Sacubitril/Valsartan vs Enalapril in Heart Failure Due to Chagas Disease: An Open-Label, Multicenter Randomized Clinical Trial.
Summary
In 922 patients with HFrEF due to Chagas disease, sacubitril/valsartan did not reduce cardiovascular death or first HF hospitalization versus enalapril over a median 25.2 months. However, sacubitril/valsartan achieved a significantly greater 12-week reduction in NT-proBNP, yielding a win ratio of 1.52.
Key Findings
- 922 randomized patients across 83 sites; median follow-up 25.2 months.
- No significant difference in cardiovascular death (23.8% vs 25.4%) or first HF hospitalization (22.1% vs 24.1%).
- Greater 12-week NT-proBNP reduction with sacubitril/valsartan (30.6% decrease) vs enalapril (5.5% decrease), yielding a stratified win ratio 1.52 (95% CI 1.28-1.82; P<.001).
Clinical Implications
For Chagas HFrEF, ARNI may be considered for biomarker reduction, but current evidence does not show superiority in hard outcomes over enalapril; guideline adoption should be cautious and context-specific.
Why It Matters
This is the largest RCT addressing guideline therapy specifically in Chagas cardiomyopathy, a neglected condition with high mortality in Latin America. It informs disease-specific expectations for ARNI therapy beyond extrapolation from non-Chagas HFrEF.
Limitations
- Open-label design may introduce performance bias
- Primary hierarchy influenced by biomarker change; lack of superiority in clinical outcomes
Future Directions
Identify Chagas subgroups (e.g., inflammatory or arrhythmic phenotypes) most likely to benefit from ARNI; test combination strategies and longer-term outcome effects; integrate mechanistic biomarkers.
Study Information
- Study Type
- RCT
- Research Domain
- Treatment
- Evidence Level
- I - Randomized controlled trial across multiple centers
- Study Design
- OTHER