ACE Inhibitor Use Shows Benefit in Microalbuminuria Without Clinical Signs of Vascular Disease

Peggy Peck

November 14, 2003

Nov. 14, 2003 (Orlando) — Treating microalbuminuria with an angiotensin-converting enzyme (ACE) inhibitor in the absence of either hypertension or hypercholesterolemia can reduce cardiovascular and renal events by 44% over a four-year period, according to late-breaking clinical trial results presented at the American Heart Association (AHA) Scientific Sessions.

Subjects randomized to the ACE inhibitor, fosinopril, experienced a 23% decrease in urinary albumin excretion ( P < .001) in addition to a reduced incidence of cardiovascular and renal events.

While treatment with fosinopril was associated with significant risk reduction, treatment with the cholesterol-lowering agent, pravastatin, did not reduce urinary albumin excretion rates and achieved a 25% nonsignificant reduction in cardiovascular and renal events, said Weik H. van Gilst, PhD, professor of cardiovascular and clinical pharmacology, University of Groningen, the Netherlands. Dr. Gilst is senior investigator of the Prevention of Renal Vascular End-Stage Disease Intervention Trial (PREVEND IT).

Dr. van Gilst noted that microalbuminuria is often overlooked or considered only minimally significant by many clinicians, and that the study results suggest a more aggressive approach to treatment of the condition is needed. "We think it is important to measure microalbuminuria and when you see it, it should raise a flag," he said at an AHA press conference.

Raymond Gibbons, MD, professor of medicine at the Mayo Medical School, Rochester, Minnesota, and chairman of the AHA's program committee, said he and other committee members were very impressed with the PREVEND IT report. He told Medscape that the " represents out-of-the-box thinking that we need in order to advance medical science." Moreover, he noted that the benefit was achieved with a low-tech approach: a simple test followed by use of established agents.

Dr. Gibbons added that most clinicians would not treat patients with small amounts of protein in their urine if the patients did not have high blood pressure. The investigators had theorized, however, that because microalbuminuria is associated with an increased cardiovascular and renal risk, treating these patients might impact survival.

PREVEND IT was a single-center, double-blind, placebo-controlled trial with a 2 x 2 factorial design that randomized 854 patients to fosinopril 20 mg or placebo and pravastatin 40 mg or matching placebo. The mean follow-up was 46 months and the primary endpoint was a composite of cardiovascular mortality, hospitalization for cardiovascular morbidity or end-stage renal disease.

The average age of patients was 51 ± 12 years and 65% were men. More than 3% had experienced a prior cardiovascular event and nearly 5% had previously used at least one cardiovascular agent. The median urinary albumin excretion rate was 22.9 mg/24h with a range of 25.8 to 41.8 mg/24h.

The overall occurrence of cardiovascular events was lower than expected, and a total of 42 subjects reached the primary endpoint, Dr. Gibbons reported.

He also suggested that while the study provided "...highly provocative information, we need more trials to verify these findings. It appears that microalbuminuria is an early marker of vascular disease."

While it is premature to issue clinical recommendations based on one study, he said, it would be prudent to suggest that microalbuminuria patients without high blood pressure or high levels of cholesterol be encouraged to diet, exercise and focus on other means of reducing risk to the vascular system.

AHA 2003 Scientific Sessions: Late-Breaking Clinical Trials. Presented Nov. 12, 2003.

Reviewed by Charlotte E. Grayson, MD