Testing for the presence of a common gene variant may enable doctors to identify which patients with heart failure would benefit from beta-blocker therapy, according to an article published online July 14 by the Proceedings of the National Academy of Sciences.

The findings are significant because it often takes several months to determine if a specific beta blocker is working for a patient, time that is especially important to a patient population in which one in five patients die within a year of diagnosis.

In a study that compared an investigational beta-blocker with placebo, researchers found a 38 percent reduction in death rate among patients who took the beta-blocker and who also had two copies of a genetic variant called arginine (Arg-389) in the beta-1 adrenergic receptor gene. In addition, the same patient subgroup had a 34 percent reduction combined number of hospitalizations and deaths. People with the other common variant, glycine (Gly-389), had no response to the drug compared with placebo.

“For the first time, we have a genetic test that will help guide us to the best treatment for individual patients with heart failure and provide what has been called personal medicine,” said principal investigator, Stephen B. Liggett, MD, professor of medicine and physiology at the University of Maryland School of Medicine and director of its cardiopulmonary genomics program. “This personalized therapy, based on genes, gives us an opportunity to tailor therapy in a way that we really were never able to do before.”

The genetic variance occurs in the beta-1 adrenergic receptor, which is the target for beta-blockers. People either have the Arg variant or the Gly variant. Dr. Liggett noted the type of variant does not predispose a person to develop heart failure.
“It has been difficult to explain the variability of response to treatment, even among patients with similar ages and other characteristics. This is especially the case with beta-blockers, one of the cornerstones in the treatment of heart failure,” said Michael Bristow, MD, PhD, a cardiologist at the University of Colorado School of Medicine and one of the study’s authors. “We hypothesized that the variability in response to beta-blockers was due to important functional genetic variation in the beta-1 receptor, and this indeed appears to be the case.”

The researchers’ conclusions are based in part on a retrospective look at data from a placebo-controlled study of the drug bucindolol, during which 1,040 heart failure patients were followed for up to four years. The study volunteers also consented to participate in a genetic sub-study which involved genotyping. The researchers looked at four parameters: whether the patients had the real drug or the placebo, and whether they had the Arg-389 receptor or the Gly-389 receptor.

The researchers also looked at genetic variants and response to beta blocker in black patients compared with whites, and found that genetics and not race determined who benefited best from the drug. “We believe it is inappropriate to use a race-based prescribing approach, because within any given ethnic or racial population there is a genetic variability with that group. Therefore, some people will have the response gene and some will not,” said Liggett.