An α 2C -Adrenergic Receptor Polymorphism Alters the Norepinephrine-Lowering Effects and Therapeutic Response of the β-Blocker Bucindolol in Chronic Heart Failure
Key result
Bucindolol reduced mortality in heart failure patients with wild-type alpha(2C)-AR (HR 0.70; 95% CI 0.51-0.96; P=0.025), but provided no survival benefit in alpha(2C) Del carriers.
Why the study?
Does the therapeutic response and norepinephrine-lowering effect of bucindolol vary by alpha(2C)-adrenergic receptor polymorphism in patients with chronic heart failure?
Population
1,040 patients with chronic heart failure from the beta-Blocker Evaluation of Survival Trial AR polymorphism…
Comparison
Bucindolol vs Placebo
Design
RCT, randomized
Follow-up
12 months
Authors
Discussion
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Implication
May warrant alpha(2C)-AR genotyping before bucindolol; extends pharmacogenomic stratification of beta-blocker therapy in HF.
Study Design
Type
RCT (n=1,040)
Randomization
randomized
Structured PICO
Does the therapeutic response and norepinephrine-lowering effect of bucindolol vary by alpha(2C)-adrenergic receptor polymorphism in patients with chronic heart failure?
P
Population
1,040 patients with chronic heart failure from the beta-Blocker Evaluation of Survival Trial, evaluated for alpha(2C)-AR gene polymorphisms.
I
Intervention
Bucindolol
C
Comparator
Placebo
O
Outcome
Systemic venous norepinephrine at 3 and 12 months posttreatment, and mortalityhard clinical
Main Result
Hazard Ratio: 0.7 (95% CI 0.51–0.96)
p-value: p=0.025
The survival benefit of bucindolol in chronic heart failure is strongly dependent on the alpha(2C)-adrenergic receptor genotype, with benefit restricted to wild-type carriers.
Cite This Study
Bristow et al. (2009) conducted an RCT in chronic heart failure (n=1,040). Bucindolol vs. Placebo was evaluated on Mortality in alpha(2C)-AR wild type patients (HR 0.70, 95% CI 0.51-0.96, p=0.025). Bucindolol reduced mortality in heart failure patients with wild-type alpha(2C)-AR (HR 0.70; 95% CI 0.51-0.96; P=0.025), but provided no survival benefit in alpha(2C) Del carriers.