Resurrected Interest in an Old and Controversial Treatment for AMI

An infusion of glucose, insulin and potassium (GIK), a simple and inexpensive adjunctive treatment for heart attacks, originally surfaced in the early 1960s and then later abandoned amid controversy-is getting another look.

An earlier study, in 1996, looked at the results of a GIK administration to diabetic patients experiencing heart attacks. Researchers found a 29-58% decrease in relative mortality within the subgroups studied that received the GIK. 

Then a second study, this time a pilot study that was published in 1998, looked at six Latin American countries, utilizing 29 hospitals and 407 people. Participants were given either high does GIK, low dose GIK or no GIK within 24 hours of onset of symptoms. Two-thirds of the group included patients who were also treated with angioplasty or thrombolytics. Results were also stratified to also look at those that suffered significant arrhythmias and/or heart failure. Those that received GIK infusions had a death rate of 6.7 percent compared to a rate of 11.5 percent for those that did not receive the infusion. The difference was even greater in those that received thrombolytics and/or cardiac catheterization----5.2 percent death rate for those receiving GIK and 15.2 percent for those that did not (a 66% relative reduction). Researchers stated that in almost every stratification, those that received GIK "showed significant benefit or a trend towards a benefit…" Results did not reveal a difference in benefit between low dose and high dose GIK. Side effects reported were few and relatively minor, with IV site-specific phlebitis being the most common (2 percent).

"The sample size is very small and perhaps the findings are influenced by chance," said the study's lead author, Rafael Diaz, MD. "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. The trial was not intended to be pilot study but rather to indicate whether a larger investigation was warranted. 

In an editorial in Circulation following the pilot study's published results in 1998, Carl S. Apstein, MD., professor of medicine and director of the Cardiac Muscle Research Laboratory at Boston University's School of Medicine, stated, "The decrease in the death rate is dramatic; the largest
reduction of just about any intervention that's been tried… 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." 

GIK's benefit appears to come from several actions. Animal research suggests the combination reduces the 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 integrity of the cellular sodium and potassium pumps. It also replaces lost potassium as a result of cell damage. It also may overcome the insulin resistance that occurs during heart attacks.

In a more recent study, Pol-GIK, however, there was no reduction in mortality noted. Researchers speculate that the patient acuity was greater in the ECLA study and advocate larger scale studies to clarify the results. 

The recently released "Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiac Care---International Consensus on Science" in the August 22, 2000 supplement to Circulation, states "GIK therapy for patients with AMI may be helpful; it is easily administered and associated with few adverse effects…Before GIK can be widely recommended, larger clinical trials are needed to further evaluate its efficacy in a broad patient group with AMI and to identify patient subgroups for which it may be particularly beneficial (Class Indeterminate).

The GIK combination was first reported as a treatment for heart attack in 1962 and examined during clinical trial in 1969. Human study results have been conflicting, historically, despite consistent benefit being noted in animal studies.