Author/Editor | Rau, T; Dungen, HD; Edelmann, F; Waagstein, F; Lainščak, M; Dimković, S; Apostolović, S; Nešković, AN; Haverkamp, W; Gelbrich, G; Eschenhagen, T | |
Title | Impact of the beta1-adrenoceptor Arg389Gly polymorphism on heart-rate responses to bisoprolol and carvedilol in heart-failure patients | |
Type | članek | |
Source | Clin Pharmacol Ther | |
Vol. and No. | Letnik 92, št. 1 | |
Publication year | 2012 | |
Volume | str. 21-8 | |
Language | eng | |
Abstract | This pharmacogenetic substudy of the prospective, double-blind, randomized CIBIS-ELD trial determined the impact of the beta1-adrenoceptor Arg189Gly polymorphism on heart-rate responses to bisoprolol or carvedilol in elderly patients with heart failure (421 with sinus rhythm, 107 with atrial fibrillation). Patients were randomized 1:1 to bisoprolol or carvedilol with a fortnightly dose-doubling scheme and guideline target doses. Patients with sinus rhythm responded essentially identically to bisoprolol and carvedilol, independent of genotype. Atrial fibrillation patients homozygous for Arg389 had a much smaller response to carvedilol than carriers of at least one Gly389 allele (mean difference 12 bpm, P < 0.00001). Carvedilol up to 2 x 12.5 mg did not reduce heart rate in Arg389Arg homozygotes at all. Interestingly, the immediate response to carvedilol did not differ between genotypes. The Arg389Gly polymorphism has a major impact on the heart-rate response to carvedilol (but not bisoprolol) in patients with heart failure plus atrial fibrillation. | |
Descriptors | HEART FAILURE, CONGESTIVE BISOPROLOL RECEPTORS, ADRENERGIC, BETA-1 POLYMORPHISM (GENETICS) HEART RATE PHARMACOGENETICS GENOTYPE ARGININE GLYCINE RANDOMIZED CONTROLLED TRIALS AGED |