Key result
In heart failure patients with atrial fibrillation, Arg389 homozygotes had a significantly smaller heart-rate response to carvedilol than Gly389 carriers (mean difference 12 bpm, P<0.00001).
Why the study?
Does the β1-adrenoceptor Arg389Gly polymorphism impact heart-rate responses to bisoprolol and carvedilol in elderly patients with heart failure?
RCT (n=528)
Double-blind
1:1
Does the β1-adrenoceptor Arg389Gly polymorphism impact heart-rate responses to bisoprolol and carvedilol in elderly patients with heart failure?
The β1-adrenoceptor Arg389Gly polymorphism significantly affects the heart-rate lowering efficacy of carvedilol, but not bisoprolol, in heart failure patients with atrial fibrillation.
Arg389 homozygotes may need alternative rate control on carvedilol in HF with AF; extends β1-adrenoceptor pharmacogenetics to β-blocker selection.
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.
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Rau et al. (2012) conducted an RCT in Heart failure (n=528). Bisoprolol or carvedilol vs. Active comparator (bisoprolol vs carvedilol) was evaluated on Heart-rate response (MD 12 bpm, p=<0.00001). In heart failure patients with atrial fibrillation, Arg389 homozygotes had a significantly smaller heart-rate response to carvedilol than Gly389 carriers (mean difference 12 bpm, P<0.00001).
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