Effects of enalapril in systolic heart failure patients with and without chronic kidney disease: Insights from the SOLVD Treatment trial

Abstract

Background Angiotensin-converting enzyme inhibitors improve outcomes in systolic heart failure (SHF). However, doubts linger about their effect in SHF patients with chronic kidney disease (CKD). Methods In the Studies of Left Ventricular Dysfunction (SOLVD) Treatment trial, 2569 ambulatory chronic HF patients with left ventricular ejection fraction ≤35% and serum creatinine level ≤2.5 mg/dL were randomized to receive either placebo (n=1284) or enalapril (n=1285). Of the 2502 patients with baseline serum creatinine data, 1036 had CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2). Results Overall, during 35 months of median follow-up, all-cause mortality occurred in 40% (502/1252) and 35% (440/1250) of placebo and enalapril patients, respectively (hazard ratio {HR}, 0.84; 95% confidence interval {CI}, 0.74–0.95; p=0.007). All-cause mortality occurred in 45% and 42% of patients with CKD (HR, 0.88; 95% CI, 0.73–1.06; p=0.164), and 36% and 31% of non-CKD patients (HR, 0.82; 95% CI, 0.69–0.98; p=0.028) in the placebo and enalapril groups, respectively (p for interaction=0.615). Enalapril reduced cardiovascular hospitalization in those with CKD (HR, 0.77; 95% CI, 0.66–0.90; p<0.001) and without CKD (HR, 0.80; 95% CI, 0.70–0.91; p<0.001). Among patients in the enalapril group, serum creatinine elevation was significantly higher in those without CKD (0.09 versus 0.04 mg/dL in CKD; p=0.003) during first year of follow-up, but there was no differences in changes in systolic blood pressure (mean drop, 7 mmHg, both) and serum potassium (mean increase, 0.2 mEq/L, both). Conclusions Enalapril reduces mortality and hospitalization in SHF patients without significant heterogeneity between those with and without CKD.

Clinical features, and in-hospital and 1-year mortalities of patients with acute heart failure and severe renal dysfunction. Data from the Italian Registry IN-HF Outcome

“…This result is reasonable in light of the data resulting from multivariable analyses which clearly indicated a link between the worse clinical conditions at the time of hospitalization associated with older age and the adverse short and long-term outcomes in our patients with severe RD and AHF. In this situation, the protective renal and cardiac effects of ACEi/ARB might play a less important role on outcome than that documented in patients with stable chronic HF without severe RD [34].…”

The Cardiorenal Syndrome: What the Cardiologist Needs to Know

“…Patients with renal dysfunction are less likely to receive RAAS-blocking drugs for fear of a further reduction of renal function [73]. Increasing evidence, though, claims that the benefit of RAAS-blocking drugs in patients with CKD is comparable to that in the non-CKD population [9,10,81,82]. As the absolute risk is higher in CKD patients, proper use of RAAS-blocking drugs might be of great importance in these patients.…”

What Physicians Need to Know About Renal Function in Outpatients with Heart Failure

“…Patients with moderate-to-severe renal dysfunction (GFR <30-45 ml/min/1.73 m 2 ) have systematically been excluded from randomized HF trials, probably because of concern that the investigational drug might cause further deterioration of kidney function. Even though substudies of the large randomized HF trials and observational studies generally indicate that patients with moderate renal dysfunction benefit at least as much from the recommended treatment as non-CKD patients [22,23,24], patients with renal dysfunction are less likely to receive modern HF treatment. Treatment nihilism due to a lack of evidence and fear of adverse events may account in part for the worsened prognosis in cardiorenal patients [6,25].…”

“…Although patients with renal dysfunction have been largely excluded from randomized HF trials, substudies indicate that the relative risk reduction achieved by angiotensin-converting enzyme inhibitors (ACEis)/angiotensin II receptor blockers (ARBs) in HF patients with moderate renal dysfunction is equal compared to patients with a normal renal function [22,29]. As the absolute risk is higher, moderate renal dysfunction would actually identify patients with a greater absolute benefit of the treatment [22].…”

“…As the absolute risk is higher, moderate renal dysfunction would actually identify patients with a greater absolute benefit of the treatment [22]. In HF patients with severe renal dysfunction (eGFR <30 ml/min/1.73 m 2 ) there are as yet no conclusive data [29].…”