Abstract
Background:
beta-Blockers (BBs) are mainstay therapy for heart failure with reduced ejection fraction. However, individual patient responses to BB vary, which may be partially due to genetic variation. The goal of this study was to derive and validate the first polygenic response predictor (PRP) for BB survival benefit in heart failure with reduced ejection fraction patients.
Methods:
Derivation and validation analyses were performed in n=1436 total HF patients of European descent and with ejection fraction
Results:
Five-fold cross-validation summaries out to 1000 single-nucleotide polymorphisms identified optimal prediction with a 44 single-nucleotide polymorphism score and cutoff at the 30th percentile. In validation testing (n=1188), greater BB exposure was associated with reduced all-cause mortality in patients with low PRP score (n=251; hazard ratio, 0.19 [95% CI, 0.04-0.51]; P=0.0075) but not high PRP score (n=937; hazard ratio, 0.84 [95% CI, 0.53-1.3]; P=0.448)-a difference that was statistically significant (P interaction, 0.0235). Results were consistent regardless of atrial fibrillation, ejection fraction (
Conclusions:
Among patients of European ancestry with heart failure with reduced ejection fraction, a PRP distinguished patients who derived substantial survival benefit from BB exposure from a larger group that did not. Additional work is needed to prospectively test clinical utility and to develop PRPs for other population groups and other medications.
Original language | English |
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Article number | 007012 |
Number of pages | 12 |
Journal | Circulation-Heart Failure |
Volume | 13 |
Issue number | 12 |
DOIs | |
Publication status | Published - Dec 2020 |
Keywords
- atrial fibrillation
- pharmacogenetics
- population groups
- precision medicine
- 2013 ACCF/AHA GUIDELINE
- ASSOCIATION TASK-FORCE
- RISK SCORE
- ADRENERGIC-RECEPTOR
- ATRIAL-FIBRILLATION
- AMERICAN-COLLEGE
- PROPENSITY SCORE
- GENETIC RISK
- VARIANTS
- COMMON
- Pharmacogenetics
- Atrial fibrillation
- Precision medicine
- Population groups