QT prolongation, torsades de pointes, and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: A systematic review - PubMed (original) (raw)
QT prolongation, torsades de pointes, and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: A systematic review
Lior Jankelson et al. Heart Rhythm. 2020 Sep.
Abstract
Chloroquine and hydroxychloroquine are now being widely used for treatment of COVID-19. Both medications prolong the QT interval and accordingly may put patients at increased risk for torsades de pointes and sudden death. Published guidance documents vary in their recommendations for monitoring and managing these potential adverse effects. Accordingly, we set out to conduct a systematic review of the arrhythmogenic effect of short courses of chloroquine or hydroxychloroquine. We searched on MEDLINE and Embase, as well as in the gray literature up to April 17, 2020, for the risk of QT prolongation, torsades, ventricular arrhythmia, and sudden death with short-term chloroquine and hydroxychloroquine usage. This search resulted in 390 unique records, of which 41 were ultimately selected for qualitative synthesis and which included data on 1515 COVID-19 patients. Approximately 10% of COVID-19 patients treated with these drugs developed QT prolongation. We found evidence of ventricular arrhythmia in 2 COVID-19 patients from a group of 28 treated with high-dose chloroquine. Limitations of these results are unclear follow-up and possible publication/reporting bias, but there is compelling evidence that chloroquine and hydroxychloroquine induce significant QT-interval prolongation and potentially increase the risk of arrhythmia. Daily electrocardiographic monitoring and other risk mitigation strategies should be considered in order to prevent possible harms from what is currently an unproven therapy.
Keywords: Arrhythmia; COVID-19; Chloroquine; Coronavirus; Hydroxychloroquine; SARS-CoV-2; Sudden death; Torsades de pointes.
© 2020 Heart Rhythm Society. All rights reserved.
Figures
Figure 1
Flowchart of study screening and selection.
Similar articles
- Effect of Chloroquine, Hydroxychloroquine, and Azithromycin on the Corrected QT Interval in Patients With SARS-CoV-2 Infection.
Saleh M, Gabriels J, Chang D, Soo Kim B, Mansoor A, Mahmood E, Makker P, Ismail H, Goldner B, Willner J, Beldner S, Mitra R, John R, Chinitz J, Skipitaris N, Mountantonakis S, Epstein LM. Saleh M, et al. Circ Arrhythm Electrophysiol. 2020 Jun;13(6):e008662. doi: 10.1161/CIRCEP.120.008662. Epub 2020 Apr 29. Circ Arrhythm Electrophysiol. 2020. PMID: 32347743 Free PMC article. - QT interval prolongation and torsade de pointes in patients with COVID-19 treated with hydroxychloroquine/azithromycin.
Chorin E, Wadhwani L, Magnani S, Dai M, Shulman E, Nadeau-Routhier C, Knotts R, Bar-Cohen R, Kogan E, Barbhaiya C, Aizer A, Holmes D, Bernstein S, Spinelli M, Park DS, Stefano C, Chinitz LA, Jankelson L. Chorin E, et al. Heart Rhythm. 2020 Sep;17(9):1425-1433. doi: 10.1016/j.hrthm.2020.05.014. Epub 2020 May 12. Heart Rhythm. 2020. PMID: 32407884 Free PMC article. - QT Interval Control to Prevent Torsades de Pointes during Use of Hydroxychloroquine and/or Azithromycin in Patients with COVID-19.
Wu TC, Sacilotto L, Darrieux FCDC, Pisani CF, Melo SL, Hachul DT, Scanavacca M. Wu TC, et al. Arq Bras Cardiol. 2020 Jun;114(6):1061-1066. doi: 10.36660/abc.20200389. Epub 2020 Jul 3. Arq Bras Cardiol. 2020. PMID: 32638906 Free PMC article. English, Portuguese. No abstract available. - Prophylactic (hydroxy)chloroquine in COVID-19: Potential relevance for cardiac arrhythmia risk.
