Year 2020, Volume 4 , Issue 11, Pages 1082 - 1085 2020-11-01

The effects and reliability of the hydroxychloroquine-azithromycin combination on the cardiac conduction system in patients with coronavirus disease 2019
Koronavirüs 2019 hastalığı olan hastalarda hidroksiklorokin-azitromisin kombinasyonunun kalp iletim sistemi üzerindeki etkileri ve güvenilirliği

Berat UĞUZ [1] , İ̇smet ZENGİN [2] , Dursun TOPAL [3] , Selvi COŞAR [4] , Selma TİRYAKİOĞLU [5] , Mustafa Adem YILMAZTEPE [6]


Aim: The COVID-19 virus influenced the world since late 2019 and affected millions of people. Although there is no unambiguous evidence in the treatment of COVID-19, the combination of hydroxychloroquine and azithromycin entered the protocols globally to reduce virus replication and take advantage of its immunomodulatory effects. It has been stated that both drugs extend QTc. However, the frequency of QTc prolongation in combinational drug use, and its effect on the primary endpoint, as well as the predictive values of QTc prolongation are not clear. Methods: A total of 135 patients who received hydroxychloroquine, azithromycin, and oseltamivir for suspected / definitive COVID-19 with viral pneumonia were examined in this single-center, retrospective study, Results: The mean age was 55.6 (19.1) years, and 61 (45%) patients were female. According to the initial ECG values, the QTc1 value was 422.44 (35.72) ms, while the QTc2 value was 446.91 (36.71) ms (P<0.001). The ECG evaluation after medication use indicated that the number of patients with a QTc value >500 ms was 6 (4.4%). The number of patients with prolongation in QTc values >60 ms was 7 (5.1%). The frequency of prolongation in QTc was 26% in intensive care unit patients, and 2% in low-risk patients in the inpatient unit. An elevation in troponin values >14 ng/L and a low GFR are predictors for QTc prolongation. None of these patients developed malignant arrhythmia or sudden cardiac death. Conclusion: Hydroxychloroquine and azithromycin combinations used in COVID-19 patients cause a prolongation in the QTc. The incidence of prolongation in QTc varies according to the comorbid characteristics and clinical status of the patients. Before starting hydroxychloroquine and azithromycin, the risk factors and clinical status of the patients should be well evaluated.
Amaç: COVID-19 virüsü 2019'un sonlarından bu yana tüm dünyayı ve milyonlarca insanı etkiledi. COVID-19 tedavisinde net bir kanıt olmamasına rağmen, hidroksiklorokin ve azitromisinin kombinasyonu, virüs replikasyonunu azaltmak ve immünomodülatör etkilerinden yararlanmak için dünya çapında protokollere girmiştir. Her iki ilacın ayrı ayrı kullanımlarında QTc'yi uzattığı belirtilmiştir. Bununla birlikte, kombinasyonel ilaç kullanımında QTc uzamasının sıklığı ve bunun birincil sonlanım noktası üzerindeki etkisi ve ayrıca QTc uzamasının prediktif değerleri net değildir. Yöntemler: Çalışma tek merkezli, retrospektif bir çalışma olarak tasarlandı. Viral pnömonili şüpheli / kesin COVID-19 nedeniyle hidroksiklorokin, azitromisin ve oseltamivir alan 135 hasta incelendi. Bulgular: Ortalama yaş 55,6 (19,1) yıldı ve 61 (%45) hasta kadındı. İlk EKG değerlerine göre QTc1 değeri 422,44 (35,72) ms, QTc2 değeri 446,91 (36,71) ms (P<0,001) bulundu. İlaç kullanımı sonrası EKG değerlendirmesi, QTc değeri >500 ms olan hasta