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Glucose-Insulin-Potassium Therapy in Patients With ST-Segment Elevation Myocardial Infarction
Rafael Díaz, MD;
Abhinav Goyal, MD, MHS;
Shamir R. Mehta, MD, MSc;
Rizwan Afzal, MSc;
Denis Xavier, MD;
Prem Pais, MD, MSc;
Susan Chrolavicius, RN, BA;
Jun Zhu, MD;
Khawar Kazmi, MD;
Lisheng Liu, MD;
Andrzej Budaj, MD, PhD;
Mohammad Zubaid, MD;
Alvaro Avezum, MD, PhD;
Mikhail Ruda, MD;
Salim Yusuf, MBBS, DPhil
JAMA. 2007;298(20):2399-2405.
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 by 30 days, 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
Author Affiliations: Etudios Cardiologica Latin America, Rosario, Argentina (Dr Díaz); Department of Epidemiology, Emory Rollins School of Public Health and Emory School of Medicine, Atlanta, Georgia (Dr Goyal); Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada (Drs Goyal, Mehta, Xavier, and Yusuf, Mr Afzal, and Ms Chrolavicius); Department of Medicine, McMaster University, Hamilton, Ontario, Canada (Drs Mehta and Yusuf, Mr Afzal, and Ms Chrolavicius); St John's Medical College National Academy of Health Sciences, Bangalore, India (Drs Xavier and Pais); Cardiovascular Institute and Fu Wai Hospital, Chinese Hypertension League Institute, Beijing, China (Drs Zhu and Liu); Aga Khan University, Karachi, Pakistan (Dr Kazmi); Postgraduate Medical School, Department of Cardiology, Grochowski Hospital, Warsaw, Poland (Dr Budaj); Mubarak Al-Kabeer Hospital, Safat, Kuwait (Dr Zubaid); Dante Pazzanese Cardiology Institute, São Paulo, Brazil (Dr Avezum); and Cardiology Research Center, Moscow, Russia (Dr Ruda).
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