open access

Vol 29, No 1 (2022)
Study Protocol
Submitted: 2021-09-18
Accepted: 2021-10-19
Published online: 2021-11-15
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IMPACT of PCSK9 inhibition on clinical outcome in patients during the inflammatory stage of the SARS-COV-2 infection: Rationale and protocol of the IMPACT-SIRIO 5 study

Jacek Kubica1, Przemysław Podhajski1, Przemysław Magielski1, Aldona Kubica2, Piotr Adamski1, Roman Junik3, Jarosław Pinkas4, Eliano P. Navarese1
DOI: 10.5603/CJ.a2021.0148
·
Pubmed: 34787891
·
Cardiol J 2022;29(1):140-147.
Affiliations
  1. Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Poland
  2. Department of Health Promotion, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Poland
  3. Department of Endocrinology and Diabetology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland
  4. Centre of Postgraduate Medical Education, School of Public Health, Warsaw, Poland

open access

Vol 29, No 1 (2022)
Study protocol — COVID-19
Submitted: 2021-09-18
Accepted: 2021-10-19
Published online: 2021-11-15

Abstract

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Abstract

Not available
Get Citation
About this article
Title

IMPACT of PCSK9 inhibition on clinical outcome in patients during the inflammatory stage of the SARS-COV-2 infection: Rationale and protocol of the IMPACT-SIRIO 5 study

Journal

Cardiology Journal

Issue

Vol 29, No 1 (2022)

Article type

Study Protocol

Pages

140-147

Published online

2021-11-15

Page views

5931

Article views/downloads

904

DOI

10.5603/CJ.a2021.0148

Pubmed

34787891

Bibliographic record

Cardiol J 2022;29(1):140-147.

Authors

Jacek Kubica
Przemysław Podhajski
Przemysław Magielski
Aldona Kubica
Piotr Adamski
Roman Junik
Jarosław Pinkas
Eliano P. Navarese

References (65)
  1. Xie Y, Wang Z, Liao H, et al. Epidemiologic, clinical, and laboratory findings of the COVID-19 in the current pandemic: systematic review and meta-analysis. BMC Infect Dis. 2020; 20(1): 640.
  2. Behrens EM, Koretzky GA. Review: cytokine storm syndrome: looking toward the precision medicine era. Arthritis Rheumatol. 2017; 69(6): 1135–1143.
  3. Corradini E, Ventura P, Ageno W, et al. SIMI-COVID-19 Collaborators. Clinical factors associated with death in 3044 COVID-19 patients managed in internal medicine wards in Italy: results from the SIMI-COVID-19 study of the Italian Society of Internal Medicine (SIMI). Intern Emerg Med. 2021; 16(4): 1005–1015.
  4. Grasselli G, Greco M, Zanella A, et al. COVID-19 Lombardy ICU Network. Risk factors associated with mortality among patients with COVID-19 in intensive care units in lombardy, Italy. JAMA Intern Med. 2020; 180(10): 1345–1355.
  5. Zangrillo A, Beretta L, Scandroglio AM, et al. COVID-BioB Study Group. Characteristics, treatment, outcomes and cause of death of invasively ventilated patients with COVID-19 ARDS in Milan, Italy. Crit Care Resusc. 2020; 22(3): 200–211.
  6. Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020; 8(5): 475–481.
  7. Mulchandani R, Lyngdoh T, Kakkar AK. Deciphering the COVID-19 cytokine storm: Systematic review and meta-analysis. Eur J Clin Invest. 2021; 51(1): e13429.
  8. Del Valle DM, Kim-Schulze S, Huang HH, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med. 2020; 26(10): 1636–1643.
  9. Mehta P, McAuley D, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020; 395(10229): 1033–1034.
  10. Navarese EP, Kołodziejczak M, Dimitroulis D, et al. From proprotein convertase subtilisin/kexin type 9 to its inhibition: state-of-the-art and clinical implications. Eur Heart J Cardiovasc Pharmacother. 2016; 2(1): 44–53.
  11. Mach F, Baigent C, Catapano AL, et al. ESC Scientific Document Group. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020; 41(1): 111–188.
  12. Ricci C, Ruscica M, Camera M, et al. PCSK9 induces a pro-inflammatory response in macrophages. Sci Rep. 2018; 8(1): 2267.
  13. Yang CL, Zeng YD, Hu ZX, et al. PCSK9 promotes the secretion of pro-inflammatory cytokines by macrophages to aggravate H/R-induced cardiomyocyte injury via activating NF-κB signalling. Gen Physiol Biophys. 2020; 39(2): 123–134.
  14. Dwivedi DJ, Grin PM, Khan M, et al. Differential expression of PCSK9 modulates infection, inflammation, and coagulation in a murine model of sepsis. Shock. 2016; 46(6): 672–680.
  15. Schuster S, Rubil S, Endres M, et al. Anti-PCSK9 antibodies inhibit pro-atherogenic mechanisms in APOE*3Leiden.CETP mice. Sci Rep. 2019; 9(1): 11079.
  16. Seidah NG, Benjannet S, Wickham L, et al. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Proc Natl Acad Sci U S A. 2003; 100(3): 928–933.
  17. Zaid A, Roubtsova A, Essalmani R, et al. Proprotein convertase subtilisin/kexin type 9 (PCSK9): hepatocyte-specific low-density lipoprotein receptor degradation and critical role in mouse liver regeneration. Hepatology. 2008; 48(2): 646–654.
  18. Ferri N, Ruscica M. Proprotein convertase subtilisin/kexin type 9 (PCSK9) and metabolic syndrome: insights on insulin resistance, inflammation, and atherogenic dyslipidemia. Endocrine. 2016; 54(3): 588–601.
  19. dos Santos C, Marshall JC. Bridging lipid metabolism and innate host defense. Sci Transl Med. 2014; 6(258): 258fs41.
  20. Walley KR, Thain KR, Russell JA, et al. PCSK9 is a critical regulator of the innate immune response and septic shock outcome. Sci Transl Med. 2014; 6(258): 258ra143.
  21. Giunzioni I, Tavori H, Covarrubias R, et al. Local effects of human PCSK9 on the atherosclerotic lesion. J Pathol. 2016; 238(1): 52–62.
  22. Momtazi-Borojeni AA, Sabouri-Rad S, Gotto AM, et al. PCSK9 and inflammation: a review of experimental and clinical evidence. Eur Heart J Cardiovasc Pharmacother. 2019; 5(4): 237–245.
  23. Gurbel PA, Navarese EP, Tantry US. Exploration of PCSK9 as a cardiovascular risk factor: is there a link to the platelet? J Am Coll Cardiol. 2017; 70(12): 1463–1466.
  24. Luquero A, Badimon L, Borrell-Pages M. PCSK9 Functions in Atherosclerosis Are Not Limited to Plasmatic LDL-Cholesterol Regulation. Front Cardiovasc Med. 2021; 8: 639727.
  25. Qi Z, Hu L, Zhang J, et al. PCSK9 (proprotein convertase subtilisin/kexin 9) enhances platelet activation, thrombosis, and myocardial infarct expansion by binding to platelet CD36. Circulation. 2021; 143(1): 45–61.
  26. Tang Z, Jiang Lu, Peng J, et al. PCSK9 siRNA suppresses the inflammatory response induced by oxLDL through inhibition of NF-κB activation in THP-1-derived macrophages. Int J Mol Med. 2012; 30(4): 931–938.
  27. Walley KR, Thain KR, Russell JA, et al. PCSK9 is a critical regulator of the innate immune response and septic shock outcome. Sci Transl Med. 2014; 6(258): 258ra143.
  28. Ruscica M, Ferri N, Fogacci F, et al. Brisighella Heart Study Group. Circulating levels of proprotein convertase subtilisin/kexin type 9 and arterial stiffness in a large population sample: data from the brisighella heart study. J Am Heart Assoc. 2017; 6(5).
  29. Bohula EA, Giugliano RP, Leiter LA, et al. Inflammatory and cholesterol risk in the FOURIER trial. Circulation. 2018; 138(2): 131–140.
  30. Robinson JG, Farnier M, Krempf M, et al. ODYSSEY LONG TERM Investigators. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015; 372(16): 1489–1499.
  31. Sabatine MS, Giugliano RP, Keech AC, et al. FOURIER Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017; 376(18): 1713–1722.
