Reduction of cardiovascular events and microvascular complications in diabetes with ACE inhibitor treatment: HOPE and MICRO-HOPE.

The Heart Outcomes Prevention Evaluation (HOPE) study, an international randomized trial, was designed to evaluate the effects of the angiotensin-converting enzyme (ACE) inhibitor ramipril and vitamin E in patients at high risk for cardiovascular events. The study did not detect any cardiovascular benefit or harm using vitamin E. Results for the vitamin E arm are not discussed here. Of 9541 patients, 3577 with diabetes received either ramipril (10 mg) or placebo. Among these patients, ramipril use was associated with a significant 25% reduction in risk for the composite endpoint of myocardial infarction (MI), stroke, or cardiovascular death after a median follow-up period of 4.5 years. This benefit was independent of any blood pressure-lowering effect. The Microalbuminuria, Cardiovascular, and Renal Outcomes in HOPE (MICRO-HOPE) substudy in this patient population showed that ramipril treatment was associated with a decreased risk of development of overt nephropathy. Use of a composite measure of microvascular complications also suggested a protective effect of ramipril treatment. An interesting finding in the HOPE study is that ramipril treatment was associated with a significant 34% reduction in new diagnoses of diabetes. The possibility that ACE inhibitor treatment with ramipril may prevent new diabetes in non-diabetic patients at high risk of the disease is to be examined prospectively in the Diabetes Reduction Assessment with ramipril and rosiglitazone (DREAM) trial.