Acarbose Treatment and the Risk of Cardiovascular Disease and Hypertension in Patients with Impaired Glucose Tolerance: The STOP-NIDDM Trial

Context: The worldwide explosive increase in type 2 diabetes mellitus and its cardiovascular morbidity are becoming major health concerns. Objective: To evaluate the effect of decreasing postprandial hyperglycemia with acarbose, an α-glucosidase inhibitor, on the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance (IGT). Design, Setting, and Participants: International, multicenter double-blind, placebo-controlled, randomized trial, undertaken in hospitals in Canada, Germany, Austria, Norway, Denmark, Sweden, Finland, Israel, and Spain from July 1998 through August 2001. A total of 1429 patients with IGT were randomized with 61 patients (4%) excluded because they did not have IGT or had no postrandomization data, leaving 1368 patients for a modified intent-to-treat analysis. Both men (49%) and women (51%) participated with a mean (SD) age of 54.5 (7.9) years and body mass index of 30.9 (4.2). These patients were followed up for a mean (SD) of 3. 3 (1.2) years. Intervention: Patients with IGT were randomized to receive either placebo (n=715) or 100 mg of acarbose 3 times a day (n=714). Main Outcome Measures: The development of major cardiovascular events (coronary heart disease, cardiovascular death, congestive heart failure, cerebrovascular event, and peripheral vascular disease) and hypertension (≥140/90 mm Hg). Results: Three hundred forty-one patients (24%) discontinued their participation prematurely, 211 in the acarbose-treated group and 130 in the placebo group; these patients were also followed up for outcome parameters. Decreasing postprandial hyperglycemia with acarbose was associated with a 49% relative risk reduction in the development of cardiovascular events (hazard ratio [HR], 0.51; 95% confidence interval [CI]; 0.28-0.95; P=.03) and a 2.5% absolute risk reduction. Among cardiovascular events, the major reduction was in the risk of myocardial infarction (HR, 0.09; 95% CI, 0.01-0.72; P=.02). Acarbose was also associated with a 34% relative risk reduction in the incidence of new cases of hypertension (HR, 0.66; 95% CI, 0.49-0.89; P=.006) and a 5.3% absolute risk reduction. Even after adjusting for major risk factors, the reduction in the risk of cardiovascular events (HR, 0.47; 95% CI, 0.24-0.90; P=.02) and hypertension (HR, 0.62; 95% CI, 0.45-0.86; P=.004) associated with acarbose treatment was still statistically significant. Conclusion: This study suggests that treating IGT patients with acarbose is associated with a significant reduction in the risk of cardiovascular disease and hypertension.