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, Jahrgang 92, Nr. 1, 1, 2012, S. 21-28.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -