Isosorbide and nifedipine for Chagas' megaesophagus: A systematic review and meta-analysis

Background Chagas disease is a neglected tropical disease. About 6 to 8 million people are chronically infected and 10% to 15% develop irreversible gastrointestinal disorders, including megaesophagus. Treatment focuses on improving symptoms, and isosorbide and nifedipine may be used for this purpose. Methodology We conducted a systematic review to evaluate the effectiveness of pharmacological treatment for Chagas’ megaesophagus. We searched MEDLINE, Embase and LILACS databases up to January 2018. We included both observational studies and RCTs evaluating the effects of isosorbide or nifedipine in adult patients with Chagas’ megaesophagus. Two reviewers screened titles and abstracts, selected eligible studies and extracted data. We assessed the risk of bias using NIH ‘Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group’ and RoB 2.0 tool. Overall quality of evidence was assessed using GRADE. Principal findings We included eight studies (four crossover RCTs, four before-after studies). Three studies evaluated the effect of isosorbide on lower esophageal sphincter pressure (LESP), showing a significant reduction (mean difference −10.52mmHg, 95%CI −13.57 to−7.47, very low quality of evidence). Three studies reported the effect of isosorbide on esophageal emptying, showing a decrease in esophageal retention rates (mean difference −22.16%, 95%CI −29.94 to −14.38, low quality of evidence). In one study, patients on isosorbide reported improvement in the frequency and severity of dysphagia (moderate quality of evidence). Studies evaluating nifedipine observed a decrease in LESP but no effect on esophageal emptying (very low and low quality of evidence, respectively). Isosorbide had a higher incidence of headache as a side effect than nifedipine. Conclusions Although limited, available evidence shows that both isosorbide and nifedipine are effective in reducing esophageal symptoms. Isosorbide appears to be more effective, and its use is supported by a larger number of studies; nifedipine, however, appears to have a better tolerability profile. Trial registration PROSPERO CRD42017055143. ClinicalTrials.gov CRD42017055143.
Author summary Chagas disease is a chronic neglected tropical disease that has increased in prevalence in the last decade. About 10% of chronically infected patients develop the digestive form of the disease. Megaesophagus is a common manifestation, and symptoms include difficulty or discomfort in swallowing and regurgitation. Treatment approaches include dietary interventions, medications, and endoscopic and surgical interventions. Regarding pharmacological treatment, only a few small studies have evaluated the effects of isosorbide and nifedipine, mainly on surrogate outcomes. According to our systematic review, the use of isosorbide reduced lower esophageal sphincter pressure, esophageal retention after meal ingestion, and the frequency and severity of dysphagia, while nifedipine reduced esophageal retention after meal ingestion. In light of this, both medications are effective in the treatment of symptoms associated with Chagas disease. Isosorbide appears to be more effective, and its use is supported by a larger number of studies; nifedipine, however, appears to have a better tolerability profile. Both drugs are valid alternatives, and the decisions about pharmacological treatment should be tailored to each patient.