ao-128 and Myocardial-Infarction

We evaluated the effects of an alpha-glucosidase inhibitor, voglibose, on cardiovascular events in patients with a previous myocardial infarction (MI) and impaired glucose tolerance (IGT).. This prospective, randomized, open, blinded-endpoint study was conducted in 112 hospitals and clinics in Japan in 3000 subjects with both previous MI and IGT receiving voglibose (0.6 mg/day, n = 424) or no drugs (n = 435) for 2 years. The Data and Safety Monitoring Board (DSMB) recommended discontinuation of the study in June 2012 after an interim analysis when the outcomes of 859 subjects were obtained. The primary endpoint was cardiovascular events including cardiovascular death, nonfatal MI, nonfatal unstable angina, nonfatal stroke, and percutaneous coronary intervention/coronary artery bypass graft. Secondary endpoints included individual components of the primary endpoint in addition to all-cause mortality and hospitalization due to heart failure.. The age, ratio of males, and HbA. Although voglibose effectively treated IGT, no additional benefits for cardiovascular events in patients with previous MI and IGT were observed. Voglibose may not be a contributing therapy to the secondary prevention in patients with MI and IGT.. Clinicaltrials.gov number: NCT00212017.

Topics: Aged; Cardiovascular Diseases; Female; Glucose Intolerance; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Secondary Prevention; Treatment Outcome

Glucagon-like peptide 1 (GLP-1) reportedly exerts a protective effect against cardiac ischemia. We hypothesized that the alpha-glucosidase inhibitor voglibose, an unabsorbable antidiabetic drug with cardioprotective effects, may act through stimulation of GLP-1 receptors. The results of the present study suggest oral administration of voglibose reduces myocardial infarct size and mitigates cardiac dysfunction in rabbits after 30 minutes of coronary occlusion and 48 hours of reperfusion. Voglibose increased basal and postprandial plasma GLP-1 levels and reduced postprandial plasma glucose levels. The infarct size-reducing effect of voglibose was abolished by treatment with exendin(9-39), wortmannin, Nomega-nitro-L-arginine methylester, or 5-hydroxydecanoate), which inhibit GLP-1 receptors, phosphoinositide 3-kinase, nitric oxide synthase, and K(ATP) channels, respectively. Western blot analysis showed that treatment with voglibose upregulated myocardial levels of phospho-Akt, phosphoendothelial nitric oxide synthase after myocardial infarction. The upregulation of phospho-Akt was inhibited by exendin(9-39) and wortmannin. These findings suggest that voglibose reduces myocardial infarct size through stimulation of GLP-1 receptors, activation of the phosphoinositide 3-kinase-Akt-endothelial nitric oxide synthase pathways, and the opening of mitochondrial K(ATP) channels. These findings may provide new insight into therapeutic strategies for the treatment of patients with coronary artery disease.

Topics: alpha-Glucosidases; Animals; Arginine; Decanoic Acids; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Heart; Hydroxy Acids; Hypoglycemic Agents; Inositol; Male; Myocardial Infarction; Myocardial Ischemia; Myocardium; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Phosphotransferases; Proto-Oncogene Proteins c-akt; Rabbits; Receptors, Glucagon; Reperfusion Injury