Single Drug May Suffice to Lower Albumin Excretion Rate

Dual RAAS blockade not superior at reducing albuminuria in patients with elevated cardiovascular risk

BLOCKING THE renin-angiotensin-aldosterone system (RAAS) with one drug may be just as effective as using two drugs at decreasing albuminuria in hypertensive patients with microalbuminuria and elevated cardiovascular risks, data suggest. Dual RAAS blockade achieves greater BP reductions, however.

The findings come from the IMPROVE [Irbesartan in the Management of Proteinuric patients at high risk for Vascular Events] study. In this double-blind trial, patients were randomly assigned to 20 weeks' treatment with a combination of the ACE inhibitor ramipril and the angiotensin receptor blocker irbesartan, or ramipril plus placebo. The primary end point was the change in albumin excretion rate (AER) from baseline.

The researchers, led by George L. Bakris, MD, of the University of Chicago-Pritzker School of Medicine, analyzed data from 369 patients, 184 in the ramipril plus irbesartan group and 185 in the ramipril monotherapy arm. All patients had a cardiovascular history and risk factors. In most patients, diabetes was the primary cause of albuminuria.

Baseline mean seated BP was 163/90 and 164/89 mm Hg in the ramipril plus irbesartan group and ramipril plus placebo groups, respectively. The mean AER in these two groups at baseline was 99.6 and 103 µg/min. At week 20, the dual-medication group had a 46% reduction in AER and the ramipril plus placebo group had a 42% reduction, a nonsignificant difference between groups.

“Thus, the combination of rampril plus irbesartan was no more effective reducing AER than ramipril plus placebo,” the authors wrote in Kidney International (2007;72:879-885).

When the investigators looked at a subgroup of patients with overt nephropathy (AER of 200 µg/min or more), they found a greater decrease in AER at week 20 in the dual RAAS blockade group. The researchers said this finding should be interpreted with caution because the subgroup had only 108 patients and the 95% confidence intervals were large in both groups.

Both treatment groups experienced significant declines in BP during the study. At 20 weeks, 17.3% of the ramipril plus irbesartan group achieved a target BP of less than 130/80 mm Hg compared with 10.8% of the ramipril plus placebo recipients. In addition, 51.9% of the ramipril plus irbesartan group achieved a BP less than 140/90 mm Hg compared with only 35.5% of the ramipril plus placebo arm.

Dr. Bakris and his colleagues noted that dual RAAS blockade was safe and well tolerated, with the incidence of adverse events and treatment-related adverse events similar between the two study arms.