Long-Term Cardiac Outcomes of Treating Chronic Chagas Disease with Benznidazole versus No Treatment

A Nonrandomized Trial

16 May 2006 | Volume 144 Issue 10 | Pages 724-734

Background: Benznidazole is effective for treating acute-stage Chagas disease, but its effectiveness for treating indeterminate and chronic stages remains uncertain.

Objective: To compare long-term outcomes of patients with nonacute Chagas disease treated with benznidazole versus outcomes of those who did not receive treatment.

Design: Clinical trial with unblinded, nonrandom assignment of patients to intervention or control groups.

Setting: Chagas disease center in Buenos Aires, Argentina.

Patients: 566 patients 30 to 50 years of age with 3 positive results on serologic tests and without heart failure.

Measurements: The primary outcome was disease progression, defined as a change to a more advanced Kuschnir group or death. Secondary outcomes included new abnormalities on electrocardiography and serologic reactivity.

Intervention: Oral benznidazole, 5 mg/kg of body weight per day for 30 days (283 patients), or no treatment (283 patients).

Results: Fewer treated patients had progression of disease (12 of 283 [4%] vs. 40 of 283 [14%]; adjusted hazard ratio, 0.24 [95% CI, 0.10 to 0.59]; P = 0.002) or developed abnormalities on electrocardiography (15 of 283 [5%] vs. 45 of 283 [16%]; adjusted hazard ratio, 0.27 [CI, 0.13 to 0.57]; P = 0.001) compared with untreated patients. Left ventricular ejection fraction (hazard ratio, 0.97 [CI, 0.94 to 0.99]; P < 0.002) and left ventricular diastolic diameter (hazard ratio, 2.45 [CI, 1.53 to 3.95]; P < 0.001) were also associated with disease progression. Conversion to negative results on serologic testing was more frequent in treated patients than in untreated patients (32 of 218 [15%] vs. 12 of 212 [6%]; adjusted hazard ratio, 2.1 [CI, 1.06 to 4.06]; P = 0.034).

Limitations: Nonrandom, unblinded treatment assignment was used, and follow-up data were missing for 20% of patients. Loss to follow-up was more common among patients who were less sick. Two uncontrolled interim analyses were conducted.

Conclusions: Compared with no treatment, benznidazole treatment was associated with reduced progression of Chagas disease and increased negative seroconversion for patients presenting with nonacute disease and no heart failure. These observations indicate that a randomized, controlled trial should now be conducted.

Editors' Notes Context The effect of antitrypanosomal drug therapy on progression of heart involvement in patients with chronic Chagas disease is uncertain. Contribution The authors assigned alternating patients with 3 positive results on serologic tests for Trypanosoma cruzi and no evidence of heart failure to receive benznidazole for 30 consecutive days (n = 283) or no treatment (n = 283). After a median follow-up of 9.8 years, 14.1% of untreated patients and 4.2% of treated patients (P = 0.002) had progression of heart disease. Cautions Assignment of patients was not randomized. Twenty percent of patients from both groups were lost to follow-up. Implications Treatment during the chronic phase of Chagas disease may reduce the risk for progression of heart disease. —The Editors

 

Author and Article Information

From Hospital Interzonal General de Agudos Eva Perón and Instituto Nacional de Parasitología Dr. Mario Fatala Chaben, Buenos Aires, Argentina.

Acknowledgments: The authors thank the directors at Hospital Eva Perón for providing a suitable setting for this research. Dr. Postan is a fellow of CONICET, Argentina.

Grant Support: None.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Rodolfo Viotti, MD, José Hernández 3440, Villa Ballester, Gral. San Martín, Buenos Aires ZC 1653, Argentina; e-mail, peron{at}millicom.com.ar.

Current Author Addresses: Dr. Viotti: José Hernández 3440, Villa Ballester, Gral. San Martín, Buenos Aires ZC 1653, Argentina.

Drs. Vigliano, Lococo, Bertocchi, Petti, Alvarez, and Armenti: Avenue Ricardo Balbin 900, San Martín, Buenos Aires ZC 1650, Argentina.

Dr. Postan: Avenue Paseo Colón 568, Buenos Aires ZC 1063, Argentina.

Author Contributions: Conception and design: R. Viotti, C. Vigliano, A. Armenti.

Analysis and interpretation of the data: R. Viotti, C. Vigliano, M. Petti, A. Armenti.

Drafting of the article: R. Viotti, C. Vigliano, G. Bertocchi, M. Postan.

Critical revision of the article for important intellectual content: B. Lococo, G. Bertocchi, M. Petti, M.G. Alvarez, M. Postan, A. Armenti.

Final approval of the article: R. Viotti, C. Vigliano, B. Lococo, G. Bertocchi, M. Petti, M. Postan, A. Armenti.

Provision of study materials or patients: R. Viotti, C. Vigliano, B. Lococo, M. Petti, M.G. Alvarez.

Statistical expertise: R. Viotti.

Administrative, technical, or logistic support: B. Lococo, G. Bertocchi, M.G. Alvarez, M. Postan.

Collection and assembly of data: R. Viotti, C. Vigliano, B. Lococo, G. Bertocchi, M. Petti, M.G. Alvarez, M. Postan.

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