REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01960946.
Single nucleotide polymorphisms (SNPs) have been associated with differential beta-blocker (BB) effects on heart rate, blood pressure, and left ventricular ejection fraction in various patient populations. This study aimed to determine if SNPs previously associated with BB response are also associated with differential survival in heart failure (HF) patients receiving BBs. HF patient data were derived from electronic health records and the Social Security Death Index. Associations and interactions between BB dose, SNP genotype, and the outcome of death were assessed using a Cox proportional-hazard model adjusting for covariates known to be associated with differential survival in HF patients. Two SNPs, ADRB1 Arg389Gly and ADRB2 Glu27Gln, displayed significant interactions (Pint = 0.043 and Pint = 0.017, respectively) with BB dose and their association with mortality. Our study suggests that ADRB2 27Glu and ADRB1 389Arg may confer a larger survival benefit with higher BB doses in patients with HF.
Adrenergic beta-Antagonists/therapeutic use , Heart Failure/drug therapy , Heart Failure/mortality , Receptors, Adrenergic, beta-1/genetics , Receptors, Adrenergic, beta-2/genetics , Adrenergic beta-Antagonists/administration & dosage , Aged , Aged, 80 and over , Dose-Response Relationship, Drug , Female , Genotype , Humans , Male , Middle Aged , Polymorphism, Genetic/genetics , Polymorphism, Single Nucleotide , Proportional Hazards Models , Survival Analysis
