Glucose-insulin-potassium therapy in patients with ST-segment elevation myocardial infarction

Rafael Díaz, Abhinav Goyal, Shamir R. Mehta, Rizwan Afzal, Denis Xavier, Prem Pais, Susan Chrolavicius, Jun Zhu, Khawar Kazmi, Lisheng Liu, Andrzej Budaj, Mohammad Zubaid, Alvaro Avezum, Mikhail Ruda, Salim Yusuf

Research output: Contribution to journalArticlepeer-review

168 Citations (Scopus)

Abstract

Context: The clinical benefit of glucose-insulin-potassium (GIK) infusion in patients with ST-segment elevation myocardial infarction (STEMI) is unclear. While some smaller trials suggest benefit, in the CREATE-ECLA trial, GIK infusion had no effect on 30-day mortality in 20 201 patients. Objectives: To determine the association between GIK infusion therapy and 30-day and 6-month outcomes in patients with STEMI. Design, Setting, and Participants: Primary analysis of the OASIS-6 GIK randomized controlled trial of 2748 patients with acute STEMI; prespecified analyses of the combined trial data from the OASIS-6 GIK and CREATE-ECLA GIK trial populations of 22 943 patients with acute STEMI; subgroup analysis on the timing of initiation of GIK infusion therapy and outcomes; and post hoc analyses exploring whether GIK infusion may cause early harm by increasing glucose and potassium levels and net fluid gain. Intervention: High-dose GIK solution consisting of 25% glucose, 50 U/L of regular insulin, and 80 mEq/L of potassium infused at 1.5 mL/kg per hour for 24 hours. Main Outcome Measures: Mortality rates at 30 days and 6 months in the OASIS-6 GIK trial and rates of death, heart failure, and the composite of death or heart failure at 3 and 30 days in the combined OASIS-6 GIK and CREATE-ECLA GIK trial populations. Results: At 6 months, 148 (10.8%) GIK infusion patients and 143 (10.4%) control patients died in the OASIS-6 trial (hazard ratio [HR], 1.04; 95% CI, 0.83-1.31; P=.72); 153 (11.1%) GIK patients and 185 (13.5%) control patients had heart failure (HR, 0.83; 95% CI, 0.67-1.02; P=.08); and 240 (17.5%) GIK patients and 264 (19.2%) control patients had a composite of death or heart failure (HR, 0.91; 95% CI, 0.76-1.08; P=.27). In the prespecified analyses of the combined trial data, there were 712 deaths (6.2%) in the GIK group and 632 deaths (5.5%) in the control group at 3 days (HR, 1.13; 95%CI, 1.02-1.26; P=.03). This difference disappeared by30days, with 1108 deaths (9.7%) in the GIK group and 1068 (9.3%) in the control group (HR, 1.04;95%CI, 0.96-1.13; P=.33). GIK therapy increased levels of glucose, potassium, and net fluid gain postinfusion, all 3 of which predicted death after adjusting for multiple confounders. Adjusting for glucose, potassium, and net fluid gain eliminated the apparent increase in mortality at 3 days observed with GIK infusion, suggesting a direct association with these factors. Administration of GIK infusion within 4 hours of symptom onset yielded no benefit compared with later initiation. Conclusions: Infusion of GIK provided no benefit and may cause early harm following STEMI. Avoidance of infusion-related hyperglycemia, hyperkalemia, and net fluid gain may be advisable in future studies of metabolic modulation in patients with STEMI. Trial Registration: clinicaltrials.gov Identifier: NCT00064428

Original languageEnglish
Pages (from-to)2399-2405
Number of pages7
JournalJAMA - Journal of the American Medical Association
Volume298
Issue number20
DOIs
Publication statusPublished - 28 Nov 2007

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