N 2 (187) 2024. P. 65–71

THE USE OF SULODEXIDE IN THE COMPLEX TREATMENT OF PATIENTS WITH ARTERIAL HYPERTENSION WITH ACCOMPANYING DIABETES IN CASE OF CORONAVIRUS DISEASE COVID-19. LITERATURE REVIEW

O. B. Voloshyna, E. A. Zubok

Odesa National Medical University, Odesa, Ukraine

DOI 10.32782/2226-2008-2024-2-11

Background. It was found that comorbidities in COVID-19, including arterial hypertension (AH) and diabetes mellitus (DM), may be risk factors for complications and reasons for hospitalization in intensive care units. Given the need for additional exposure to micro– and macrovascular disorders in comorbidities, the data on the use of sulodexide in such comorbid pathology in patients with COVID-19 attract attention.

Aim. The purpose of the review is to assess the effectiveness of sulodexide in the complex treatment of patients with arterial hypertension with accompanying diabetes in COVID-19.

Methods. The search was conducted in open databases PubMed/MEDLINE. Articles with original data, systematic reviews, metaanalyses, and Guidelines of International medical societies published before March 1, 2024 were included.

Results. Combined glycosaminoglycan sulodexide demonstrated a positive effect on micro- and macrovascular disorders in patients with DM micro- and macrovascular disorders. Anticoagulant, antithrombotic action of sulodexide, its ability to induce the release of tumor necrosis factor, improve the rheological properties of blood and the function of the endothelium of vessels explains the positive clinical effects in cardiovascular diseases, in particular, in hypertension and COVID-19. The use of sulodexide in patients with COVID-19 contributed to reducing the need for hospitalization in intensive care units and the need for oxygen.

Conclusions. It has been established that the use of sulodexide in the basic therapy of patients with comorbid pathology facilitates the correction of most symptoms in COVID-19 and long-term post-covid syndrome.

Key words: arterial hypertension, diabetes mellitus, COVID-19, sulodexide.

