In a significant advancement for patients suffering from heart failure due to Chagas disease, the drug combination sacubitril/valsartan has proven superior to enalapril. This finding was highlighted by a notable reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, according to groundbreaking research presented at the ESC Congress 2025.
Chagas disease, caused by the Trypanosoma cruzi parasite, continues to be a major health concern, affecting over 7 million people, primarily in Latin America. The disease is transmitted through contact with the feces or urine of infected triatomine bugs, but can also spread through contaminated food, blood transfusions, organ transplants, and from mother to child during birth. As migration patterns shift, Chagas disease is increasingly seen in North America, Europe, Asia, and Australia. The most severe manifestation, Chagas cardiomyopathy, occurs in 30-40% of infected individuals over time.
New Insights from the PARACHUTE-HF Trial
The PARACHUTE-HF trial, led by Professor Renato Lopes from Duke University Medical Center, represents the first prospective randomized study targeting heart failure in Chagas disease patients. Conducted across 80 sites in Brazil, Argentina, Mexico, and Colombia, the trial compared the efficacy of sacubitril/valsartan against enalapril in a large cohort of patients.
Eligibility for the trial required a confirmed diagnosis of Chagas disease, a left ventricular ejection fraction of 40% or less, and elevated NT-proBNP levels. Participants were randomized to receive either sacubitril/valsartan or enalapril, with the primary endpoint being a composite of cardiovascular death, first hospitalization for heart failure, and changes in NT-proBNP levels.
“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,” explained Professor Lopes.
Trial Results and Implications
The trial enrolled 922 patients with an average age of 64, of whom 42% were women. The results showed that sacubitril/valsartan was associated with a 52% higher likelihood of achieving a better primary outcome compared to enalapril. Over a median follow-up of 25 months, the rates of cardiovascular death and first heart failure hospitalization were similar between the two groups. However, the significant reduction in NT-proBNP levels at 12 weeks was a key differentiator, with a median change of -30.6% for sacubitril/valsartan compared to -5.5% for enalapril.
The safety profiles of both medications were comparable, with adverse event-related discontinuations occurring in 6.1% of the sacubitril/valsartan group versus 9.8% in the enalapril group.
Global Health Impact and Future Directions
The findings of the PARACHUTE-HF trial underscore the potential for targeted pharmacological treatments in managing Chagas-related heart failure. Professor Lopes emphasized the importance of this research, noting, “Our study provides the first randomized trial evidence to support a pharmacological treatment specifically in this high-risk population.”
This development aligns with the global health focus of the ESC Congress, showcasing the potential for international collaborations among cardiologists and infectious disease specialists. The trial not only highlights the need for further studies to better understand chronic Chagas cardiomyopathy but also sets a precedent for evaluating new therapies for neglected diseases.
As the medical community continues to grapple with the challenges posed by Chagas disease, the PARACHUTE-HF trial offers a promising path forward. By enhancing our understanding and treatment of this condition, researchers hope to improve outcomes for millions of patients worldwide.
