Speaker
Renato Lopes MD, PhD
Professor of Medicine, Division of Cardiology
Duke University Medical Center
Duke Clinical Research Institute
Keywords
Heart Failure; Chagas Disease; Underserved Population
Key Points
- Chagas disease is a condition caused by the parasite Trypanosoma cruzi. One of the complications of Chagas is heart failure (HF). Though Latin America has historically borne the brunt of Chagas-related HF, incidence is increasing globally.
- Chagas-related HF has unique characteristics, with lower prevalence of hypertension and diabetes, worse health-related quality of life, and higher hospitalization and mortality rates when compared to other types of HF. In short, though patients with Chagas-related HF are less likely to have classic HF risk factors, their event rates are higher. Furthermore, there’s a lack of clinical evidence to guide their treatment.
- Prevention And Reduction of Adverse outcomes in Chagasic Heart failUre Trial Evaluation (PARACHUTE-HF) was a prospective randomized trial evaluating the effect of sacubitril/valsartan compared with enalapril in improving a hierarchical composite endpoint including cardiovascular (CV) death, HF hospitalization, and reduction in NT-proBNP levels – in that order, on the basis of clinical importance.
- The study population consisted of 922 patients from 83 sites in 4 Latin American countries: Argentina, Brazil, Colombia, and Mexico. Participants had HF with reduced ejection fraction (HFrEF) and a confirmed diagnosis of Chagas disease.
- After 12 weeks, the study team found that sacubitril/valsartan was superior to enalapril with respect to the hierarchical composite endpoint. These results were primarily driven by a 32% reduction in average NT-proBNP levels.
- There were some limitations, including COVID-19-related changes in clinical practice that may have affected HF hospitalization rates and the observed treatment effect.
- PARACHUTE-HF was the first major randomized trial studying HF treatment in HFrEF patients with Chagas disease. While sacubitril/valsartan has extensive clinical and real-world data supporting its effectiveness for HFrEF, this trial further supports its use in treating this specific population.
- There is a need for rigorously conducted clinical trials in Chagas disease to better define the cardiovascular benefit/risk profile of new treatment options for this neglected and high-risk population. This trial provides a model for international collaboration among cardiologists and infectious disease physicians with a shared goal.
Discussion Themes
The pathophysiology of Chagas is complex. It includes chronic, low-intensity myocarditis, which can lead to changes in coagulation pathways and thrombotic events; a neurological tropism, which can cause sudden arrythmias; and an autoimmune component.
Dr. Lopes emphasized the impact that an intentional and informed coordinating center; carefully selected sites; deeply invested PIs; and a strong Data and Safety Monitoring Board (DSMB) had on the success of PARACHUTE-HF.