard models were used to evaluate the hazard ratios of stroke/SE and MB.


Of the NVAF population (n = 466,991), 33.4% (n = 155,959) had multimorbidity, including 36,921 apixaban, 10,248 dabigatran, 45,509 rivaroxaban, and 63,281 warfarin patients. Compared to warfarin, apixaban and rivaroxaban were associated with a lower risk of stroke/SE (hazard ratio [HR] 0.63, 95% CI 0.54–0.74; HR 0.70, 95% CI 0.64–0.77, respectively). Apixaban and dabigatran were associated with a lower risk of MB (HR 0.61, 95% CI 0.56–0.67; HR 0.75, 95% CI 0.66–0.86, respectively) and rivaroxaban was associated with a higher risk of MB (HR 1.06, 95% CI 1.01–1.12) compared to warfarin.


Among patients with NVAF and six or more comorbid conditions, NOACs were associated with varying risk of stroke/SE and MB compared to warfarin and to each other. Rather than a “one drug fits all” approach, our results may be useful for appropriate OAC treatment for multimorbid patients.


Deitelzweig, S., Keshishian, A., Kang, A. et al. Use of Non-Vitamin K Antagonist Oral Anticoagulants Among Patients with Nonvalvular Atrial Fibrillation and Multimorbidity. Adv Ther (2021).

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