Key result
High metoprolol levels linked to ~15.6-fold higher bradycardia risk in women, but not men.
Why the study?
Although metoprolol plasma concentration is higher in women than men, the same dose is recommended, leaving it unclear whether concentration is associated with stronger heart-rate reduction and bradycardia in women.
Does higher metoprolol plasma concentration increase the risk of bradycardia in women compared to men?
Cohort (n=79)
No
Does higher metoprolol plasma concentration increase the risk of bradycardia in women compared to men?
Odds Ratio: 15.6 (95% CI 1.1–217.3)
Women exhibit a significantly higher risk of metoprolol-induced bradycardia at elevated plasma concentrations than men, highlighting the need for sex-specific dosing considerations.
High metoprolol concentrations were associated with bradycardia in women but not men; leaves open whether sex-specific dosing improves safety.
Background: Metoprolol, a beta-blocker, is used to reduce the heart rate. Although it has been demonstrated that the metoprolol plasma concentration is higher in women than in men, the same dose is recommended. In this study, we investigated whether the metoprolol concentration was associated with a stronger heart-rate reduction and bradycardia in women than in men. Methods: This study is part of the Rotterdam Study (RS), a population-based prospective cohort study. Blood samples from a random subset of 2000 participants were used to assess metoprolol plasma levels. An analysis of heart rate (beats per minute, bpm) and bradycardia (<60 bpm) was performed in metoprolol users with an ECG at the day of blood collection to study sex-specific differences in heart rate and the risk of bradycardia. Results: In total, 40 women and 39 men were included. There was a statistically significant association between metoprolol concentration and heart rate in women (p-value: 0.014) but not in men (p-value: 0.639). Furthermore, women in the highest concentration group had a more than 15-times-higher risk of bradycardia than women in the lowest concentration group (OR = 15.6; 95% CI = 1.1, 217.3); however, this was not seen in men (OR = 1.3; 95% CI = 0.1, 12.4). After adjustment for age, BMI, time between blood sample and ECG, hypertension, myocardial infarction, heart failure, atrial fibrillation, digoxin use, and calcium channel blocker use, the association between concentration and bradycardia in women remained statistically significant. Conclusions: Women, but not men, had a statistically significantly lower heart rate at higher metoprolol plasma concentration and a statistically significantly increased risk of bradycardia.
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Hendriksen et al. (2022) conducted a cohort in Metoprolol users (n=79). Higher metoprolol plasma concentration (≥150 µg/L) vs. Lowest metoprolol plasma concentration (<20 µg/L) was evaluated on Bradycardia (<60 bpm) (OR 15.6, 95% CI 1.1, 217.3). Women in the highest metoprolol concentration group had a significantly increased risk of bradycardia compared to those in the lowest group (OR 15.6), an association not observed in men.
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