Beta-blocker Therapy Could Be Risky for Some Heart Patients

Heart-attack and angina patients placed on beta-blocker therapy have a much greater risk of dying if they carry specific variations in genes that help control the sympathetic nervous system, researchers have found.

The findings, if supported by additional research, could eventually change the way some heart patients are treated.

"In our investigation of acute coronary syndrome patients discharged on beta-blocker therapy, we were able to associate the risk of death with the characteristics of the patients' beta-adrenergic receptor genes," said Howard McLeod, a professor at the Washington University School of Medicine in St. Louis and a co-author of the study published Wednesday in The Journal of the American Medical Association.

The researchers identified high-, intermediate- and low-risk groups that had particular variations in the genes that interact with beta-blocker drugs. The high-risk individuals have a risk of death that is five times greater in the first three years after starting the drugs than those in the low-risk group.

The results shouldn't stop anyone from taking beta blockers for now, said the lead author, Dr. David Lanfear, formerly at Washington University and now at the Henry Ford Hospital in Detroit.

"Further investigation is needed to determine whether the effect seen is due to the lack of efficacy of beta blockers in higher-risk patients (no matter what their gene function) or if genotype alone is responsible for a worse outcome," he added. The research team is setting up a larger study to confirm the results.

Beta-adrenergic receptors in the sympathetic nervous system _ nerves that radiate out from the spine into central organs and control blood pressure, heartbeat and digestion _ respond to adrenaline. This network is central to the "fight or flight" response.

Beta-blocker drugs halt this interaction, slowing the heartbeat and lowering blood pressure to relieve stress on the heart. They also block impulses that can cause heart-rhythm disturbances.

Long-term therapy with beta blockers is standard care for most heart patients, and is generally effective at reducing stress on the heart and prolonging survival.

But recent research has shown that variations in beta-receptor genes affect the benefits of the drugs in heart patients. Studies show that blood pressure and heart function did not improve in those with certain forms of the gene.

Humans have two types of beta-adrenergic receptors, beta-1 and beta-2. In the new study, the researchers found no difference in survival rates linked to variations in beta-1, but significant differences depending on patterns in the beta-2 gene.

The beta-2 gene typically has two points of sequence variation, one carried by about 39 percent of the population and another that's found in about 16 percent of humans.

The study involved 735 coronary-syndrome patients from two Kansas City, Mo., hospitals. The average age of the patients was 60, and 81 percent of them were on beta-blocker therapy. The next phase of study will involve 4,500 heart patients at 20 hospitals around the country.

Heart patients on beta blockers with either of the two genetic variations made up the high-risk group. At the end of three years, 20 percent of this group had died.

But those who had the more common gene pattern had only a 6 percent mortality rate and were considered low-risk. Patients with any other combination of beta-2 variations were classified at intermediate-risk, and had an overall 11 percent risk of death after three years.

"Our study makes it clear how powerful genetic analysis is, and how important it can be for individual patients," said Dr. John Spertus, director of cardiovascular education and outcome research at the Mid America Heart Institute in Kansas City, and senior author of the study.

"It gives a hint of what medical practice will be like down the road when we can put such knowledge to practical use every day."

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