Two Beta-Blocker Drugs Equal In Treating Heart Failure

May 24, 1999

DALLAS, May 25 -- The first direct comparison of two beta-blocker drugs for the treatment of congestive heart failure found that an older, cheaper drug is as effective as the newest one on the market, researchers report in today's Circulation: Journal of the American Heart Association.

Beta-blockers, which reduce the heart's workload and were developed to treat high blood pressure and chest pain, also have been found to be effective for treating congestive heart failure (CHF). The newest beta-blocker, carvedilol, is the only one that has Food and Drug Administration approval specifically for treatment of heart failure. Carvedilol is at least three times more expensive than metoprolol, the other beta-blocker tested in the study.

"Carvedilol is a different kind of beta-blocker that has additional effects, and we wanted to find out if these differences are important for patients. With beta-blocker use becoming more prevalent in treating heart failure, choosing an effective drug is important," says Marrick L. Kukin, M.D., director of the heart failure program at Mount Sinai Medical Center, New York City, and lead author of the study.

The study, designed to compare carvedilol with metoprolol, included 46 men and 21 women, ages 29 to 87, with CHF, in which the heart becomes too weak to pump blood. Shortness of breath and fatigue are symptoms of CHF, the only form of heart disease that is increasing in the U.S. population. Researchers compared the drug's effectiveness in increasing stamina for exercising; the heart's pumping ability; symptoms, and blood levels of antioxidants. Antioxidants soak up the free radicals that help form the fatty obstructions, called plaque, in blood vessels, which can trigger a heart attack or stroke.

Individuals taking either of the beta-blockers for six months felt better, were able to exercise longer without becoming exhausted, and had a 5 percent increase in the ejection fraction test that measures the heart's pumping ability. A normal ejection fraction is about 50 percent. "Because the most common heart problem in people over 65 is congestive heart failure, which causes more hospitalizations than any other disease, anything that improves quality of life for these patients will have wide-ranging public health effects," says Kukin.

Most of the participants in the study had moderate heart failure, defined by breathlessness and fatigue after walking up one flight of stairs, or severe heart failure, characterized by similar symptoms while walking less than one block on level ground. Fourteen patients, seven in each drug group, were unable to continue treatment due to adverse side effects.

Beta-blocker drugs work on the body's sympathetic nervous system, which pours hormones like adrenaline into the bloodstream in response to stress. In response to high levels of these hormones, the heart beats faster and has to work harder. CHF patients have high levels of these stress-related hormones, a sort of chronic panic mode. By blocking that response, beta-blockers make the heart beat more efficiently.

"Years ago, we were all taught in medical school to never use beta-blockers in heart failure because the initial dose makes the condition worse. Now we know that if treatment is initiated very slowly and the dosage is gradually increased, the majority of stable heart failure patients can tolerate the drug," says Kukin. Stable patients are those who are not hospitalized, do not have fluid congestion and have a systolic blood pressure above 85 mmHg.

The two drugs had parallel benefits. "However, we only can start a beta-blocker with very low dosages. Carvedilol is the only one available in very low doses," he says.

In their study, the researchers had a pharmacist crush metoprolol tablets and repackage the powder in capsules to obtain low-enough doses for initiating therapy.

Because metoprolol is an older medication and now generic, the manufacturer has not sought FDA approval for a low-dose form -- a problem that may be solved by a new extended release form currently in development, Kukin says.

The researchers were surprised to find that patients in both groups had beneficial decreases in antioxidant measurements because only carvedilol has been shown in animal studies to have antioxidant activity, says Kukin.

Co-researchers include Jill Kalman, M.D.; Robert H. Charney, M.D., Daniel Levy, M.D.; Cathleen Buchholz-Varley, N.P.; Ofelia N. Ocampo, N.P.; all of Mount Sinai School of Medicine, New York, and Calvin Eng, M.D., of Mount Sinai and the Bronx VA Medical Center.
Media advisory: Dr. Kukin can be reached at 212-241-3161. His fax number is 212-289-5971. (Please do not publish telephone numbers.)

American Heart Association

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