Polypharmacy and the Efficacy and Safety of Rivaroxaban versus Warfarin in the Prevention of Stroke in Patients With Nonvalvular Atrial Fibrillation.
Circulation. 2015 Dec 16;
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 KA, Patel MR
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.
PMID: 26673560 [PubMed - as supplied by publisher]