Key result
CYP2D6 poor and intermediate metabolizers had a significantly greater reduction in heart rate in response to metoprolol (P<0.0001), but blood pressure and adverse effect rates did not differ.
Why the study?
Do CYP2D6 polymorphisms influence the clinical efficacy and tolerability of metoprolol tartrate in patients with uncomplicated hypertension?
Observational (n=281)
Do CYP2D6 polymorphisms influence the clinical efficacy and tolerability of metoprolol tartrate in patients with uncomplicated hypertension?
p-value: p=<0.0001
CYP2D6 polymorphisms significantly affect heart rate reduction but not blood pressure response or tolerability in hypertensive patients treated with metoprolol tartrate.
CYP2D6 status need not alter metoprolol dosing for BP control or safety in hypertension; leaves open targeted research on heart rate response.
Metoprolol is a selective β-1 adrenergic receptor blocker that undergoes extensive metabolism by the polymorphic enzyme cytochrome P450 2D6 (CYP2D6). Our objective was to investigate the influence of CYP2D6 polymorphisms on the efficacy and tolerability of metoprolol tartrate. Two hundred and eighty-one participants with uncomplicated hypertension received 50 mg of metoprolol twice daily followed by response-guided titration to 100 mg twice daily. Phenotypes were assigned based on results of CYP2D6 genotyping and copy number variation assays. Clinical response to metoprolol and adverse effect rates were analyzed in relation to CYP2D6 phenotypes using appropriate statistical tests. Heart rate response differed significantly by CYP2D6 phenotype (P < 0.0001), with poor and intermediate metabolizers showing greater reduction. However, blood pressure response and adverse effect rates were not significantly different by CYP2D6 phenotype. Other than a significant difference in heart rate response, CYP2D6 polymorphisms were not determinants of variability in metoprolol response or tolerability.
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Hamadeh et al. (2014) conducted an observational in Uncomplicated hypertension (n=281). CYP2D6 polymorphisms (poor and intermediate metabolizer phenotypes) vs. Other CYP2D6 phenotypes was evaluated on Clinical response (heart rate and blood pressure) and adverse effect rates (p=<0.0001). CYP2D6 poor and intermediate metabolizers had a significantly greater reduction in heart rate in response to metoprolol (P<0.0001), but blood pressure and adverse effect rates did not differ.
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