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Sacubitril/Valsartan Versus Enalapril in Chagas Cardiomyopathy With Heart Failure With Reduced Ejection Fraction: A

Shaikh Muhammad Daniyal1, Sabula Tabish1, Muhammad Burhan1

  • 1From the Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan.

Cardiology in Review
|April 2, 2026
PubMed

Insights

Sacubitril-valsartan did not significantly improve major clinical outcomes for heart failure with reduced ejection fraction (HFrEF) due to Chagas cardiomyopathy compared to enalapril. However, it substantially lowered NT-proBNP levels with a similar safety profile.

Area of Science:

  • Cardiology
  • Infectious Diseases
  • Pharmacology

Background:

  • Chagas cardiomyopathy is a primary cause of heart failure with reduced ejection fraction (HFrEF) in endemic areas.
  • Patients with Chagas cardiomyopathy are underrepresented in heart failure trials, creating uncertainty about treatment efficacy.
  • Guideline-directed therapies, including sacubitril-valsartan, require evaluation in this specific population.

Purpose of the Study:

  • To evaluate the efficacy and safety of sacubitril-valsartan versus enalapril in patients with HFrEF due to Chagas cardiomyopathy.
  • To assess the impact on cardiovascular mortality, HF hospitalization, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels.

Main Methods:

  • Systematic review and meta-analysis of randomized controlled trials (RCTs) sourced from PubMed, Cochrane (CENTRAL), Scopus, and Embase.
  • Included three RCTs with a total of 1225 patients comparing sacubitril-valsartan to enalapril.
  • Primary outcomes: composite of cardiovascular death or HF hospitalization, all-cause mortality. Secondary outcomes: NT-proBNP change, adverse events.

Main Results:

  • Sacubitril-valsartan did not significantly reduce the composite endpoint of cardiovascular mortality or HF hospitalization (RR: 0.92; P=0.216) compared to enalapril.
  • No significant difference in all-cause mortality was observed between sacubitril-valsartan and enalapril (RR: 0.96; P=0.691).
  • Sacubitril-valsartan demonstrated a significantly greater reduction in NT-proBNP levels (MD: -31.00%; P<0.01) with comparable safety profiles regarding renal dysfunction, hypotension, and hyperkalemia.

Conclusions:

  • In patients with HFrEF due to Chagas cardiomyopathy, sacubitril-valsartan did not improve hard clinical outcomes compared to enalapril.
  • Sacubitril-valsartan showed a significant reduction in NT-proBNP and a similar safety profile.
  • Findings highlight the need for dedicated, large-scale outcome trials for this neglected population due to unique disease pathophysiology.

Keywords:
Chagas cardiomyopathyNT-proBNPheart failuremeta-analysissacubitril-valsartan

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