Zannad F et al. (2006) Prevention of cardiovascular events in end-stage renal disease: results of a randomized trial of fosinopril and implications for future studies. Kidney Int 70: 1318–1324

Cardiovascular events (CVEs) cause substantial mortality and morbidity in patients with end-stage renal disease (ESRD). Angiotensin-converting-enzyme inhibitors, such as fosinopril, have proved to be both well-tolerated and efficacious for the prevention of CVEs in a range of clinical trials, yet these trials have tended to exclude patients with ESRD. This double-blind, multicenter, randomized controlled study assessed the safety and efficacy of fosinopril in 397 ESRD patients who were on hemodialysis and who had left ventricular hypertrophy.

The primary end point of the study was the occurrence of a first major CVE within the 2-year study period. After adjustment for baseline characteristics, the authors identified a nonsignificant trend towards lower incidence of CVEs in the fosinopril-treated group (dose titrated to 20 mg/day) than in the placebo group (relative risk 0.80, 95% CI 0.59–1.10; P = 0.099). Results also indicated that treatment with fosinopril might be of benefit for the subset of patients with hypertension; these patients exhibited an improvement in blood pressure during the 24-month study (relative risk 1.85, 95% CI 1.18–2.89; P = 0.008). Fosinopril-treated subjects were more likely to suffer adverse gastrointestinal events, but the drug did not increase the rate of hyperkalemia.

At 32.7%, the CVE rate was lower than anticipated, and consequently the study was underpowered to detect a significant association between treatment with fosinopril and reduced risk of CVEs. Zannad et al. suggest that a further study of approximately 1,000 patients would have sufficient power to confirm both the efficacy and the favorable safety profile of fosinopril in patients with ESRD.