Microalbuminuria, Cardiovascular, and Renal Outcomes - Heart Outcomes Prevention Evaluation - MICRO-HOPE

Description:

The MICRO-HOPE was a substudy of the HOPE study. It was a prospective, randomized, double-blind, placebo-controlled, multicenter trial with a two-by-two factorial design, designed to assess the value of ramipril and vitamin E in preventing diabetic nephropathy in diabetic patients with microalbuminuria, and the development of microalbuminuria in diabetic patients not presenting with this condition at baseline.

Hypothesis:

In patients with diabetes at high risk of cardiovascular events, treatment with ramipril and vitamin E delays the development of overt diabetic nephropathy in patients with microalbuminuria at baseline, and the development of microalbuminuria in diabetic patients without this condition at baseline.

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

Principal Findings:

Of all 9,541 participants in the HOPE study, 3,654 (39.3%) had diabetes. Albumin/creatinine ratio was measured in 3,498 (98%) at baseline, 2,914 (83%) at one year, and 2,671 (86%) at the end of the study. Median follow-up was 4.5 years.

In participants without baseline microalbuminuria, the risk of new microalbuminuria was nonsignificantly reduced in the ramipril group (relative risk reduction [RRR] 9% [-4 to 20], p=0.17). One hundred seventeen (7%) patients in the ramipril group and 149 (8%) patients in the control group developed overt nephropathy (RRR 24% [3-40], p=0.027).

Restriction of the definition of overt nephropathy to include only people in whom 24-hour urine results were available gave similar results: 100 (6%) participants in the ramipril group and 124 (7%) in the placebo group were affected (RRR 22% [-2 to 40], p=0.07).

Interpretation:

Among patients with diabetes at high risk of cardiovascular events, treatment with ramipril lowered the incidence of the development of overt nephropathy.

References:

Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. Lancet 2000;355:253-9.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Vascular Medicine, Lipid Metabolism, Nonstatins, Smoking

Keywords: Coronary Artery Disease, Stroke, Vitamin E, Follow-Up Studies, Risk Factors, Diabetic Nephropathies, Creatinine, Ramipril, Peripheral Vascular Diseases, Smoking, Cholesterol, HDL, Lipoproteins, HDL, Diabetes Mellitus


< Back to Listings