Abstract
Background: Poor metabolizers (PMs) of CYP2D6 have been reported to have increased adverse effects, (1) lower blood pressure (BP) and lower heart rate when using metoprolol compared with extensive metabolizers (EMs)(2, 3). In this study we wanted to see if there was an association between PMs or heterozygous extensive metabolizers (HEMs) and orthostatic intolerance compared with EMs. We also wanted to see if PMs and HEMs tolerated lower doses of metoprolol than EMs. Methods: 63 ST-elevation myocardial infarction (STEMI)- or non-ST-elevation myocardial infarction (NSTEMI)- patients were treated with metoprolol before discharge and tested after 3 months using continuous, non-invasive BP monitoring using an inflatable finger cuff (Nexfin®). The normal allele (*1), defect alleles (*3-6) and reduced function alleles (*9,*10,*17 and *41) to CYP2D6 were examined. Patients were grouped into PMs (*1/*1), HEMs (*1/red, *1/defect, reduced/reduced and reduced/defect) or PMs (defect/defect). Continuous BP was measured during 10 minutes in supine position and 14 min standing. Results: Systolic/diastolic ∆BP after 30 sec and maximal ∆BP were -9/-3.5 mmHg and -16/-4.5 mmHg, respectively, in the EM group compared with -5/-3 mmHg (p=0.256/0.532) and -7/-2 mmHg (p=0.069/0.116), respectively, in the HEM group and -7.5/5 mmHg (p=0.841/0.192) and -12.5/5.5 mmHg (p=0.667/0.105), respectively, in the PM group. 27.8% of the patients in the EM group reported dizziness compared with 34.5% in the HEM group (p=0.753) and 50% in the PM group (p=0.447). Average dosage of metoprolol succinate extended-release tablets was 54.8 mg in the EM group compared with 68 mg (p=0.238) in the HEM group and 62.5 mg in the PM group (p=0.687). Conclusions: There was no difference in decrease of BP after 14 min of standing or dosage of metoprolol succinate in PMs or HEMs compared with EMs. More patients in the PM group reported symptoms than in the HEM and EM groups, but these differences were not statistically significant.