IMPORTANCE: Elevated plasma glucose levels in patients with acute coronary syndrome (ACS) on hospital admission are associated with increased mortality. Clinical trials of glucose regulation have provided inconsistent results with respect to cardiovascular outcomes, perhaps because target glucose levels have been suboptimal. OBJECTIVE: To study the effectiveness and safety of intensive glucose management in patients with ACS who have hyperglycemia, aiming at strict blood glucose normalization. DESIGN, SETTING, AND PARTICIPANTS: Single-center, prospective, open-label, randomized clinical trial in a large teaching hospital. Patients with ACS with an admission plasma glucose level of 140 to 288 mg/dL were eligible for inclusion and enrolled from July 23, 2008, to February 8, 2012. Patients with insulin-dependent diabetes mellitus were excluded. Informed consent was obtained from 294 patients, who were randomized. Of these, 93.6% received percutaneous coronary intervention (PCI). INTERVENTIONS:Intensive glucose management strategy, aiming at a plasma glucose level of 85 to 110 mg/dL by using intravenous insulin, or to conventional expectative glucose management. MAIN OUTCOMES AND MEASURES: End points were assessed according to the intention-to-treat principle. The primary end point was high-sensitivity troponin T value 72 hours after admission (hsTropT72); secondary end points, area under the curve of creatine kinase, myocardial band (AUC-CK-MB), release and myocardial perfusion scintigraphy findings at 6 weeks' follow-up. RESULTS: In the intensive management arm, median hsTropT72 was 1197 ng/L (25th and 75th percentiles of distribution, 541-2296 ng/L) vs 1354 ng/L (530-3057 ng/L) in the conventional arm (P = .41). Median AUC-CK-MB was 2372 U/L (1242-5004 U/L) vs 3171 U/L (1620-5337 U/L) (P = .18). The difference in median extent of myocardial injury measured by myocardial perfusion scintigraphy was not significant (2% vs 4%) (P = .07). Severe hypoglycemia (<50 mg/dL) was rare and occurred in 13 patients. Before discharge, death or a spontaneous second myocardial infarction occurred in 8 patients (5.7%) vs 1 (0.7%) (P = .04). CONCLUSIONS AND RELEVANCE Intensive glucose regulation did not reduce infarct size in hyperglycemic patients with ACS treated withPCI, and was associated with harm. Future studies should focus on patients with ACS who have persistently elevated blood glucose after PCI, and should evaluate alternative strategies for optimizing glycemia. TRIAL REGISTRATION: www.trialregister.nl Identifier: NTR1205.
RCT Entities:
IMPORTANCE: Elevated plasma glucose levels in patients with acute coronary syndrome (ACS) on hospital admission are associated with increased mortality. Clinical trials of glucose regulation have provided inconsistent results with respect to cardiovascular outcomes, perhaps because target glucose levels have been suboptimal. OBJECTIVE: To study the effectiveness and safety of intensive glucose management in patients with ACS who have hyperglycemia, aiming at strict blood glucose normalization. DESIGN, SETTING, AND PARTICIPANTS: Single-center, prospective, open-label, randomized clinical trial in a large teaching hospital. Patients with ACS with an admission plasma glucose level of 140 to 288 mg/dL were eligible for inclusion and enrolled from July 23, 2008, to February 8, 2012. Patients with insulin-dependent diabetes mellitus were excluded. Informed consent was obtained from 294 patients, who were randomized. Of these, 93.6% received percutaneous coronary intervention (PCI). INTERVENTIONS: Intensive glucose management strategy, aiming at a plasma glucose level of 85 to 110 mg/dL by using intravenous insulin, or to conventional expectative glucose management. MAIN OUTCOMES AND MEASURES: End points were assessed according to the intention-to-treat principle. The primary end point was high-sensitivity troponin T value 72 hours after admission (hsTropT72); secondary end points, area under the curve of creatine kinase, myocardial band (AUC-CK-MB), release and myocardial perfusion scintigraphy findings at 6 weeks' follow-up. RESULTS: In the intensive management arm, median hsTropT72 was 1197 ng/L (25th and 75th percentiles of distribution, 541-2296 ng/L) vs 1354 ng/L (530-3057 ng/L) in the conventional arm (P = .41). Median AUC-CK-MB was 2372 U/L (1242-5004 U/L) vs 3171 U/L (1620-5337 U/L) (P = .18). The difference in median extent of myocardial injury measured by myocardial perfusion scintigraphy was not significant (2% vs 4%) (P = .07). Severe hypoglycemia (<50 mg/dL) was rare and occurred in 13 patients. Before discharge, death or a spontaneous second myocardial infarction occurred in 8 patients (5.7%) vs 1 (0.7%) (P = .04). CONCLUSIONS AND RELEVANCE Intensive glucose regulation did not reduce infarct size in hyperglycemicpatients with ACS treated with PCI, and was associated with harm. Future studies should focus on patients with ACS who have persistently elevated blood glucose after PCI, and should evaluate alternative strategies for optimizing glycemia. TRIAL REGISTRATION: www.trialregister.nl Identifier: NTR1205.
Authors: Stacey A Seggelke; Mark C Lindsay; Ingrid Hazlett; Rebecca Sanagorski; Robert H Eckel; Cecilia C Low Wang Journal: Curr Diab Rep Date: 2017-08 Impact factor: 4.810
Authors: Cindya P Iswandi; Victor J van den Berg; Suat Simsek; Daan van Velzen; Edwin Ten Boekel; Jan-Hein Cornel; Sanneke de Boer; Maarten de Mulder; K Martijn Akkerhuis; Eric Boersma; Victor A Umans; Isabella Kardys Journal: Diab Vasc Dis Res Date: 2021 Nov-Dec Impact factor: 3.291