Cardiovascular adverse events associated with hydroxychloroquine and chloroquine: A comprehensive pharmacovigilance analysis of pre‐COVID‐19 reports. Issue 3 (22nd September 2020)

• Record Type: Journal Article
• Authors: Goldman, Adam; Bomze, David; Dankner, Rachel; Hod, Hanoch; Meirson, Tomer; Boursi, Ben; Maor, Elad
• Is Part Of: British journal of clinical pharmacology. Volume 87:Issue 3(2021)
• Page Start: 1432
• Page End: 1442
• Publication Date: 2020-09-22
• Subjects: cardiovascular adverse events -- chloroquine -- COVID‐19 -- FDA adverse events reporting system (FAERS) -- hydroxychloroquine -- pharmacovigilance; Pharmacology -- Periodicals; Drugs -- Periodicals; 615.1
• DOI: 10.1111/bcp.14546
• Languages: English
• ISSNs: 0306-5251

Abstract

Abstract : Aim: There is a clinical need for safety data regarding hydroxychloroquine (HCQ) and chloroquine (CQ) during the coronavirus (COVID‐19) pandemic. We analysed real‐world data using the U.S. Food and Drug Administration Adverse Events Reporting System (FAERS) database to assess HCQ/CQ‐associated cardiovascular adverse events (CVAEs) in pre‐COVID‐19 reports. Methods: We conducted disproportionality analysis of HCQ/CQ in the FAERS database (07/2014‐9/2019), using reporting odds ratio (ROR) and the lower bound of the information component 95% credibility interval (IC025 ). Results: The full database contained 6 677 225 reports with a mean (±SD) age of 53 (±17) years and 74% females. We identified 4895 reports of HCQ/CQ related adverse events, of which 696 (14.2%) were CVAEs. Compared with the full database, HCQ/CQ use was associated with a higher reporting rate of major CVAEs, including cardiomyopathy (n = 86 [1.8%], ROR = 29.0 [23.3‐35.9]), QT prolongation (n = 43 [0.9%], ROR = 4.5 [3.3‐6.1]), cardiac arrhythmias (n = 117 [2.4%], ROR = 2.2 [1.8‐2.7]) and heart failure (n = 136 [2.8%], ROR = 2.2 [1.9‐2.7], all IC₀₂₅ > 0). No statistically significant differences were observed between sex and age groups. CVAEs were reported more often in patients with systemic lupus erythematosus and Sjogren's syndrome. HCQ/CQ‐associated CVAEs demonstrated subsequent hospitalization and mortality rates of 39% and 8%, respectively. Overdose reports demonstrated an increased frequency of QT prolongation and ventricular arrhythmias (35% and 25%, respectively). Conclusion: In a real‐world setting, HCQ/CQ treatment is associated with higher reporting rates of various CVAEs, particularly cardiomyopathy, QT prolongation, cardiac arrhythmias and heart failure. HCQ/CQ‐associated CVAEs result in high rates of severe outcomes and should be carefully considered as an off‐label indication, especially for patients with cardiac disorders.