Avtor/Urednik		Rau, T; Dungen, HD; Edelmann, F; Waagstein, F; Lainščak, M; Dimković, S; Apostolović, S; Nešković, AN; Haverkamp, W; Gelbrich, G; Eschenhagen, T
Naslov		Impact of the beta1-adrenoceptor Arg389Gly polymorphism on heart-rate responses to bisoprolol and carvedilol in heart-failure patients
Tip		članek
Vir		Clin Pharmacol Ther
Vol. in št.		Letnik 92, št. 1
Leto izdaje		2012
Obseg		str. 21-8
Jezik		eng
Abstrakt		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.
Deskriptorji		HEART FAILURE, CONGESTIVE BISOPROLOL RECEPTORS, ADRENERGIC, BETA-1 POLYMORPHISM (GENETICS) HEART RATE PHARMACOGENETICS GENOTYPE ARGININE GLYCINE RANDOMIZED CONTROLLED TRIALS AGED