Polypharmacy and the Efficacy and Safety of Rivaroxaban Versus Warfarin in the Prevention of Stroke in Patients With Nonvalvular Atrial Fibrillation.

Journal Article (Journal Article;Multicenter Study)

BACKGROUND: Patients with atrial fibrillation (AF) often take multiple medications. METHODS AND RESULTS: We examined characteristics and compared adjusted outcomes between rivaroxaban and warfarin according to number of concomitant baseline medications and the presence of combined cytochrome P450 3A4 and P-glycoprotein inhibitors in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study. At baseline, 5101 patients (36%) were on 0 to 4 medications, 7298 (51%) were on 5 to 9, and 1865 (13%) were on ≥ 10. Although polypharmacy was not associated with higher risk of stroke or non-central nervous system embolism (adjusted hazard ratio, 1.02 for ≥ 10 versus 0-4 medications; 95% confidence interval, 0.76-1.38), it was associated with higher risks of the combined end point of stroke, non-central nervous system embolism, vascular death, or myocardial infarction (adjusted hazard ratio, 1.41 for ≥ 10 versus 0-4 medications; 95% confidence interval, 1.18-1.68) and nonmajor clinically relevant or major bleeding (adjusted hazard ratio, 1.47 for ≥ 10 versus 0-4 medications; 95% confidence interval, 1.31-1.65). There was no significant difference in primary efficacy (adjusted interaction P=0.99) or safety outcomes (adjusted interaction P=0.87) between treatment groups by number of medications. Patients treated with 0 to 4 medications had lower rates of major bleeding with rivaroxaban (adjusted hazard ratio, 0.71; 95% confidence interval, 0.52-0.95; interaction P=0.0074). There was no evidence of differential outcomes in those treated with ≥ 1 combined cytochrome P450 3A4 and P-glycoprotein inhibitors. CONCLUSIONS: In a population of patients with atrial fibrillation, two thirds were on ≥ 5 medications. Increasing medication use was associated with higher risk of bleeding but not stroke. Rivaroxaban was tolerated across complex patients on multiple medications. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00403767.

Full Text

Duke Authors

Cited Authors

  • Piccini, JP; Hellkamp, AS; Washam, JB; Becker, RC; Breithardt, G; Berkowitz, SD; Halperin, JL; Hankey, GJ; Hacke, W; Mahaffey, KW; Nessel, CC; Singer, DE; Fox, KAA; Patel, MR

Published Date

  • January 26, 2016

Published In

Volume / Issue

  • 133 / 4

Start / End Page

  • 352 - 360

PubMed ID

  • 26673560

Electronic International Standard Serial Number (EISSN)

  • 1524-4539

Digital Object Identifier (DOI)

  • 10.1161/CIRCULATIONAHA.115.018544


  • eng

Conference Location

  • United States