Preview

Sechenov Medical Journal

Advanced search

The study of cardiotoxicity of hydroxychloroquine and azithromycine combination in hospitalized patients with COVID-19

https://doi.org/10.47093/2218-7332.2020.11.2.29-39

Abstract

Hydroxychloroquine (HCH) is included in guidelines for treatment of novel coronavirus infection (COVID-19). Data on increased risk of cardiovascular complications when using it have been published.

Aim. To evaluate the safety and tolerability of HCH and azithromycine (AZM) combination for the treatment of the patients with COVID-19 in recommended by Russian Ministry of Health doses in real practice.

Methods. 132 patients (62 men and 70 women of average age 59.2 ± 9.3 years), 59% of whom had cardiovascular comorbidities, were included in prospective сohort study. 112 patients took HCH + AZM (group 1) and 20 patients took other medications without potential cardiotoxicity (group 2). At the admission to the hospital and after 5–7 days of the treatment corrected QT interval was calculated, new rhythm and conduction disorders, other side effects and hospital mortality have been registering. Relative risk (RR) and 95% confidence interval (CI) were calculated.

Results. Elongation of corrected QT-interval within the normal range was registered in 22.3% of patients in group 1 and in 15% — in group 2. An increase in the QT length to the upper limit of the norm (480 msec) was observed in 1.8% of patients in group 1. There were no statistically significant differences between the groups in the number of patients with prolonged QT interval (RR = 1.488, 95% CI: 0.496–4.466, р = 0.478). The occurrence of new arrhythmias, conduction disturbances and allergic reactions was not recorded. Tolerability of combination HCH + AZM was satisfactory in the majority of patients. The hospital mortality in group 1 was 1.8%, in group 2 — 5% without statistically significant difference (p = 0.374).

Conclusion. A combination of HCL + AZM according to the scheme recommended by the Ministry of Health of the Russian Federation for the treatment of the patients with COVID-19 and cardiovascular comorbidity in inpatient conditions is safe.

About the Authors

Yu. N. Belenkov
Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Yuri N. Belenkov, MD, PhD, DMSc, Academician of RAS, Professor, Head of Department of Hospital Therapy No. 1

8/2, Trubetskaya str., Moscow, 119991



I. V. Menshikova
Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Irina V., MD, PhD, DMSc, Professor, Department of Hospital Therapy No. 1

8/2, Trubetskaya str., Moscow, 119991

+7 (910) 478-46-71



I. S. Ilgisonis
Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Irina S. Ilgisonis, MD, PhD, Associate Professor, Department of Hospital Therapy No. 1

8/2, Trubetskaya str., Moscow, 119991



Yu. I. Naimann
Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Yulia I. Naimann, MD, PhD, Assistant Professor, Department of Hospital Therapy No. 1

8/2, Trubetskaya str., Moscow, 119991



Yu. V. Pak
Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Yulia V. Pak, MD, PhD, rheumatologist, Department of Rheumatology, University Clinical Hospital No. 1

8/2, Trubetskaya str., Moscow, 119991



I. R. Kolosova
Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Irina R. Kolosova, MD, PhD, rheumatologist, Department of Rheumatology, University Clinical Hospital No. 1

8/2, Trubetskaya str., Moscow, 119991



A. S. Rakovskaya
Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Alina S. Rakovskaya, rheumatologist, Department of Rheumatology, University Clinical Hospital No. 1

8/2, Trubetskaya str., Moscow, 119991



References

1. WHO. Coronavirus disease 2019 (COVID-19) Situation. Report — 51. URL: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200311-sitrep-51-covid-19.pdf?sfvrsn=1ba62e57_10 (accessed 13.06.2020).

2. Wiersinga W.J., Rhodes A., Cheng A.C., et al. Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): review. JAMA. 2020; ePub 10.07.2020: E1–E13. https://doi.org/10.1001/jama.2020.12839 PMID: 32648899

3. Hoffman M., Kleine-Weber H., Schroeder S., et al. SARS-CoV-2 entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020; 181(2): 271–80. e8. https://doi.org/10.1016/j.cell.2020.02.052 PMID: 32142651

4. Sungnak W., Huang N., Becavin C., et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med. 2020; 26(5): 681–7. https://doi.org/10.1038/s41591-020-0868-6 PMID: 32327758

5. Clerkin K.J., Fried J.A., Raikhelkar J., et al. Coronavirus disease 2019 (COVID-2019) and cardiovascular disease. Circulation. 2020; 141(20): 1648–55. https://doi.org/10.1161/CIRCULATIONAHA.120.046941 PMID:32200663

6. Goshua G., Pine A.B., Meizlish M.L., et al. Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study. Lancet Hematol. 2020; 7(8): e575–82. https://doi.org/10.1016/S2352-3026(20)30216-7 PMID: 32619411

7. Varga Z., Flammer A.J., Staiger P., et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020; 395(10234): 1417–18. https://doi.org/10.1016/S0140-6736(20)30937-5 PMID:32325026

8. Xu Z., Shi L., Wang Y., et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020; 8(4): 420–2. https://doi.org/10.1016/S2213-2600(20)30076-X PMID: 32085846

9. Huang C., Wang Y., Li X., et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 2020; 395(10223): 497–506. https://doi.org/10.1016/S0140-6736(20)30183-5 PMID: 31986264

