Trial of Benznidazole for Chronic Chagas’ Cardiomyopathy

Study Questions:

Does treatment with antiparasitic agent benznidazole affect outcomes of patients with Chagas’ cardiomyopathy?


The BENEFIT trial was a prospective, multicenter, randomized study involving 2,854 patients with Chagas’ cardiomyopathy. Subjects received benznidazole or placebo for up to 80 days and were followed for a mean of 5.4 years. The primary outcome in the time-to-event analysis was the first event of any of the components of the composite outcome: death, resuscitated cardiac arrest, sustained ventricular tachycardia, insertion of a pacemaker or implantable cardioverter-defibrillator, cardiac transplantation, new heart failure, stroke, or other thromboembolic event.


The primary outcome occurred in 28% of patients in the benznidazole group and in 29% in the placebo group (hazard ratio, 0.93; p = 0.31). The rates of conversion to negative polymerase-chain-reaction (PCR) results (PCR conversion) were 47% and 33%, respectively, at 5 years or more (p < 0.001). The effect of treatment on PCR conversion varied according to country. However, the rates of PCR conversion did not correspond to effects on clinical outcome (p = 0.16 for interaction).


Trypanocidal therapy with benznidazole for 80 days in patients with Chagas’ cardiomyopathy reduced serum parasite detection, but did not significantly reduce cardiac clinical deterioration through 5 years of follow-up.


While most cardiologists in the United States have not had much exposure to patients with Chagas’ cardiomyopathy, the condition places a large burden on the population of Central and South America. Migration patterns on the continent may eventually change that. It is estimated that 300,000 infected immigrants reside in the United States. There are more than 5 million people with the chronic parasitic infection of Trypanosoma cruzi in the Americas, of whom up to 25% have or will eventually develop cardiomyopathy. There has been a growing movement toward broader treatment of chronically infected adults, including those with early cardiomyopathy, in the hope that such treatment will reduce progression of the disease. Unfortunately, the large randomized clinical trial BENEFIT has shown that treatment with benznidazole for 80 days did not affect clinical outcomes over a period of 5 years, although it was effective in reducing serum parasite detection. It may have been too late in the evolution of the disease for the antiparasitic treatment to provide benefit or perhaps this well designed and conducted study did not last long enough to show such a benefit.

Clinical Topics: Arrhythmias and Clinical EP, Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Prevention, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Acute Heart Failure, Heart Transplant

Keywords: Antiparasitic Agents, Arrhythmias, Cardiac, Chagas Cardiomyopathy, Defibrillators, Implantable, Heart Arrest, Heart Failure, Heart Transplantation, Nitroimidazoles, Pacemaker, Artificial, Parasites, Polymerase Chain Reaction, Primary Prevention, Stroke, Tachycardia, Ventricular, Trypanosoma cruzi

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