HF due to Chagas disease remains a major clinical concern, with limited evidence supporting guideline-recommended therapy choices. A multicenter randomized trial in the Journal of the American Medical Association compared sacubitril/valsartan with enalapril in adults with HFrEF caused by Chagas disease.

The trial enrolled 922 participants across 83 centers in Argentina, Brazil, Colombia, and Mexico. A total of 462 individuals received sacubitril/valsartan and 460 received enalapril. All participants had left ventricular ejection fraction ≤40% and elevated NT-proBNP or B-type natriuretic peptide (BNP). A hierarchical composite evaluated cardiovascular death, first HF hospitalization, and relative NT-proBNP change from baseline to 12 weeks using a win-ratio approach.

Over a median follow-up of 25.2 months, cardiovascular death occurred in 23.8% receiving sacubitril/valsartan and 25.4% receiving enalapril. First HF hospitalization occurred in 22.1% vs 24.1%, respectively. Sacubitril/valsartan achieved a 30.6% median NT-proBNP reduction at 12 weeks, compared with 5.5% for enalapril, yielding a stratified win ratio of 1.52 (95% CI 1.28-1.82; P<.001).

Clinical outcomes were similar between therapies, but the more pronounced biomarker improvement suggests a potential early mechanistic benefit with sacubitril/valsartan in this population.