Risk of emergent bradycardia associated with the use of carvedilol and metoprolol in routine clinical practice

摘要

Background: Large randomized trials have reported mixed results regarding the risk of bradycardia between metoprolol and carvedilol. We compared the incidence of emergent bradycardia (measured by an emergency department visit or hospitalization due to bradycardia) for patients initiating metoprolol and carvedilol. Methods: Adult beneficiaries of Medi-Cal, the State of California Medicaid program, without a diagnosis of bradycardia who initiated metoprolol or carvedilol between May 1, 2004, and November 1, 2009, were included. Cox proportional hazard regression analysis was performed to model the time to first occurrence of emergent bradycardia after initiation of the study drugs as a dependent variable and the study drug (metoprolol vs carvedilol) as the primary predictor with adjustments for total daily metoprolol-equivalent dose, formulations, and use of nonstudy drugs as time-varying covariates, as well as demographics and comorbidities. Results: Among 38,186 subjects, 77.7% initiated metoprolol and 22.3% initiated carvedilol. The incidence of emergent bradycardia was low and comparable between the drugs (18.1 per 1000 person-years using metoprolol vs 17.7 per 100 person-years using carvedilol; unadjusted hazard ratio, 1.07; 95% confidence interval, 0.76-1.49). However, carvedilol users had substantially different population characteristics compared with metoprolol users. After adjustments for demographics, comorbidities, metoprolol-equivalent dose, formulations, and use of nonstudy drugs, initiation of metoprolol was associated with an increased risk of emergent bradycardia compared with that of carvedilol (adjusted hazard ratio, 1.64; 95% confidence interval, 1.14-2.36). Conclusions: Initiation of metoprolol is associated with an increased risk of emergent bradycardia compared with carvedilol, although the overall incidence of emergent bradycardia is low in routine clinical practice.