Groundbreaking Findings from PARACHUTE-HF Trial

In a remarkable breakthrough for millions affected by Chagas disease, the PARACHUTE-HF trial reveals that patients with heart failure due to Chagas cardiomyopathy benefit significantly more from sacubitril/valsartan (Entresto) than from traditional ACE inhibitors. Unveiled at the European Society of Cardiology Congress 2025, this study marks the first randomized trial focusing on medical treatments for this neglected condition.

Shedding Light on a Neglected Disease

Felix Ramires, MD, who participated in the study, emphasized the long road to achieving these results. 'This is a neglected population,' he stated, highlighting that heart failure is a dire complication of Chagas, a tropical disease caused by the Trypanosoma cruzi parasite. Despite its prevalence in South and Central America, affecting roughly 6 to 7 million globally, around 300,000 individuals are estimated to be infected in the United States alone.

The PARACHUTE-HF Study: Methodology and Participants

Conducted across 83 sites in Mexico, Colombia, Argentina, and Brazil, the trial involved 922 participants, comparing sacubitril/valsartan dosed at 200 mg twice daily against enalapril at 10 mg twice daily. Most participants were in functional classes II/III, with a substantial percentage having prior heart failure hospitalizations. The study's initial mean left ventricular ejection fraction (LVEF) stood at a concerning 29.8%.

Impressive Results: More Wins for Sacubitril/Valsartan

In a methodical approach known as the win ratio, which compares clinical outcomes based on importance, the study found that sacubitril/valsartan significantly outperformed enalapril. Patients on the ARNI experienced a greater reduction in NT-proBNP levels—a critical biomarker for heart failure—showing a decline from 1,801 pg/mL at baseline to 1,236 pg/mL after just 12 weeks, surpassing the enalapril group’s stagnant results.

Safety and Tolerability of ARNI Treatment

The treatment with sacubitril/valsartan was well tolerated, with fewer adverse events leading to discontinuation compared to enalapril. While there was a slightly higher incidence of symptomatic hypotension in the ARNI group, this didn't deter from its overall superior performance.

Looking Ahead: The Future of Chagas Heart Failure Treatment

Scott Solomon, MD, who discussed the results post-presentation, linked PARACHUTE-HF findings with the landmark PARADIGM-HF trial, which underscored the efficacy of sacubitril/valsartan in heart failure with reduced ejection fraction (HFrEF). Although PARACHUTE-HF was notably smaller than PARADIGM-HF, its outcomes point towards a likely path for improved treatment in Chagas patients, suggesting that established heart failure therapies may transcend specific etiologies.

As research continues, the implications of this trial could reshape treatment protocols for millions suffering from Chagas cardiomyopathy, transforming a once-overlooked condition into a focal point for innovative therapy.