Discarded Treatment For Heart Attacks May Yet Prove To Be A Life-Saver

November 23, 1998

DALLAS, Nov. 24 -- A simple and inexpensive treatment for heart attacks -- originally developed in the early 1960s and now largely abandoned -- appears now to have significant life-saving powers, according to a new study.

A trial in six Latin American countries provides new evidence supporting the use of a combination of glucose, insulin, and potassium (GIK) in people suffering heart attacks, researchers report in today's Circulation: Journal of the American Heart Association. K is the chemical symbol for potassium.

In the pilot trial involving 407 people suffering a heart attack, patients treated with the GIK combination within 24 hours after symptoms had an overall death rate of about half that of people who did not get GIK.

"The decrease in the death rate is dramatic; the largest reduction of just about any intervention that's been tried," says Carl S. Apstein, M.D., whose editorial on the study appears in today's Circulation. He is professor of medicine and director of the Cardiac Muscle Research Laboratory at Boston University's School of Medicine. "The mechanism of efficacy is also completely different, in that it alters heart muscle metabolism and biochemistry to protect the region of the heart deprived of oxygen by a heart attack."

The 407 people in the trial included 252 individuals treated with either a clot-dissolving drug or a balloon-tipped catheter inserted into the vessels to open clogged blood vessels. People who received GIK infusions had a death rate of 6.7 percent versus an 11.5 percent death rate among those who did not get the combination. However, among the 252 people who received therapy to open clogged blood vessels, the mortality rate was 5.2 percent in the GIK-treated group, compared to 15.2 percent in those who did not receive GIK.

Patients were randomized to one of three groups: high-dose or low-dose GIK, or no GIK. There were no significant differences in results or adverse effects between the two GIK groups. Some people in all three groups received reperfusion therapy and some did not.

According to the researchers, almost every study finding, including the number of patients suffering heart failure or severe irregular heartbeats, showed either significant benefit or a trend towards a benefit in patients who received GIK.

"The sample size is very small and perhaps the findings are influenced by chance," says the study's lead author, Rafael Diaz, M.D. "So instead of looking for the magnitude of the benefit, we should look for the direction of the benefit. And the direction of the benefit is consistently positive."

Diaz is co-director of the cardiovascular medicine division of the Instituto Cardiovascular de Rosario in Argentina and the co-director of the ECLA Collaborative Group, which carried out the study at 29 hospitals in Argentina, Brazil, Chile, Mexico, Uruguay and Venezuela.

GIK's protective powers may stem from several actions, says Diaz. Animal research suggests the combination reduces the harmful high concentrations of free fatty acids during the hyperacute phase of a heart attack. The combination provides additional glucose, which heart muscles can metabolize even without oxygen to produce enough energy to help them maintain their membranes and the "pumps" that move sodium and potassium in and out of cells. It also replaces potassium lost as a result of cell damage. And it may inhibit the insulin resistance that occurs in heart attacks. Insulin resistance prevents cells from using insulin effectively.

The trial was not intended to determine GIK's effectiveness in heart attack patients, but to decide whether a larger investigation of the combination was warranted. The ECLA group is now organizing a worldwide study and has recruited about 200 of the over 400 centers it plans to involve in a trial of GIK in 10,000 heart attack patients.

In the upcoming trial, the GIK II International Study, each patient will undergo reperfusion therapy and none will receive the drug more than 12 hours after the onset of symptoms. It is scheduled to conclude in 2001.

"We are expecting a reduction in death of about 15 or 20 percent among patients treated with GIK," Diaz says. "Nobody can expect a reduction of more than 20 or 25 percent, because heart attack is a very prevalent disease with high rates of mortality."

The GIK combination was first reported as a treatment for heart attack in 1962. During the next decade, it was used by some physicians, but clinical studies came to conflicting conclusions about its effectiveness.

However, some researchers continued animal studies with GIK and "it very consistently showed a protective effect," Apstein says. "So there was this disparity for 25 or 30 years between what was shown to work in animals and what was never shown to work in patients."

The ECLA group began developing its study in 1994. Last year, British researchers using only those studies that met the criteria for being well-designed, concluded that giving GIK could reduce the death rate in heart attack patients by up to 48 percent.

Patients who received GIK had "few and minor side effects," Diaz says, with the most prevalent being a mild case of phlebitis at the site of the injection. Phlebitis is the term used to describe the stiffness, inflammation or pain occurring when a vein is punctured.

"If this reduction in heart attack death rates is confirmed in further studies, GIK has the potential to prevent about 75,000 heart attack deaths per year in the U.S.," says Apstein.

Co-authors of the paper are Ernesto C. Paolasso, M.D.; Leopoldo S. Piegas, M.D.; Carols D. Tajer, M.D.; Manuel Gil Moreno, M.D.; Ramon Corvalan, M.D.; Jesus E. Isea, M.D.; and Graciela Romero, M.D.
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CONTACT:

For journal copies only, please call 214-706-1173 or 1396

For other information, call Brian Henry: 214-706-1135 or Carole Bullock: 214-706-1279

Media advisory: Dr. Diaz can be reached by phone at 54-41-49-3045, by fax at 54-41-24-2071 or by e-mail at ecla@satlink.com. Dr. Apstein can be reached by phone at 617-638-4033 or by e-mail at capstein@bu.edu. (Please do not publish numbers.)
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American Heart Association

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