It is unknown whether angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) have a positive, neutral, or negative effect on clinical outcomes in patients with coronavirus disease 2019 (COVID-19).OBJECTIVE To determine whether discontinuation compared with continuation of ACEIs or ARBs changed the number of days alive and out of the hospital through 30 days.
DESIGN, SETTING, AND PARTICIPANTSA randomized clinical trial of 659 patients hospitalized in Brazil with mild to moderate COVID-19 who were taking ACEIs or ARBs prior to hospitalization
Background-QT interval parameters are potential prognostic markers of arrhythmogenicity risk and cardiovascular mortality and have never been evaluated in Chagas' disease. Methods and Results-Outpatients (738) in the chronic phase of Chagas' disease were enrolled in a long-term follow-up study. Maximal heart rate-corrected QT (QTc) and T-wave peak-to-end (TpTe) intervals and QRS, QT, JT, QTapex, and TpTe dispersions and variation coefficients were measured manually and calculated from 12-lead ECGs obtained on admission. Clinical, radiological, and 2-dimensional echocardiographic data were also recorded. Primary end points were all-cause, Chagas' disease-related, and sudden cardiac mortalities. During a follow-up of 58Ϯ39 months, 62 patients died, 54 of Chagas' disease-related causes and 40 suddenly. Multivariate Cox survival analysis revealed that the QT-interval dispersion (QTd) (hazard ratio, 1.45; 95% confidence interval, 1.29 to 1.63; PϽ0.001, for 10-ms increments) and left ventricular (LV) end-systolic dimension (hazard ratio, 1.36; 95% confidence interval, 1.21 to 1.53; PϽ0.001, for 5-mm increments) were the strongest independent predictors for all end points. The maximum QTc interval (QTcmax) could substitute for QTd with a worse predictive performance. Other predictors were heart rate, presence of pathological Q waves, frequent premature ventricular contractions (PVCs), and isolated left anterior fascicular block (LAFB) on the ECGs. Kaplan-Meier survival curves demonstrated that a QTd Ն65 ms or a QTcmax Ն465 ms 1/2 discriminated the 2 groups with significantly different prognoses. Conclusions-Electrocardiographic QTd and echocardiographic LV end-systolic dimension were the most important mortality predictors in patients with Chagas' disease. Heart rate, the presence on ECG of pathological Q waves, frequent PVCs, and isolated LAFB refined the mortality risk stratification. (Circulation. 2003;108:305-312.)
The Naranjo algorithm was a useful tool to reduce the underreporting of ADRs. Events were common, but were associated with low morbidity and were reversible upon discontinuation of drug treatment. Moreover, there were no fatal events; therefore, benznidazole treatment was considered safe.
Chagas disease is a neglected chronic condition that presents high morbidity and mortality burden, with considerable psychological, social, and economic impact. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on collaboration and contribution of renowned Brazilian experts with vast knowledge and experience on various aspects of the disease. It is the result of close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. This document shall strengthen the development of integrated control measures against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research.
Background
Chagas disease (CD) remains an important endemic disease in Latin America. However, CD became globalized in recent decades. The majority of the chronically infected individuals did not receive etiologic treatment for several reasons, among them the most conspicuous is the lack of access to diagnosis. The impact of trypanocidal treatment on CD chronic phase, without cardiac involvement (indeterminate form ICF), is yet to be determined. We aimed to evaluate the effect of trypanocidal treatment with benznidazole (BZN) on the rate of progression to Chagas heart disease in patients with ICF.
Methods
This is a retrospective cohort observational study including patients with ICF treated with BZN and compared to a group of non-treated patients matched for age, sex, region of origin, and the year of cohort entry. We reviewed the medical charts of all patients followed from May 1987 to June 2020 at the outpatient center of the Evandro Chagas National Institute of Infectious Diseases (INI) of the Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil. Patients’ follow-up included at least one annual medical visit and one annual electrocardiogram (ECG). Echocardiographic exams were performed at baseline and during the follow-up. Disease progression from ICF to cardiac form was defined by changes in baseline ECG. Cumulative incidence and the incidence rate were described in the incidence analysis. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for the association between BZN and CD progression, cardiovascular events or death.
Findings
One hundred and fourteen treated patients met the study inclusion criteria. A comparison group of 114 non-treated patients matched for age, sex, region of origin, and the year of cohort entry was also included, totalizing 228 patients. Most patients included in the study were male (70.2%), and their mean age was 31.3 (+7.4) years. Over a median follow-up of 15.1 years (ranging from 1.0 to 32.4), the cumulative CD progression incidence in treated patients was 7.9% vs. 21.1% in the non-treated group (
p
= 0.04) and the CD progression rate was 0.49 per 1.000 patients/year in treated patients vs. 1.10 per 1.000 patients/year for non-treated patients (
p
= 0.02). BZN treatment was associated with a decreased risk of CD progression in both unadjusted (HR 0.46; 95%CI 0.21 to 0.98) and adjusted (HR 0.43; 95%CI 0.19 to 0.96) models and with a decreased risk of occurrence of the composite of cardiovascular events only in the adjusted (HR 0.15; 95%CI 0.03 to 0.80) model. No association was observed between BZN treatment and mortality.
Interpretation
In a long-term follow-up, BZN treatment was associated with a decreased incidence of CD progression from ICF to the cardiac form and also with a decreased risk of cardiovascular events. Therefore, our results indicate that BZN treatment for C...
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