  32. Schwartz GG, Steg PG, Szarek M, et al. ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018; 379(22): 2097–2107.
  33. Navarese EP, Andreotti F, Raggi P, et al. Baseline low-density lipoprotein cholesterol to predict the extent of cardiovascular benefit from lipid-lowering therapies: a review. Eur Heart J Cardiovasc Pharmacother. 2019; 5(1): 47–54.
  34. Navarese EP, Kołodziejczak M, Petrescu A, et al. Role of proprotein convertase subtilisin/kexin type 9 inhibitors in patients with coronary artery disease undergoing percutaneous coronary intervention. Expert Rev Cardiovasc Ther. 2018; 16(6): 419–429.
  35. Navarese EP, Robinson JG, Kowalewski M, et al. Association between baseline LDL-C level and total and cardiovascular mortality after LDL-C lowering: a systematic review and meta-analysis. JAMA. 2018; 319(15): 1566–1579.
  36. Navarese EP, Kolodziejczak M, Schulze V, et al. Effects of proprotein convertase subtilisin/kexin type 9 antibodies in adults with hypercholesterolemia: a systematic review and meta-analysis. Ann Intern Med. 2015; 163(1): 40–51.
  37. Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal. J Heart Lung Transplant. 2020; 39(5): 405–407.
  38. Romagnoli S, Peris A, De Gaudio AR, et al. SARS-CoV-2 and COVID-19: From the Bench to the Bedside. Physiol Rev. 2020; 100(4): 1455–1466.
  39. 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.
  40. Fajgenbaum DC, June CH. Cytokine storm. N Engl J Med. 2020; 383(23): 2255–2273.
  41. Gautret P, Million M, Jarrot PA, et al. Natural history of COVID-19 and therapeutic options. Expert Rev Clin Immunol. 2020; 16(12): 1159–1184.
  42. Santa Cruz A, Mendes-Frias A, Oliveira AI, et al. Interleukin-6 is a biomarker for the development of fatal severe acute respiratory syndrome coronavirus 2 pneumonia. Front Immunol. 2021; 12: 613422.
  43. Laguna-Goya R, Utrero-Rico A, Talayero P, et al. IL-6-based mortality risk model for hospitalized patients with COVID-19. J Allergy Clin Immunol. 2020; 146(4): 799–807.e9.
  44. Aziz M, Fatima R, Assaly R. Elevated interleukin-6 and severe COVID-19: A meta-analysis. J Med Virol. 2020; 92(11): 2283–2285.
  45. Grifoni E, Vannucchi V, Valoriani A, et al. Interleukin-6 added to CALL score better predicts the prognosis of COVID-19 patients. Intern Med J. 2021; 51(1): 146–147.
  46. Herold T, Jurinovic V, Arnreich C, et al. Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. J Allergy Clin Immunol. 2020; 146(1): 128–136.e4.
  47. Liu T, Zhang J, Yang Y, et al. The role of interleukin-6 in monitoring severe case of coronavirus disease 2019. EMBO Mol Med. 2020; 12(7): e12421.
  48. Hadjadj J, Yatim N, Barnabei L, et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science. 2020; 369(6504): 718–724.
  49. Garbers C, Heink S, Korn T, et al. Interleukin-6: designing specific therapeutics for a complex cytokine. Nat Rev Drug Discov. 2018; 17(6): 395–412.
  50. Scheller J, Chalaris A, Schmidt-Arras D, et al. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta. 2011; 1813(5): 878–888.
  51. Angriman F, Ferreyro B, Burry L, et al. Interleukin-6 receptor blockade in patients with COVID-19: placing clinical trials into context. Lancet Respir Med. 2021; 9(6): 655–664.
  52. Kalil AC, Patterson TF, Mehta AK, et al. ACTT-2 Study Group Members. Baricitinib plus remdesivir for hospitalized adults with Covid-19. N Engl J Med. 2021; 384(9): 795–807.
  53. Wijaya I, Andhika R, Huang I, et al. The use of Janus Kinase inhibitors in hospitalized patients with COVID-19: Systematic review and meta-analysis. Clin Epidemiol Glob Health. 2021; 11: 100755.
  54. Chen CX, Wang JJ, Li H, et al. JAK-inhibitors for coronavirus disease-2019 (COVID-19): a meta-analysis. Leukemia. 2021; 35(9): 2616–2620.
  55. Lescure FX, Honda H, Fowler R, et al. Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Resp Med. 2021; 9(5): 522–532.
  56. Gordon AC, Mouncey PR, Al-Beidh F, et al. REMAP-CAP Investigators. Interleukin-6 receptor antagonists in critically ill patients with COVID-19. N Engl J Med. 2021; 384(16): 1491–1502.
  57. Khan FA, Stewart I, Fabbri L, et al. Systematic review and meta-analysis of anakinra, sarilumab, siltuximab and tocilizumab for COVID-19. Thorax. 2021; 76(9): 907–919.
  58. Chen CX, Hu F, Wei J, et al. Systematic review and meta-analysis of tocilizumab in persons with coronavirus disease-2019 (COVID-19). Leukemia. 2021; 35(6): 1661–1670.
  59. Luquero A, Badimon L, Borrell-Pages M. PCSK9 functions in atherosclerosis are not limited to plasmatic ldl-cholesterol regulation. Front Cardiovasc Med. 2021; 8: 639727.
  60. Qi Z, Hu L, Zhang J, et al. PCSK9 (proprotein convertase subtilisin/kexin 9) enhances platelet activation, thrombosis, and myocardial infarct expansion by binding to platelet CD36. Circulation. 2021; 143(1): 45–61.
  61. www worldometers info. (accessed 2021).
  62. Kubica A. Self-reported questionnaires for a comprehensive assessment of patients after acute coronary syndrome. Med Res J. 2019; 4(2): 106–109.
  63. Michalski P, Kasprzak M, Kosobucka A, et al. Sociodemographic and clinical determinants of the functioning of patients with coronary artery disease. Med Res J. 2021; 6(1): 21–27.
  64. Buszko K, Pietrzykowski Ł, Michalski P, et al. Validation of the Functioning in Chronic Illness Scale (FCIS). Med Res J. 2018; 3(2): 63–69.
  65. Kubica A, Kosobucka A, Michalski P, et al. Self-reported questionnaires for assessment adherence to treatment in patients with cardiovascular diseases. Med Res J. 2018; 2(4): 115–122.

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