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Am J Med. 2019 May;132(5):596-604.e11. doi: 10.1016/j.amjmed.2018.12.023. Epub 2019 Jan 9.

Comparative Stroke, Bleeding, and Mortality Risks in Older Medicare Patients Treated with Oral Anticoagulants for Nonvalvular Atrial Fibrillation.

Author information

1
Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research. Electronic address: david.graham1@fda.hhs.gov.
2
Office of Biostatistics, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Md.
3
Acumen LLC, Burlingame, Calif.
4
Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research.
5
Office of New Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Md.
6
Acumen LLC, Burlingame, Calif; Department of Economics, Stanford University, Stanford, Calif.
7
Centers for Medicare & Medicaid Services, Washington, DC.

Abstract

BACKGROUND:

Nonvitamin K antagonist oral anticoagulants (NOACs) are alternatives to warfarin in patients with nonvalvular atrial fibrillation. Randomized trials compared NOACs with warfarin, but none have compared individual NOACs against each other for safety and effectiveness.

METHODS:

We performed a retrospective new-user cohort study of patients with nonvalvular atrial fibrillation enrolled in US Medicare who initiated warfarin (n = 183,318), or a standard dose of dabigatran (150 mg twice daily; n = 86,198), rivaroxaban (20 mg once daily; n = 106,389), or apixaban (5 mg twice daily; n = 73,039) between October 2010 and September 2015. Propensity score-adjusted Cox proportional hazards regression was used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the outcomes of thromboembolic stroke, intracranial hemorrhage, major extracranial bleeding, and all-cause mortality, comparing each NOAC with warfarin, and with each other NOAC.

RESULTS:

Compared with warfarin, each NOAC was associated with reduced risks of thromboembolic stroke (20%-29% reduction; P = .002 [dabigatran], P < 0.001 [rivaroxaban, apixaban]), intracranial hemorrhage (35%-62% reduction; P < 0.001 [each NOAC]), and mortality (19%-34% reduction; P < .001 [each NOAC]). The NOACs were similar for thromboembolic stroke but rivaroxaban was associated with increased risks of intracranial hemorrhage (vs dabigatran: HR = 1.71; 95% CI, 1.35-2.17), major extracranial bleeding (vs dabigatran: HR = 1.32; 95% CI, 1.21-1.45; vs apixaban: HR = 2.70; 95% CI, 2.38-3.05), and death (vs dabigatran: HR = 1.12; 95% CI, 1.01-1.24; vs apixaban: HR = 1.23; 95% CI, 1.09-1.38). Dabigatran was associated with reduced risk of intracranial hemorrhage (HR = 0.70; 95% CI ,0.53-0.94) and increased risk of major extracranial bleeding (HR = 2.04; 95% CI, 1.78-2.32) compared with apixaban.

CONCLUSIONS:

Among patients treated with standard-dose NOAC for nonvalvular atrial fibrillation and warfarin users with similar baseline characteristics, dabigatran, rivaroxaban, and apixaban were associated with a more favorable benefit-harm profile than warfarin. Among NOAC users, dabigatran and apixaban were associated with a more favorable benefit-harm profile than rivaroxaban.

KEYWORDS:

Anticoagulants; Apixaban; Atrial fibrillation; Comparative effectiveness; Comparative safety; Dabigatran; Rivaroxaban; Warfarin

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