Prevention of Renal and Vascular End-stage Disease Intervention Trial - PREVEND IT

Nov 17, 2004
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Date Presented:
01/01/2003
Date Published:
01/01/2004
Date Updated:
11/17/2004
Original Posted Date:
11/17/2004
References

Description:

The goal of the trial was to evaluate if urinary albumin excretion levels are associated with cardiovascular events in patients with microalbuminuria excretion and without hypertension and hypercholesterolemia, and to evalute if treatment with pravastatin or the ACE-inhibitor fosinopril is associated with a reduction in microalbuminuria excretion and cardiovascular events.

Hypothesis:

Among patients with microalbuminuria excretion and without hypertension and hypercholesterolemia, treatment with pravastatin or the ACE-inhibitor fosinopril will be associated with a reduction in microalbuminuria excretion and cardiovascular events.

Study Design

Study Design:

Patients Screened: 8592
Patients Enrolled: 854
Mean Follow Up: 4 years
Mean Patient Age: Mean age 51 years
Female: 35

Patient Populations:

Microalbuminuria at initial spot urine and in 2 seperate occasions over 24 hours of 15-300 mg; systolic blood pressure <160; diastolic blood pressure <100; total cholesterol <308 mg/dL.

Exclusions:

Use of anti-hypertensive medication or hyperlipidemic medication.

Primary Endpoints:

Cardiovascular death, cardiovascular hospitalizations, or end-stage renal disease

Drug/Procedures Used:

Patients were randomized to the ACE-inhibitor fosinopril (20 mg; n=425) or matching placebo (n=429). Using a factorial design, patients were also randomized to pravastatin (40 mg; n=427) or matching placebo (n=427).

Principal Findings:

Median urinary albumin excretion was 22.8 mg/24 hr (interquartile range 15.8-41.3 mg/24 hr). In the fosinopril randomization, median urinary albumin excretion was reduced in the fosinopril arm by 26% at 3 months compared with placebo (p<0.001), a reduction that was maintained at 4 year follow-up (p<0.001). SBP increased by 2.10 mmHg in the placebo arm and was reduced by 5.13 mmHg in the fosinopril arm (p<0.05). The composite primary endpoint of CV death, CV hospitalizations, or end-stage renal disease occurred less frequently in the fosinopril arm vs placebo, although not significantly (3.9% vs 6.5%, hazard ratio [HR] 0.60, 95% CI 0.33-1.10, p=0.098). The difference was primarily driven by the occurrance of stroke (2.3% in placebo vs 0.2% in fosinopril, HR=0.10, p=0.03).

In the pravastatin randomization, total cholesterol was reduced by 2.32 md/dl in the placebo arm and 43.3 mg/dl in the pravastatin arm (p<0.05). LDL was reduced by 8.11 md/dl in the placebo arm and 45.6 mg/dl in the pravastatin arm (p<0.05). There was no difference in median urinary albumin excretion in the pravastatin arm vs placebo at 3 month follow-up (-3.1%, p=NS) or 4 year (-1.85%, p=NS). There was no difference in the composite primary endpoint of CV death, CV hospitalizations, or end-stage renal disease (4.8% vs 5.6%, HR 0.87, 95% CI 0.49-1.57, p=0.65). MI occurred less frequently in the pravastatin arm vs placebo (1.8% vs 3.5%).

Interpretation:

Among patients with microalbuminuria excretion and without hypertension and hypercholesterolemia, treatment with the ACE-inhibitor fosinopril was associated with a reduction in microalbuminuria excretion and cardiovascular events, but treatment with pravastatin was not associated with a reduction in microalbuminuria excretion or cardiovascular events at 4 year follow-up. The present study is the first to show a an association between microalbuminuria and CV events in patients without hypertension or hypercholesterolemia, and may be a possible risk marker for increased events. Given the reduction in SBP in the fosinopril arm and the reduction in cholesterol in the pravastatin arm, it is not clear if the risk reduction is truly attributable to reduced microalbuminuria or to other effects of the therapies tested.

References:

Asselbergs FW, et al. Effects of Fosinopril and Pravastatin on Cardiovascular Events in Subjects With Microalbuminuria. Circulation 2004; 110:2809-2816.

Presented by Dr Wiek H van Gilst and Dr. Folkert Asselbergs at AHA 2003, Orlando, FL

Keywords: Fosinopril, Stroke, Follow-Up Studies, Kidney Failure, Chronic, Risk Reduction Behavior, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypercholesterolemia, Cholesterol, Pravastatin, Hypertension


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