Madrid, Spain – 1 September 2025: In patients with heart failure (HF) caused by Chagas disease, sacubitril/valsartan was superior to enalapril for the composite primary endpoint, predominantly driven by a significant reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP), according to late-breaking research presented in a Hot Line session today at ESC Congress 2025.1
Chagas disease, caused by Trypanosoma cruzi infection, remains a serious health problem affecting more than 7 million people, primarily from Latin America.2 T. cruzi parasites are mainly transmitted by contact with faeces/urine of infected triatomine bugs. T. cruzi can also be transmitted by consumption of contaminated food/beverages, during pregnancy or birth, through blood/blood products, organ transplantation and laboratory accidents. Chagas disease is spreading around the world, predominantly due to migration of infected patients to other regions, including North America, Europe, Asia and Australia. Chagas cardiomyopathy is considered the most common and serious manifestation of chronic Chagas disease, occurring in 30–40% of infected people during long-term follow-up.2,3
“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 Renato Lopes from Duke University Medical Center, Durham, USA, Principal Investigator of the PARACHUTE-HF trial. “There have been no prospective randomised trials testing the effects of standard treatments in patients with Chagas disease and HF. In the general HF population, the angiotensin receptor–neprilysin inhibitor, sacubitril/valsartan improved HF outcomes vs. the angiotensin-converting enzyme inhibitor, enalapril,4 and we compared these two agents in the largest trial in patients with Chagas disease and HF conducted to date.”
PARACHUTE-HF was an academic-led, open-label, blinded-endpoint adjudication, randomised trial conducted at more than 80 sites in Brazil, Argentina, Mexico and Colombia. Eligibility criteria included a diagnosis of Chagas disease confirmed by at least two different serological tests positive for Trypanosoma cruzi infection, left ventricular ejection fraction (LVEF) ≤40%, New York Heart Association functional class II to IV symptoms and NT-proBNP ≥600 pg/ml or ≥400 pg/ml and hospitalisation for HF within the last 12 months. Participants were randomised 1:1 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 primary endpoint was a hierarchical composite outcome consisting of cardiovascular death, first hospitalisation for HF and the relative change from baseline to week 12 in NT-proBNP, analysed using a win ratio approach.5
In total, 922 patients were randomised. The mean age was 64 years, 42.0% were women, mean LVEF was 29.8% and 44.4% had had prior hospitalisation for HF.
Following pairwise comparisons, sacubitril/valsartan was associated with a 52% higher likelihood of a better primary outcome compared with enalapril (stratified unmatched win ratio 1.52; 95% confidence interval [CI] 1.28 to 1.82; p<0.001). Over a median of 25 months’ follow-up, rates were similar for sacubitril/valsartan vs. enalapril for cardiovascular death (hazard ratio [HR] 0.95; 95% CI 0.73 to 1.23) and first HF hospitalisation (HR 0.92; 95% CI 0.70 to 1.20). 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 those assigned to sacubitril-valsartan and −5.5% in those assigned to enalapril (ratio of adjusted geometric mean change 0.68; 95% CI 0.62 to 0.75).
The safety profiles of the two agents were similar, with discontinuations due to adverse events occurring in 6.1% of patients with sacubitril/valsartan and 9.8% with enalapril.
Concluding, Professor Lopes said: “In patients with HF caused by Chagas disease, sacubitril/valsartan was superior to enalapril with respect to the primary outcome, predominantly driven by the 32% reduction in NT-proBNP levels at week 12. Our study provides the first randomised trial evidence to support a pharmacological treatment specifically in this high-risk population. PARACHUTE-HF shows that much-needed studies to better characterise chronic Chagas cardiomyopathy and to define the benefit/risk of new therapies in this condition are possible. In line with the global health spotlight of ESC Congress, the PARACHUTE-HF trial provides a successful model for international collaborations – in this field among cardiologists and infectious disease physicians − with the shared goal of evaluating the impact of new therapies on cardiovascular outcomes in patients with neglected diseases.”
ENDS
Notes to editor
This press release accompanies both a presentation and an ESC press conference at ESC Congress 2025.
It does not necessarily reflect the opinion of the European Society of Cardiology.
Funding: The study was funded by the Novartis Pharma AG.
Disclosures: Professor Lopes reports research grants or contracts from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, Sanofi-Aventis and Novartis; funding for educational activities or lectures from Pfizer, Daiichi Sankyo, Novartis and Novo Nordisk; and funding for consulting from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Novartis and Novo Nordisk.
References and notes:
1‘PARACHUTE-HF: Randomised trial comparing sacubitril/valsartan with enalapril in patients with HFrEF caused by chronic Chagas cardiomyopathy’ presented during HOT LINE 9 on 1 September 2025 at 08:15 to 08:27 in Madrid (Main Auditorium).
2World Health Organization. Chagas disease (also known as American trypanosomiasis). Available at: https://www.who.int/news-room/fact-sheets/detail/chagas-disease-(american-trypanosomiasis)
3Nascimento BR, Naback ADN, Santos BMP, et al. Prevalence of clinical forms of Chagas disease: a systematic review and meta-analysis - data from the RAISE study. Lancet Reg Health Am. 2024;30:100681.
4McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993–1004.
5Bocchi EA, Echeverria LE, Demacq C, et al. Sacubitril/valsartan versus enalapril in chronic Chagas cardiomyopathy: Rationale and design of the PARACHUTE-HF trial. JACC Heart Fail. 2024;12:1473–1486.
ESC Press Office
Tel: +33 661401884
Email: press@escardio.org
The hashtag for ESC Congress 2025 is #ESCCongress
Follow us on LinkedIn @European Society of Cardiology News
Journalists are invited to become accredited and register here.
Check out the ESC Media and Embargo Policy.
It is the world’s largest gathering of cardiovascular professionals, disseminating ground-breaking science both onsite in Madrid and online – from 29 August to 1 September 2025. Explore the scientific programme. More information is available from the ESC Press Office at press@escardio.org.
About the European Society of Cardiology
The ESC brings together healthcare professionals from more than 150 countries, working to advance cardiovascular medicine and help people to live longer, healthier lives.