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《JAMA，5月1日，Assessment of QT Intervals in a Case Series of Patients With COVID-19 Infection Treated With Hydroxychloroquine Alone or in Combination With Azithromycin in an Intensive Care Unit》

  • 来源专题：COVID-19科研动态监测
  • 编译者： zhangmin
  • 发布时间：2020-05-02

  • Assessment of QT Intervals in a Case Series of Patients With Coronavirus Disease 2019 (COVID-19) Infection Treated With Hydroxychloroquine Alone or in Combination With Azithromycin in an Intensive Care Unit

    Francis Bessière, MD, PhD1,2; Hugo Roccia, MD3; Antoine Delinière, MD1,2; et al Rome Charrière, MD4; Philippe Chevalier, MD, PhD1,2; Laurent Argaud, MD, PhD3; Martin Cour, MD, PhD2

    Author Affiliations Article Information

    JAMA Cardiol. Published online May 1, 2020. doi:10.1001/jamacardio.2020.1787

    The novel coronavirus disease 2019 (COVID-19) outbreak is an ongoing situation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).1 Studies in patients with mild to moderate COVID-19 symptoms have suggested benefits of hydroxychloroquine alone or in combination with azithromycin against SARS-CoV-2 and raised hope for treating the disease.2 As a result, these treatments are increasingly used off-label for patients with COVID-19, including for those in intensive care units (ICUs).2,3 However, both medications are known to induce QT prolongation via a human Ether-à-go-go–related gene potassium channel blockade, which can promote life-threatening ventricular arrhythmias.4,5 Safety data for these treatments are largely lacking for patients with COVID-19. This is even more relevant for critically ill patients who are particularly exposed to electrolyte imbalance and/or drugs leading to an increased risk of QT prolongation.6 Therefore, we aimed to examine the safety of hydroxychloroquine with or without azithromycin regarding QT interval in ICU patients with COVID-19.

  • 原文来源：https://jamanetwork.com/journals/jamacardiology/fullarticle/2765633?resultClick=1
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  • 《Nature，4月24日，The QT interval in patients with COVID-19 treated with hydroxychloroquine and azithromycin》
    • 来源专题：COVID-19科研动态监测
    • 编译者：zhangmin
    • 发布时间：2020-04-25
    • The QT interval in patients with COVID-19 treated with hydroxychloroquine and azithromycin Ehud Chorin, Matthew Dai, Eric Shulman, Lalit Wadhwani, Roi Bar-Cohen, Chirag Barbhaiya, Anthony Aizer, Douglas Holmes, Scott Bernstein, Michael Spinelli, David S. Park, Larry A. Chinitz & Lior Jankelson Nature Medicine (2020) To the Editor — The SARS-CoV-2 pandemic has caused more than 1.6 million positive cases and more than 95,000 confirmed deaths as of 10 April 2020 (ref. 1). Although there are no approved drugs to prevent or treat SARS-CoV-2 infection2, a recent report suggested that the combination of hydroxychloroquine and azithromycin (HY/AZ) may have a favorable effect on the clinical outcomes and viral loads of infected patients3; this resulted in massive adoption of the regimen by clinicians worldwide. However, both medications have been independently shown to increase the risk in other populations for QT-interval prolongation, drug-induced torsades de pointes (a form of polymorphic ventricular tachycardia) and drug-induced sudden cardiac death.
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  • 《MedRxiv，4月10日，Safety of hydroxychloroquine, alone and in combination with azithromycin》
    • 来源专题：COVID-19科研动态监测
    • 编译者：xuwenwhlib
    • 发布时间：2020-04-11
    • Safety of hydroxychloroquine, alone and in combination with azithromycin, in light of rapid wide-spread use for COVID-19: a multinational, network cohort and self-controlled case series study Jennifer C.E Lane, James Weaver, Kristin Kostka, Talita Duarte-Salles, Maria Tereza F. Abrahao, Heba Alghoul, Osaid Alser, Thamir M Alshammari, Patricia Biedermann, Edward Burn, Paula Casajust, Mitch Conover, Aedin C. Culhane, Alexander Davydov, Scott L. DuVall, Dmitry Dymshyts, Sergio Fernández Bertolín, Kristina Fišter, Jill Hardin, Laura Hester, George Hripcsak, Seamus Kent, Sajan Khosla, Spyros Kolovos, Christophe G. Lambert, Johan ver der Lei, Ajit A. Londhe, Kristine E. Lynch, Rupa Makadia, Andrea V. Margulis, Michael E. Matheny, Paras Mehta, Daniel R. Morales, Henry Morgan-Stewart, Mees Mosseveld, Danielle Newby, Fredrik Nyberg, Anna Ostropolets, Rae Woong Park, Albert Prats-Uribe, Gowtham A. Rao, Christian Reich, Jenna Reps, Peter Rijnbeek, Selva Muthu Kumaran Sathappan, Martijn Schuemie, Sarah Seager, Anthony Sena, Azza Shoaibi, Matthew Spotnitz, Marc A. Suchard, Joel Swerdel, Carmen Olga Torre, David Vizcaya, Haini Wen, Marcel de Wilde, Seng Chan You, Lin Zhang, Oleg Zhuk, Patrick Ryan, Daniel Prieto-Alhambra doi: https://doi.org/10.1101/2020.04.08.20054551 Abstract Background: Hydroxychloroquine has recently received Emergency Use Authorization by the FDA and is currently prescribed in combination with azithromycin for COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin. Methods: New user cohort studies were conducted including 16 severe adverse events (SAEs). Rheumatoid arthritis patients aged 18+ and initiating hydroxychloroquine were compared to those initiating sulfasalazine and followed up over 30 days. Self-controlled case series (SCCS) were conducted to further establish safety in wider populations. Separately, SAEs associated with hydroxychloroquine-azithromycin (compared to hydroxychloroquine-amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, Netherlands, Spain, UK, and USA. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (CalHRs) according to drug use. Estimates were pooled where I2<40%. Results: Overall, 956,374 and 310,350 users of hydroxychloroquine and sulfasalazine, and 323,122 and 351,956 users of hydroxychloroquine-azithromycin and hydroxychloroquine-amoxicillin were included. No excess risk of SAEs was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. SCCS confirmed these findings. However, when azithromycin was added to hydroxychloroquine, we observed an increased risk of 30-day cardiovascular mortality (CalHR2.19 [1.22-3.94]), chest pain/angina (CalHR 1.15 [95% CI 1.05-1.26]), and heart failure (CalHR 1.22 [95% CI 1.02-1.45]) Conclusions: Short-term hydroxychloroquine treatment is safe, but addition of azithromycin may induce heart failure and cardiovascular mortality, potentially due to synergistic effects on QT length. We call for caution if such combination is to be used in the management of Covid-19. *注，本文为预印本论文手稿，是未经同行评审的初步报告，其观点仅供科研同行交流，并不是结论性内容，请使用者谨慎使用.
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