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Glucose-Insulin-Potassium Therapy in Patients with ST-Segment Elevation Myocardial Infarction
494 and other variables that differ from swine. Furthermore, the conclusions of the study may not apply to bystander CPR performed by two rescuers without interruptions in compressions when two ventilations are delivered.
e DARK CHOCOLATE IMPROVES CORONARY VASOMOTION AND REDUCES PLATELET REACTIVITY. Lammer AJ, Hermann F, Sudano I, et al. Circulation 2007;116:2376 – 82. This randomized, double-blinded, case-control trial evaluated the effect on coronary vascular and platelet function by flavonoid-rich dark chocolate, a substance with known antioxidant properties. Twenty-two heart transplant patients scheduled for routine coronary angiography were randomized to two groups; one receiving 40 g dark chocolate (70% cocoa) and the control group receiving 40 g of cocoa-free chocolate. Two hours after ingestion of dark chocolate, control subjects were evaluated for serum levels of flavonoids catechin and epicatechin, coronary artery diameter, coronary vasomotion (% change of diameter) after cold pressor test, shear stress-dependent platelet function, and three different biomarkers of oxidative stress. Serum epicatechin concentration increased significantly after dark chocolate ingestion, although no change was noted in catechin concentrations. Coronary artery diameter increased significantly (2.36 ¡ 2.51 mm) after dark chocolate ingestion, although no change was noted after control ingestion. Endothelium-dependent coronary vasomotion (percent change of artery diameter induced by cold pressor test) improved significantly after dark chocolate ingestion (4.5% vs. ⫺4.6%). No significant change was noted between groups for two of the oxidative stress biomarkers (TRAP assay—total radical-reducing antioxidant potential and FRAP assay—ferric-reducing antioxidant potential), although 8-isoprostanes were reduced significantly after dark chocolate consumption and their levels were not altered after control consumption. Shear stressdependent platelet adhesion decreased from 4.9% to 3.8% in the dark chocolate group and was not significantly altered in the control group. The authors conclude that a short-term effect of flavonoid-rich dark chocolate results in improved coronary vasodilatation, improved coronary vasomotion and shear stressdependent platelet adhesion. [Zachary D. Tebb, MD, Denver Health Medical Center, Denver, CO] Comment: Although this study is limited by the small sample size, the physiologic effects of dark chocolate are impressive, although prospective, long-term randomized studies with mortality and morbidity outcomes are needed to determine the potential of dark chocolate to beneficially affect atherothrombosis in a clinical setting. It should be noted that industry collaboration occurred in this study.
e GLUCOSE-INSULIN-POTASSIUM THERAPY IN PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION. Diaz R, Goyal A, Mehta, SR, et al. JAMA 2007;298:2399 – 405.
Abstracts This study reviewed the data from both the Clinical Trial of Reviparin and Metabolic Modulation in Acute Myocardial Infarction Treatment and Evaluation - Estudios Clinicos Latino America (CREATE-ECLA) and the Organization for the Assessment of Strategies for Ischemic Syndromes-6 (OASIS-6) trial. The primary intervention of both trials was a glucoseinsulin-potassium (GIK) infusion for 24 h after the diagnosis of ST-segment elevation MI (STEMI). The objective was to examine the clinical outcomes at 30 days and 6 months in the OASIS-6 trial and 30-day outcomes in the combined trial population. The primary outcomes were death, heart failure, and composite of death or heart failure. Subgroup analysis was also performed for the timing of initiation of GIK infusion. The combined trials had a total population of 22,943 patients with acute STEMI. Time to clinical events between intervention and controls were compared using the log-rank statistic with the Cox proportional hazards model used to estimate hazards ratios. The analysis of the OASIS-6 trial showed no difference between GIK and control groups at 30 days or 6 months for major outcomes. The combination of the trials also showed no difference in intervention vs. control in the categories of death (p ⫽ 0.33), heart failure (p ⫽ 0.82), or for the composite of death or heart failure (p ⫽ 0.99). Additionally, no further benefit was found in the subgroup analysis of symptom onset to time of randomization to therapy. The authors conclude that GIK infusion provides no further benefit in STEMI, and the avoidance of infusion-related hyperglycemia, hyperkalemia, and net fluid gain may be advisable. [Andrew French, MD, Denver Health Medical Center, Denver, CO] Comment: This study is limited by the fact that it is retrospective and combines the data from two heterogeneous study populations. Nevertheless, it adds further evidence as to the lack of efficacy of GIK therapy in patients with STEMI.
