Original Article

Impact of Statin or Angiotensin Converting Enzyme Inhibitor/Angiotensin Receptor Blocker on the In-Hospital Mortality of COVID-19 Patients

Abstract

Background: It is important to determine the risk factors that contribute to the mortality of a disease and take measures to prevent or alleviate it. In the case of COVID-19, old age, male gender, and comorbidities such as diabetes (DM) and hypertension (HTN) have been identified as potential risk factors. However, there is conflicting information on the effects of statins and ACEI/ARB in COVID-19 patients admitted to the ICU, particularly those with diabetes or hypertension. This study aims to investigate the effects of these drugs on the in-hospital prognosis of ICU COVID-19 patients, with a focus on patients with DM or HTN.
Methods: During 18 months, we conducted a descriptive-analytical observational analysis on 391 patients who were admitted to the ICU. The study focused on COVID-19 patients and aimed to identify mortality risk factors by assessing their demographic, clinical, pharmaceutical, laboratory, and imaging data. We statistically analyzed the data to achieve this goal.
Results: Out of 391 patients, 83 received statins and 89 received ACEI/ARBs. The research has revealed that the use of ACEI/ARBs in COVID-19 patients admitted to the ICU may increase the risk of endotracheal intubation (P<0.0001) and mortality (P<0.0001). Additionally, patients treated with these drugs are more likely to experience secondary bacterial infections (P=0.007) and venous thromboembolism events (P=0.015). The results of a recent study analyzing diabetic and hypertensive patients hospitalized in ICU showed that there is no significant difference in clinical outcomes between COVID-19 patients who used ACEI/ARB and those who did not. Our study has found that the use of statins in diabetic patients is linked to a reduction in mortality rate (0.008) and secondary bacterial infections (P=0.035) of COVID-19 patients admitted to the ICU. In multivariate logistic regression, the use of statin or ACE/ARB was not identified as the mortality prediction factor.
Conclusion: Statins can help reduce mortality rates among COVID-19 patients, especially in diabetic patients, hospitalized in the ICU. So, they should be used to manage cardiovascular risk factors and lower the mortality risk. Statins and ACEI/ARB drugs were not predictors of mortality and did not decrease survival rates during ICU hospitalization.

