Infusion of glucose, insulin, and potassium yielded no benefit for patients with ST-segment elevation myocardial infarction in two large clinical trials, and the treatment may even cause harm, suggests an analysis of data on almost 23,000 patients.
Twenty-four-hour glucose-insulin-potassium (GIK) infusion exerted no favorable effect on any important clinical end point, and it appeared to raise mortality in the early postinfarction period, researchers wrote in the JAMA.
Several small studies have supported the use of GIK infusion to treat STEMI, but the Clinical Trial of Reviparin and Metabolic Modulation in Acute Myocardial Infarction Treatment and Evaluation—Estudios Clinicos Latino America (CREATE-ECLA), which enrolled more than 20,000 subjects, showed only a neutral effect.
A second large-scale clinical study assessing the treatment—the Organization for the Assessment of Strategies for Ischemic Syndromes-6 (OASIS-6) trial—was halted early when the CREATE-ECLA results were announced. The data from the first 2,748 subjects in the OASIS-6 trial have just been analyzed and combined with the CREATE-ECLA findings.
Dr. Rafael Diaz of Estudios Cardiologica Latin America, Rosario, Argentina, and his associates have reported the 30-day outcomes for 22,943 subjects in both studies.
There were no differences between STEMI patients who received GIK infusions and control subjects who received standard care in 30-day rates of death (9.7% vs. 9.3%), heart failure (16.5% vs. 16.7%), or the combined end point of death or heart failure (20.3% vs. 20.4%) in the combined analysis. Similarly, in subgroup analyses comparing patients who were treated immediately (within 2 hours) after symptom onset, those treated soon (within 4 hours), and those treated later (after 4 hours), GIK infusion did not reduce mortality in any group.
“We observed a higher rate of death and the composite of death or heart failure at 3 days in patients allocated to GIK therapy, compared with controls. Between 4 and 30 days, there were lower rates of death and the composite of death or heart failure in the GIK infusion group than in the control group, and the overall effect of GIK therapy on 30-day outcomes was neutral.
“It is possible that despite its early harmful effects, GIK therapy may have delayed benefits that neutralize its early hazard, but a more likely explanation for the observed 'late benefit' is postrandomization (survivor) bias,” the investigators said (JAMA 2007;298:2399–405).
It appears that rather than simply ensuring normalized glucose levels, potassium levels, and fluid balance after STEMI, GIK infusion may actually induce hyperglycemia, hyperkalemia, and net fluid gain, they said.
The OASIS-6 trial was funded by Sanofi Aventis, Organon, and GlaxoSmithKline.