Cor Vasa 2021, 63(4):475-480 | DOI: 10.33678/cor.2021.025

Hydroxychloroquine versus hydroxychloroquine-azithromycin combination therapy on QT interval prolongation of COVID-19 patients: a systematic review and meta-analysis

Yohanes Krisnantyo Adi Pinanditoa, Qorina Nadya Salfia, Kezia Warokka Putria, Jefferson Caesarioa, I Gusti Hanif Rahmadia, Melisa Suhargoa, Aulia Rafikasaria, Rerdin Julariob, Subur Prajitnoc
a Medical Co-Assistant Faculty of Medicine, Airlangga University, Surabaya, Indonesia
b Cardiology Department, Dr. Soetomo General Hospital, Surabaya, Indonesia
c Public Health and Preventive Medicine Department Faculty of Medicine, Airlangga University, Surabaya, Indonesia

Research related to the treatment of COVID-19 put hydroxychloroquine (HCQ)-based as a treatment option. The effectiveness of HCQ can be increased if combined with azithromycin (AZM). However, HCQ can trigger arrhythmias in the form of QT interval prolongation. Combining AZM to HCQ might also amplify the risk of QT prolongation. Since the mechanism remains elusive, a systematic review study of existing research is absolutely necessary. This study aimed to compare the incidence of QT interval prolongation in COVID-19 patients who received HCQ therapy with those who received HCQ-AZM therapy. The design used is comparative study of two independent groups. Data were collected from journals published online, from January to July 2020, regarding the comparison of QT interval prolongation between COVID-19 patients treated with HCQ only and those treated with HCQ-AZM combination, which had undergone a systematic review. Five studies that met the criteria were obtained, which included a total sample of 477 people in France and the United States. The data were then analysed descriptively and statistically. Statistical analysis was done using the fixed-effects model from the pooling of the research. It was found that there is no significant difference statistically in the QT interval prolongation between HCQ therapy group and HCQ-AZM therapy group (OR 1.294; 95% CI 0.707-2.370).

Keywords: Azithromycin, COVID-19, Hydroxychloroquine, QT interval prolongation

Received: January 13, 2021; Revised: February 7, 2021; Accepted: February 9, 2021; Published: August 25, 2021  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Pinandito YKA, Salfi QN, Putri KW, Caesario J, Rahmadi IGH, Suhargo M, et al.. Hydroxychloroquine versus hydroxychloroquine-azithromycin combination therapy on QT interval prolongation of COVID-19 patients: a systematic review and meta-analysis. Cor Vasa. 2021;63(4):475-480. doi: 10.33678/cor.2021.025.
Download citation

