Clinical Question: Does benazepril (Lotensin) improve renal outcomes for patients with a creatinine level greater than 3.0 mg per dL (270 μmol per L)?

Setting: Outpatient (specialty)

Study Design: Randomized controlled trial (double-blinded)

Allocation: Concealed

Synopsis: Angiotensin-converting enzyme (ACE) inhibitors are known to slow the increase in serum creatinine levels in patients with or without diabetes who have mild to moderate renal insufficiency (serum creatinine = 1.5 to 3.0 mg per dL [130 to 270 μmol per L]). In this study (cosponsored by Novartis and the People's Liberation Army of China), Chinese patients without diabetes who had more severe renal dysfunction (serum creatinine = 3.1 to 5.0 mg per dL [270 to 440 μmol per L]) were studied to determine if this renal protective effect occurs at higher levels of dysfunction. The authors identified 422 patients, 141 with a serum creatinine level between 1.5 and 3.0 mg per dL and 281 with a serum creatinine level between 3.1 and 5.0 mg per dL. Their mean age was 45 years, and one half were women.

The authors put all of the patients through an eight-week active run-in period to test their tolerance of the study drug, benazepril. This resulted in the exclusion of 94 patients, mostly for dry cough (n = 72) but also because of an acute increase in serum creatinine (n = 9), hyperkalemia (n = 5), and poor adherence (n = 8). This type of active run-in inflates the apparent effectiveness of the study drug.

All remaining patients received drugs other than ACE inhibitors or angiotensin receptor blockers to control their blood pressure, because the goal was to identify any potential benefit of the ACE inhibitor above and beyond that of better blood pressure control. The authors randomized the 224 remaining patients with serum creatinine levels from 3.1 to 5.0 mg per dL to receive benazepril 10 mg twice daily or placebo. The 104 patients with a serum creatinine level between 1.5 and 3.0 mg per dL received benazepril 10 mg twice daily. Patients were followed for a mean of 3.4 years and told to avoid sodium and potassium in their diet. The primary outcome was a combination of doubling of the serum creatinine level with the need for dialysis or transplantation, or death. The primary outcome was reached by 41 percent of patients in the benazepril group and 60 percent in the placebo group (P = .004; number needed to treat = 5; 95% confidence interval, 3 to 18).

There was a 51 percent reduction in the risk of doubling the serum creatinine (P = .02) and a 40 percent reduction in the risk of end-stage renal disease (P = .02) in the treatment group. There was only one death in the study population, and adverse events were similar between groups. The results of this study cannot be replicated in clinical practice because the initial trial therapy with benzapril eliminated patients who responded poorly to the treatment.

Bottom Line: In a group of patients without diabetes and with serum creatinine levels between 3.0 and 5.0 mg per dL, benazepril slows the progression of renal disease. These patients were carefully monitored for any changes in renal function during the first eight weeks and were carefully screened and monitored to detect any early adverse effects on renal function. (Level of Evidence: 1b)

Used with permission from Ebell M. ACEI slows progression of renal dysfunction (creat 3.0–5.0 mg/dl). Accessed February 10, 2006, at: http://www.InfoPOEMs.com.