Polypharmacy and the Efficacy and Safety of Rivaroxaban versus Warfarin in the Prevention of Stroke in Patients With Nonvalvular Atrial Fibrillation
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 CYP3A4 and P-glycoprotein inhibitors in ROCKET AF. At baseline, 5101 (36%) patients were on 0-4 medications, 7298 (51%) were on 5-9, and 1865 (13%) were on ≥10. While polypharmacy was not associated with higher risk of stroke or non-central nervous system (CNS) embolism (adjusted hazard ratio [HR] 1.02 for ≥10 vs. 0-4, 95% CI 0.76-1.38), it was associated with higher risks of the combined endpoint of stroke, non-CNS embolism, vascular death, or myocardial infarction (adjusted HR 1.41 for ≥10 vs. 0-4, 95% CI 1.18-1.69), and non-major clinically relevant or major bleeding (adjusted HR 1.47 for ≥10 vs. 0-4, 95% CI 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 0-4 medications had lower rates of major bleeding with rivaroxaban (adjusted HR 0.71, 95% CI 0.52-0.95, interaction p=0.0074). There was no evidence of differential outcomes in those treated with ≥1 combined CYP3A4 and P-glycoprotein inhibitors.
Conclusions—In a population of patients with AF, 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 Information—ClinicalTrials.gov. Identifier: NCT00403767.
- Received July 16, 2015.
- Revision received December 2, 2015.
- Accepted December 11, 2015.