Cardiovascular biomarkers in patients with acute decompensated heart failure randomized to sacubitril-valsartan or enalapril in the PIONEER-HF trial.

Published

Journal Article

AIMS: Circulating high-sensitivity cardiac troponin (hsTn) and soluble ST2 (sST2) reflect myocardial stress in patients with heart failure (HF). Production of cyclic guanosine 3'5' monophosphate (cGMP) in response to activation of natriuretic peptide receptors reduces cardiac afterload and preload. We assessed the effects of sacubitril/valsartan on these biomarkers in patients with reduced ejection fraction and acute decompensated HF (ADHF). METHODS AND RESULTS: PIONEER-HF was a randomized, double-blind trial of sacubitril/valsartan vs. enalapril in hospitalized patients with ADHF following haemodynamic stabilization. We measured circulating hsTnT, sST2, and urinary cGMP at baseline, 1, 2 (sST2, cGMP), 4, and 8 weeks (n = 694 with all baseline biomarkers). Ratios of geometric means (timepoint/baseline) were determined and compared as a ratio for sacubitril/valsartan vs. enalapril. Compared with enalapril, sacubitril/valsartan led to a significantly greater decline in hsTnT and sST2. This effect emerged as early as 1 week for sST2 and was significant for both at 4 weeks with a 16% greater reduction in hsTnT (P < 0.001) and 9% greater reduction in sST2 (P = 0.0033). Serial urinary cGMP increased with sacubitril/valsartan compared with enalapril (P < 0.001, 1 week). The significant differences between treatment groups for each biomarker were sustained at 8 weeks. In an exploratory multivariable-adjusted analysis of cardiovascular death or HF-rehospitalization, the concentrations of hsTnT, sST2 at week 1 were significantly associated with subsequent outcome. CONCLUSION: Biomarkers of myocardial stress are elevated in patients with ADHF and associated with outcome. Compared with enalapril, sacubitril/valsartan reduces myocardial injury and haemodynamic stress as reflected by biomarkers, with an onset that is apparent within 1-4 weeks. CLINICAL TRIALS REGISTRATION: NCT02554890 clinical.trials.gov.

Full Text

Duke Authors

Cited Authors

  • Morrow, DA; Velazquez, EJ; DeVore, AD; Prescott, MF; Duffy, CI; Gurmu, Y; McCague, K; Rocha, R; Braunwald, E

Published Date

  • October 21, 2019

Published In

Volume / Issue

  • 40 / 40

Start / End Page

  • 3345 - 3352

PubMed ID

  • 31093657

Pubmed Central ID

  • 31093657

Electronic International Standard Serial Number (EISSN)

  • 1522-9645

Digital Object Identifier (DOI)

  • 10.1093/eurheartj/ehz240

Language

  • eng

Conference Location

  • England