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Pharmacotherapy. 2019 Feb;39(2):196-203. doi: 10.1002/phar.2213. Epub 2019 Jan 28.

Influence of Polypharmacy on the Effectiveness and Safety of Rivaroxaban Versus Warfarin in Patients With Nonvalvular Atrial Fibrillation.

Author information

Department of Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs, Connecticut.
Evidence-Based Practice Center, Hartford Hospital, Hartford, Connecticut.
Department of Cardiac Electrophysiology, Southcoast Health System, Fall River, Massachusetts.
New England Health Analytics, LLC, Granby, Connecticut.
Real-World Evidence Generation, Bayer AG, Berlin, Germany.



Patients with nonvalvular atrial fibrillation (NVAF) often have multiple comorbidities requiring concomitant medications in addition to their oral anticoagulant (OAC). The objective of this study was to evaluate the impact of polypharmacy on the effectiveness and safety of rivaroxaban versus warfarin in patients with NVAF managed in routine clinical practice.


Retrospective claims analysis.


United States Truven MarketScan database (November 2012-March 2017).


Adults who were OAC naïve during the 12 months before the day of the first qualifying rivaroxaban or warfarin dispensing (index date); had at least two International Classification of Diseases, Ninth or Tenth Revision diagnosis codes for atrial fibrillation without codes suggesting valvular heart disease; had at least 12 months of continuous insurance coverage prior to the qualifying OAC dispensing; and were experiencing polypharmacy (concomitant prescription claims for five or more unique chronic medication claims) were included. Patients who had concomitant prescription claims for ≥ 10 unique chronic medication claims constituted the substantial polypharmacy cohort used in the secondary analysis. Patients receiving rivaroxaban were propensity-score matched in a 1:1 ratio to patients receiving warfarin (13,981 patients in each polypharmacy OAC group, and 1765 patients in each substantial polypharmacy OAC group).


Patients were followed until occurrence of an event (stroke or systemic embolism [SSE] combined [primary effectiveness outcome] or major bleeding [primary safety outcome]), OAC discontinuation or switch (30-day permissible gap), insurance disenrollment, or end of follow-up period. Rates of SSE, ischemic stroke, and major bleeding were compared by using Cox regression, reported as hazard ratios (HRs) and 95% confidence intervals (CIs). In patients with NVAF taking five or more chronic medications, rivaroxaban was associated with a 34% (95% CI 12-50) and 40% (95% CI 16-57) hazard reduction of SSE and ischemic stroke, respectively. Occurrence of major bleeding was similar between OAC cohorts (HR 1.08, 95% CI 0.92-1.28). A secondary analysis in patients with NVAF with substantial polypharmacy (taking ≥ 10 chronic medications) was also performed. Similar trends in SSE (HR 0.44), ischemic stroke alone (HR 0.62), and major bleeding (HR 1.07) were observed in patients with NVAF who had substantial polypharmacy, although 95% CIs crossed 1.0 for each outcome in this smaller study cohort.


This real-world study suggests that in the setting of polypharmacy and NVAF, rivaroxaban is an effective and safe alternative to warfarin.


anticoagulants; atrial fibrillation; polypharmacy; rivaroxaban; warfarin

[Indexed for MEDLINE]

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