sayısının 6 (%4,4) olduğunu gösterdi. QTc değerlerinde >60 ms uzaması olan hasta sayısı 7 (%5,1) idi. QTc'de uzama sıklığı yoğun bakım hastalarında %26 iken, yataklı servis birimindeki düşük riskli hastalarda sıklık %2 idi. Troponin değerlerinde >14 ng/L yükselme ve düşük GFR, QTc uzaması için belirleyicilerdir. Bu hastaların hiçbirinde malign bir aritmi veya ani kalp durması gelişmedi. Sonuç: COVID-19 hastalarında kullanılan hidroksiklorokin ve azitromisin kombinasyonları QTc'de uzamaya neden olur. QTc'de uzama insidansı, hastaların komorbid özelliklerine ve klinik durumuna göre değişir. Hidroksiklorokin ve azitromisine başlamadan önce, hastaların risk faktörleri ve klinik durumu iyi değerlendirilmelidir.
  • 1. WHO-Director-General’s opening remarks at the media briefing on COVID-19-11 March 2020.[https://www.who.int/dg/speeches/detail/who-director-general-s-opening –remarks –at-the-media-briefing-on-covid-19-11-march-2020]
  • 2. World Health Organization. [https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports]
  • 3. Republic of Turkey Ministery of Health Official Website . [https://covid19bilgi.saglik.gov.tr/tr]
  • 4. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019- nCoV) in vitro. Cell Res 2020 Feb 4 [Epub ahead of print]. doi: 10.1038/s41422-020-0282-0.
  • 5. Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of chloroquine on viral infections: an old drug against today's diseases. The Lancet infectious diseases. 2003;3(11):722-7. doi: 10.1016/S1473-3099(03)00806-5
  • 6. Vincent MJ, Bergeron E, Benjannet S, Bobbie R Erickson, Pierre E Rollin, Thomas G Ksiazek, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virology Journal. 2005;2(1):1-10. doi: 10.1186/1743-422X-2-69
  • 7. Chen C-Y, Wang F-L, Lin C-C. Chronic Hydroxychloroquine Use Associated with QT Prolongation and Refractory Ventricular Arrhythmia. Clinical Toxicology. 2006;44(2): doi: 10.1080/15563650500514558
  • 8. Chugh SS, Reinier K, Singh T, Uy-Evanado A, Socoteanu C, Peters D, et al. Clinical perspectıve. Circulation. 2009;119(5):663-70. doi: 10.1161/CIRCULATIONAHA.108.797035
  • 9. .Gautret P, Lagier JC, Parola P, Hoang VT, Medded L, Morgan Maılhe et al. Hydroxycloroquine and azithromycin as a treatment of COVID-19:preliminary results of an open-label non-randomized clinical trial. medRxiv 2020.03.16.20037135. doi:. 10.1101/2020.03.16.20037135
  • 10. Choi Y, LimH-S, Chung D. Choi J, Yoon D. Risk evaluation of azithromycin-induced QT prolongtion in real world practise. BioMed Research İnternational. 2018;ID1574806. doi: 10.1155/2018/1574806
  • 11. Republic of Turkey Ministery of Health COVID-19(SarS –CoV-2 ) guide 25.03.2020 https://www.tahud.org.tr/file/4f42cbfd-bbd9-4bf4-91b0-29698f53f198/COVID-19_Rehberi.pdf
  • 12. Tisdale JE, Jaynes HA, Kingery JR, Mourad NA, Trujillo TN, Overholser BR, et al. Development and validation of a risk score to predict Qt interval prolongtion in hospitalized patients.Circ Cardiovasc Qual Outcomes. 2013;6(4):479-87. doi: 10.116/cırcoutcomes.113.000152
  • 13. Dutkowski R, Smithb JR, Davies BE. Safety and pharmacokinetics of oseltamivir at standard and high dosages. International Journal of Antimicrobial Agents. 2010;35:461–7. doi: 10.1016/j.ijantimicag.2009.12.023
Primary Language en
Subjects Cardiac and Cardiovascular Systems
Journal Section Research article
Authors