ЛІТЕРАТУРА
  1. Ogunmuyiwa Oluwatoyosi. “Hypertension and Diabetes Comorbidity: Factors that are Associated with their Joint Occurrence”. Thesis, Georgia State University, 2023. doi: https://doi.org/10.57709/35480760.
  2. de Boer IH, Bangalore S, Benetos A, et. аl. Diabetes and Hypertension: A Position Statement by the American Diabetes Association. Diabetes Care. 2017; 40(9): 1273–1284. doi: 10.2337/dci17-0026. PMID: 28830958.
  3. Williams B, Mancia G, Spiering W, et al. ESC Scientific Document Group. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018; 39(33): 3021–3104. doi: 10.1093/eurheartj/ehy339.
  4. Mancia G, Kreutz R, Brunström M, et al. 2023 ESH Guidelines for the management of arterial hypertension. The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA). J Hypertens. 2023; 41(12): 1874–2071. doi: 10.1097/ HJH.0000000000003480.
  5. Voloshyna O, Zbitneva V, Zubok E, et al. Peculiarities of Arterial Hypertension Course in Patients with Concomitant Diabetes Mellitus in the Post-COVID Period. 2022; Lviv clinical bulletin. 2022, 1(37)–2(38): 75–80. https://doi.org/10.25040/ lkv2022.01-02.075 (in Ukrainian).
  6. Zbitnieva V, Voloshyna O, Balashova I, Zubok E, Dukova O, Kovalchuk L. Peculiarities of ambulatory blood pressure monitoring in patients who have suffered from COVID-19. perspekt. 2023; 28(4): 71–9. Available from: https:// journals.uran.ua/index.php/2307-0404/article/view/294034 (in Ukrainian).
  7. Voloshyna OB, Kovalchuk LI, Balashova IV, Buheruk VV, Zbitnieva VO. Coronavirus disease: impact on risk and clinical course of cardiovascular diseases. Odesa Medical Journal. 2023; 2(183): 98–103. doi: 10.32782/2226-2008-2023-2-18 (in Ukrainian).
  8. Hoppensteadt DA, Fareed J. Pharmacological profile of sulodexide. Int Angiol. 2014; 33(3): 229–35. PMID: 24936531.
  9. Coccheri S, Mannello F. Development and use of sulodexide in vascular diseases: implications for treatment. Drug Des Devel Ther. 2013; 8: 49–65. doi: 10.2147/DDDT.S6762.
  10. Bigmini AA, Chebil A, Gambaro G., Matuška J. Sulodexide for Diabetic-Induced Disabilities: A Systematic Review and Meta-Analysis 2021. Advances in Therapy. 2021; 38: 1483–1513, https://doi.org/10.6084/m9.figshare.13526489.
  11. Thiruvoipati T, Kielhorn CE, Armstrong EJ. Peripheral artery disease in patients with diabetes: Epidemiology, mechanisms, and outcomes. World J Diabetes. 2015; 6(7): 961–9. doi: 10.4239/wjd.v6.i7.961.
  12. Low Wang CC, Blomster JI, Heizer G, et al. EUCLID Trial Executive Committee and Investigators. Cardiovascular and Limb Outcomes in Patients With Diabetes and Peripheral Artery Disease: The EUCLID Trial. J Am Coll Cardiol. 2018; 72(25): 3274–3284. doi: 10.1016/j.jacc.2018.09.078.
  13. Enea I, Martelli E. Focus on the Prevention of Acute Limb Ischemia: Centrality of the General Practitioner from the Point of View of the Internist. J Clin Med. 2023; 12(11): 3652. doi: 10.3390/jcm12113652.
  14. Hirsch AT, Murphy TP, Lovell MB, et al. Gaps in public knowledge of peripheral arterial disease: The first national PAD public awareness survey. 2007; 116(18): 2086–2094. doi: 10.1161/CIRCULATIONAHA.107.725101.
  15. Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio Thoracic Surgery (EACTS): The Task force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology developed with special contribution of the European heart Rhythm Association (EHRA) of the ESC. Heart J. 2021; 42: 373–398. doi: 10.1093/eurheartj/ehaa612.
  16. Aboyans V, Ricco JB, Bartelink ML, et al. 2017 ESC guidelines on the diagnosis and treatment of Periphera Arterial Diseases in collaboration with the European Society for Vascular Surgery (ESVS) Heart J. 2018; 39: 763–821. doi: 10.1093/ eurheartj/ehx095.
  17. Coccheri S, Mannello F. Development and use of sulodexide in vascular diseases: implications for treatment. Drug Des Dev Ther. 2013; 8: 49–65. https://doi.org/10.2147/DDDT.S6762.
