Amiodarone for arrhythmia in patients with Chagas disease: A systematic review and individual patient data meta-analysis

Background: Chagas disease is a neglected chronic condition caused by Trypanosoma cruzi, with high prevalence and burden in Latin America. Ventricular arrhythmias are common in patients with Chagas cardiomyopathy, and amiodarone has been widely used for this purpose. The aim of our study was to assess the effect of amiodarone in patients with Chagas cardiomyopathy. Methodology: We searched MEDLINE, Embase and LILACS up to January 2018. Data from randomized and observational studies evaluating amiodarone use in Chagas cardiomyopathy were included. Two reviewers selected the studies, extracted data and assessed risk of bias. Overall quality of evidence was accessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Principal findings: We included 9 studies (3 before-after studies, 5 case series and 1 randomized controlled trial). Two studies with a total of 38 patients had the full dataset, allowing individual patient data (IPD) analysis. In 24-hour Holter, amiodarone reduced the number of ventricular tachycardia episodes in 99.9% (95%CI 99.8%-100%), ventricular premature beats in 93.1% (95%CI 82%-97.4%) and the incidence of ventricular couplets in 79% (RR 0.21, 95%CI 0.11–0.39). Studies not included in the IPD analysis showed a reduction of ventricular premature beats (5 studies), ventricular tachycardia (6 studies) and ventricular couplets (1 study). We pooled the incidence of adverse side effects with random effects meta-analysis; amiodarone was associated with corneal microdeposits (61.1%, 95%CI 19.0–91.3, 5 studies), gastrointestinal events (16.1%, 95%CI 6.61–34.2, 3 studies), sinus bradycardia (12.7%, 95%CI 3.71–35.5, 6 studies), dermatological events (10.6%, 95%CI 4.77–21.9, 3 studies) and drug discontinuation (7.68%, 95%CI 4.17–13.7, 5 studies). Quality of evidence ranged from moderate to very low. Conclusions: Amiodarone is effective in reducing ventricular arrhythmias, but there is no evidence for hard endpoints (sudden death, hospitalization). Although our findings support the use of amiodarone, it is important to balance the potential benefits and harms at the individual level for decision-making. Author summary: Chagas disease is a chronic neglected tropical disease, with high prevalence and burden in Latin America. About 30% of chronically infected patients develop Chagas cardiomyopathy. Ventricular arrhythmias are common in patients with Chagas cardiomyopathy and treatment approaches include medications, resynchronization therapy, and implantable cardioverter defibrillator. Studies published from 1980 to 1990 have evaluated the effect of amiodarone. According to our systematic review and individual patient meta-analysis, amiodarone reduced ventricular tachycardia, ventricular premature beats and incidence of ventricular couplets. Although the strong evidence of clinical benefit with arrhythmia reduction, this information should be interpreted with caution, since arrhythmia is a surrogate outcome and since its clinical impact on death and hospitalization reduction over time is not clear. Little information was identified related to hard endpoints. Regarding side effects, our systematic review observed that amiodarone was associated with corneal microdeposits, gastrointestinal events, sinus bradycardia, dermatological events, pneumonitis, hypothyroidism and drug discontinuation. The currently available evidence shows that amiodarone seems to be an effective antiarrhythmic drug for patients with Chagas disease, especially in settings where an implantable cardioverter defibrillator is not available or affordable, but that a balance between potential benefits and harms at the individual level is needed.