Sacubitril/valsartan and cardiovascular biomarkers among patients with recent COVID-19 infection: The PARACOR-19 randomized clinical trial.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Wiley Country of Publication: England NLM ID: 100887595 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0844 (Electronic) Linking ISSN: 13889842 NLM ISO Abbreviation: Eur J Heart Fail Subsets: MEDLINE
    • Publication Information:
      Publication: 2014- : Chichester : Wiley
      Original Publication: Amsterdam ; New York : Elsevier Science, c1999-
    • Subject Terms:
      Biphenyl Compounds* ; Aminobutyrates*/therapeutic use ; Valsartan* ; Drug Combinations* ; COVID-19*/complications ; COVID-19*/blood ; Biomarkers*/blood ; Heart Failure*/drug therapy ; Heart Failure*/blood ; Angiotensin Receptor Antagonists*/therapeutic use ; Peptide Fragments*/blood; Humans ; Male ; Female ; Double-Blind Method ; Middle Aged ; Aged ; Tetrazoles/therapeutic use ; Tetrazoles/administration & dosage ; SARS-CoV-2 ; Natriuretic Peptide, Brain/blood ; Troponin T/blood ; Interleukin-1 Receptor-Like 1 Protein/blood ; COVID-19 Drug Treatment
    • Abstract:
      Aims: The PARACOR-19 randomized controlled trial (RCT) was designed to examine the effects of sacubitril/valsartan on markers of cardiac injury, inflammation, structure, and function among patients who have recovered from acute coronavirus disease 2019 (COVID-19) infection.
      Methods and Results: PARACOR-19 was a single-centre, double-blind RCT of patients with cardiovascular risk factors and a history of COVID-19 infection 4-16 weeks prior to enrolment. Patients were randomized to sacubitril/valsartan (titrated to the maximum dose of 97/103 mg twice daily) versus matching placebo. Co-primary endpoints were change from baseline to 12 weeks in high-sensitivity cardiac troponin T (hs-cTnT) and soluble ST2 (sST2). Exploratory endpoints included change from baseline to 12 weeks in additional circulating biomarkers. Overall, 42 patients were randomized between August 2021 and March 2023 (n = 20 sacubitril/valsartan, n = 22 placebo). Median (25th-75 th ) time from COVID-19 diagnosis to enrolment was 67 (48-80) days. Median age was 67 (62-71) years, 48% were female, and 91% were White. Compared with placebo, sacubitril/valsartan did not have a significant effect on the co-primary endpoints of change from baseline in hs-TnT and sST2 (all p ≥ 0.29). In exploratory analyses, sacubitril/valsartan led to a 46% greater reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and 51% greater reduction in C-terminal telopeptide of collagen type I (CITP). Permanent drug discontinuation occurred in four patients in the sacubitril/valsartan group and three patients in the placebo group. There were no deaths and one patient was hospitalized in each group.
      Conclusion: In this pilot RCT of patients who recovered from acute COVID-19, sacubitril/valsartan did not lower hs-cTnT or sST2 compared with placebo. Exploratory analyses suggested potential benefits of sacubitril/valsartan on cardiac wall stress and collagen turnover as measured by NT-proBNP and CITP. Sacubitril/valsartan was well tolerated.
      Clinical Trial Registration: ClinicalTrials.gov NCT04883528.
      (© 2024 European Society of Cardiology.)
    • References:
      Yancy CW, Fonarow GC. Coronavirus disease 2019 (COVID‐19) and the heart – Is heart failure the next chapter? JAMA Cardiol 2020;5:1216–1217. https://doi.org/10.1001/jamacardio.2020.3575.
      Puntmann VO, Carerj ML, Wieters I, Fahim M, Arendt C, Hoffmann J, et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID‐19). JAMA Cardiol 2020;5:1265–1273. https://doi.org/10.1001/jamacardio.2020.3557.
      Lindner D, Fitzek A, Brauninger H, Aleshcheva G, Edler C, Meissner K, et al. Association of cardiac infection with SARS‐CoV‐2 in confirmed COVID‐19 autopsy cases. JAMA Cardiol 2020;5:1281–1285. https://doi.org/10.1001/jamacardio.2020.3551.