1. Yuki K, Fujiogi M, Koutsogiannaki S. COVID-19 pathophysiology: A review. Clin Immunol. 2020;215:108427.
2. Mina B, Newton A, Hadda V. Noninvasive ventilation in treatment of respiratory failure-related COVID-19 infection: review of the literature. Can Respir J. 2022;2022.
3. Fajgenbaum DC, Rader DJ. Teaching old drugs new tricks: statins for COVID-19? Cell Metab. 2020;32(2):145-7.
4. Davies JT, Delfino SF, Feinberg CE, et al. Current and emerging uses of statins in clinical therapeutics: a review. Lipid Insights. 2016;9:LPI. S37450.
5. Al-Kuraishy HM, Al-Gareeb AI, Hussien NR, Al-Naimi MS, Rasheed HA. Statins an oft-prescribed drug is implicated in peripheral neuropathy: The time to know more. J Pak Med Assoc. 2019;69(Suppl 3):S108-s12.
6. Al-Kuraishy HM, Al-Gareeb AI, Samy OM. Statin therapy improves serum Annexin A1 levels in patients with acute coronary syndrome: A case-controlled study. Int J Crit Illn Inj Sci. 2021;11(1):4-8.
7. Vandermeer ML, Thomas AR, Kamimoto L, et al. Association between use of statins and mortality among patients hospitalized with laboratory-confirmed influenza virus infections: a multistate study. J Infect Dis. 2012;205(1):13-9.
8. Reiner Ž, Hatamipour M, Banach M, et al. Statins and the COVID-19 main protease: in silico evidence on direct interaction. Arch Med Sci. 2020;16(3):490-6.
9. Hamming I, Timens W, Bulthuis M, Lely A, Navis Gv, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J of Pathol. 2004;203(2):631-7.
10. Barkauskas CE, Cronce MJ, Rackley CR, et al. Type 2 alveolar cells are stem cells in adult lung. J Clin Invest. 2013;123(7):3025-36.
11. Henry BM, Vikse J, Benoit S, Favaloro EJ, Lippi G. Hyperinflammation and derangement of renin-angiotensin-aldosterone system in COVID-19: a novel hypothesis for clinically suspected hypercoagulopathy and microvascular immunothrombosis. Clin Chim Acta. 2020;507:167-73.
12. Lee C, Choi WJ. Overview of COVID-19 inflammatory pathogenesis from the therapeutic perspective. Arch Pharm Res. 2021;44:99-116.
13. D’Ardes D, Boccatonda A, Rossi I, et al. COVID-19 and RAS: unravelling an unclear relationship. Int J Mol Sci. 2020;21(8):3003.
14. Banu N, Panikar SS, Leal LR, Leal AR. Protective role of ACE2 and its downregulation in SARS-CoV-2 infection leading to Macrophage Activation Syndrome: Therapeutic implications. Life Sci. 2020;256:117905.
15. Gurwitz D. Angiotensin receptor blockers as tentative SARS‐CoV‐2 therapeutics. Drug Dev Res. 2020;81(5):537-40.
16. Liu Y, Yang Y, Zhang C, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci. 2020;63:364-74.
17. Wang K, Gheblawi M, Oudit GY. Angiotensin converting enzyme 2: a double-edged sword. Circulation. 2020;142(5):426-8.
18. Walia R. ACEI or not to ACEI: Review on using ACEI and ARBs on COVID-19 patients (preprint). em Inglês | medRxiv | ID: ppzbmed-1011012023032523287550. 2023.
19. Hansell DM, Bankier AA, MacMahon H, McLoud TC, Muller NL, Remy J. Fleischner Society: glossary of terms for thoracic imaging. Radiology. 2008;246(3):697-722.
20. Gholinataj Jelodar M, Rafieian S, Allah Dini A, et al. Analyzing Trends in Demographic, Laboratory, Imaging, and Clinical Outcomes of ICU-Hospitalized COVID-19 Patients. Can J Infect Dis Med Microbiol. 2023;2023:3081660.
21. Rossi GP, Sanga V, Barton M. Potential harmful effects of discontinuing ACE-inhibitors and ARBs in COVID-19 patients. Elife. 2020;9:e57278.
22. Sriram K, Insel PA. Risks of ACE inhibitor and ARB usage in COVID‐19: evaluating the evidence. Clin Pharmacol Ther. 2020;108(2):236-41.
23. Hariharan A, Hakeem AR, Radhakrishnan S, Reddy MS, Rela M. The role and therapeutic potential of NF-kappa-B pathway in severe COVID-19 patients. Inflammopharmacology. 2021;29:91-100.
24. Verdecchia P, Cavallini C, Spanevello A, Angeli F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur J Intern Med. 2020;76:14-20.
25. Tseng YH, Yang RC, Lu TS. Two hits to the renin‐angiotensin system may play a key role in severe COVID‐19. Kaohsiung J Med Sci. 2020;36(6):389-92.
26. Lee C, Choi WJ. Overview of COVID-19 inflammatory pathogenesis from the therapeutic perspective. Arch Pharm Res. 2021;44(1):99-116.
27. Mancia G, Rea F, Ludergnani M, Apolone G, Corrao G. Renin–angiotensin–aldosterone system blockers and the risk of Covid-19. N Engl J Med. 2020;382(25):2431-40.
28. Fosbøl EL, Butt JH, Østergaard L, et al. Association of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use with COVID-19 diagnosis and mortality. JAMA. 2020;324(2):168-77.
29. Braude P, Carter B, Short R, et al. The influence of ACE inhibitors and ARBs on hospital length of stay and survival in people with COVID-19. Int J Cardiol Heart Vasc. 2020;31:100660.
30. Pan M, Vasbinder A, Anderson E, et al. Angiotensin‐converting enzyme inhibitors, angiotensin II receptor blockers, and outcomes in patients hospitalized for COVID‐19. J Am Heart Assoc. 2021;10(24):e023535.
