Study Design

Study Design:

Patients Enrolled: 3,654
Mean Follow Up: Median duration of follow-up was 4.5 years
Mean Patient Age: Mean age was 65.4 years
Female: 37%

Patient Populations:

Diabetic patients aged ≥55 years with history of cardiovascular disease (coronary artery disease, stroke, or peripheral vascular disease), or diabetes plus at least one other cardiovascular risk factor (total cholesterol >5.2 mmol/l, high-density lipoprotein cholesterol ≤0.9 mmol/l, and current smoking)

Exclusions:

Dipstick-positive proteinuria or established diabetic nephropathy, other severe renal disease, hyperkalemia, congestive heart failure, low ejection fraction (<0.4), uncontrolled hypertension, recent myocardial infarction or stroke (<4 weeks), and use of or hypersensitivity to vitamin E or angiotensin-converting enzyme inhibitors

Primary Endpoints:

Development of overt diabetic nephropathy

Secondary Endpoints:

Development of microalbuminuria in diabetic patients without this condition at baseline

Drug/Procedures Used:

Patients were randomly assigned to ramipril (10 mg/day) or placebo, and vitamin E (400 IU/day) or placebo according to a two-by-two factorial design. The albumin/creatinine ratio was measured in a subset of patients at baseline, one year, and at the end of the study.

Microalbuminuria was defined as a ratio of 2 mg/mmol or higher. Overt nephropathy was diagnosed when the albumin/creatinine ratio was higher than 36 mg/mmol, if the 24-hour urine albumin was 300 mg or more, or if the 24-hour urine protein was 500 mg or more.

Concomitant Medications:

Standard treatment for diabetic patients at high risk for cardiovascular events such as insulin, oral hypoglycemic agents, aspirin, diuretics, beta-blockers, calcium-channel blockers, and hyperlipaedemic drugs