Effects of fosinopril and pravastatin on cardiovascular events in subjects with microalbuminuria

Background - Microalbuminuria is associated with increased risk of cardiovascular events. We assessed whether therapeutic intervention aimed at lowering urinary albumin excretion would reduce cardiovascular events in microalbuminuric subjects ( 15 to 300 mg/24 hours). Methods and Results - From the Prevention of Renal and Vascular Endstage Disease (PREVEND) cohort ( n = 8592), 1439 subjects fulfilled the inclusion criteria of the PREVEND Intervention Trial ( PREVEND IT). Of these subjects, 864 were randomized to fosinopril 20 mg or matching placebo and to pravastatin 40 mg or matching placebo. The mean follow-up was 46 months, and the primary end point was cardiovascular mortality and hospitalization for cardiovascular morbidity. Mean age was 51 +/- 12 years; 65% of subjects were male, and 3.4% had a previous cardiovascular event. Mean cholesterol level was 5.8 +/- 1.0 mmol/L, mean systolic/diastolic blood pressure was 130 +/- 18/ 76 +/- 10 mm Hg, and median urinary albumin excretion was 22.8 (15.8 to 41.3) mg/24 hours. The primary end point occurred in 45 subjects (5.2%). Fosinopril reduced urinary albumin excretion by 26% ( P < 0.001). Subjects treated with fosinopril showed a 40% lower incidence of the primary end point ( hazard ratio 0.60 [95% CI 0.33 to 1.10], P = 0.098, log-rank). Pravastatin did not reduce urinary albumin excretion, and subjects treated with pravastatin showed a 13% lower incidence of the primary end point than subjects in the placebo group (0.87 [0.49 to 1.57], P = 0.649, log-rank). Conclusions - In microalbuminuric subjects, treatment with fosinopril had a significant effect on urinary albumin excretion. In addition, fosinopril treatment was associated with a trend in reducing cardiovascular events. Treatment with pravastatin did not result in a significant reduction in urinary albumin excretion or cardiovascular events.