Risk of Emergent Bradycardia Associated with Initiation of Immediate- or Slow-Release Metoprolol

OBJECTIVES To estimate and compare the risk of emergent bradycardia associated with starting immediate-release (IR) and slow-release (SR) formulations of metoprolol. DESIGN Retrospective analysis of administrative claims data. DATA SOURCE State of California Medicaid program (Medi-Cal) claims database. PATIENTS A total of 31,574 adults beginning metoprolol between May 1, 2004, and November 1, 2009, without a pharmacy claim for a beta blocker within the previous 6 months of metoprolol initiation; patients with a primary or secondary diagnosis of symptomatic bradycardia, pacemaker, or implantable cardioverter-defibrillator placement before metoprolol initiation were excluded. MEASUREMENTS AND MAIN RESULTS The study outcome was the time to first occurrence of emergent bradycardia, measured at an emergency department visit or hospitalization due to diagnosis of symptomatic bradycardia, after metoprolol initiation. We calculated the incidence and compared the risk of emergent bradycardia by using a proportional hazards model that included the metoprolol formulation with adjustment for total daily metoprolol dose and the use of other drugs as time-varying covariates, as well as demographics and comorbidities. Among 31,574 patients starting metoprolol, 18,516 (58.6%) used the IR formulation. The incidence of emergent bradycardia was 19.1/1000 person-years overall but was nearly twice as common in patients using the IR versus the SR formulation (24.1/1000 person-yrs in the IR group versus 12.9/1000 person-yrs in the SR group, unadjusted hazard ratio [HR] 1.81, 95% confidence interval [CI] 1.28-2.56). Adjustment for other drugs also associated with symptomatic bradycardia (cytochrome P450 2D6 inhibitors, class I or III antiarrhythmics, and atrioventricular node-blocking agents), metoprolol dose, and other participant characteristics somewhat attenuated the association (adjusted HR 1.48, 95% CI 1.03-2.13). CONCLUSION The risk of emergent bradycardia associated with metoprolol initiation was higher with the IR formulation than the SR formulation, although the absolute risk was low.