Microalbuminuria, Cardiovascular, and Renal Outcomes - Heart Outcomes Prevention Evaluation - MICRO-HOPE
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.
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.
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
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)
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
Development of overt diabetic nephropathy
Development of microalbuminuria in diabetic patients without this condition at baseline
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.
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
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).
Among patients with diabetes at high risk of cardiovascular events, treatment with ramipril lowered the incidence of the development of overt nephropathy.
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.
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
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