7/31/97
CONTACT:
Jody Sumrall, (415) 723-7897 or 723-6911; e-mail [email protected]
COMMENT:
Dr. Paul Heidenreich, (415) 723-3287
FOR IMMEDIATE RELEASE
BETA-BLOCKERS BENEFICIAL IN TREATING HEART FAILURE
STANFORD -- Beta-blockers, a class of heart drugs long deemed risky for people with heart failure, can actually prevent deaths in those patients, according to a data reanalysis conducted by a research fellow at the Stanford University School of Medicine.
Cardiologist Dr. Paul Heidenreich pooled and reanalyzed results from 17 small studies of beta-blocker treatments in heart failure patients. Those studies had been mostly inconclusive because of their small size. But Heidenreich's "meta-analysis" demonstrated a clear, statistically significant benefit from treatment.
That benefit is equivalent to one death saved for every 35 patients treated over a nine-month period. Many heart attack therapies show similar levels of effectiveness, noted Heidenreich, a research fellow in Stanford's Department of Health Research and Policy.
The new findings are reported in the July Journal of the American College of Cardiology.
Heart failure is a chronic reduction in the pumping ability of a damaged heart, causing symptoms such as fatigue, shortness of breath and swelling in the legs. It sometimes follows a heart attack or heart infection, but in many other cases, its cause remains unknown.
With the new study, beta-blockers join certain vasodilator drugs, such as ACE inhibitors, as the only treatments shown to prolong survival for people with heart failure, Heidenreich said.
Beta-blockers are commonly used to lower blood pressure. They prevent catecholamines, a family of hormones produced by the sympathetic nervous system, from delivering their message. By keeping blood vessels unaware of a circulating catecholamine called norepinephrine, beta- blockers stop the vessels from contracting, and thereby lower blood pressure.
Beta-blockers also counteract another catecholamine called epinephrine, which usually acts on the heart, making it beat more strongly. Beta-blockers slow the heart -- an effect that would seem to make this treatment too risky for patients with an already damaged heart.
"For a long time it was thought that you should never use these drugs for people with heart failure," Heidenreich said.
For this reason, doctors have been very cautious in trials administering beta-blockers to patients with heart failure. Although the small trials, when viewed individually, showed that giving the drugs in cases of heart failure was not a disaster, any subtler trends were impossible to spot.
To see if pooling the results could give a more definitive answer, Heidenreich used a powerful statistical method called meta-analysis. The project began as part of a statistics class he was taking for a master's degree in health services research. Heidenreich started by classifying the 35 published trials that were relevant. He found that only 17 of the trials met his four criteria: The patients had heart failure before the trial; occurrence and cause of death were reported; the trial ran for three months or more; and the trial was placebo- controlled.
For each trial, he figured the degree of benefit or harm from the treatment, as well as the trustworthiness of this result. The confidence level was based mainly on how many people were in a given trial. Heidenreich then weighted each result (depending, again, on the size of the trial) and calculated a summary value.
That value clearly showed that the beta-blockers were beneficial. "And because we included all 17 trials," he said, "we can be much more sure of our results."
Thwarting epinephrine with beta-blockers works even though production of the hormone is the body's defense response to a damaged heart, Heidenreich said. When epinephrine is produced, he explained, "initially there's probably an improvement" as the heart revs up again after a heart attack or infection. But all that work takes it toll, and over time the heart is damaged more. "More epinephrine is produced, and more damage is done. Over the long run, this response actually makes things worse," he said.
Counteracting that response is where the beta-blockers come in.
Some people do not tolerate beta-blockers, Heidenreich noted, "but for people who can tolerate them, it looks as though they will definitely benefit." The benefit in these patients probably lasts at least a year, but more studies are needed to determine whether longer treatments are useful, he said.
In addition to his work as a research fellow, Heidenreich serves as a part-time staff physician in cardiology at the Veterans Affairs Palo Alto Health Care System. Also participating in the beta-blocker study were Dr. Tina Lee, a research fellow in the Department of Health Research and Policy at Stanford, and Dr. Barry Massie, a professor of medicine at the University of California, San Francisco. Ingram Olkin, a Stanford professor of statistics, taught the statistics class.
Heidenreich and Lee are supported by the federal Agency for Health Care Policy and Research.
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