Prevention of cardiovascular events in end-stage renal disease: Results of a randomized trial of fosinopril and implications for future studies

Abstract

Cardiovascular events (CVEs) are the leading cause of death in chronic hemodialysis patients. Results of trials in non-end-stage renal disease (ESRD) patients cannot be extrapolated to patients with ESRD. It is critical to test cardiovascular therapies in these high-risk patients who are usually excluded from major cardiovascular trials. The study objective was to evaluate the effect of fosinopril on CVEs in patients with ESRD. Eligible patients were randomized to fosinopril 5 mg titrated to 20 mg daily (n=196) or placebo (n=201) plus conventional therapy for 24 months. The primary end point was combined fatal and nonfatal first major CVEs (cardiovascular death, resuscitated death, nonfatal stroke, heart failure, myocardial infarction, or revascularization). No significant benefit for fosinopril was observed in the intent to treat analysis (n=397) after adjusting for independent predictors of CVEs (RR=0.93, 95% confidence interval (CI) 0.68-1.26, P=0.35). The per protocol secondary supportive analysis (n=380) found a trend towards benefit for fosinopril (adjusted RR=0.79 (95% CI 0.59-1.1, P=0.099)). In the patients who were hypertensive at baseline, systolic and diastolic blood pressures were significantly decreased in the fosinopril as compared to the placebo group. After adjustment for risk factors, trends were observed suggesting fosinopril may be associated with a lower risk of CVEs. These trends may have become statistically significant had the sample size been larger, and these findings warrant further study.

Diagnosis and Management of Cardiovascular Disease in Advanced and End‐Stage Renal Disease

“…In patients with ESRD, small studies investigating the effect of ACE inhibition on LVH have shown variable results 12, 76. The Fosinopril in Dialysis study (FOSIDIAL), a randomized controlled trial conducted to evaluate the efficacy of fosinopril in helping prevent major adverse cardiac events in patients on dialysis, found no statistically significant difference between the 2 arms in reducing the risk of major adverse cardiac events 83. However, this study was underpowered because of a small sample size, and fewer than expected major adverse cardiac events occurred in the study groups.…”

The Challenge of Sudden Death in Dialysis Patients

“…In hemodialyzed patients, a prospective controlled trial with the angiotensin-converting enzyme (ACE) inhibitor fosinopril had no significant impact on mortality, although the per-protocol analysis showed a borderline effect (66). Recently, however, some small, underpowered studies showed improved mortality and reduction of cardiovascular events in dialysis patients on candesartan and on different ARB in an unpublished further small multicenter study (56).…”

Assessment and Management of Hypertension in Patients on Dialysis

“…After 4 years of follow-up, there were no differences between the two treatment groups in the primary end point of cardiovascular events that included cardiovascular death. 131 Another smaller trial compared candesartan versus placebo in HD patients, but noted a nearly 3-fold reduction in cardiovascular events with active treatment versus placebo. 132 These conflicting results indicate the need for larger studies.…”