Antiparasitics for Chagas cardiomyopathy: Benznidazole has significant antiparasitic activity but not progression of serious heart problems

The BENEFIT trial has shown that a 40 to 80 day treatment with the antiparasitic medication Benznidazole ( Rochagan, Radanil ) significantly has reduced parasite activity, but not progression of serious heart problems over a 5-year period among patients with Chagas disease cardiomyopathy.

The findings were published in the New England Journal of Medicine ( NEJM ).

The study has demonstrated that Benznidazole has significant antiparasitic activity but there was regional variability both in the parasitic response as well as progression of heart problems.

Recent data have indicated that parasite persistence may play a pivotal role in the pathogenesis of chronic Chagas cardiomyopathy, but until now researchers did not know whether antiparasitic treatment could prevent this.
The results confirm that with the current treatment, significant reductions in parasite DNA detection can be achieved.
The lack of benefit in reducing the progression of cardiomyopathy may have been related to strain susceptibility or insufficient long-term activity against the parasite.

BENEFIT ( BENznidazole Evaluation For Interrupting Trypanosomiasis Trial ) included 2,854 patients from 5 countries in Central and South America.

All patients had serologic evidence of the Trypanosoma cruzi parasite which causes Chagas, as well as electrocardiographic and other typical cardiac abnormalities characteristic of Chagas cardiomyopathy.

The Trypanosoma cruzi parasite is transmitted to humans by triatomine insects and is curable when treated early with antiparasitics. However, it is often not recognised at this stage and 30-40% of chronic infections lead to cardiomyopathy within 10-30 years.

The patients were randomised to treatment with placebo or Benznidazole for 40-80 days, with the primary outcome of the study being a composite of all cause death, resuscitated cardiac arrest, sustained ventricular tachycardia, insertion of pacemaker or cardiac defibrillator, cardiac transplantation, development of new heart failure, and stroke, or systemic or pulmonary thromboembolic events.

After an average follow-up of 5.4 years, the primary outcome occurred in a similar percentage of patients in the treatment and placebo arms ( 27.5% and 29.1% respectively; hazard ratio [ HR ] 0.93; 95% confidence interval [ CI ] 0.81-1.07; P=0.31 ).

Parasite persistence was significantly reduced after treatment, compared to placebo ( 66.2% versus 33.5% ), an effect that was not fully maintained after 5 years ( 46.7% versus 33.1% respectively [ all P less than 0.0001 ] ).

Reduction in parasite DNA detection varied among participating countries with a significantly lower response observed in Colombia and El Salvador compared to other countries ( odds ratio [ OR ] 1.33 and 0.96 at 2 and 5 or more years ).

BENEFIT is the largest trial to date to examine the impact of Benznidazole treatment in patients with chronic Chagas cardiomyopathy.

Approximately 7 million people world wide are infected by Trypanosoma cruzi and, given the favorable risk/benefit ratio observed in BENEFIT, treatment during the early stages of chronic Chagas infection should be strongly encouraged.
The need to treat patients with established cardiomyopathy needs further research to determine whether different dosing and duration schemes as well as geographic susceptibility may in fact identify patients with chronic Chagas cardiomyopathy that benefit from trypanocidal therapy. ( Xagena )

Source: European Society of Cardiology ( ESC ), 2015



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