Abstract Body: Introduction: Most studies evaluated the efficacy of treatment for chagas disease with the reduction of parasite detection as a primary outcome. However, little is known about the mortality rate associated with benznidazole or nifurtimox in chagas disease patients. Thus, we aimed to investigate all-cause mortality and cardiovascular-related mortality among chagas disease patients treated with benznidazole or nifurtimox.

Method: Systematic review and meta-analysis were conducted including randomized control trial studies and cohort studies in patients who received benznidazole or nifurtimox for chagas disease treatment, using online databases including PubMed, Embase, CENTRAL, LILAC, and sciELO up to May 1, 2024. The primary outcomes were all-cause mortality or cardiovascular-related mortality. Studies focused on patients with HIV-coinfection were excluded.

Result: We included 15 studies involving 3837 patients, with 14 studies on benznidazole (n=3552) and 3 studies (n=285) on nifurtimox. Overall, all-cause mortality over follow-up was 1.96% [95% Confidence Interval (CI): 0.58-3.93], and 2.21% [95% CI: 0.45-4.89] for cardiovascular-related mortality. All-cause mortality was 1.04% [95% CI: 0.00-4.61] for the nifurtimox group and 2.07% [95% CI: 0.51-4.39] for the benznidazole group. Cardiovascular-related mortality was 3.03% [95% CI: 0.00-9.25] for the nifurtimox group and 2.10% [95% CI: 0.25-5.16] for the benznidazole group.

Conclusion: This study is one of the first studies that conducted a meta-analysis to provide mortality outcomes in chagas disease patients. Our study estimated an increase in individuals of all-cause mortality and cardiovascular-related mortality over the study period. Further investigations are needed to understand mortality by phase of chagas disease, comorbidities, and cardiomyopathy-related signs to better understand the long-term effect of patients treated for chagas disease.