RESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic. Hydroxychloroquine (HCQ)-associated cardiovascular adverse events (CVAEs) have been increasingly reported. AIM: This study aimed to present an observational, retrospective, and comprehensive pharmacovigilance analysis of CVAE associated with HCQ in patients with and without COVID-19 using the US Food and Drug Administration Adverse Events Reporting System (FAERS) data from January 2020 to December 2020. METHOD: We identified 3302 adverse event reports from the FAERS database in the year 2020 and divided them into COVID-19 and non-COVID-19 groups, respectively. Then we analyzed whether there were differences in CVAEs between the two groups. RESULTS: We found that CVAE was higher in cases with COVID-19 compared to those without COVID-19, odds ratio (OR) of 1.26 and a 95% confidence interval (95% CI) of 1.02-1.54. Cases with COVID-19 treated with HCQ exhibited relatively higher proportions of torsade de points (TdP) and QT prolongation (OR 3.10, 95% CI 2.24-4.30), shock-associated TdP (OR 2.93, 95% CI 2.13-4.04), cardiac arrhythmias (OR 2.07, 95% CI 1.60-2.69), cardiac arrhythmia terms (including bradyarrhythmias and tachyarrhythmias) (OR 2.15, 95% CI 1.65-2.80), bradyarrhythmias (including conduction defects and disorders of sinus node function) (OR 2.56, 95% CI 1.86-3.54), and conduction defects (OR 2.56, 95% CI 1.86-3.54). CONCLUSION: Our retrospective observational analysis suggested that the proportion of CVAE associated with HCQ, especially TdP and QT prolongation, was higher in patients with COVID-19. Understanding the effects of COVID-19 on the cardiovascular system is essential to providing comprehensive medical care to patients receiving HCQ treatment.
Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Sistema Cardiovascular , Síndrome do QT Longo , Humanos , Hidroxicloroquina/efeitos adversos , COVID-19/epidemiologia , Farmacovigilância , Estudos Retrospectivos , Bradicardia/induzido quimicamente , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/epidemiologia , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/tratamento farmacológico , Doença do Sistema de Condução Cardíaco/induzido quimicamente , Doença do Sistema de Condução Cardíaco/tratamento farmacológico , Proteínas de Ligação a DNARESUMO
J waves may be observed during coronary angiography (CAG), but they have not been fully studied. We investigated the characteristics of J waves in 100 consecutive patients during CAG. The patients and their family members had no history of cardiac arrest. Approximately 60% of patients had ischemic heart disease, previous myocardial infarction, or angina pectoris, but at the time of this study, the right coronary artery was shown to be normal or patent after stenting. Electrocardiogram was serially recorded to monitor J waves and alteration of the QRS complex during CAG. In 12 patients (12%), J waves (0.249 ± 0.074 mV) newly appeared during right CAG, and in another 13 patients (13%), preexisting J waves increased from 0.155 ± 0.060 mV to 0.233 ± 0.133 mV during CAG. Left CAG induced no J waves or augmentation of J waves. Distinct alterations were observed in the QRS complex during CAG of both coronary arteries. Mechanistically, myocardial ischemia induced by contrast medium was considered to result in a local conduction delay, and when it occurred in the inferior wall, the site of the late activation of the ventricle, the conduction delay was manifested as J waves. In conclusion, J waves were confirmed to emerge or increase during angiography of the right but not the left coronary artery. Myocardial ischemia induced by contrast medium caused a local conduction delay that was manifested as J waves in the inferior wall, the site of the late activation of the ventricle.
Assuntos
Doença do Sistema de Condução Cardíaco/epidemiologia , Angiografia Coronária , Isquemia Miocárdica/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Angina Pectoris/diagnóstico , Angina Pectoris/fisiopatologia , Doença do Sistema de Condução Cardíaco/induzido quimicamente , Doença do Sistema de Condução Cardíaco/fisiopatologia , Meios de Contraste/efeitos adversos , Eletrocardiografia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/fisiopatologia , Isquemia Miocárdica/induzido quimicamente , Isquemia Miocárdica/fisiopatologiaRESUMO
Long QT syndrome type 3 (LQT-3) is a disease related to abnormal cardiac sodium channel function (Nav 1.5), usually due to augmented late sodium current (INaL ), and may lead to ventricular fibrillation. Amiodarone is approved for ventricular fibrillation. Thus, we investigated whether pacing frequency impacts the ability of amiodarone to reverse the arrhythmic phenotype observed in LQT-3. Anemone neurotoxin 2 (ATX-II, here named only ATX) was used to enhance INaL in mice left ventricular myocytes (LVM). A video detector system monitored sarcomere shortening. At 1 Hz, amiodarone attenuated sarcomere shortening only at 10 µmol/L; at 3 and 5 Hz, 0.1 and 1 µmol/L amiodarone also reduced sarcomere shortening. However, no effect of amiodarone was observed on time to 50% of sarcomere contraction and relaxation. In LVM exposed to ATX (10 nmol/L), an arrhythmic phenotype was observed, and it was more severe when cells were paced at 1 Hz. Amiodarone failed to reverse the ATX induced phenotype at different pacing frequencies. Thus, our results suggest that amiodarone's ability to reverse arrhythmias induced by augmentation of INaL is limited. These findings suggest further experimentation will be required to clarify whether a clinical effect can be ascribed to an effect of amiodarone on other ion channels in LQT-3.
