WASHINGTON, DC—At the ACC.17 Scientific Session, study authors reported that sacubitril/valsartan was effective in both ischemic and non-ischemic cardiomyopathy, including the major subgroups of non-ischemic etiology (eg, idiopathic or hypertensive cause of heart failure).

Where heart failure and reduced ejection fraction (HFrEF) is known to have various causes and etiology, “it has been suggested that the effectiveness of certain treatments varies by etiology,” said Joanne Simpson, from University of Glasgow, Glasgow, U.K. She and coauthors conducted a post hoc analysis to examine the effect of sacubitril/valsartan vs. enalapril according to etiology in the validly randomized patients of the PARADIGM-HF trial. 

The PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure) trial randomized 8,399 HFrEF patients. At trial enrollment, etiology was reported as either ischemic or non-ischemic; the non-ischemic etiology was further divided as idiopathic, hypertensive, infective/viral, alcoholic, valvular, diabetic, drug-related, peripartum-related, or other. For the analysis, study authors classified non-ischemic etiology as idiopathic, hypertensive, and all others. 

“The primary endpoint in PARADIGM-HF was the composite of cardiovascular [CV] death or HF hospitalization and we also examined the effect of treatment on CV death alone,” Simpson explained. 

Study authors observed that patients with non-ischemic etiology “were more often younger, more likely to be female, have higher resting heart rate, and higher NT-proBNP level than patients with an ischemic etiology.” The data showed the benefit of sacubitril/valsartan vs. enalapril was consistent across the different etiology subgroups.

The rate of the primary composite endpoint was as follows: ischemic (13.6 per 100 patient-years [enalapril] vs. 11.0 per 100 patient-years [sacubitril/valsartan], HR 0.81, 95% CI: 0.73–0.91), idiopathic non-ischemic (13.0 per 100 patient-years vs. 9.0 per 100 patient-years, HR 0.70, 95% CI: 0.56–0.86), hypertensive non-ischemic (11.9 per 100 patients-years vs. 8.9 per 100 patient-years, HR 0.74, 95% CI: 0.57–0.98), and other non-ischemic (12.1 per 100 patient-years vs. 11.8 per 100 patient-years, HR 0.97, 95% CI: 0.73–1.29). 

The rate of CV death was as follows: ischemic (7.7 [enalapril] vs. 6.4 [sacubitril/valsartan]), idiopathic non-ischemic (8.0 vs. 5.2), hypertensive non-ischemic (6.4 vs. 5.3), and other non-ischemic (6.6 vs. 5.7), respectively. Simpson and coauthors concluded, “No evidence of etiology affecting the treatment effect was seen.”