Research Article: Effectiveness and safety of oral anticoagulants in older adults with non-valvular atrial fibrillation and heart failure

Date Published: March 25, 2019

Publisher: Public Library of Science

Author(s): Alpesh Amin, Alessandra B. Garcia Reeves, Xiaoyan Li, Amol Dhamane, Xuemei Luo, Manuela Di Fusco, Anagha Nadkarni, Keith Friend, Lisa Rosenblatt, Jack Mardekian, Xianying Pan, Huseyin Yuce, Allison Keshishian, Pasquale Abete.


Direct oral anticoagulants (DOACs) are at least as efficacious and safe as warfarin among non-valvular atrial fibrillation (NVAF) patients; limited evidence is available regarding NVAF patients with heart failure (HF). US Medicare enrollees with NVAF and HF initiating DOACs (apixaban, rivaroxaban, dabigatran) or warfarin were selected. Propensity score matching and Cox models were used to estimate the risk of stroke/systemic embolism (SE), major bleeding (MB), and major adverse cardiac events (MACE) comparing DOACs versus warfarin and DOACs versus DOACs. We identified 10,570 apixaban-warfarin, 4,297 dabigatran-warfarin, 15,712 rivaroxaban-warfarin, 4,263 apixaban-dabigatran, 10,477 apixaban-rivaroxaban, and 4,297 dabigatran-rivaroxaban matched pairs. Compared to warfarin, apixaban had lower rates of stroke/SE (hazard ratio = 0.64, 95% confidence interval = 0.48–0.85), MB (hazard ratio = 0.66, 0.58–0.76), and MACE (hazard ratio = 0.73,0.67–0.79); dabigatran and rivaroxaban had lower rates of MACE (hazard ratio = 0.87,0.77–0.99; hazard ratio = 0.84, 0.79–0.89, respectively). Rivaroxaban had a lower stroke/SE rate (hazard ratio = 0.65, 0.52–0.81) and higher MB rate (hazard ratio = 1.18, 1.08–1.30) versus warfarin. Compared to dabigatran and rivaroxaban, apixaban had lower MB (hazard ratio = 0.71, 0.57–0.89; hazard ratio = 0.55, 0.49–0.63) and MACE rates (hazard ratio = 0.80, 0.69–0.93; hazard ratio = 0.86, 0.79–0.94), respectively. All DOACs had lower MACE rates versus warfarin; differences were observed in stroke/SE and MB. Our findings provide insights about OAC therapy among NVAF patients with HF.

Partial Text

Atrial fibrillation (AF), the most common cardiac dysrhythmia in the United States, increases the risk of stroke 5-fold and is associated with 15–20% of all strokes [1], ultimately leading to a higher risk of functional or neurological deficits and a higher mortality rate [2,3]. Non-valvular AF (NVAF) and heart failure (HF) are some of the most common cardiac conditions, and they often coexist [4]. The prevalence of HF among NVAF patients ranges from 27–64% in randomized control trials [5–8] and 21–48% in real-world studies [9–11]. Both conditions affect the elderly and share many of the same risk factors, which synergistically increase the risk of stroke/systemic embolism (SE) [12–14].

This was a retrospective observational analysis using US fee-for-service Medicare data from the Center for Medicare and Medicaid Services, from January 01, 2012 through September 30, 2015. Medicare provides health insurance coverage for >38 million people aged ≥65 years as well as for those with end-stage kidney disease or a disability. Medicare data captures comprehensive demographic and clinical information using enrollment records as well as International Classification of Diseases, 9th Revision, Clinical Modification, Healthcare Common Procedure Coding System codes, and National Drug Codes. This observational study was conducted under the provisions of Privacy Rule 45 CFR 164.514(e). The study was exempt from institutional review board review and approval because there was no collection or use of personally identifiable information in the conduct of this study [22].

A total of 63,206 NVAF patients with HF meeting eligibility criteria were identified, of which 10,615 (16.8%) were prescribed apixaban, 4,297 (6.8%) were prescribed dabigatran, 15,921 (25.2%) were prescribed rivaroxaban, and 32,373 (51.2%) were prescribed warfarin (S1 Fig).

To the best of our knowledge, this real-world observational study is the largest Medicare study of NVAF patients diagnosed with HF, which evaluated the use of DOACs versus warfarin and DOACs versus DOACs. All DOACs were associated with a lower rate of MACE, driven by all-cause mortality. Differences were observed across DOACs versus warfarin in stroke/SE and MB events. Apixaban and rivaroxaban were both associated with a lower rate of stroke/SE, while apixaban use had a lower rate of MB, and rivaroxaban use had a higher rate of MB, compared to warfarin. Additionally, apixaban had lower rates of MB and MACE, compared to both dabigatran and rivaroxaban. The trends were relatively consistent when the patients were separated by standard- and lower-dose.

When compared to warfarin, apixaban use was associated with a lower rate of stroke/SE, MB, and MACE; dabigatran was associated with a lower rate of MACE; and rivaroxaban was associated with a lower rate of stroke/SE, and MACE and a higher rate of MB in this large Medicare population of NVAF patients diagnosed with HF. In addition, our DOACs versus DOACs analysis showed that apixaban was associated with lower rates of MB and MACE compared to dabigatran and rivaroxaban. Lastly, dabigatran use showed higher rates of stroke/SE, but lower rates of MB compared to rivaroxaban. Findings from this observational analysis provide important insights regarding the use of OAC therapy among patients with comorbid NVAF and HF in a real-world setting.




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