Assuntos
Amiodarona/farmacologia , Doença do Sistema de Condução Cardíaco/tratamento farmacológico , Síndrome do QT Longo/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacologia , Amiodarona/uso terapêutico , Animais , Doença do Sistema de Condução Cardíaco/induzido quimicamente , Doença do Sistema de Condução Cardíaco/fisiopatologia , Células Cultivadas , Venenos de Cnidários/farmacologia , Modelos Animais de Doenças , Humanos , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/fisiopatologia , Masculino , Camundongos , Miócitos Cardíacos/fisiologia , Canal de Sódio Disparado por Voltagem NAV1.5/metabolismo , Cultura Primária de Células , Bloqueadores do Canal de Sódio Disparado por Voltagem/uso terapêuticoAssuntos
Aminopiridinas , Neoplasias da Mama , Doença do Sistema de Condução Cardíaco , Purinas , Aminopiridinas/efeitos adversos , Aminopiridinas/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Doença do Sistema de Condução Cardíaco/induzido quimicamente , Doença do Sistema de Condução Cardíaco/epidemiologia , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Metástase Neoplásica , Purinas/efeitos adversos , Purinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de RiscoRESUMO
BACKGROUND AND OBJECTIVE: Risk-minimization measures (RMM), including label revisions were implemented in Europe for domperidone because of evidence of increased incidence of cardiac arrhythmia and sudden cardiac death. In accordance with the guideline on good pharmacovigilance practices, the European Medicines Agency Pharmacovigilance Risk Assessment Committee requested to conduct two studies to evaluate the effectiveness of these risk minimization measures. METHODS: In Belgium, France, Germany, Spain, and the UK, surveys were conducted to assess physicians' knowledge on the updated domperidone labeling information, and a drug-utilization study (DUS) was conducted using healthcare databases to assess domperidone prescribing patterns before and after the RMM. Four DUS sensitivity analyses (scenarios) evaluated uncertainty regarding domperidone treatment duration and indication. RESULTS: Among 1805 physicians participating in the survey, most were aware of the approved indication (nausea and vomiting, 80%), treatment duration (≤ 7 days, 70%), and maximum adult daily dose (10 mg three times daily, 84%). Only 33% selected the on-label indication from a list of indications for which they would prescribe domperidone. Awareness was low for medications contraindicated for concomitant use (26%) and contraindicated conditions (4%). In the DUS, under the optimistic scenario, a large improvement in labeling compliance from pre- to post-implementation period was observed in France (27% vs. 69%), while Belgium, Germany, Spain, and the UK showed small improvements (< 10%). In the other scenarios, there was little to no improvement in compliance with the revised labeling from the pre- to post-implementation periods in most countries. CONCLUSIONS: The survey findings documented that most physicians in all five countries were aware of the main aspects of the revised labeling. Results of the DUS were inconclusive regarding the effect of the RMM and compliance with the revised labeling for all countries except France.
Assuntos
Antieméticos/uso terapêutico , Domperidona/uso terapêutico , Rotulagem de Medicamentos/normas , Uso de Medicamentos/normas , Médicos/normas , Adulto , Antieméticos/efeitos adversos , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/prevenção & controle , Doença do Sistema de Condução Cardíaco/induzido quimicamente , Doença do Sistema de Condução Cardíaco/epidemiologia , Doença do Sistema de Condução Cardíaco/prevenção & controle , Estudos Transversais , Morte Súbita Cardíaca/etiologia , Domperidona/efeitos adversos , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/tratamento farmacológico , Náusea/epidemiologia , Estudos Retrospectivos , Medição de Risco , Inquéritos e Questionários , Vômito/tratamento farmacológico , Vômito/epidemiologiaAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doença do Sistema de Condução Cardíaco/induzido quimicamente , Imidazóis/efeitos adversos , Oximas/efeitos adversos , Piridonas/efeitos adversos , Pirimidinonas/efeitos adversos , Idoso de 80 Anos ou mais , Doença do Sistema de Condução Cardíaco/diagnóstico , Doença do Sistema de Condução Cardíaco/fisiopatologia , Eletrocardiografia , Feminino , Sistema de Condução Cardíaco/efeitos dos fármacos , Sistema de Condução Cardíaco/fisiopatologia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/fisiopatologia , Humanos , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
We report a 48-day-old female infant, who developed cardiac conduction abnormalities and seizures secondary to supratherapeutic doses of oral flecainide. Flecainide was started in this infant for treatment of supraventricular tachycardia. The drug was withdrawn with successful normalization of the QRS complex and no further recurrence of seizures. The Naranjo probability score for adverse drug reaction was 8, making the causality "probable." The case restates an important message that physicians should be aware of the side effects of the drugs that they prescribe, especially of those drugs which have a narrow therapeutic window.