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Purpose: Two oral metoprolol formulations – immediate release (IR) and slow-release (SR) – have different pharmacokinetics at the same total daily dose. We compared the incidence of emergency room visits or hospitalizations due to bradycardia between the two formulations in beneficiaries of Medi-Cal, the State of California Medicaid program.
Methods: We identified adults initiating metoprolol use between May 1, 2004 and November 1, 2009 who had no pharmacy claim for a beta blocker within the previous 6 months of metoprolol initiation. We used International Classification of Diseases-9 codes to exclude those who had a primary or secondary diagnosis of bradycardia or pacemaker placement before metoprolol initiation. The primary outcome was time to first occurrence of an emergency room visit or hospitalization due to bradycardia after metoprolol initiation. Metoprolol formulation (IR vs. SR) was included in a proportional hazards model, with adjustment for total daily metoprolol dose and the use of other drugs as time-varying covariates as well as demographics and co-morbidities.
Results: A total of 31,991 subjects were included in the analysis. In the IR group, 117 had a bradycardic event (0.62%; 2.14 per 1000 person-months) whereas 49 had one in the SR group (0.37%; 1.13 per 1000 person-months). The IR formulation significantly increased the risk of a bradycardic event compared with the SR formulation (unadjusted hazard ratio (HR) 1.83, 95% confidence interval (CI) 1.31-2.55; adjusted HR 1.64, 95% CI 1.16-2.33). The use of a cytochrome P450 2D6 inhibitor (HR 1.47, 95% CI 1.07-2.01), an antiarrhythmics (HR 2.31, 95% CI 1.22-4.38), and an atrioventricular node-blocking agent (HR 2.34, 95% CI 1.67-3.30) also significantly increased risk of a bradycardic event.
Conclusions: Use of the IR instead of the SR formulation of metoprolol is associated with an increased risk of serious bradycardia events requiring emergency care, though the absolute risk is low.