10. Li L.Q., Huang T., Wang Y.Q., et al. COVID-19 patients’ clinical characteristics, discharge rate, and fatality rate of meta-analysis. J.MedVirol. 2020; 92(6): 577–83. https://doi.org/10.1002/jmv.25757 PMID: 32162702

11. Zhou D., Dai S.M., Tong Q. COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression. J Antimicbob Chemother. 2020; 75(7): 1667–70. https://doi.org/10.1093/jac/dkaa114 PMID: 32196083

12. Wang M., Cao R., Zhang L., et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020; 30(3): 269–71. https://doi.org/10.1038/s41422-020-0282-0 PMID: 32020029

13. 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. Int J Antimicrob Agents. 2020; 56(1): 105949. https://doi.org/10.1016/j.ijantimicag.2020.105949 PMID: 32205204

14. Revmatologiya. Farmakoterapiya bez oshibok: rukovodstvo dlya vrachey. Pod red. V.I. Mazurova, O.M. Lesnyak [Rheumatology. Pharmacotherapy without mistakes]. Moscow: E-noto; 2017. 109 p. (In Russian).

15. Rossiiskie klinicheskie rekomendatsii. Revmatologiya. Pod red. E.L. Nasonova. [Russian clinical guidelines. Rheumatology]. Moscow: GEOTAR-Media; 2020. 448 p. (In Russian).

16. Vremennye metodicheskie rekomendatsii «Profilaktika, diagnostika i lechenie novoi koronavirusnoi infektsii (COVID-19)», versiya 5, utverzhdeny Ministerstvom zdravookhraneniya RF 08.04.2020 [Temporary guidelines “Prevention, diagnosis and treatment of new coronavirus infection (COVID-19)", version 5, approved by the Ministry of Health of the Russian Federation 08.04.2020]. (In Russian). URL: https://static-1.rosminzdrav.ru/system/attachments/attaches/000/049/951/original/09042020_%D0%9C%D0%A0_COVID-19_v5.pdf (accessed 25.04.2020)

17. Cortegiani A., Ingoglia G., Ippolito M., et al. A systemic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care. 2020; 57: 279–83. https://doi.org/10.1016/j.jcrc.2020.03.005 PMID: 32173110

18. Gao J., Tian Z., Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19-associated pneumonia in clinical studies. Biosci Trends. 2020; 14(1): 72–3. https://doi.org/10.5582/bst.2020.01047 PMID: 32074550

19. Delang L., Neyts J. Medical treatment options for COVID-19. European Heart Journal: Acute Cardivascular Care. 2020; 9(3): 209–14. https://doi.org/10.1177/2048872620922790 PMID:32363880

20. Rosenberg E.S., Dufort E.M., Udo T., et al. Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York State. JAMA. 2020; 323(24): 2493–502. https://doi.org/10.1001/jama.2020.8630 PMID: 32392282

21. Nguyen L.S., Dolladille C., Drici M.-D., et al. Cardiovascular toxicities associated with hydroxychloroquine and azithromycin: an analysis of the World Health Organization Pharmacovigilance Database. Circulation. 2020; 142(3): 303–5. https://doi.org/10.1161/CIRCULATIONAHA.120.048238 PMID: 32442023

22. Richardson S., Hirsch J.S., Narasimhan M., et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA. 2020; 323(20): 2052–59. https://doi.org/10.1001/jama.2020.6775 PMID: 32320003

23. Docherty A.B., Harrison E.M., Green C.A., et al. ISARIC4C investigators. Features of 20133 UK patients in hospital with COVID-19 using the ISARIC WHO Clinical Characterization Protocol: prospective observational cohort study. BMJ. 2020; 369: m1985. https://doi.org/10.1136/bmj.m1985 PMID: 32444460

24. Garg S., Kim L., Whitaker M., et al. Hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease 2019 — COVID-NET, 14 States, March 1–30, 2020. MMWR Morb Mortal Wkly Rep. 2020; 69 (15): 458–64. https://doi.org/10.15585/mmwr.mm6915e3 PMID: 32298251

25. Grasselli G., Zangrillo A., Zanella A., et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020; 323(16): 1574–81. https://doi.org/10.1001/jama.2020.5394 PMID: 32250385

26. Long B., Brady W.J., Koyfman A., et al. Cardiovascular complications in COVID-19. Am J Emerg Med. 2020; 38(7): 1504–7. https://doi.org/10.1016/j.ajem.2020.04.048 PMID: 32317203

27. Guzik T.J., Mohiddin S.A., Dimarco A., et al. COVID-19 and cardiovascular system: implications for risk assessment, diagnosis and treatment options. Cardiovasс Res. 2020; 116(10): 1666–87. https://doi.org/10.1093/cvr/cvaa106 PMID: 32352535

28. Ruan S. Likelihood of survival of coronavirus disease 2019. Lancet Infect Dis. 2020; 20(6): 630–31. https://doi.org/10.1016/S1473-3099(20)30257-7 PMID: 32240633

29. Yang L., Tu L. Implication of gastrointestinal manifestations of COVID-19. Lancet Gastroenterol Hepatol. 2020 Jul; 5(7): 629–30. https://doi.org/10.1016/S2468-1253(20)30132-1.PMID: 32405602


Views: 567


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2218-7332 (Print)
ISSN 2658-3348 (Online)