  18. Higgins JP, Li T, Deeks JJ. Choosing effect measures and computing estimates of effect, version 6.0. In: Higgins J, Thomas J, Chandler J, Cumpston M, Li T, Page M, et al., editors. Cochrane handbook for systematic reviews of interventions. New York: Wiley. 2019, p. 143–76.
  19. Packham DK, Wolfe R, Reutens AT, et al. Collaborative Study Group. Sulodexide fails to demonstrate renoprotection in overt type 2 diabetic nephropathy. J Am Soc Nephrol. 2012; 23(1): 123–30. doi: 10.1681/ASN.2011040378.
  20. Li H, Ke W, Liu J, He X Jr, Liu L, Li Y. Effect of intravenous and oral therapy with sulodexide on diabetic nephropathy. 2017; 66: 597.
  21. Achour A, Kacem M, Dibej K, Skhiri H, Bouraoui S, El May M. One year course of oral sulodexide in the management of diabetic nephropathy. J Nephrol. 2005; 18(5): 568–74.
  22. Blouza S, Dakhli S, Abid H, et al. Efficacy of low-dose oral sulodexide in the management of diabetic nephropathy. J Nephrol. 2010; 23(4): 415–24.
  23. Olde Engberink RHG, Vogt L. The renoprotective effects of sulodexide. Drug Design, Development and Therapy. 2016: 1233–1234. doi: 10.2147/DDDT.S102814
  24. Olde Engberink RH, Heerspink HJ, de Zeeuw D, Vogt L. Blood pressure-lowering effects of sulodexide depend on albuminuria severity: post hoc analysis of the sulodexide microalbuminuria and macroalbuminuria studies. Br J Clin Pharmacol. 2016; 82(5): 1351–7. https://doi.org/10.1111/bcp.13062.
  25. Olde Engberink RH, Rorije NM, LambersHeerspink HJ, De Zeeuw D, van den Born BJ, Vogt L. The blood pressure lowering potential of sulodexide – a systematic review and meta-analysis. Br J Clin Pharmacol. 2015; 80(6): 1245–53. doi: 10.1111/ bcp.12722.
  26. Tang, X, Peng, L, Li, S. GW29-e0893 Sulodexide effectively alleviated urine protein in patients with hypertension. J Am Coll Cardiol. 2018; 72 (16_Supplement): 155. https://doi.org/10.1016/j.jacc.2018.08.709.
  27. Condorelli M, Chiariello M, Dagianti A, et al. IPO-V2: a prospective, multicenter, randomized, comparative clinical investigation of the effects of sulodexide in preventing cardiovascular accidents in the first year after acute myocardial infarction. J Am Coll Cardiol. 1994; 23(1): 27–34. doi: 10.1016/0735-1097(94)90498-7.
  28. Gaddi A, Galetti C, Illuminati B, Nascetti S. Meta-analysis of some results of clinical trials on sulodexide therapy in peripheral occlusive arterial disease. J Int Med Res. 1996; 24(5): 389–406. doi: 10.1177/030006059602400501.
  29. Coccheri S, Scondotto G, Agnelli G, Palazzini E, Zamboni V. Sulodexide in the treatment of intermittent claudication. Results of a randomized, double blind, multicentre, placebo-controlled study. EurHeart J. 2002; 23(13): 1057–1065.
  30. Lasierra-Cirujeda J, Coronel P, Aza MJ, Gimeno M. Use of sulodexide in patients with peripheral vascular disease. J Blood Med. 2010; 1: 105–115.
  31. Jarzabek K, Gabryel B, Urbanek T. Sulodexide in the treatment of vascular disease: its therapeutic action on the endothelium. Phlebol Rev. 2016; 24 (4): 51–59. doi: https://doi.org/10.5114/pr.2016.67742.
  32. Gonzalez-Ochoa AJ, Raffetto JD, Hernández AG, et al. Sulodexide in the Treatment of Patients with Early Stages of COVID-19: A Randomized Controlled Trial. Thromb Haemost. 2021; 121(7): 944–954 doi: 10.1055/a-1414-5216.
  33. Rajewska-Tabor J, Sosińska-Zawierucha P, Pyda M, Lesiak M, Bręborowicz A. Protective role of N-acetylcysteine and Sulodexide on endothelial cells exposed on patients’ serum after SARS-CoV-2 infection. Front Cell Infect Microbiol. 2023; 13: 1268016. doi: 10.3389/fcimb.2023.1268016.
  34. Ciszewicz M, Polubinska A, Antoniewicz A, Suminska-Jasinska K, Breborowicz A. Sulodexide suppresses inflammation in human endothelial cells and prevents glucose cytotoxicity. Transl Res. 2009; 153(3): 118–123. doi: 10.1016/j.trsl.2008.12.007.
  35. Wu C, Chen X, Cai Y, et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020; 180(7): 934–943. doi: 10.1001/ jamainternmed.2020.0994.
