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Effect of metoprolol exposure following myocardial infarction on future cardiovascular events: a Mendelian randomization study
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Effect of metoprolol exposure following myocardial infarction on future cardiovascular events: a Mendelian randomization study
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Effect of metoprolol exposure following myocardial infarction on future cardiovascular events: a Mendelian randomization study
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Journal Article
Effect of metoprolol exposure following myocardial infarction on future cardiovascular events: a Mendelian randomization study
2025
Overview
Purpose
The clinical benefit of up-titration of metoprolol to a guideline-recommended target dose after myocardial infarction (MI) is unknown. Our aim was to investigate whether variation in metoprolol exposure determined by cytochrome p450 enzyme 2D6 (CYP2D6
)
influences the occurrence of major adverse cardiovascular events (MACE) and cardiovascular death (CV death) among patients treated with metoprolol after MI.
Method
This Mendelian randomization study was performed using individual-level data from 1554 patients treated with metoprolol after an acute MI. CYPD26 genotype was applied as a binary genetic instrument assigning patients into two metoprolol exposure groups: CYP2D6 normal metabolizers (NM) (low exposure) and CYP2D6 intermediate and poor metabolizers (IM + PM) (high exposure). The null hypothesis of no association between the CYP2D6 metabolizer subgroup and MACE or CV death was tested using the Cox proportional hazards model. All-cause mortality and individual components of MACE were included as secondary outcomes.
Results
In total, 879 (56.6%) patients were classified as NM and 675 (43.4%) as IM + PM. During the 3-year follow-up, 56 patients (6.4%) in the NM group had an outcome of MACE, and 24 (2.7%) patients died from CV disease. Corresponding frequency in the IM + PM group was 47 (7.0%) and 22 (3.3%), respectively. There was no association between genotype and MACE [unadjusted HR 1.12 (CI 0.76, 1.65)] or CV death [unadjusted HR 1.20 (CI 0.67, 2.14)], or between the CYP2D6 group and any of the secondary outcomes.
Conclusion
In patients treated with metoprolol after MI, variation in metoprolol exposure determined by CYP2D6 did not impact the occurrence of cardiovascular events.
Publisher
Springer Berlin Heidelberg,Springer Nature B.V
Subject
Adrenergic beta-1 Receptor Antagonists - administration & dosage
/ Adrenergic beta-1 Receptor Antagonists - adverse effects
/ Adrenergic beta-1 Receptor Antagonists - therapeutic use
/ Aged
/ Biomedical and Life Sciences
/ Cardiovascular Diseases - genetics
/ Cardiovascular Diseases - mortality
/ Cytochrome P-450 CYP2D6 - genetics
/ Cytochrome P-450 CYP2D6 - metabolism
/ Death
/ Female
/ Genotype
/ Humans
/ Male
/ Mendelian Randomization Analysis
/ Metoprolol - administration & dosage
/ Metoprolol - adverse effects
/ Metoprolol - therapeutic use
/ Myocardial Infarction - drug therapy
/ Myocardial Infarction - genetics
