Cardiovascular adverse events associated with hydroxychloroquine and chloroquine: A comprehensive pharmacovigilance analysis of pre-COVID-19 reports

Br J Clin Pharmacol. 2021 Mar;87(3):1432-1442. doi: 10.1111/bcp.14546. Epub 2020 Sep 22.


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.

Keywords: COVID-19; FDA adverse events reporting system (FAERS); cardiovascular adverse events; chloroquine; hydroxychloroquine; pharmacovigilance.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Antimalarials / adverse effects*
  • Antimalarials / therapeutic use
  • COVID-19 / complications
  • COVID-19 Drug Treatment*
  • Cardiovascular Diseases / chemically induced*
  • Cardiovascular Diseases / epidemiology
  • Chloroquine / adverse effects*
  • Chloroquine / therapeutic use
  • Databases, Factual
  • Drug Overdose
  • Female
  • Humans
  • Hydroxychloroquine / adverse effects*
  • Hydroxychloroquine / therapeutic use
  • Male
  • Middle Aged
  • Odds Ratio
  • Pharmacovigilance*
  • Treatment Outcome


  • Antimalarials
  • Hydroxychloroquine
  • Chloroquine