  36. Bikdeli B, Madhavan MV, Gupta A, et al. Global COVID-19 Thrombosis Collaborative Group. Pharmacological Agents Targeting Thromboinflammation in COVID-19: Review and Implications for Future Research. Thromb Haemost. 2020; 120(7): 1004–1024. doi:10.1055/s-0040-1713152.
  37. Fröhlich GM, Jeschke E, Eichler U, et al. Impact of oral anticoagulation on clinical outcomes of COVID-19: a nationwide cohort study of hospitalized patients in Germany. Clin Res Cardiol. 2021; 110: 1041–1050. doi: 10.1007/s00392-020-01783-x.
  38. Yang J, Zheng Y, Gou X, et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int J Infect Dis. 2020; 94: 91–95. doi: 10.1016/j.ijid.2020.03.017.
  39. Lippi G, Wong J, Henry BM. Hypertension in patients with coronavirus disease 2019 (COVID-19): a pooled analysis. Pol Arch Intern Med. 2020; 130(4): 304–309. doi: 10.20452/pamw.15272.
  40. Zuin M, Rigatelli G, Zuliani G, Rigatelli A, Mazza A, Roncon L. Arterial hypertension and risk of death in patients with COVID-19 infection: Systematic review and meta-analysis. J Infect. 2020; 81(1): 84–86. doi: 10.1016/j.jinf.2020.03.059.
  41. Badawi A, Ryoo SG. Prevalence of comorbidities in the Middle East respiratory syndrome coronavirus (MERS-CoV): a systematic review and meta-analysis. J. Infect. Dis. 2016; 49: 129–133. doi: 10.1016/j.ijid.2016.06.015.
  42. Akkus E, Sahin M. Related molecular mechanisms of COVID-19, hypertension, and diabetes. Am J Physiol Endocrinol Metab. 2020; 318(6): 881. doi: 10.1152/ajpendo.00164.2020.
  43. Zheng YY, Ma YT, Zhang JY, Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020; 17(5): 259–260. doi: 10.1038/s41569-020-0360-5.
  44. Turner AJ, Hiscox JA, Hooper NM. ACE2: from vasopeptidase to SARS virus receptor. Trends Pharmacol. Sci. 2004; 25: 291–294. doi: 10.1016/j.tips.2004.04.001.
  45. Cheng H, Wang Y, Wang GQ. Organ-protective effect of angiotensin-converting enzyme 2 and its effect on the prognosis of COVID-19. J Med Virol. 2020; 92(7): 726–730. doi: 10.1002/jmv.25785.
  46. Aiyegbusi OL, Hughes SE, Turner G, et al. Symptoms, complications and management of long COVID: a review. J R Soc Med. 2021; 114(9): 428–442. doi: 10.1177/01410768211032850.
  47. Sivan M, Taylor S. NICE guideline on long COVID. BMJ (Clinical Research ed). 2020; 371: 4938. doi: 10.1136/bmj. m4938.
  48. Charfeddine S, Amor HIH, Jdidi J, et al. Long COVID 19 Syndrome: Is It Related to Microcirculation and Endothelial Dysfunction? Insights From TUN-EndCOV Study. Front Cardiovasc Med. 2021; 8: 745758. doi: 10.3389/fcvm.2021.745758.
  49. Charfeddine S, Ibnhadjamor H, Jdidi J, et al. Sulodexide Significantly Improves Endothelial Dysfunction and Alleviates Chest Pain and Palpitations in Patients With Long-COVID-19: Insights From TUN-EndCOV Study. Front Cardiovasc Med. 2022; 9: 866113. doi: 10.3389/fcvm.2022.866113.
  50. Szolnoky G, González-Ochoa AJ. Sulodexide: A Benefit for Cardiovascular Sequelae of Long COVID Patients? Clin Appl Thromb Hemost. 2022; 28:10760296221084300. doi: 10.1177/10760296221084300.
  51. Szolnoky G. Sulodexide may be a real alternative to low molecular weight heparins in the prevention of COVID-19 induced vascular complications. Dermatol Ther. 2020; 33(6): 14437. doi: 10.1111/dth.14437.
  52. Schulman S, Harenberg J. Anticoagulant Treatment of COVID-19 as Early as Possible-Sulodexide and Perspectives. Thromb Haemost. 2021; 121(7): 849–853. doi: 10.1055/a-1477-3569.
  53. Ferrandis R, Sierra P, Gomez-Luque A. COVID-19 thromboprophylaxis. New evidence. Rev Esp Anestesiol Reanim (Engl Ed). 2024; 71(1): 34–47. doi: 10.1016/j.redare.2022.11.004.
  54. Ansari SA, Merza N, Salman M, et al. Safety and efficacy of antithrombotics in outpatients with symptomatic COVID-19: A systematic review and meta-analysis. Curr Probl Cardiol. 2024; 49(4): 102451. doi: 10.1016/j.cpcardiol.2024.102451.
  55. Schulman S, Sholzberg M, Spyropoulos AC, et al. ISTH guidelines for antithrombotic treatment in COVID-19. J Thromb Haemost. 2022; 20(10): 2214–2225. doi: 10.1111/jth.15808.
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