e PERSISTENCE OF CONTRADICTED CLAIMS IN THE LITERATURE. Tatsioni A, Bonitsis NG, Ioannidis JPA. JAMA 2007;298:2517–26. The objectives of this study were to examine what happens to the scientific literature when a highly prominent claim is refuted, and to understand how these benefits continue to be defended in the literature. To this effect, the highly disputed beneficial claims of the use of vitamin E for cardiovascular disease were analyzed via retrospective review of citation counts as well as characteristics of the citing articles. Articles from 1997, 2001, and 2005 were sampled that referenced two highly cited epidemiologic studies that proposed major cardiovascular benefits associated with vitamin E in 1993. These years were chosen as representative of before, early, and late after publication of refuting evidence, respectively. Articles from 2005 were also separately sampled that referenced the most cited contradicting randomized trial (HOPE trial, published in 2000). When the context of the citation was pertinent to the association between vitamin E and cardiovascular disease prevention, the overall stance of the article was categorized as favorable, equivocal, or unfavorable. The main hypoth-
e DARK CHOCOLATE IMPROVES CORONARY VASOMOTION AND REDUCES PLATELET REACTIVITY. Lammer AJ, Hermann F, Sudano I, et al. Circulation 2007;116:2376 – 82. This randomized, double-blinded, case-control trial evaluated the effect on coronary vascular and platelet function by flavonoid-rich dark chocolate, a substance with known antioxidant properties. Twenty-two heart transplant patients scheduled for routine coronary angiography were randomized to two groups; one receiving 40 g dark chocolate (70% cocoa) and the control group receiving 40 g of cocoa-free chocolate. Two hours after ingestion of dark chocolate, control subjects were evaluated for serum levels of flavonoids catechin and epicatechin, coronary artery diameter, coronary vasomotion (% change of diameter) after cold pressor test, shear stress-dependent platelet function, and three different biomarkers of oxidative stress. Serum epicatechin concentration increased significantly after dark chocolate ingestion, although no change was noted in catechin concentrations. Coronary artery diameter increased significantly (2.36 ¡ 2.51 mm) after dark chocolate ingestion, although no change was noted after control ingestion. Endothelium-dependent coronary vasomotion (percent change of artery diameter induced by cold pressor test) improved significantly after dark chocolate ingestion (4.5% vs. ⫺4.6%). No significant change was noted between groups for two of the oxidative stress biomarkers (TRAP assay—total radical-reducing antioxidant potential and FRAP assay—ferric-reducing antioxidant potential), although 8-isoprostanes were reduced significantly after dark chocolate consumption and their levels were not altered after control consumption. Shear stressdependent platelet adhesion decreased from 4.9% to 3.8% in the dark chocolate group and was not significantly altered in the control group. The authors conclude that a short-term effect of flavonoid-rich dark chocolate results in improved coronary vasodilatation, improved coronary vasomotion and shear stressdependent platelet adhesion. [Zachary D. Tebb, MD, Denver Health Medical Center, Denver, CO] Comment: Although this study is limited by the small sample size, the physiologic effects of dark chocolate are impressive, although prospective, long-term randomized studies with mortality and morbidity outcomes are needed to determine the potential of dark chocolate to beneficially affect atherothrombosis in a clinical setting. It should be noted that industry collaboration occurred in this study.
e GLUCOSE-INSULIN-POTASSIUM THERAPY IN PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION. Diaz R, Goyal A, Mehta, SR, et al. JAMA 2007;298:2399 – 405.
Abstracts This study reviewed the data from both the Clinical Trial of Reviparin and Metabolic Modulation in Acute Myocardial Infarction Treatment and Evaluation - Estudios Clinicos Latino America (CREATE-ECLA) and the Organization for the Assessment of Strategies for Ischemic Syndromes-6 (OASIS-6) trial. The primary intervention of both trials was a glucoseinsulin-potassium (GIK) infusion for 24 h after the diagnosis of ST-segment elevation MI (STEMI). The objective was to examine the clinical outcomes at 30 days and 6 months in the OASIS-6 trial and 30-day outcomes in the combined trial population. The primary outcomes were death, heart failure, and composite of death or heart failure. Subgroup analysis was also performed for the timing of initiation of GIK infusion. The combined trials had a total population of 22,943 patients with acute STEMI. Time to clinical events between intervention and controls were compared using the log-rank statistic with the Cox proportional hazards model used to estimate hazards ratios. The analysis of the OASIS-6 trial showed no difference between GIK and control groups at 30 days or 6 months for major outcomes. The combination of the trials also showed no difference in intervention vs. control in the categories of death (p ⫽ 0.33), heart failure (p ⫽ 0.82), or for the composite of death or heart failure (p ⫽ 0.99). Additionally, no further benefit was found in the subgroup analysis of symptom onset to time of randomization to therapy. The authors conclude that GIK infusion provides no further benefit in STEMI, and the avoidance of infusion-related hyperglycemia, hyperkalemia, and net fluid gain may be advisable. [Andrew French, MD, Denver Health Medical Center, Denver, CO] Comment: This study is limited by the fact that it is retrospective and combines the data from two heterogeneous study populations. Nevertheless, it adds further evidence as to the lack of efficacy of GIK therapy in patients with STEMI.
e PERSISTENCE OF CONTRADICTED CLAIMS IN THE LITERATURE. Tatsioni A, Bonitsis NG, Ioannidis JPA. JAMA 2007;298:2517–26. The objectives of this study were to examine what happens to the scientific literature when a highly prominent claim is refuted, and to understand how these benefits continue to be defended in the literature. To this effect, the highly disputed beneficial claims of the use of vitamin E for cardiovascular disease were analyzed via retrospective review of citation counts as well as characteristics of the citing articles. Articles from 1997, 2001, and 2005 were sampled that referenced two highly cited epidemiologic studies that proposed major cardiovascular benefits associated with vitamin E in 1993. These years were chosen as representative of before, early, and late after publication of refuting evidence, respectively. Articles from 2005 were also separately sampled that referenced the most cited contradicting randomized trial (HOPE trial, published in 2000). When the context of the citation was pertinent to the association between vitamin E and cardiovascular disease prevention, the overall stance of the article was categorized as favorable, equivocal, or unfavorable. The main hypoth-