title: Impact of the β1-adrenoceptor Arg389Gly polymorphism on heart-rate responses to bisoprolol and carvedilol in heart-failure patients.
abstract: This pharmacogenetic substudy of the prospective, double-blind, randomized CIBIS-ELD trial determined the impact of the β1-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 × 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.
authors.affiliation: Department of Experimental Pharmacology and Toxicology and Cardiovascular Research Centre, University Medical Centre Hamburg Eppendorf, Hamburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Rau
authors.forename: H-D
authors.initials: HD
authors.lastname: Düngen
authors.forename: F
authors.initials: F
authors.lastname: Edelmann
authors.forename: F
authors.initials: F
authors.lastname: Waagstein
authors.forename: M
authors.initials: M
authors.lastname: Lainščak
authors.forename: S
authors.initials: S
authors.lastname: Dimković
authors.forename: S
authors.initials: S
authors.lastname: Apostolović
authors.forename: A N
authors.initials: AN
authors.lastname: Nešković
authors.forename: W
authors.initials: W
authors.lastname: Haverkamp
authors.forename: G
authors.initials: G
authors.lastname: Gelbrich
authors.forename: T
authors.initials: T
authors.lastname: Eschenhagen
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics; D000368:Aged; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D017298:Bisoprolol / Q000008:administration & dosage / Q000493:pharmacokinetics; D002227:Carbazoles / Q000008:administration & dosage / Q000493:pharmacokinetics; D000077261:Carvedilol; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D006339:Heart Rate / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011412:Propanolamines / Q000008:administration & dosage / Q000493:pharmacokinetics; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D002227:Carbazoles; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; D000077261:Carvedilol; D017298:Bisoprolol