Offerhaus JA, Wilde AAM, Remme CA. Offerhaus JA, et al. Heart Rhythm. 2020 Sep;17(9):1480-1486. doi: 10.1016/j.hrthm.2020.07.001. Epub 2020 Jul 3. Heart Rhythm. 2020. PMID: 32622993 Free PMC article. Review. - Cardiac safety of off-label COVID-19 drug therapy: a review and proposed monitoring protocol.
Naksuk N, Lazar S, Peeraphatdit TB. Naksuk N, et al. Eur Heart J Acute Cardiovasc Care. 2020 Apr;9(3):215-221. doi: 10.1177/2048872620922784. Epub 2020 May 6. Eur Heart J Acute Cardiovasc Care. 2020. PMID: 32372695 Free PMC article. Review.
Cited by
- Prolonged QT Interval in SARS-CoV-2 Infection: Prevalence and Prognosis.
Farré N, Mojón D, Llagostera M, Belarte-Tornero LC, Calvo-Fernández A, Vallés E, Negrete A, García-Guimaraes M, Bartolomé Y, Fernández C, García-Duran AB, Marrugat J, Vaquerizo B. Farré N, et al. J Clin Med. 2020 Aug 21;9(9):2712. doi: 10.3390/jcm9092712. J Clin Med. 2020. PMID: 32839385 Free PMC article. - Adverse effects of remdesivir, hydroxychloroquine and lopinavir/ritonavir when used for COVID-19: systematic review and meta-analysis of randomised trials.
Izcovich A, Siemieniuk RA, Bartoszko JJ, Ge L, Zeraatkar D, Kum E, Qasim A, Khamis AM, Rochwerg B, Agoritsas T, Chu DK, McLeod SL, Mustafa RA, Vandvik P, Brignardello-Petersen R. Izcovich A, et al. BMJ Open. 2022 Mar 2;12(3):e048502. doi: 10.1136/bmjopen-2020-048502. BMJ Open. 2022. PMID: 35236729 Free PMC article. - Adverse Cardiovascular Effects of Anti-COVID-19 Drugs.
Liu D, Zeng X, Ding Z, Lv F, Mehta JL, Wang X. Liu D, et al. Front Pharmacol. 2021 Aug 25;12:699949. doi: 10.3389/fphar.2021.699949. eCollection 2021. Front Pharmacol. 2021. PMID: 34512335 Free PMC article. Review. - COVID-19-Associated Cardiovascular Complications.
Lee CCE, Ali K, Connell D, Mordi IR, George J, Lang EM, Lang CC. Lee CCE, et al. Diseases. 2021 Jun 29;9(3):47. doi: 10.3390/diseases9030047. Diseases. 2021. PMID: 34209705 Free PMC article. Review. - QTc interval prolongation, inflammation, and mortality in patients with COVID-19.
Gulletta S, Della Bella P, Pannone L, Falasconi G, Cianfanelli L, Altizio S, Cinel E, Da Prat V, Napolano A, D'Angelo G, Brugliera L, Agricola E, Landoni G, Tresoldi M, Rovere PQ, Ciceri F, Zangrillo A, Vergara P. Gulletta S, et al. J Interv Card Electrophysiol. 2022 Mar;63(2):441-448. doi: 10.1007/s10840-021-01033-8. Epub 2021 Jul 22. J Interv Card Electrophysiol. 2022. PMID: 34291390 Free PMC article.
References
- Centers for Disease Control and Prevention Information for Clinicians on Therapeutic Options for Patients with COVID-19. https://www.cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-options.html Available at:
- Plaquenil (hydroxychloroquine sulfate). Product monograph. Sanofi-Aventis Canada Inc; Laval, Quebec, Canada: August 2019.
- Roden D.M. Drug-induced prolongation of the QT interval. N Engl J Med. 2004;350:1013–1022. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous