Amiodarone or implantable cardioverter-defibrillator in chagas cardiomyopathy: the CHAGASICS randomized clinical trial

IMPORTANCE: Over 10 000 people with Chagas disease experience sudden cardiac death (SCD) annually, mostly caused by ventricular fibrillation. Amiodarone hydrochloride and the implantable cardioverter-defibrillator (ICD) have been empirically used to prevent SCD in patients with chronic Chagas cardiomyopathy. OBJECTIVE: To test the hypothesis that ICD is more effective than amiodarone therapy for primary prevention of all-cause mortality in patients with chronic Chagas cardiomyopathy and moderate to high mortality risk, assessed by the Rassi score. DESIGN, SETTING, AND PARTICIPANTS: CHAGASICS is an open-label, randomized clinical trial. The study enrolled patients from 13 centers in Brazil from May 30, 2014, to August 13, 2021, with the last follow-up November 8, 2021. Patients with serological findings positive for Chagas disease, a Rassi risk score of at least 10 points (intermediate to high risk), and at least 1 episode of nonsustained ventricular tachycardia were eligible to participate. Data were analyzed from May 3, 2022, to June 16, 2023. INTERVENTIONS: Patients were randomized 1:1 to receive ICD or amiodarone (with a loading dose of 600 mg after randomization). MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause mortality, and secondary outcomes included SCD, hospitalization for heart failure, and necessity of a pacemaker during the entire follow-up. RESULTS: The study was stopped prematurely for administrative reasons, with 323 patients randomized (166 in the amiodarone group and 157 in the ICD group), rather than the intended 1100 patients. Analysis was by intention to treat at a median follow-up of 3.6 (IQR, 1.8-4.4) years. Mean (SD) age was 57.4 (9.8) years, 185 patients (57.3%) were male, and the mean (SD) left ventricular ejection fraction was 37.0% (11.6%). There were 60 deaths (38.2%) in the ICD arm and 64 (38.6%) in the amiodarone group (hazard ratio [HR], 0.86 [95% CI, 0.60-1.22]; P = .40). The rates of SCD (6 [3.8%] vs 23 [13.9%]; HR, 0.25 [95% CI, 0.10-0.61]; P = .001), bradycardia requiring pacing (3 [1.9%] vs 27 [16.3%]; HR, 0.10 [95% CI, 0.03-0.34]; P < .001), and heart failure hospitalization (14 [8.9%] vs 28 [16.9%]; HR, 0.46 [95% CI, 0.24-0.87]; P = .01) were lower in the ICD group compared with the amiodarone arm. CONCLUSIONS AND RELEVANCE: In patients with chronic Chagas cardiomyopathy at moderate to high risk of mortality, ICD did not reduce the risk of all-cause mortality. However, ICD significantly reduced the risk of SCD, pacing need, and heart failure hospitalization compared with amiodarone therapy. Further studies are warranted to confirm the evidence generated by this trial.

Long-term outcomes among stable post-acute myocardial infarction patients living in rural versus urban areas: insights from the prospective, observational TIGRIS registry.

BACKGROUND: Insights on the differences in clinical outcomes, quality of life (QoL) and health resource utilisation (HRU) with different levels of care available to post-acute myocardial infarction (AMI) populations in rural and urban settings are limited. METHODS: The long-Term rIsk, clinical manaGement, and healthcare Resource utilisation of stable coronary artery dISease (TIGRIS), a prospective, observational registry, enrolled 8452 patients aged ≥50 years 1-3 years post-AMI from June 2013 to November 2014 from 24 countries in Asia Pacific/Australia, Europe, North America and South America. Differences in QoL (measured using the EuroQol Research Foundation instrument) and HRU between patients in rural and urban settings were evaluated in this post hoc analysis. The incidence of clinical endpoints (cardiovascular (CV) death, AMI, unstable angina with urgent revascularisation and stroke; bleeding; and all-cause mortality) was analysed. Data were collected at baseline and every 6 months for 24 months. RESULTS: There were fewer hospitalisations and visits to general practitioners (GPs) and cardiologists in the rural versus urban populations (adjusted event rate ratio (ERR)=0.90 (95% CI, 0.82 to 1.00, p=0.04); ERR=0.84 (95% CI, 0.78 to 0.92, p<0.001); ERR=0.86 (95% CI, 0.81 to 0.92, p<0.001), respectively). No statistically significant differences were observed between rural and urban populations in all-cause death, AMI, unstable angina with urgent revascularisation, CV death, stroke, major bleeding events and health-related QoL. The adjusted incidence rate ratio was 0.92 (95% CI, 0.74 to 1.15) for the composite of CV death, AMI and stroke. CONCLUSIONS: Living in rural areas was associated with fewer GP/cardiologist visits and hospitalisations; no significant differences in clinical outcomes and QoL were observed. TRIAL REGISTRATION NUMBER: NCT01866904.

Diabetes association with self-reported health, resource utilization, and prognosis post-myocardial infarction.

BACKGROUND: Diabetes mellitus (DM) is associated with increased cardiovascular (CV) risk. We compared health-related quality of life (HRQoL), healthcare resource utilization (HRU), and clinical outcomes of stable post-myocardial infarction (MI) patients with and without DM. HYPOTHESIS: In post-MI patients, DM is associated with worse HRQoL, increased HRU, and worse clinical outcomes. METHODS: The prospective, observational long-term risk, clinical management, and healthcare Resource utilization of stable coronary artery disease study obtained data from 8968 patients aged ≥50 years 1 to 3 years post-MI (369 centers; 25 countries). Patients with ≥1 of the following risk factors were included: age ≥65 years, history of a second MI >1 year before enrollment, multivessel coronary artery disease, creatinine clearance ≥15 and <60 mL/min, and DM treated with medication. Self-reported health status was assessed at baseline, 1 and 2 years and converted to EQ-5D scores. The main outcome measures were baseline HRQoL and HRU during follow-up. RESULTS: DM at enrollment was 33% (2959 patients, 869 insulin treated). Mean baseline EQ-5D score (0.86 vs 0.82; P < .0001) was higher; mean number of hospitalizations (0.38 vs 0.50, P < .0001) and mean length of stay (LoS; 9.3 vs 11.5; P = .001) were lower in patients without vs with DM. All-cause death and the composite of CV death, MI, and stroke were significantly higher in DM patients, with adjusted 2-year rate ratios of 1.43 (P < .01) and 1.55 (P < .001), respectively. CONCLUSIONS: Stable post-MI patients with DM (especially insulin treated) had poorer EQ-5D scores, higher hospitalization rates and LoS, and worse clinical outcomes vs those without DM. Strategies focusing specifically on this high-risk population should be developed to improve outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01866904 (https://clinicaltrials.gov).