Publication Date

1-1-2025

Journal

EClinicalMedicine

DOI

10.1016/j.eclinm.2024.102972

PMID

39810938

PMCID

PMC11732499

PubMedCentral® Posted Date

12-24-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

hagas disease, Chagas cardiomyopathy, Trypanosoma cruzi, Antitrypanosomal therapy, Benznidazole, Nifurtimox, Meta-analysis, Disease progression

Abstract

BACKGROUND: Endemic in more than 20 countries, Chagas disease affects 6.3 million people worldwide, leading to 28,000 new infections and 7700 deaths each year. Previous meta-analyses on antiparasitic treatment need updates to encompass recent studies and to assess key clinically meaningful endpoints. This study aims to evaluate the impact of antitrypanosomal therapy in preventing or reducing disease progression and mortality in chronic Chagas disease.

METHODS: We performed a systematic review and meta-analysis of studies reporting the cardiovascular outcomes of antitrypanosomal therapy in patients with chronic Chagas disease. We searched Ovid Embase, Ovid MEDLINE, Ovid Global Health, Scopus, Web of Science Core Collection, Cochrane Library, PubMed, Google Scholar, and Virtual Health Library databases from inception to May 18, 2024. We included aggregated data from randomized controlled studies and observational reports (full articles and abstracts) featuring antiparasitic interventions with benznidazole or nifurtimox compared to a control group. Primary outcomes were electrocardiogram (ECG) changes, disease progression, cardiovascular death, and overall mortality. A customized risk of bias scale assessed the methodological quality of studies, and a random-effects model estimated the pooled risk ratios. This investigation was registered in PROSPERO (CRD42023495755).

FINDINGS: Out of 4666 reports screened, 23 met the pre-specified inclusion criteria (8972 participants). Compared to no treatment or placebo, antiparasitic treatment led to a reduction in i) ECG changes (17 studies, 4994 participants: risk ratio (RR): 0.48, 95% CI 0.36-0.66, p < 0.001;

INTERPRETATION: We found compelling evidence that antiparasitic treatment significantly reduces the risk of ECG changes, disease progression, cardiovascular death, and overall mortality in chronic Chagas disease. Although the quality of evidence ranges from low to intermediate, with considerable heterogeneity across studies, the potential benefits are substantial. These findings support the broader use of trypanocidal therapy in the management of Chagas disease, though further research remains necessary.

FUNDING: This study had no funding source.

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