The role of insulin therapy and glucose normalisation in patients with acute coronary syndrome

Patients with acute myocardial infarction (AMI) and diabetes mellitus, as well as patients admitted with elevated blood glucose without known diabetes, have impaired outcome. Therefore intensive glucose-lowering therapy with insulin (IGL) has been proposed in diabetic or hyperglycaemic patients and has been shown to improve survival and reduce incidence of adverse events. The current manuscript provides an overview of randomised controlled trials investigating the effect of IGL. Furthermore, systematic glucose–insulin–potassium infusion (GIK) has been studied to improve outcome after AMI. In spite of positive findings in some early studies, GIK did not show any beneficial effects in recent clinical trials and thus this concept has been abandoned. While IGL targeted to achieve normoglycaemia improves outcome in patients with AMI, achievement of glucose regulation is difficult and carries the risk of hypoglycaemia. More research is needed to determine the optimal glucose target levels in AMI and to investigate whether computerised glucose protocols and continuous glucose sensors can improve safety and efficacy of IGL

Effect of additional treatment with EXenatide in patients with an Acute Myocardial Infarction (EXAMI): study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Myocardial infarction causes irreversible loss of cardiomyocytes and may lead to loss of ventricular function, morbidity and mortality. Infarct size is a major prognostic factor and reduction of infarct size has therefore been an important objective of strategies to improve outcomes. In experimental studies, glucagon-like peptide 1 and exenatide, a long acting glucagon-like peptide 1 receptor agonist, a novel drug introduced for the treatment of type 2 diabetes, reduced infarct size after myocardial infarction by activating pro-survival pathways and by increasing metabolic efficiency.</p> <p>Methods</p> <p>The EXAMI trial is a multi-center, prospective, randomized, placebo controlled trial, designed to evaluate clinical outcome of exenatide infusion on top of standard treatment, in patients with an acute myocardial infarction, successfully treated with primary percutaneous coronary intervention. A total of 108 patients will be randomized to exenatide (5 μg bolus in 30 minutes followed by continuous infusion of 20 μg/24 h for 72 h) or placebo treatment. The primary end point of the study is myocardial infarct size (measured using magnetic resonance imaging with delayed enhancement at 4 months) as a percentage of the area at risk (measured using T2 weighted images at 3-7 days).</p> <p>Discussion</p> <p>If the current study demonstrates cardioprotective effects, exenatide may constitute a novel therapeutic option to reduce infarct size and preserve cardiac function in adjunction to reperfusion therapy in patients with acute myocardial infarction.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01254123">NCT01254123</a></p

The impact of glucose-insulin-potassium infusion in acute myocardial infarction on infarct size and left ventricular ejection fraction [ISRCTN56720616]

BACKGROUND: Favorable clinical outcomes have been observed with glucose-insulin-potassium infusion (GIK) in acute myocardial infarction (MI). The mechanisms of this beneficial effect have not been delineated clearly. GIK has metabolic, anti-inflammatory and profibrinolytic effects and it may preserve the ischemic myocardium. We sought to assess the effect of GIK infusion on infarct size and left ventricular function, as part of a randomized controlled trial. METHODS: Patients (n = 940) treated for acute MI by primary percutaneous coronary intervention (PCI) were randomized to GIK infusion or no infusion. Endpoints were the creatinine kinase MB-fraction (CK-MB) and left ventricular ejection fraction (LVEF). CK-MB levels were determined 0, 2, 4, 6, 24, 48, 72 and 96 hours after admission and the LVEF was measured before discharge. RESULTS: There were no differences between the two groups in the time course or magnitude of CK-MB release: the peak CK-MB level was 249 ± 228 U/L in the GIK group and 240 ± 200 U/L in the control group (NS). The mean LVEF was 43.7 ± 11.0 % in the GIK group and 42.4 ± 11.7% in the control group (P = 0.12). A LVEF ≤ 30% was observed in 18% in the controls and in 12% of the GIK group (P = 0.01). CONCLUSION: Treatment with GIK has no effect on myocardial function as determined by LVEF and by the pattern or magnitude of enzyme release. However, left ventricular function was preserved in GIK treated patients

