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Impact of the β1-adrenoceptor Arg389Gly polymorphism on heart-rate responses to bisoprolol and carvedilol in heart-failure patients.

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Impact of the β1-adrenoceptor Arg389Gly polymorphism on heart-rate responses to bisoprolol and carvedilol in heart-failure patients. / Rau, Thomas; Düngen, H-D; Edelmann, F; Waagstein, F; Lainščak, M; Dimković, S; Apostolović, S; Nešković, A N; Haverkamp, W; Gelbrich, G; Eschenhagen, Thomas.

In: CLIN PHARMACOL THER, Vol. 92, No. 1, 1, 2012, p. 21-28.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Rau, T, Düngen, H-D, Edelmann, F, Waagstein, F, Lainščak, M, Dimković, S, Apostolović, S, Nešković, AN, Haverkamp, W, Gelbrich, G & Eschenhagen, T 2012, 'Impact of the β1-adrenoceptor Arg389Gly polymorphism on heart-rate responses to bisoprolol and carvedilol in heart-failure patients.', CLIN PHARMACOL THER, vol. 92, no. 1, 1, pp. 21-28. <http://www.ncbi.nlm.nih.gov/pubmed/22617224?dopt=Citation>

APA

Rau, T., Düngen, H-D., Edelmann, F., Waagstein, F., Lainščak, M., Dimković, S., Apostolović, S., Nešković, A. N., Haverkamp, W., Gelbrich, G., & Eschenhagen, T. (2012). Impact of the β1-adrenoceptor Arg389Gly polymorphism on heart-rate responses to bisoprolol and carvedilol in heart-failure patients. CLIN PHARMACOL THER, 92(1), 21-28. [1]. http://www.ncbi.nlm.nih.gov/pubmed/22617224?dopt=Citation

Vancouver

Rau T, Düngen H-D, Edelmann F, Waagstein F, Lainščak M, Dimković S et al. Impact of the β1-adrenoceptor Arg389Gly polymorphism on heart-rate responses to bisoprolol and carvedilol in heart-failure patients. CLIN PHARMACOL THER. 2012;92(1):21-28. 1.

Bibtex

@article{4b80049f4db641dfb7781251e32649cf,
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 ?1-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.",
keywords = "Humans, Male, Aged, Female, Treatment Outcome, Double-Blind Method, Polymorphism, Single Nucleotide, Dose-Response Relationship, Drug, Adrenergic beta-1 Receptor Antagonists/administration & dosage/pharmacokinetics, *Atrial Fibrillation/complications/drug therapy/genetics, *Bisoprolol/administration & dosage/pharmacokinetics, *Carbazoles/administration & dosage/pharmacokinetics, *Heart Failure/complications/drug therapy/genetics, *Heart Rate/drug effects/genetics, *Propanolamines/administration & dosage/pharmacokinetics, Receptors, Adrenergic, beta-1/*genetics, Humans, Male, Aged, Female, Treatment Outcome, Double-Blind Method, Polymorphism, Single Nucleotide, Dose-Response Relationship, Drug, Adrenergic beta-1 Receptor Antagonists/administration & dosage/pharmacokinetics, *Atrial Fibrillation/complications/drug therapy/genetics, *Bisoprolol/administration & dosage/pharmacokinetics, *Carbazoles/administration & dosage/pharmacokinetics, *Heart Failure/complications/drug therapy/genetics, *Heart Rate/drug effects/genetics, *Propanolamines/administration & dosage/pharmacokinetics, Receptors, Adrenergic, beta-1/*genetics",
author = "Thomas Rau and H-D D{\"u}ngen and F Edelmann and F Waagstein and M Lain{\v s}{\v c}ak and S Dimkovi{\'c} and S Apostolovi{\'c} and Ne{\v s}kovi{\'c}, {A N} and W Haverkamp and G Gelbrich and Thomas Eschenhagen",
year = "2012",
language = "English",
volume = "92",
pages = "21--28",
journal = "CLIN PHARMACOL THER",
issn = "0009-9236",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Impact of the β1-adrenoceptor Arg389Gly polymorphism on heart-rate responses to bisoprolol and carvedilol in heart-failure patients.

AU - Rau, Thomas

AU - Düngen, H-D

AU - Edelmann, F

AU - Waagstein, F

AU - Lainščak, M

AU - Dimković, S

AU - Apostolović, S

AU - Nešković, A N

AU - Haverkamp, W

AU - Gelbrich, G

AU - Eschenhagen, Thomas

PY - 2012

Y1 - 2012

N2 - This pharmacogenetic substudy of the prospective, double-blind, randomized CIBIS-ELD trial determined the impact of the ?1-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.

AB - This pharmacogenetic substudy of the prospective, double-blind, randomized CIBIS-ELD trial determined the impact of the ?1-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.

KW - Humans

KW - Male

KW - Aged

KW - Female

KW - Treatment Outcome

KW - Double-Blind Method

KW - Polymorphism, Single Nucleotide

KW - Dose-Response Relationship, Drug

KW - Adrenergic beta-1 Receptor Antagonists/administration & dosage/pharmacokinetics

KW - Atrial Fibrillation/complications/drug therapy/genetics

KW - Bisoprolol/administration & dosage/pharmacokinetics

KW - Carbazoles/administration & dosage/pharmacokinetics

KW - Heart Failure/complications/drug therapy/genetics

KW - Heart Rate/drug effects/genetics

KW - Propanolamines/administration & dosage/pharmacokinetics

KW - Receptors, Adrenergic, beta-1/genetics

KW - Humans

KW - Male

KW - Aged

KW - Female

KW - Treatment Outcome

KW - Double-Blind Method

KW - Polymorphism, Single Nucleotide

KW - Dose-Response Relationship, Drug

KW - Adrenergic beta-1 Receptor Antagonists/administration & dosage/pharmacokinetics

KW - Atrial Fibrillation/complications/drug therapy/genetics

KW - Bisoprolol/administration & dosage/pharmacokinetics

KW - Carbazoles/administration & dosage/pharmacokinetics

KW - Heart Failure/complications/drug therapy/genetics

KW - Heart Rate/drug effects/genetics

KW - Propanolamines/administration & dosage/pharmacokinetics

KW - Receptors, Adrenergic, beta-1/genetics

M3 - SCORING: Journal article

VL - 92

SP - 21

EP - 28

JO - CLIN PHARMACOL THER

JF - CLIN PHARMACOL THER

SN - 0009-9236

IS - 1

M1 - 1

ER -