Safety and tolerability of benznidazole in older patients with chronic Chagas disease

Current guidelines recommend treating chronic Chagas disease (CD) with benznidazole up to 50 years of age, with individualized decisions in older individuals due to limited safety data. We aimed to compare the safety, tolerability and long-term outcomes of benznidazole in individuals above and below 50 years. We conducted a retrospective cohort study at Vall d’Hebron-Drassanes (Barcelona), including individuals aged 35-69 years treated with benznidazole between 2008 and 2017. Participants were divided into two age groups: (35-49 and 50-69 years), with biannual follow-up. The primary outcome was treatment discontinuation due to toxicity. Secondary outcomes included adverse events (AEs), cardiac progression, and other clinical events over 5 years. A total of 339 patients were included, of whom 59 (17.4%) were ≥50 years. AEs occurred in 82% of individuals, with no significant differences between groups (p=0.50). Cutaneous reactions were the most frequent AEs (54%), and did not differ significantly by age (57% vs. 46%, p=0.11). Treatment discontinuation due to toxicity was similar in older and younger individuals (20.3% vs. 13.7%; p=0.19). Cardiac progression was more frequent in older individuals (1.73 vs. 0.68 events/100 person-years; p=0.03), though this was not significant after adjustment (p=0.52). New cardiovascular risk factors and malignancies were more frequent in older individuals. Benznidazole was associated with a high frequency of adverse events and a clinically relevant rate of treatment discontinuation, with no statistically significant differences between age groups. These findings support considering benznidazole in selected individuals over 50, suggesting that age alone should not prevent treatment.