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Acute QT Interval Modifications During Hydroxychloroquine-Azithromycin Treatment in the Context of COVID-19 Infection


      Among candidate drugs to treat coronavirus disease 2019 (COVID-19), the combination of hydroxychloroquine (HCQ) and azithromycin (AZ) has received intense worldwide attention. Even as the efficacy of this combination is under evaluation, clinicians have begun to use it largely. As these medications are known to prolong the QT interval, we analyzed serial electrocardiograms recorded in patients hospitalized for COVID-19 pneumonia and treated with HCQ + AZ. Fifty consecutive patients received the combination of HCQ (600 mg/d for 10 days) and AZ (500 mg/d on day 1 and 250 mg/d from day 2 to day 5). Twelve-lead electrocardiograms were recorded before treatment, at day 3, at day 5, and at discharge. The median age of patients was 68 years (interquartile range, 53-81 years); 28 (56%) were men. The main comorbidities were hypertension (36%; n=18) and diabetes (16%; n=8). The mean corrected QT (QTc) interval was 408 ms at baseline and increased up to 437 ms at day 3 and to 456 ms at day 5. Thirty-eight patients (76%) presented short-term modifications of the QTc duration (>30 ms). Treatment discontinuation was decided in 6 patients (12%), leading to QTc normalization in 5 of them. No deaths and no cardiac arrhythmic events were observed in this cohort. Our report confirms that a short duration treatment with HCQ + AZ modifies the QTc interval. The treatment had to be discontinued for QTc modifications in 12% of patients. Nevertheless, in inpatients hospitalized for COVID-19, we did not observe any clinically relevant consequences of these transitory modifications. In conclusion, when patients are treated with HCQ + AZ, cardiac monitoring should be regularly performed and hospital settings allow monitoring under in safe conditions.

      Abbreviations and Acronyms:

      AZ (azithromycin), COVID-19 (coronavirus disease 2019), ECG (electrocardiogram), HCQ (hydroxychloroquine), IQR (interquartile range), TdP (torsades de pointes)
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      1. Coronavirus disease 2019 (COVID-19): situation report – 85. World Health Organization website.
        • Kupferschmidt K.
        • Cohen J.
        Race to find COVID-19 treatments accelerates.
        Science. 2020; 367: 1412-1413
        • Yao X.
        • Ye F.
        • Zhang M.
        • et al.
        In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [published online ahead of print March 9, 2020].
        (Clin Infect Dis)
        • Gautret P.
        • Lagier J.C.
        • Parola P.
        • et al.
        Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial [published online ahead of print March 20, 2020].
        (Int J Antimicrob Agents)
        • Chen Z.
        • Hu J.
        • Zhang Z.
        • et al.
        Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial [published online ahead of print March 31, 2020].
        • Mahevas M.
        • Tran V.T.
        • Roumier M.
        • et al.
        No evidence of clinical efficacy of hydroxychloroquine in patients hospitalised for COVID-19 infection and requiring oxygen: results of a study using routinely collected data to emulate a target trial [published online ahead of print April 14, 2020].
        • Lenzer J.
        Covid-19: US gives emergency approval to hydroxychloroquine despite lack of evidence.
        BMJ. 2020; 369: m1335
        • Yazdany J.
        • Kim A.H.J.
        Use of hydroxychloroquine and chloroquine during the COVID-19 pandemic: what every clinician should know [published online ahead of print March 31, 2020].
        (Ann Intern Med)
        • Giudicessi J.R.
        • Noseworthy P.A.
        • Friedman P.A.
        • Ackerman M.J.
        Urgent guidance for navigating and circumventing the QTc-prolonging and torsadogenic potential of possible pharmacotherapies for coronavirus disease 19 (COVID-19) [published online ahead of print April 7, 2020].
        (Mayo Clin Proc)
      2. COVID-19: chloroquine and hydroxycloroquine only to be used in clinical trials or emergency use programmes. European Medicines Agency website.
        • Lakkireddy D.R.
        • Chung M.K.
        • Gopinathannair R.
        • et al.
        Guidance for cardiac electrophysiology during the coronavirus (COVID-19) pandemic from the Heart Rhythm Society COVID-19 Task Force; Electrophysiology Section of the American College of Cardiology; and the Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology, American Heart Association [published online ahead of print March 31, 2020].
      3. Médicaments utilisés chez les patients atteints du COVID-19: une surveillance renforcée des effets indésirables - Point d'information [in French]. Agnce National de sécurité du médicament et des produits de santé (ANSM) website.
        • Mzayek F.
        • Deng H.
        • Mather F.J.
        • et al.
        Randomized dose-ranging controlled trial of AQ-13, a candidate antimalarial, and chloroquine in healthy volunteers.
        PLoS Clin Trials. 2007; 2: e6
        • Pukrittayakamee S.
        • Tarning J.
        • Jittamala P.
        • et al.
        Pharmacokinetic interactions between primaquine and chloroquine.
        Antimicrob Agents Chemother. 2014; 58: 3354-3359
        • Ursing J.
        • Rombo L.
        • Eksborg S.
        • et al.
        High-dose chloroquine for uncomplicated Plasmodium falciparum malaria is well tolerated and causes similar QT interval prolongation as standard-dose chloroquine in children.
        Antimicrob Agents Chemother. 2020; 64
        • Juurlink D.N.
        The cardiovascular safety of azithromycin.
        CMAJ. 2014; 186: 1127-1128
        • Fossa A.A.
        • Wisialowski T.
        • Duncan J.
        • Deng S.
        • Dunne M.
        Azithromycin/chloroquine combination does not increase cardiac instability despite an increase in monophasic action potential duration in the anesthetized guinea pig.
        Am J Trop Med Hyg. 2007; 77: 929-938
        • Juurlink D.N.
        Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection.
        CMAJ. 2020; 192: E450-E453
        • Chorin E.
        • Dai M.
        • Shulman E.
        • et al.
        The QT interval in patients with SARS-CoV-2 infection treated with hydroxychloroquine/azithromycin [published online ahead of print April 3, 2020].
        • Li M.
        • Ramos L.G.
        Drug-induced QT prolongation and torsades de pointes.
        P T. 2017; 42: 473-477
        • Haugaa K.H.
        • Bos J.M.
        • Tarrell R.F.
        • Morlan B.W.
        • Caraballo P.J.
        • Ackerman M.J.
        Institution-wide QT alert system identifies patients with a high risk of mortality.
        Mayo Clin Proc. 2013; 88: 315-325