1. Cardiovascular biomarkers in patients with acute decompensated heart failure randomized to sacubitril-valsartan or enalapril in the PIONEER-HF trial
- Author
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Eric J. Velazquez, Ricardo Rocha, David A. Morrow, Eugene Braunwald, Yared Gurmu, Adam D. DeVore, Kevin McCague, Margaret F. Prescott, and Carol I. Duffy
- Subjects
Male ,medicine.medical_specialty ,Acute decompensated heart failure ,Tetrazoles ,030204 cardiovascular system & hematology ,Sacubitril ,Angiotensin Receptor Antagonists ,03 medical and health sciences ,0302 clinical medicine ,Enalapril ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Cyclic GMP ,Aged ,Heart Failure ,Ejection fraction ,business.industry ,Aminobutyrates ,Biphenyl Compounds ,Hemodynamics ,Middle Aged ,medicine.disease ,Interleukin-1 Receptor-Like 1 Protein ,Troponin ,Drug Combinations ,Preload ,Treatment Outcome ,Valsartan ,Heart failure ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,Sacubitril, Valsartan ,medicine.drug - Abstract
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 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 NCT 02554890 clinical.trials.gov
- Published
- 2019