      Salah HM, Fudim M, O'Neil ST, Manna A, Chute CG, Caughey MC. Post‐recovery COVID‐19 and incident heart failure in the National COVID Cohort Collaborative (N3C) study. Nat Commun 2022;13:4117. https://doi.org/10.1038/s41467‐022‐31834‐y.
      Acanfora D, Ciccone MM, Scicchitano P, Acanfora C, Casucci G. Neprilysin inhibitor‐angiotensin II receptor blocker combination (sacubitril/valsartan): Rationale for adoption in SARS‐CoV‐2 patients. Eur Heart J Cardiovasc Pharmacother 2020;6:135–136. https://doi.org/10.1093/ehjcvp/pvaa028.
      Cunningham JW, Claggett BL, O'Meara E, Prescott MF, Pfeffer MA, Shah SJ, et al. Effect of sacubitril/valsartan on biomarkers of extracellular matrix regulation in patients with HFpEF. J Am Coll Cardiol 2020;76:503–514. https://doi.org/10.1016/j.jacc.2020.05.072.
      Januzzi JL Jr, Prescott MF, Butler J, Felker GM, Maisel AS, McCague K, et al.; PROVE‐HF Investigators. Association of change in N‐terminal pro‐B‐type natriuretic peptide following initiation of sacubitril‐valsartan treatment with cardiac structure and function in patients with heart failure with reduced ejection fraction. JAMA 2019;322:1085–1095. https://doi.org/10.1001/jama.2019.12821.
      Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. Renin‐angiotensin‐aldosterone system inhibitors in patients with Covid‐19. N Engl J Med 2020;382:1653–1659. https://doi.org/10.1056/NEJMsr2005760.
      Morrow DA, Velazquez EJ, DeVore AD, Prescott MF, Duffy CI, Gurmu Y, et al. Cardiovascular biomarkers in patients with acute decompensated heart failure randomized to sacubitril‐valsartan or enalapril in the PIONEER‐HF trial. Eur Heart J 2019;40:3345–3352. https://doi.org/10.1093/eurheartj/ehz240.
      Cunningham JW, Vaduganathan M, Claggett BL, Zile MR, Anand IS, Packer M, et al. Effects of sacubitril/valsartan on N‐terminal pro‐B‐type natriuretic peptide in heart failure with preserved ejection fraction. JACC Heart Fail 2020;8:372–381. https://doi.org/10.1016/j.jchf.2020.03.002.
      McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al.; PARADIGM‐HF Investigators and Committees. Angiotensin‐neprilysin inhibition versus enalapril in heart failure. N Engl J Med 2014;371:993–1004. https://doi.org/10.1056/NEJMoa1409077.
      Solomon SD, McMurray JJV, Anand IS, Ge J, Lam CSP, Maggioni AP, et al.; PARAGON‐HF Investigators and Committees. Angiotensin‐neprilysin inhibition in heart failure with preserved ejection fraction. N Engl J Med 2019;381:1609–1620. https://doi.org/10.1056/NEJMoa1908655.
    • Contributed Indexing:
      Keywords: Biomarkers; COVID‐19; Sacubitril/valsartan
    • Molecular Sequence:
      ClinicalTrials.gov NCT04883528
    • Accession Number:
      0 (Biphenyl Compounds)
      0 (Aminobutyrates)
      80M03YXJ7I (Valsartan)
      0 (Drug Combinations)
      WB8FT61183 (sacubitril and valsartan sodium hydrate drug combination)
      0 (Biomarkers)
      0 (Angiotensin Receptor Antagonists)
      0 (Peptide Fragments)
      0 (pro-brain natriuretic peptide (1-76))
      0 (Tetrazoles)
      114471-18-0 (Natriuretic Peptide, Brain)
      0 (Troponin T)
      0 (Interleukin-1 Receptor-Like 1 Protein)
      0 (IL1RL1 protein, human)
    • Publication Date:
      Date Created: 20240511 Date Completed: 20240627 Latest Revision: 20240828
    • Publication Date:
      20240830
    • Accession Number:
      10.1002/ejhf.3199
    • Accession Number:
      38733160