Comparative Safety and Effectiveness of Direct-Acting Oral Anticoagulants Versus Warfarin: a National Cohort Study of Nursing Home Residents

UMMS Affiliation

Department of Population and Quantitative Health Sciences; Department of Medicine, Division of Cardiovascular Medicine

Publication Date


Document Type



Cardiology | Cardiovascular Diseases | Clinical Epidemiology | Epidemiology | Geriatrics


BACKGROUND: Research comparing direct-acting oral anticoagulants (DOACs) to warfarin has excluded nursing home residents, a vulnerable and high-risk population.

OBJECTIVE: To compare the safety and effectiveness of DOACs versus warfarin.

DESIGN: New-user cohort study (2011-2016).

PATIENTS: US nursing home residents aged > 65 years with non-valvular atrial fibrillation enrolled in fee-for-service Medicare for > 6 months.

EXPOSURES: Initiators of DOACs (2881 apixaban, 1289 dabigatran, 3735 rivaroxaban) were 1:1 propensity matched to warfarin initiators.

MAIN MEASURES: Outcomes included ischemic stroke or transient ischemic attack (i.e., ischemic cerebrovascular event), bleeding (extracranial or intracranial), other vascular events, death, and a composite of all outcomes. Absolute rate differences (RD) and cause-specific hazard ratios (HR) with 95% confidence intervals (CI) were estimated. Subgroup analyses were performed by alignment of DOAC dosing with labeling.

KEY RESULTS: Median age (84 years), CHA2DS2-Vasc (5), and ATRIA risk scores (3) were similar across medications. Clinical outcome rates were similar for dabigatran and rivaroxaban users versus warfarin users. However, ischemic cerebrovascular event rates were higher among dabigatran and rivaroxaban users that received reduced dosages without an indication. Overall, apixaban users had higher ischemic cerebrovascular event rates (HR 1.86; 95% CI 1.00-3.45) and lower bleeding rates (HR 0.66; 95% CI 0.49-0.88), but outcome rates varied by dosing alignment. Mortality rates (per 100 person-years) were lower for apixaban (RDs - 9.30; 95% CI - 13.18 to - 5.42), dabigatran (RDs - 10.79; 95% CI - 14.98 to - 6.60), and rivaroxaban (RDs - 8.92; 95% CI - 12.01 to - 5.83) versus warfarin; composite outcome findings were similar.

CONCLUSIONS: Among US nursing home residents, the DOACs were each associated with lower mortality versus warfarin. Misaligned DOAC dosing was common in nursing homes and was associated with clinical and mortality outcomes. Overall, DOAC users had lower rates of adverse outcomes including mortality compared with warfarin users.


anticoagulants, atrial fibrillation, comparative effectiveness, nursing homes

DOI of Published Version



Alcusky M, Tjia J, McManus DD, Hume AL, Fisher M, Lapane KL. Comparative Safety and Effectiveness of Direct-Acting Oral Anticoagulants Versus Warfarin: a National Cohort Study of Nursing Home Residents. J Gen Intern Med. 2020 Apr 6. doi: 10.1007/s11606-020-05777-3. Epub ahead of print. PMID: 32291717. Link to article on publisher's site

Journal/Book/Conference Title

Journal of general internal medicine

PubMed ID


Related Resources

Link to Article in PubMed