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Cardiac Toxicity of Chloroquine or Hydroxychloroquine in Patients With COVID-19: A Systematic Review and Meta-regression Analysis
- Source :
- Mayo Clinic Proceedings: Innovations, Quality & Outcomes, Vol 5, Iss 1, Pp 137-150 (2021), Mayo Clinic Proceedings: Innovations, Quality & Outcomes
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- ImportanceThe antimalarial agents chloroquine (CQ) and hydroxychloroquine (HCQ) have been proposed as a potential treatment for COVID-19 due their effect on several cellular processes that impact viral replication. Although more than 100 ongoing trials are testing their efficacy, CQ and HCQ are being used widely in clinical practice, exposing COVID-19 patients to potentially significant cardiac adverse effects.ObjectiveTo systematically review the literature and estimate the risk of cardiac toxicity in patients receiving CQ or HCQ for COVID-19.Data SourcesA systematic search was conducted on May 27, 2020 of Ovid EBM Reviews, Ovid Embase (1974+), Ovid Medline (1946+ including epub ahead of print, in-process & other non-indexed citations), Scopus (1970+) and Web of Science (1975+) and preprint servers (Medrvix and ResearchSquare) and manual search of references lists.Study SelectionStudies that included COVID-19 patients treated with CQ or HCQ, with or without azithromycin, were included as follows: (1) COVID-19 patient population, (2) the study included more than 10 patients receiving either one of the medications, (3) reported electrocardiographic changes and/or cardiac arrhythmias.Data Extraction and SynthesisStudy characteristics and endpoints incidence were extracted. Due to the very low incidence of torsades de pointes (TdP) and other endpoints (rare events), the arcsine transformation was used to obtain a pooled estimate of the different incidences using a random-effects meta-analysis. Meta-regression analyses were used to assess whether the incidence of different endpoints significantly varied by multiple study-level variables specified a priori.Main Outcomes and MeasuresPooled Incidence of: (1) change in QTc value from baseline ≥ 60 ms, (2) QTc ≥ 500 ms, (3) the composite of endpoint 1 and 2, (4) TdP arrhythmia or ventricular tachycardia (VT) or cardiac arrest, (5) discontinuation of treatment due to drug-induced QT prolongation or arrhythmias.ResultsA total of 19 studies with a total of 5652 patients were included. All included studies were of high methodological quality in terms of exposure ascertainment or outcome assessment. Among 2719 patients treated with CQ or HCQ, only two episodes of TdP were reported; the pooled incidence of TdP arrhythmia or VT or cardiac arrest was 3 per 1000, 95% CI (0-21), I2=96%, 18 studies with 3725 patients. Among 13 studies of 4334 patients, the pooled incidence of discontinuation of CQ or HCQ due to prolonged QTc or arrhythmias was 5%, 95% CI (1-11), I2=98%. The pooled incidence of change in QTc from baseline of ≥ 60 ms was 7%, 95% CI (3-14), I2=94% (12 studies of 2008 patients). The pooled incidence of QTc ≥ 500 ms was 6%, 95% CI (2-12), I2=95% (16 studies of 2317 patients). Among 11 studies of 3127 patients, the pooled incidence of change in QTc from baseline of ≥ 60 ms or QTc ≥ 500 ms was 9%, 95% CI (3-17), I2=97%. Mean/median age, coronary artery disease, hypertension, diabetes, concomitant QT prolonging medications, ICU care, and severity of illness in the study populations explained between-studies heterogeneity.Conclusions and RelevanceTreatment of COVID-19 patients with CQ or HCQ is associated with a significant risk of drug-induced QT prolongation, which is a harbinger for drug-induced TdP/VT or cardiac arrest. CQ/HCQ use resulted in a relatively higher incidence of TdP as compared to drugs withdrawn from the market for this particular adverse effect. Therefore, these agents should be used only in the context of randomized clinical trials, in patients at low risk for drug-induced QT prolongation, with adequate safety monitoring.Key PointsQuestionWhat are the risks of different cardiac toxicities in patients receiving chloroquine (CQ) or hydroxychloroquine (HCQ) for COVID-19.FindingsIn this systematic review, treatment of COVID-19 patients with CQ or HCQ is associated with a clinically significant risk of drug-induced QT prolongation, and torsades de pointes (TdP) arrhythmia/ventricular tachycardia/cardiac arrest in a relatively higher incidence compared to drugs withdrawn from the market for such adverse effects.MeaningThese agents should be used only in the context of clinical trials, in patients at low risk for drug-induced QT prolongation, with adequate safety monitoring.
- Subjects :
- medicine.medical_specialty
hydroxychloroquine
Torsades
Hypertension, (HTN)
Context (language use)
Torsades de pointes
QT prolongation
Ventricular tachycardia, (VT)
030204 cardiovascular system & hematology
Coronavirus disease 2019, (COVID-19)
Hydroxychloroquine, (HCQ)
QT interval
Article
law.invention
Coronary artery disease
03 medical and health sciences
0302 clinical medicine
law
Internal medicine
Severity of illness
medicine
030212 general & internal medicine
Adverse effect
Chronic kidney disease, (CKD)
lcsh:R5-920
Coronary artery disease, (CAD)
business.industry
Incidence (epidemiology)
COVID-19
Hydroxychloroquine
General Medicine
medicine.disease
Chloroquine, (CQ)
Intensive care unit
Discontinuation
meta-analysis
Diabetes mellitus, (DM)
Intensive care unit, (ICU)
Severe acute respiratory syndrome coronavirus 2, (SARS-CoV-2)
Torsades de pointes, (TdP)
lcsh:Medicine (General)
business
Congestive heart failure, (CHF)
medicine.drug
Subjects
Details
- ISSN :
- 25424548
- Volume :
- 5
- Database :
- OpenAIRE
- Journal :
- Mayo Clinic Proceedings: Innovations, Quality & Outcomes
- Accession number :
- edsair.doi.dedup.....4f807ae3abc60c731cd07a2edd1442f7
- Full Text :
- https://doi.org/10.1016/j.mayocpiqo.2020.10.005