Second Trial Finds Infusion No Help in STEMI


ATLANTA, Nov. 27 -- Heart attack victims do not benefit from an infusion of glucose, insulin, and potassium soon after the event, researchers here said.
Action Points
Explain to interested patients that small studies had suggested that an infusion of glucose, insulin, and potassium would benefit patients with ST-segment elevation myocardial infarction.
Note that this report shows that the infusion does no good and may perhaps do some harm in the first few days after a heart attack.
The finding marks the second time the so-called GIK therapy has been found wanting in patients with ST-segment elevation myocardial infarction (STEMI), Abhinav Goyal, M.D., of the Emory Rollins School of Public Health, and colleagues reported in the Nov. 28 issue of the Journal of the American Medical Association.
In fact, patients getting the GIK infusion appeared to have a slightly higher risk of death during the first three days after heart attack, although at 30 days there was no difference between them and controls, the researchers said.
The findings were not a surprise, the researchers said. In 2005, many of the same investigators reported that the therapy had a neutral effect in the 20,201 patients in a large randomized, controlled trial, the CREATE-ECLA study.
The current study, dubbed Organization for the Assessment of Strategies for Ischemic Syndromes-6 (OASIS-6), was stopped early when the CREATE results were published.
Both studies were two-by-two factorial designs, in which patients were randomized in a blinded fashion to get placebo or an anticoagulant drug -- fondaparinux (Arixtra) in the OASIS-6 trial and reviparin (Clivarine) in the CREATE study -- as well as the GIK infusion or no infusion, in an open-label fashion.
In this report, Dr. Goyal said, the researchers presented data on the 2,748 patients with acute STEMI who were randomized in OASIS-6 to get either GIK or no infusion before the study was halted.
They also reported a combined analysis of all patients in both trials.
The researchers found that in the OASIS-6 study, there were no differences at 30 days between the GIK infusion and the control groups in death (P=0.36), heart failure (P=0.31), or death and heart failure combined (P=0.41).
When the two studies were combined -- yielding 22,943 patients available for analysis -- the 30-day results were much the same.
However, when the researchers looked at the first three days after the heart attack, they found:
712 deaths (or 6.2%) in the GIK group and 632 deaths (or 5.5%) in the control group, for a hazard ratio of 1.13 and a 95% confidence interval from 1.02 to 1.26, which was significant at P=0.03.
1,509 death or heart failure events in the GIK group (or 15.8%) and 1,388 events in the control group (or 14.5%) for a hazard ratio of 1.09 and a 95% confidence interval from 1.02 to1.18, which was significant at P=0.02.
There was a consistent but nonsignificant increase in the number of heart failures in the GIK group, the researchers said.
In the following 27 days, the researchers said, GIK infusion was associated with a significantly lower occurrence of heart failure and the composite outcome of death or heart failure, as well as a nonsignificant decrease in the risk of death.
Overall, however, the GIK infusion had no effect on any outcome, they said.
The finding of a short-term risk increase, followed by a longer-term benefit, was probably a case of "survivor bias," the researchers said, especially since statistically controlling for glucose, potassium, and fluid balance eliminated much of the effect.
"The early harmful effects of GIK therapy largely may be explained by its propensity to increase glucose, potassium, and net fluid gain," the researchers concluded.
The bottom line, Dr. Goyal and colleagues said, is that "GIK infusion does not produce a favorable clinical effect in patients with STEMI."
Future studies of metabolic modulations in STEMI patients should try to avoid methods that increase glucose, potassium, and fluids, they added.
The study was supported by sanofi-aventis, Organon, and GlaxoSmithKline.
Dr. Goyal reported no conflicts. However, three of the study authors -- Andrzej Budaj, M.D., Ph.D., of Grochowski Hospital in Warsaw and Shamir Mehta, M.D., and Salim Yusuf, M.B.B.S., D.Phil., both of McMaster University in Hamilton, Ont. -- reported financial links to sanofi- aventis and GlaxoSmithKline.
Primary source: Journal of the American Medical AssociationSource reference: Díaz R, et al "Glucose-insulin-potassium therapy in patients With ST-segment elevation myocardial infarction" JAMA 2007; 298(20): 2399-2405.