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Benznidazole reduces parasite detection, does not improve cardiac deterioration in Chagas’ cardiomyopathy
LONDON — Trypanocidal therapy with benznidazole in patients with established Chagas’ cardiomyopathy did not reduce cardiac deterioration, despite a reduction in serum parasite detection, according to 5-year data from the BENEFIT study.
Researchers randomly assigned 2,854 patients with Chagas’ cardiomyopathy to benznidazole or placebo for up to 80 days and followed them for an average of 5.4 years.
Chagas’s disease is the third most common parasitic disease in the world, Carlos A. Morillo, MD, said during a press conference. According to current estimates, up to 7 million people worldwide are infected and more than 36,000 new cases are reported each year, he said.
It is postulated that Trypanosoma cruzi low-level parasitemia may cause cardiomyopathy; however, the effect of trypanocidal therapy in Chagas’ cardiomyopathy was unknown, according to the researchers.
The primary endpoint was the first incidence of any components of a composite outcome of death, resuscitated cardiac arrest, sustained ventricular tachycardia, pacemaker or implantable cardioverter defibrillator implantation, cardiac transplantation, new HF, stroke or other thrombotic event. The primary endpoint occurred in 27.5% of patients assigned benznidazole vs. 29.1% assigned placebo (HR = 0.93; 95% CI, 0.81-1.07).
When the researchers assessed blood samples obtained from 1,896 patients at baseline, 60.5% tested positive for T. cruzi. The treatment group had a higher rate of conversion to negative polymerase chain reaction (PCR) results at the end of treatment (66.2% vs. 33.5%), at 2 years (55.4% vs. 35.3%) and at 5 years or later (46.7% vs. 33.1%; P < .001 for all).
The multicenter study enrolled patients from five countries in Central America and South America. Results indicated that the treatment effect on PCR conversion varied by geographic region, Morillo said during the press conference. In Brazil, the OR for conversion was 3.03 (95% CI, 2.12-4.34) at 2 years and 1.87 (95% CI, 1.33-2.63) at 5 years or later; in Colombia and El Salvador, the ORs were 1.33 (95% CI, 0.9-1.98) and 0.96 (95% CI, 0.63-1.45), respectively; and in Argentina and Bolivia, the ORs were 2.63 (95% CI, 1.89-3.66) and 2.79 (95% CI, 1.99-3.92), respectively. However, the researchers observed that PCR conversion did not correspond to effect on clinical outcomes (P for interaction = .16).
Benznidazole was well tolerated, and permanent discontinuation was lower than previously reported, Morillo said.
“BENEFIT is the largest study in Chagas’ disease and the most comprehensive program ever conducted and will inform research into the field for some time,” he said, adding that the trial took 13 years from its inception and created a large network of investigators interested in this disease. “It has furthered our knowledge of Chagas’ disease and response to trypanocidal therapy. … We need further research to determine whether different dosing and duration schemes as well as geographic susceptibility may improve results.” – by Katie Kalvaitis
References:
Morillo CA, et al. Hot Line V: Heart Failure. Presented at: European Society of Cardiology Congress; Aug. 29-Sept. 2, 2015; London.
Morillo CA, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1507574.
Disclosure: Morillo reports no relevant financial disclosures.