Serious Cardiovascular Adverse Events Associated with Hydroxychloroquine/Chloroquine Alone or with Azithromycin in Patients with COVID-19: A Pharmacovigilance Analysis of the FDA Adverse Event Reporting System (FAERS)
Public Deposited- Creator
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Zhao, Y.
- Other Affiliation: Capital Medical University
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Zhang, J.
- Affiliation: Gillings School of Global Public Health, Department of Biostatistics
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Zheng, K.
- Other Affiliation: Beijing Cancer Hospital
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Thai, S.
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology
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Simpson, R.J., Jr.
- Affiliation: School of Medicine, Department of Medicine
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Kinlaw, A.C.
- Affiliation: Eshelman School of Pharmacy, Division of Pharmaceutical Outcomes and Policy
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Xu, Y.
- Other Affiliation: Peking University First Hospital
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Wei, J.
- Other Affiliation: University of South Carolina
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Cui, X.
- Other Affiliation: Capital Medical University
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Buse, J.B.
- Affiliation: School of Medicine, Department of Medicine
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Stürmer, T.
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology
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Wang, T.
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology
- Abstract
- Background: The use of hydroxychloroquine or chloroquine (HCQ/CQ) as monotherapy or combined with azithromycin for the treatment of coronavirus disease 2019 (COVID-19) may increase the risk of serious cardiovascular adverse events (SCAEs). Objective: Our objective was to describe and evaluate the risk of SCAEs with HCQ/CQ as monotherapy or combined with azithromycin compared with that for therapeutic alternatives. Methods: We performed a disproportionality analysis and descriptive case series using the US FDA Adverse Event Reporting System. Results: Compared with remdesivir, HCQ/CQ was associated with increased reporting of SCAEs (reporting odds ratio [ROR] 2.1; 95% confidence interval [CI] 1.8–2.5), torsade de pointes (TdP)/QTc prolongation (ROR 35.4; 95% CI 19.4–64.5), and ventricular arrhythmia (ROR 2.5; 95% CI 1.6–3.9); similar results were found in comparison with other therapeutic alternatives. Compared with lopinavir/ritonavir, HCQ/CQ was associated with increased reporting of ventricular arrhythmia (ROR 10.5; 95% CI 3.3–33.4); RORs were larger when HCQ/CQ was used in combination with azithromycin. In 2020, 312 of the 575 reports of SCAEs listed concomitant use of HCQ/CQ and azithromycin, including QTc prolongation (61.4%), ventricular arrhythmia (12.0%), atrial fibrillation (8.2%), TdP (4.9%), and cardiac arrest (4.4%); 88 (15.3%) cases resulted in hospitalization and 79 (13.7%) resulted in death. In total, 122 fatal QTc prolongation-related cardiovascular reports were associated with 1.4 times higher odds of reported death than those induced by SCAEs; 87 patients received more than one QTc-prolonging agent. Conclusions: Patients treated with HCQ/CQ monotherapy or HCQ/CQ + azithromycin may be at increased risk of SCAEs, TdP/QTc prolongation, and ventricular arrhythmia. Cardiovascular risks need to be considered when evaluating the benefit/harm balance of treatment with HCQ/CQ, especially with the concurrent use of QTc-prolonging agents and cytochrome P450 3A4 inhibitors when treating COVID-19.
- Date of publication
- 2022
- Keyword
- serotonin uptake inhibitor
- QT prolongation
- male
- monotherapy
- cerebrovascular accident
- chloroquine
- oxidoreductase inhibitor
- amoxicillin
- insulin
- hypomagnesemia
- sepsis
- combination drug therapy
- vulnerable population
- cytochrome P450 3A4
- hyperlipidemia
- cardiovascular risk
- risk factor
- major clinical study
- human
- diabetes mellitus
- drug safety
- risk assessment
- serotonin 3 antagonist
- heart infarction
- antiarrhythmic agent
- heart arrest
- heart left ventricle hypertrophy
- adult
- pharmacovigilance
- patient monitoring
- tricyclic antidepressant agent
- atrial fibrillation
- Article
- hypertension
- loop diuretic agent
- neuroleptic agent
- outcome assessment
- cardiovascular disease
- Medical Dictionary for Regulatory Activities
- hydroxychloroquine
- heart muscle ischemia
- hypokalemia
- risk benefit analysis
- simvastatin
- azithromycin
- fatality
- kidney disease
- bradycardia
- treatment duration
- quinoline derived antiinfective agent
- lopinavir plus ritonavir
- hospitalization
- heart ventricle arrhythmia
- coronavirus disease 2019
- obesity
- female
- hypocalcemia
- macrolide
- torsade des pointes
- heart failure
- donepezil
- loading drug dose
- antifungal agent
- comorbidity
- clinical decision making
- remdesivir
- DOI
- Identifier
- Resource type
- Article
- Rights statement
- In Copyright
- Journal title
- Drugs - Real World Outcomes
- Journal volume
- 9
- Journal issue
- 2
- Page start
- 231
- Page end
- 241
- Language
- English
- Funder
- American Diabetes Association, ADA
- Eli Lilly and Company
- Patient-Centered Outcomes Research Institute, PCORI
- Intarcia Therapeutics
- Novo Nordisk
- AstraZeneca
- Amgen
- National Institute on Aging, NIA: R01 AG056479, R01 CA174453, R01 HL118255, R21-HD080214
- University of North Carolina Wilmington, UNCW
- Sanofi
- GlaxoSmithKline, GSK
- BASF
- National Institutes of Health, NIH: P30DK124723, U01DK098246, U54DK118612, UC4DK108612, UL1TR002489
- Zafgen
- Johnson and Johnson, J&J
- Cirius Therapeutics
- ISSN
- 2199-1154
- Publisher
- Adis
Relations
- Parents:
- In Collection:
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