TY - JOUR
T1 - Polypharmacy and the Efficacy and Safety of Rivaroxaban Versus Warfarin in the Prevention of Stroke in Patients With Nonvalvular Atrial Fibrillation
AU - Piccini, Jonathan P
AU - Hellkamp, Anne S
AU - Washam, Jeffrey B
AU - Becker, Richard C
AU - Breithardt, Günter
AU - Berkowitz, Scott D
AU - Halperin, Jonathan L
AU - Hankey, Graeme J
AU - Hacke, Werner
AU - Mahaffey, Kenneth W
AU - Nessel, Christopher C
AU - Singer, Daniel E
AU - Fox, Keith A A
AU - Patel, Manesh R
N1 - © 2015 American Heart Association, Inc.
PY - 2016/1/26
Y1 - 2016/1/26
N2 - 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.
AB - 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.
U2 - 10.1161/CIRCULATIONAHA.115.018544
DO - 10.1161/CIRCULATIONAHA.115.018544
M3 - Article
C2 - 26673560
SN - 0009-7322
VL - 133
SP - 352
EP - 360
JO - Circulation
JF - Circulation
IS - 4
ER -