Orcid: 0000-0002-4834-5572
Author: Berat UĞUZ (Primary Author)
Institution: Bursa City Hospital
Country: Turkey


Orcid: 0000-0003-0758-649X
Author: İ̇smet ZENGİN
Institution: Bursa City Hospital
Country: Turkey


Orcid: 0000-0001-7053-2131
Author: Dursun TOPAL
Institution: Bursa City Hospital
Country: Turkey


Orcid: 0000-0002-0867-3264
Author: Selvi COŞAR
Institution: Bursa City Hospital
Country: Turkey


Orcid: 0000-0003-3443-6593
Author: Selma TİRYAKİOĞLU
Institution: Bursa City Hospital
Country: Turkey


Orcid: 0000-0001-5328-5749
Author: Mustafa Adem YILMAZTEPE
Institution: Bursa City Hospital
Country: Turkey


Dates

Publication Date : November 1, 2020

Bibtex @research article { josam811354, journal = {Journal of Surgery and Medicine}, issn = {}, eissn = {2602-2079}, address = {jsurgmed@gmail.com}, publisher = {Fatih BAŞAK}, year = {2020}, volume = {4}, pages = {1082 - 1085}, doi = {10.28982/josam.811354}, title = {The effects and reliability of the hydroxychloroquine-azithromycin combination on the cardiac conduction system in patients with coronavirus disease 2019}, key = {cite}, author = {Uğuz, Berat and Zengi̇n, İ̇smet and Topal, Dursun and Coşar, Selvi and Ti̇ryaki̇oğlu, Selma and Yılmaztepe, Mustafa Adem} }
APA Uğuz, B , Zengi̇n, İ , Topal, D , Coşar, S , Ti̇ryaki̇oğlu, S , Yılmaztepe, M . (2020). The effects and reliability of the hydroxychloroquine-azithromycin combination on the cardiac conduction system in patients with coronavirus disease 2019 . Journal of Surgery and Medicine , 4 (11) , 1082-1085 . DOI: 10.28982/josam.811354
MLA Uğuz, B , Zengi̇n, İ , Topal, D , Coşar, S , Ti̇ryaki̇oğlu, S , Yılmaztepe, M . "The effects and reliability of the hydroxychloroquine-azithromycin combination on the cardiac conduction system in patients with coronavirus disease 2019" . Journal of Surgery and Medicine 4 (2020 ): 1082-1085 <http://jsurgmed.com/en/pub/issue/57748/811354>
Chicago Uğuz, B , Zengi̇n, İ , Topal, D , Coşar, S , Ti̇ryaki̇oğlu, S , Yılmaztepe, M . "The effects and reliability of the hydroxychloroquine-azithromycin combination on the cardiac conduction system in patients with coronavirus disease 2019". Journal of Surgery and Medicine 4 (2020 ): 1082-1085
RIS TY - JOUR T1 - The effects and reliability of the hydroxychloroquine-azithromycin combination on the cardiac conduction system in patients with coronavirus disease 2019 AU - Berat Uğuz , İ̇smet Zengi̇n , Dursun Topal , Selvi Coşar , Selma Ti̇ryaki̇oğlu , Mustafa Adem Yılmaztepe Y1 - 2020 PY - 2020 N1 - doi: 10.28982/josam.811354 DO - 10.28982/josam.811354 T2 - Journal of Surgery and Medicine JF - Journal JO - JOR SP - 1082 EP - 1085 VL - 4 IS - 11 SN - -2602-2079 M3 - doi: 10.28982/josam.811354 UR - https://doi.org/10.28982/josam.811354 Y2 - 2020 ER -
EndNote %0 Journal of Surgery and Medicine The effects and reliability of the hydroxychloroquine-azithromycin combination on the cardiac conduction system in patients with coronavirus disease 2019 %A Berat Uğuz , İ̇smet Zengi̇n , Dursun Topal , Selvi Coşar , Selma Ti̇ryaki̇oğlu , Mustafa Adem Yılmaztepe %T The effects and reliability of the hydroxychloroquine-azithromycin combination on the cardiac conduction system in patients with coronavirus disease 2019 %D 2020 %J Journal of Surgery and Medicine %P -2602-2079 %V 4 %N 11 %R doi: 10.28982/josam.811354 %U 10.28982/josam.811354
ISNAD Uğuz, Berat , Zengi̇n, İ̇smet , Topal, Dursun , Coşar, Selvi , Ti̇ryaki̇oğlu, Selma , Yılmaztepe, Mustafa Adem . "The effects and reliability of the hydroxychloroquine-azithromycin combination on the cardiac conduction system in patients with coronavirus disease 2019". Journal of Surgery and Medicine 4 / 11 (November 2020): 1082-1085 . https://doi.org/10.28982/josam.811354
AMA Uğuz B , Zengi̇n İ , Topal D , Coşar S , Ti̇ryaki̇oğlu S , Yılmaztepe M . The effects and reliability of the hydroxychloroquine-azithromycin combination on the cardiac conduction system in patients with coronavirus disease 2019. J Surg Med. 2020; 4(11): 1082-1085.
Vancouver Uğuz B , Zengi̇n İ , Topal D , Coşar S , Ti̇ryaki̇oğlu S , Yılmaztepe M . The effects and reliability of the hydroxychloroquine-azithromycin combination on the cardiac conduction system in patients with coronavirus disease 2019. Journal of Surgery and Medicine. 2020; 4(11): 1082-1085.
IEEE B. Uğuz , İ. Zengi̇n , D. Topal , S. Coşar , S. Ti̇ryaki̇oğlu and M. Yılmaztepe , "The effects and reliability of the hydroxychloroquine-azithromycin combination on the cardiac conduction system in patients with coronavirus disease 2019", Journal of Surgery and Medicine, vol. 4, no. 11, pp. 1082-1085, Nov. 2020, doi:10.28982/josam.811354