31. Liu Q, Fu W, Zhu Cj, et al. Effect of continuing the use of renin–angiotensin system inhibitors on mortality in patients hospitalized for coronavirus disease 2019: a systematic review, meta-analysis, and meta-regression analysis. BMC Infect Dis. 2023;23(1):1-14.
32. Acharya S, Kumar S, Kabra R, et al. Impact of angiotensin receptor blocker as antihypertensive in assessing mortality in patients of COVID-19: A single tertiary care center study. J Educ Health Promot. 2023;12:30.
33. Flacco ME, Martellucci CA, Bravi F, et al. Treatment with ACE inhibitors or ARBs and risk of severe/lethal COVID-19: a meta-analysis. Heart. 2020;106(19):1519-1524.
34. Chansrichavala P, Chantharaksri U, Sritara P, Chaiyaroj SC. Atorvastatin attenuates TLR4-mediated NF-[kappa] B activation in a MyD88-dependent pathway. Asian Pac J Allergy Immunol. 2009;27(1):49.
35. Chansrichavala P, Chantharaksri U, Sritara P, Chaiyaroj SC. Atorvastatin attenuates TLR4-mediated NF-kappaB activation in a MyD88-dependent pathway. Asian Pac J Allergy Immunol. 2009;27(1):49-57.
36. McAuley DF, Laffey JG, O'Kane CM, et al. Simvastatin in the acute respiratory distress syndrome. N Engl J Med. 2014;371(18):1695-703.
37. Truwit JD, Bernard GR, Steingrub J, et al. Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med. 2014;370(23):2191-200.
38. Kow CS, Hasan SS. Meta-analysis of effect of statins in patients with COVID-19. Am J Cardiol. 2020;134:153-5.
39. Daniels LB, Sitapati AM, Zhang J, et al. Relation of statin use prior to admission to severity and recovery among COVID-19 inpatients. Am J Cardiol.. 2020;136:149-55.
40. De Spiegeleer A, Bronselaer A, Teo JT, et al. The effects of ARBs, ACEis, and statins on clinical outcomes of COVID-19 infection among nursing home residents. J Am Med Dir Assoc. 2020 \;21(7):909-914.e2.
41. Grasselli G, Greco M, Zanella A, \ et al. Risk factors associated with mortality among patients with COVID-19 in intensive care units in Lombardy, Italy. JAMA Intern Med. 2020;180(10):1345-55.
42. Yan H, Valdes AM, Vijay A, et al. Role of drugs used for chronic disease management on susceptibility and severity of COVID‐19: a large case‐control study. Clin Pharmacol Ther. 2020;108(6):1185-94.
43. Krishnan S, Patel K, Desai R, et al. Clinical comorbidities, characteristics, and outcomes of mechanically ventilated patients in the State of Michigan with SARS-CoV-2 pneumonia. J Clin Anesth. 2020;67:110005.
44. Hariyanto TI, Kurniawan A. Statin therapy did not improve the in-hospital outcome of coronavirus disease 2019 (COVID-19) infection. Diabetes Metab Syndr. 2020;14(6):1613-5.
45. Kouhpeikar H, Khosaravizade Tabasi H, et al. Statin use in COVID-19 hospitalized patients and outcomes: a retrospective study. Front Cardiovasc Med. 2022;9:820260.
46. Ayeh SK, Abbey EJ, Khalifa BA, et al. Statins use and COVID-19 outcomes in hospitalized patients. PLoS One. 2021;16(9):e0256899.
47. Daniels LB, Ren J, Kumar K, et al. Relation of prior statin and anti-hypertensive use to severity of disease among patients hospitalized with COVID-19: Findings from the American Heart Association's COVID-19 Cardiovascular Disease Registry. PLoS One. 2021;16(7):e0254635.
48. Scheen AJ. Statins and clinical outcomes with COVID-19: Meta-analyses of observational studies. Diabetes Metab. 2021;47(6):101220.
49. Xavier DP, Chagas GCL, Gomes LGF, Ferri-Guerra J, Oquet REH. Effects of statin therapy in hospitalized adult COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials. Einstein (Sao Paulo). 2023;21:eRW0351.
50. Ren Y, Wang G, Han D. Statins in hospitalized COVID-19 patients: A systematic review and meta-analysis of randomized controlled trials. J Med Virol. 2023;95(6):e28823.
51. Kollias A, Kyriakoulis KG, Kyriakoulis IG, et al. Statin use and mortality in COVID-19 patients: Updated systematic review and meta-analysis. Atherosclerosis. 2021;330:114-21.
52. Lohia P, Kapur S, Benjaram S, et al. Statins and clinical outcomes in hospitalized COVID-19 patients with and without Diabetes Mellitus: a retrospective cohort study with propensity score matching. Cardiovasc Diabetol. 2021;20(1):140.
53. Saeed O, Castagna F, Agalliu I, et al. Statin Use and In-Hospital Mortality in Patients With Diabetes Mellitus and COVID-19. J Am Heart Assoc. 2020;9(24):e018475.
54. Wargny M, Potier L, Gourdy P, et al. Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORONADO study. Diabetologia. 2021;64(4):778-94.
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IssueVol 12, No 2 (Spring 2024) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/jpc.v12i2.16187
Keywords
Statin COVID-19 Mortality Intensive Care Unit

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Gholinataj Jelodar M, Mirzaei S, Hajimaghsoudi M. Impact of Statin or Angiotensin Converting Enzyme Inhibitor/Angiotensin Receptor Blocker on the In-Hospital Mortality of COVID-19 Patients. J Pharm Care. 2024;12(2):94-107.