Emerging role of pharmacogenomics in heart failure.
OBJECTIVE
The promise of pharmacogenomics is that it will one day result in targeted heart failure therapy that maximizes individual benefit and diminishes risk. Recent reports from the Beta Blocker Evaluation Survival and African American Heart Failure clinical trials provide a roadmap of how this promise may soon be realized. This review will discuss recent investigations of pharmacogenomics in heart failure, and the challenge of converting genomic heterogeneity into a usable clinical tool.


RESULTS
Genomic analysis from randomized clinical trials has been increasingly utilized to investigate genetic variables that affect drug response. Analysis from the Beta Blocker Evaluation Survival Trial, demonstrates the impact of beta-blockers on survival was primarily in patients with the beta-1 adrenergic receptor Arg389Arg genotype. The efficacy of angiotensin-converting enzyme inhibitors and the combination of isosorbide dinitrate and hydralazine differs in black and white heart failure cohorts. Initial reports from the African American Heart Failure Trial demonstrate the impact of aldosterone synthase polymorphism on left ventricle remodeling, outcomes and the impact of isosorbide dinitrate and hydralazine. Investigations from the African American Heart Failure Trial will continue to focus on determining the genomic bases for observed racial differences in therapeutic efficacy. An era of polygenic analysis, aided by Genome Wide Association Studies, should soon be upon us.


CONCLUSIONS
Modern clinical trials will increasingly have a pharmacogenetic component to allow more efficient targeting of therapeutics. Investigators are beginning to delineate the genomic basis for differences in drug efficacy between black and white heart failure cohorts. Pharmacogenomics will have an increasing role in the treatment of heart failure patients.
McNamara
Dennis M
DM
University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA. mcnamaradm@upmc.edu
D001741:Black or African American; D018740:Genetic Heterogeneity; D005838:Genotype; D006333:Heart Failure / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D016032:Randomized Controlled Trials as Topic; D044465:White People