Pharmacological interventions for treating heart failure in patients with Chagas cardiomyopathy

Review question
We reviewed pharmacological interventions for treating heart failure in people with Chagas cardiomyopathy.

Named in honour of the Brazilian physician Carlos Chagas, Chagas disease is caused by the Trypanosoma cruzi parasite. It is common in Latin and Central America and leads to Chagas cardiomyopathy (heart muscle disease). It is an important cause of heart failure. The number of people infected with Chagas disease has been estimated to be about 10 to 12 million worldwide; around 20% to 30% of individuals infected with Trypanosoma cruzi will develop symptomatic heart disease at some point during their lives. In the Americas in 2005, there were estimated to be 7,694,500 people infected by Trypanosoma cruzi and 1,772,365 suffering from chagasic cardiomyopathy. Infected people from endemic countries in Latin America are migrating throughout the world. As a result, what was thought to be a health problem in the Americas is rapidly becoming a world health problem. It has been estimated that 300,167 individuals with Trypanosoma cruzi infection live in the United States, with 30,000 to 45,000 cardiomyopathy cases and 63 to 315 congenital infections annually. Standard treatment options for non-Chagas disease heart failure are used for treating Chagas disease-related heart failure. However, because of fundamental differences in the affected populations, it is important to assess the benefits and harms of pharmacological interventions for Chagas disease-related heart failure.

Study characteristics
We identified one new trial, so there are now three studies involving 108 participants. All studies were conducted in Brazil during 2004, 2007, and 2012. Two trials evaluated the effects of carvedilol versus placebo; one trial assessed rosuvastatin versus placebo.

Key results
The results were inconclusive that carvedilol reduced all-cause mortality or improved quality of life more than placebo. The safety profile of carvedilol for Chagas cardiomyopathy remains unclear. One study assessed the effect of rosuvastatin versus placebo, but did not show an effect size. Therefore, the results from available clinical trials neither support nor reject the use of carvedilol or rosuvastatin in treating this clinical entity. Further investigation is warranted to investigate the exact applicability of conventional heart failure treatment agents in Chagas cardiomyopathy.

Quality of evidence
Our confidence in the results of this review is very low because the included trials had a high risk of bias and were small. which generated imprecise results.

Date searched: 15 February 2016.

Authors' conclusions: 

This first update of our review found very low-quality evidence for the effects of either carvedilol or rosuvastatin, compared with placebo, for treating heart failure in people with Chagas disease. The three included trials were underpowered and had a high risk of bias. There were no conclusive data to support or reject the use of either carvedilol or rosuvastatin for treating Chagas cardiomyopathy. Unless randomised clinical trials provide evidence of a treatment effect, and the trade-off between potential benefits and harms is established, policy-makers, clinicians, and academics should be cautious when recommending or administering either carvedilol or rosuvastatin to treat heart failure in people with Chagas disease. The efficacy and safety of other pharmacological interventions for treating heart failure in people with Chagas disease remains unknown.

Read the full abstract...

Chagas disease-related cardiomyopathy is a major cause of morbidity and mortality in Latin America. Despite the substantial burden to the healthcare system, there is uncertainty regarding the efficacy and safety of pharmacological interventions for treating heart failure in people with Chagas disease. This is an update of a Cochrane review published in 2012.


To assess the clinical benefits and harms of current pharmacological interventions for treating heart failure in people with Chagas cardiomyopathy.

Search strategy: 

We updated the searches in the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2016, Issue 1), MEDLINE (Ovid; 1946 to to February Week 1 2016), EMBASE (Ovid; 1947 to 2016 Week 07), LILACS (1982 to 15 February 2016), and Web of Science (Thomson Reuters; 1970 to 15 February 2016). We checked the reference lists of included papers. We applied no language restrictions.

Selection criteria: 

We included randomised clinical trials (RCTs) that assessed the effects of pharmacological interventions to treat heart failure in adult patients (18 years or older) with symptomatic heart failure (New York Heart Association classes II to IV), regardless of the left ventricular ejection fraction stage (reduced or preserved), with Chagas cardiomyopathy. We did not apply limits to the length of follow-up. Primary outcomes were all-cause mortality, cardiovascular mortality at 30 days, time-to-heart decompensation, disease-free period (at 30, 60, and 90 days), and adverse events.

Data collection and analysis: 

Two authors independently performed study selection, 'Risk of bias' assessment and data extraction. We estimated relative risk (RR) and 95% confidence intervals (CIs) for dichotomous outcomes. We measured statistical heterogeneity using the I² statistic. We used a fixed-effect model to synthesize the findings. We contacted authors for additional data. We developed 'Summary of findings' (SoF) tables and used GRADE methodology to assess the quality of the evidence.

Main results: 

In this update, we identified one new trial. Therefore, this version includes three trials (108 participants). Two trials compared carvedilol against placebo and another assessed rosuvastatin versus placebo. All trials had a high risk of bias.

Meta-analysis of two trials showed a lower proportion of all-cause mortality in the carvedilol groups compared with the placebo groups (RR 0.69; 95% CI 0.12 to 3.88, I² = 0%; 69 participants; very low-quality evidence). Neither of the trials reported on cardiovascular mortality, time-to-heart decompensation, or disease-free periods.

One trial (30 participants) found no difference in hospital readmissions (RR 1.00; 95% CI 0.31 to 3.28; very low-quality of evidence) or reported adverse events (RR 0.92; 95% CI 0.67 to 1.27; very low-quality of evidence) between the carvedilol and placebo groups.

There was very low-quality evidence from two trials of inconclusive effects on quality of life (QoL) between the carvedilol and placebo groups. One trial (30 participants) assessed QoL with the Minnesota Living With Heart Failure Questionnaire (21 items; item scores range from 0 to 5; a lower MLHFQ score is better). The MD was -14.74; 95% CI -24.75 to -4.73. The other trial (39 participants) measured QoL with the Medical Outcomes Study 36-item short-form health survey (SF-36; item scores range from 0 to 100; higher SF-36 score is better). Data were not provided.

One trial (39 participants) assessed the effect of rosuvastatin versus placebo. The trial did not report on any primary outcomes or adverse events. There was very low-quality evidence of uncertain effects on QoL (no data were provided).