Modifying effect of dual antiplatelet therapy on incidence of stent thrombosis according to implanted drug-eluting stent type

Aim To investigate the putative modifying effect of dual antiplatelet therapy (DAPT) use on the incidence of stent thrombosis at 3 years in patients randomized to Endeavor zotarolimus-eluting stent (E-ZES) or Cypher sirolimus-eluting stent (C-SES). Methods and results Of 8709 patients in PROTECT, 4357 were randomized to E-ZES and 4352 to C-SES. Aspirin was to be given indefinitely, and clopidogrel/ticlopidine for ≥3 months or up to 12 months after implantation. Main outcome measures were definite or probable stent thrombosis at 3 years. Multivariable Cox regression analysis was applied, with stent type, DAPT, and their interaction as the main outcome determinants. Dual antiplatelet therapy adherence remained the same in the E-ZES and C-SES groups (79.6% at 1 year, 32.8% at 2 years, and 21.6% at 3 years). We observed a statistically significant (P = 0.0052) heterogeneity in treatment effect of stent type in relation to DAPT. In the absence of DAPT, stent thrombosis was lower with E-ZES vs. C-SES (adjusted hazard ratio 0.38, 95% confidence interval 0.19, 0.75; P = 0.0056). In the presence of DAPT, no difference was found (1.18; 0.79, 1.77; P = 0.43). Conclusion A strong interaction was observed between drug-eluting stent type and DAPT use, most likely prompted by the vascular healing response induced by the implanted DES system. These results suggest that the incidence of stent thrombosis in DES trials should not be evaluated independently of DAPT use, and the optimal duration of DAPT will likely depend upon stent type (Clinicaltrials.gov number NCT00476957

Clinical outcomes of state-of-the-art percutaneous coronary revascularization in patients with de novo three vessel disease: 1-year results of the SYNTAX II study

Aims: To investigate if recent technical and procedural developments in percutaneous coronary intervention (PCI) significantly influence outcomes in appropriately selected patients with three-vessel (3VD) coronary artery disease. Methods and results: The SYNTAX II study is a multicenter, all-comers, open-label, single arm study that investigated the impact of a contemporary PCI strategy on clinical outcomes in patients with 3VD in 22 centres from four European countries. The SYNTAX-II strategy includes: heart team decision-making utilizing the SYNTAX Score II (a clinical tool combining anatomical and clinical factors), coronary physiology guided revascularisation, implantation of thin strut bio-resorbable-polymer drug-eluting stents, intravascular ultrasound (IVUS) guided stent implantation, contemporary chronic total occlusion revascularisation techniques and guideline-directed medical therapy. The rate of major adverse cardiac and cerebrovascular events (MACCE [composite of all-cause death, cerebrovascular event, any myocardial infarction and any revascularisation]) at one year was compared to a predefined PCI cohort from the original SYNTAX-I trial selected on the basis of equipoise 4-year mortality between CABG and PCI. As an exploratory endpoint, comparisons were made with the historical CABG cohort of the original SYNTAX-I trial. Overall 708 patients were screened and discussed within the heart team; 454 patients were deemed appropriate to undergo PCI. At one year, the SYNTAX-II strategy was superior to the equipoise-derived SYNTAX-I PCI cohort (MACCE SYNTAX-II 10.6% vs. SYNTAX-I 17.4%; HR 0.58, 95% CI 0.39-0.85, P= 0.006). This difference was driven by a significant reduction in the incidence of MI (HR 0.27, 95% CI 0.11-0.70, P= 0.007) and revascularisation (HR 0.57, 95% CI 0.37-0.9, P = 0.015). Rates of all-cause death (HR 0.69, 95% CI 0.27-1.73, P = 0.43) and stroke (HR 0.69, 95% CI 0.10-4.89, P = 0.71) were similar. The rate of definite stent thrombosis was significantly lower in SYNTAX-II (HR 0.26, 95% CI 0.07-0.97, P = 0.045). Conclusion: At one year, clinical outcomes with the SYNTAX-II strategy were associated with improved clinical results compared to the PCI performed in comparable patients from the original SYNTAX-I trial. Longer term follow-up is awaited and a randomized clinical trial with contemporary CABG is warranted