Document Detail

Impact of the β1-adrenoceptor Arg389Gly polymorphism on heart-rate responses to bisoprolol and carvedilol in heart-failure patients.
MedLine Citation:
PMID:  22617224     Owner:  NLM     Status:  MEDLINE    
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.
T Rau; H-D Düngen; F Edelmann; F Waagstein; M Lainščak; S Dimković; S Apostolović; A N Nešković; W Haverkamp; G Gelbrich; T Eschenhagen
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2012-05-23
Journal Detail:
Title:  Clinical pharmacology and therapeutics     Volume:  92     ISSN:  1532-6535     ISO Abbreviation:  Clin. Pharmacol. Ther.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-06-21     Completed Date:  2012-09-04     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  0372741     Medline TA:  Clin Pharmacol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  21-8     Citation Subset:  AIM; IM    
Department of Experimental Pharmacology and Toxicology and Cardiovascular Research Centre, University Medical Centre Hamburg Eppendorf, Hamburg, Germany.
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MeSH Terms
Adrenergic beta-1 Receptor Antagonists / administration & dosage,  pharmacokinetics
Atrial Fibrillation* / complications,  drug therapy,  genetics
Bisoprolol* / administration & dosage,  pharmacokinetics
Carbazoles* / administration & dosage,  pharmacokinetics
Dose-Response Relationship, Drug
Double-Blind Method
Heart Failure* / complications,  drug therapy,  genetics
Heart Rate* / drug effects,  genetics
Polymorphism, Single Nucleotide
Propanolamines* / administration & dosage,  pharmacokinetics
Receptors, Adrenergic, beta-1 / genetics*
Treatment Outcome
Reg. No./Substance:
0/Adrenergic beta-1 Receptor Antagonists; 0/Carbazoles; 0/Propanolamines; 0/Receptors, Adrenergic, beta-1; 0K47UL67F2/carvedilol; 66722-44-9/Bisoprolol
Erratum In:
Clin Pharmacol Ther. 2012 Sep;92(3):397

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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