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

Stephen J Greene; RaKavius Chambers; Joseph B Lerman; Josephine Harrington; Christopher R deFilippi; David C Wendell; Han W Kim; Cynthia L Green; Javed Butler; G Michael Felker

doi:10.1002/ejhf.3199

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

Eur J Heart Fail. 2024 May 11. doi: 10.1002/ejhf.3199. Online ahead of print.

Authors

Affiliations

¹ Duke Clinical Research Institute, Durham, NC, USA.
² Division of Cardiology, Duke University School of Medicine, Durham, NC, USA.
³ University of Virginia School of Medicine, Charlottesville, VA, USA.
⁴ Inova Schar Heart and Vascular Institute, Falls Church, VA, USA.
⁵ Baylor Scott and White Research Institute, Dallas, TX, USA.
⁶ Department of Medicine, University of Mississippi, Jackson, MS, USA.

PMID: 38733160
DOI: 10.1002/ejhf.3199

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.

Keywords: Biomarkers; COVID‐19; Sacubitril/valsartan.

Associated data

ClinicalTrials.gov/NCT04883528