Physicians' Academy for Cardiovascular Education

NOAC safe and effective in NVAF patients taking at least 5 other chronic medications

Influence of Polypharmacy on the Effectiveness and Safety of Rivaroxaban versus Warfarin in Patients with Nonvalvular Atrial Fibrillation

Literature - Martinez BK, Baker WL, Sood NA et al., - Pharmacotherapy. First published: 31 December 2018

Introduction and methods

Comorbidities are common in patients with nonvalvular atrial fibrillation (NVAF)[1]. A consequence of having multiple comorbidities is that patients with NVAF are at higher risk of thromboembolic events [2], and that they need multiple, chronic, non-anticoagulant medication [1, 3-6]. Polypharmacy is associated with a risk of drug-drug interactions [4], thrombotic events and major bleeding [5], and decreased time in therapeutic range (TTR) in patients receiving warfarin [7].

This study aimed to evaluate the comparative effectiveness and safety of rivaroxaban versus warfarin in patients with NVAF managed in routine clinical practice with varying degrees of polypharmacy. To this end, a retrospective claims analysis of United States Truven MarketScan data from November 2012 – March 2017 was performed. Truven MarketScan is a combination of a commercial and a Medicare supplemental database, and covers all age groups and both government and public organizations, which overall represent about 240 million lives.

Patients naïve for oral anticoagulants (OAC) in the 12 months preceding the day of the first qualifying rivaroxaban or warfarin dispensing (index date) were included. Included patients had at least 2 inpatient or outpatient ICD codes for AF (except codes suggesting valvular disease), had polypharmacy with ≥5 unique chronic medications. A secondary analysis was performed in individuals with substantial polypharmacy (≥10 chronic medications). Each eligible rivaroxaban user was propensity-score matched to a warfarin user, separately for the ≥5 and ≥10 polypharmacy analyses. The primary effectiveness outcome was stroke or systemic embolism (SSE) and major bleeding the primary safety outcome.

Main results


These data suggest that rivaroxaban is associated with lower rates of SSE and ischemic stroke and similar rates of bleeding in patients with NVAF who take at least 5 non-OAC chronic medications, as compared with warfarin. No significant difference between treatment groups was seen in patients taking at least 10 chronic medications.


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