References

  1. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;395:507-513. Go to original source... Go to PubMed...
  2. Geleris J, Sun Y, Platt J, et al. Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19. N Engl J Med 2020;382:2411-2418. Go to original source... Go to PubMed...
  3. Savarino A, Boelaert JR, Cassone A, et al. Effects of chloroquine on viral infections: an old drug against todays diseases. Lancet Infect Dis 2003;3:722-727. Go to original source... Go to PubMed...
  4. Celi̇k I, Onay-Besi̇kci̇ A, Ayhan-Kilcigi̇l G. Approach to the mechanism of action of hydroxychloroquine on SARS-CoV-2: a molecular docking study. J Biomol Structur Dyn 2020 Jul 17:1-7. doi: 10.1080/07391102.2020.1792993. Epub ahead of print. Go to original source... Go to PubMed...
  5. Hashem A, Alghamdi B, Algaissi A, et al. Therapeutic use of chloroquine and hydroxychloroquine in COVID-19 and other viral infections: A narrative review. Travel Med Infect Dis 2020;35:101735. Go to original source... Go to PubMed...
  6. Tanriverdİ E, Çörtük M, Yildirim BZ, et al. The use of hydroxychloroquine plus azithromycin and early hospital admission are beneficial in Covid-19 patients: Turkey experience with real-life data. Turk J Med Sci 2021;51:10-15. Go to original source... Go to PubMed...
  7. Tran DH, Sugamata R, Hirose T, et al. Azithromycin, a 15-membered macrolide antibiotic, inhibits influenza A(H1N1)pdm09 virus infection by interfering with virus internalization process. J Antibiot (Tokyo) 2019;72:759-768. Go to original source... Go to PubMed...
  8. Andreani J, Bideau ML, Duflot I, et al. In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect. Microb Pathog 2020;145:104228. Go to original source... Go to PubMed...
  9. Roden D, Harrington R, Poppas A, Russo A. Considerations for Drug Interactions on QTc Interval in Exploratory COVID-19 Treatment. J Am Coll Cardiol 2020;75:2623-2624. Go to original source... Go to PubMed...
  10. Funck-Brentano C, Salem J, et al. Response to the editorial "COVID-19 in patients with cardiovascular diseases". Arch Cardiovasc Dis 2020;113:367-368. Go to original source... Go to PubMed...
  11. Bessière F, Roccia H, Delinière A, et al. 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. JAMA Cardiology 2020;5:1067. Go to original source... Go to PubMed...
  12. Saleh M, Gabriels J, Chang D, et al. Effect of Chloroquine, Hydroxychloroquine, and Azithromycin on the Corrected QT Interval in Patients With SARS-CoV-2 Infection. Circ Arrhythm Electrophysiol 2020;13:e008662. Go to original source... Go to PubMed...
  13. Ramireddy A, Chugh H, Reinier K, et al. Experience With Hydroxychloroquine and Azithromycin in the Coronavirus Disease 2019 Pandemic: Implications for QT Interval Monitoring. J Am Heart Assoc 2020;9:e017144. Go to original source... Go to PubMed...
  14. Mercuro N, Yen C, Shim D, et al. Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19). JAMA Cardiology 2020;5:1036. Go to original source... Go to PubMed...
  15. Enzmann M, Erickson M, Grindeland C, et al. Treatment and preliminary outcomes of 150 acute care patients with COVID-19 in a rural health system in the Dakotas. Epidemiol Infect 2020;148:e124. Go to original source... Go to PubMed...
  16. FDA, 2020. FDA Cautions against Use of Hydroxychloroquine or Chloroquine for COVID-19 outside of the Hospital Setting or a Clinical Trial Due to Risk of Heart Rhythm Problems. FDA. https://www.fda.gov/drugs/drug-safety-and-availability/fda-cautions-against-use-hydroxychloroquine-or-chloroquine-covid-19-outsid e-hospital-setting-or.
  17. WHO, 2020. "Solidarity" clinical trial for COVID-19 treatments. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coro navirus-2019-ncov/solidarity-clinical-trial-for-covid-19-treatments. Accessed 1st June 2020.
  18. Singh H, Chauhan P, Kakkar AK. Hydroxychloroquine for the treatment and prophylaxis of COVID-19: The journey so far and the road ahead. Eur J Pharmacol 2021;890:173717. Go to original source... Go to PubMed...
  19. Covid-19, 2020. Interim Guidance on Management Pending Empirical Evidence. From an American Thoracic Society-led International Task Force. https://www.thoracic.or g/professionals/clinical-resources/disease-related-resources/covid-19-guidance.pdf.
  20. Revised advisory on the use of Hydroxychloroquine (HCQ) as prophylaxis for SARS-CoV- 2 infection. https://www.icmr.gov.in/pdf/covid/techdoc/V5_Revised_advisory_on _the_use_of_HCQ_SARS_CoV2_infection.pdf, 2020.
  21. Gautret P, Lagier J, Parola P et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents 2020;56:105949. Go to original source... Go to PubMed...
  22. Cipriani A, Zorzi A, Ceccato D, et al. Arrhythmic profile and 24-hour QT interval variability in COVID-19 patients treated with hydroxychloroquine and azithromycin. Int J Cardiol 2020;316:280-284. Go to original source... Go to PubMed...
  23. Popescu C, Fischer P. Hydroxychloroquine-azithromycin for COVID-19 - Warranted or dangerous? Travel Med Infect Dis 2020;35:101764. Go to original source... Go to PubMed...
  24. Jankelson L, Karam G, Becker M, et al. QT prolongation, torsades de pointes, and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: A systematic review. Heart Rhythm 2020;17:1472-1479. Go to original source... Go to PubMed...

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0), which permits non-comercial use, distribution, and reproduction in any medium, provided the original publication is properly cited. No use, distribution or reproduction is permitted which does not comply with these terms.





Cor et Vasa

You are accessing a site intended for medical professionals, not the lay public. The site may also contain information that is intended only for persons authorized to prescribe and dispense medicinal products for human use.

I therefore confirm that I am a healthcare professional under Act 40/1995 Coll. as amended by later regulations and that I have read the definition of a healthcare professional.