Sacubitril/valsartan and cardiac injury/stress and systemic inflammatory biomarkers in acute heart failure: a prespecified secondary analysis of the PREMIER study.

AIMS: Acute heart failure (AHF) is accompanied by myocardial injury, wall stress, and systemic inflammatory activation. Whether initiating sacubitril/valsartan (Sac/Val) after haemodynamic stabilization modifies cardiac injury/stress and systemic inflammatory biomarkers is uncertain. METHODS AND RESULTS: The Program Angiotensin-Neprilysin Inhibition in Admitted Patients with Worsening Heart Failure (PREMIER) study was a multicentre, prospective, randomised, open-label trial with blinded endpoint assessment. Within 7 days of hospitalisation and after haemodynamic stabilisation, inpatients previously treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) were randomised to switch to Sac/Val or continue ACEI/ARB. In this pre-specified secondary analysis, high-sensitivity cardiac troponin T (hs-cTnT), soluble ST2 (sST2), C-reactive protein (CRP), and growth differentiation factor-15 (GDF-15) were measured at baseline and week 8. N-terminal pro-B-type natriuretic peptide (NT-proBNP) was also assessed. Among 365 patients with complete cardiac injury/stress and systemic inflammatory biomarker data, all biomarkers generally decreased over 8 weeks, but between-group differences in biomarker changes were not significant. In exploratory biomarker-stratified analyses, only baseline CRP showed a nominal treatment interaction for NT-proBNP (p for interaction=0.012). CONCLUSION: In haemodynamically stabilised patients hospitalised for AHF, no differential effects of Sac/Val versus continued ACEI/ARB therapy on cardiac injury/stress and systemic inflammatory biomarkers were demonstrated over 8 weeks. These findings do not support a broad biomarker-defined anti-inflammatory or cardioprotective effect of Sac/Val in this setting.