In the PARACHUTE-HF study of patients with heart failure (HF) as result of Chagas disease, sacubitril/valsartan was superior to enalapril with respect to the primary endpoint of cardiovascular death, hospitalization for HF or the relative change from baseline to week 12 in NT-proBNP.

The trial, presented at ESC Congress 2025, was conducted at more than 80 sites in Brazil, Argentina, Mexico and Colombia. Researchers randomly assigned 922 patients to either sacubitril/valsartan (50 or 100 mg twice daily titrated to a target of 200 mg twice daily) or enalapril (2.5 or 5 mg twice daily titrated to a target of 10 mg twice daily). The mean age of participants was 64 years, 42% were women, nearly 45% had a prior hospitalization for HF, and the mean LVEF was 30%.

Overall results found sacubitril/valsartan was associated with a 52% higher likelihood of a better primary outcome compared with enalapril. Over an average follow-up period of 25 months, rates of cardiovascular death and first hospitalization for HF were similar across both groups. However, study investigators said the significant difference in the primary outcome was predominantly driven by the percent change in NT-proBNP from baseline to 12 weeks (logarithmic median change from baseline was −30.6% in the sacubitril/valsartan group and −5.5% in the enalapril group). In terms of safety, discontinuations due to adverse events occurred in 6.1% of patients receiving sacubitril/valsartan and 9.8% receiving enalapril.

"HF caused by Chagas disease has unique clinical features with worse prognosis than other causes of HF despite the fact that patients are often younger and have fewer comorbidities," said Principal Investigator Renato D. Lopes, MD, PhD, FACC. "Our study provides the first randomized trial evidence to support a pharmacological treatment specifically in this high-risk population. PARACHUTE-HF shows that much-needed studies to better characterize chronic Chagas cardiomyopathy and to define the benefit/risk of new therapies in this condition are possible."

Beyond the clinical results, Lopes also noted that the PARACHUTE-HF trial offers a successful model for global collaborations between cardiologists and infectious disease physicians when it comes to evaluating the impact of new therapies on patients with rare or neglected diseases.