Combinatorial Pharmacogenetic Interactions of Bucindolol and β1, α2C Adrenergic Receptor Polymorphisms
Key result
The combination of beta1389 Arg/Arg and any alpha2C genotype identified a subpopulation where bucindolol reduced all-cause mortality or cardiac transplantation by 43% (HR 0.57) compared to placebo.
Why the study?
Does bucindolol efficacy vary by combinations of β1389 and α2C322-325 adrenergic receptor polymorphisms in patients with heart failure?
Population
1,040 patients with heart failure (substudy of a clinical trial)
Comparison
Bucindolol vs Placebo
Design
Cohort
Authors
Discussion
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Member takes
Implication
Adrenergic genotypes may identify bucindolol-responsive HF subgroups; leaves open prospective randomized confirmation before practice change.
Study Design
Type
RCT (n=1,040)
Blinding
Double-blind
Randomization
Yes
Multicenter
Yes
Structured PICO
Does bucindolol efficacy vary by combinations of β1389 and α2C322-325 adrenergic receptor polymorphisms in patients with heart failure?
P
Population
1,040 patients with advanced chronic heart failure and reduced left ventricular ejection fraction enrolled in the BEST trial DNA substudy.
I
Intervention
Bucindolol
C
Comparator
Placebo
O
Outcome
Efficacy across six clinical endpoints
Main Result
Hazard Ratio: 0.57 (95% CI 0.36–0.89)
p-value: p=0.012
Combinations of β1 and α2C adrenergic receptor polymorphisms identify heart failure subpopulations with enhanced, intermediate, or no efficacy from bucindolol.
Limitations
- Pharmacogenetic data were generated and analyzed after the trial's main results were published.
- Approximately two-thirds of the patients were enrolled into the DNA substudy after being randomized into the parent trial (late entry).
Cite This Study
O’Connor et al. (2012) conducted an RCT in Advanced chronic heart failure (n=1,040). Bucindolol vs. Placebo was evaluated on All-cause mortality or cardiac transplantation in the beta1389 Arg/Arg + any alpha2C genotype group (Group 1/2) (HR 0.57, 95% CI 0.36-0.89, p=0.012). The combination of beta1389 Arg/Arg and any alpha2C genotype identified a subpopulation where bucindolol reduced all-cause mortality or cardiac transplantation by 43% (HR 0.57) compared to placebo.