key: cord-0922658-mzc8zl9v
authors: Nguyen, Lee S.; Dolladille, Charles; Drici, Milou-Daniel; Fenioux, Charlotte; Alexandre, Joachim; Mira, Jean-Paul; Moslehi, Javid J.; Roden, Dan M.; Funck-Brentano, Christian; Salem, Joe-Elie
title: Cardiovascular Toxicities Associated With Hydroxychloroquine and Azithromycin: An Analysis of the World Health Organization Pharmacovigilance Database
date: 2020-05-22
journal: Circulation
DOI: 10.1161/circulationaha.120.048238
sha: 546fe6f447cffcc518e081d09fbbfa9587ef9acb
doc_id: 922658
cord_uid: mzc8zl9v

nan

The proportion that resulted in death for TdP/VT cases was 8.4% (7/83) with hydroxychloroquine and 20.2% (52/257) with azithromycin versus 0% (0/53) and 5.4% (12/223) for LQT without TdP/VT with hydroxychloroquine and azithromycin, respectively (P<0.001 for both). The corresponding death rate was 20.7% (42/203) for heart failure associated with hydroxychloroquine. The dose of hydroxychloroquine was higher in heart failure compared with LQT and/or TdP/VT cases (200 [IQR=200;400] versus 200 [IQR=200;200] mg/d, P=0.033).

The main limitation is that without data on numbers exposed in VigiBase, this work cannot assess the incidence or risk for QT prolongation with these drugs. However, our results are consistent with the facts that these CV-ADRs are found in the US Food and Drug Administration's labels of hydroxychloroquine and azithromycin, and that both drugs are referenced as having a known risk of TdP on the CredibleMeds website. 4 These CV-ADRs are important to bear in mind in the setting of COVID-19 with patients presenting additional risk factors of LQT/TdP caused by inflammation with elevated interleukin-6, hypokalemia, numerous interacting drugs, bradycardia, and higher hydroxychloroquine dosages. 5 In conclusion, reports of potentially lethal acute cardiac proarrhythmogenic effects leading to ventricular arrhythmias have been described mainly with azithromycin but also with hydroxychloroquine. Their combination yielded an even stronger signal. Hydroxychloroquine was also associated with potentially lethal heart failure when exposure was prolonged over several months.

Data sharing: The data, analytic methods, and study materials are available to other researchers for purposes of reproducing the results or replicating the procedure at http://www.vigiaccess.org/.

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The authors thank Banook group/Cardiabase, Nancy-France http://www.banookgroup.com/ (Yasmin Khan) for providing the Holter and ECG systems to evaluate prospectively the impact of hydroxychloroquine and azithromycin on ventricular arrhythmia in a current cohort of treated patients with COVID-19, as a follow-up study of this work. They also thank the staff of the AP.HP.Sorbonne clinical investigation center (Maria Martin, Francois Gueguin, Dr Paul Gougis, Dr Bruno Pinna) for their involvement in the latter study and their current effort to better study adverse drug reactions associated with COVID-19 drugs.

The supplied data from VigiBase come from various sources. The likelihood of a causal relationship is not the same in all reports. The information does not represent the opinion of the World Health Organization. The authors report no conflicts.