Sacubitril/valsartan therapy and cardio-inflammatory biomarkers response in acute heart failure
S Doi, A Tanaka, G Yoshioka, T Imai, Y Matsue, K Kida, Y J Akashi, K NodeAbstract
Background
Acute heart failure (AHF) can cause myocardial injury and trigger an inflammatory response, contributing to poor clinical outcomes. Sacubitril/valsartan (Sac/Val) can attenuate myocardial injury and modulate immune response; however, its treatment effects on relevant cardio-inflammatory biomarkers in patients with AHF remain unclear.
Purpose
This study aimed to evaluate the effects of Sac/Val on cardio-inflammatory biomarkers in patients with AHF after haemodynamic stabilisation.
Methods
Program Angiotensin-Neprilysin Inhibition in Admitted Patients with Worsening Heart Failure (PREMIER) is an investigator-initiated, multicentre, prospective, randomised, open-label, blinded endpoint pragmatic trial for inpatients after an AHF event. After haemodynamic stabilisation within seven days of hospitalisation because of an AHF event, eligible patients were allocated either to switch to Sac/Val initiation from background angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACEI/ARB) therapy or to continue ACEI/ARB. Changes in cardiac troponin T (TnT), soluble ST2 (sST2), C-reactive protein (CRP), and growth differentiation factor-15 (GDF-15) levels from baseline to eight weeks were compared between participants treated with Sac/Val and ACEI/ARB. We compared the proportional changes in the geometric mean N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels by individual biomarker strata. Additionally, these analyses were conducted within subgroups defined by baseline left ventricular ejection fraction (LVEF <40% and ≥40%).
Results
This study included a total of 375 patients (median age; 75 years, 120 women) with complete biomarker data. The median NT-proBNP level was 1800 pg/mL, median LVEF was 37.0%, and 206 patients (54.9%) had an LVEF <40% at baseline. The baseline characteristics were similar between the arms. Compared to ACEI/ARB, Sac/Val showed modest reductions in the biomarkers, but these differences were not statistically significant (Figure 1). Although cardio-inflammatory biomarkers, excluding CRP, in patients with LVEF <40% were generally lower than those with LVEF ≥40%, Sac/Val did not cause greater reductions in those levels than ACEI/ARB irrespective of LVEF status. In biomarker-stratified analyses, Sac/Val led to greater reductions in NT-proBNP than ACEI/ARB among patients with higher TnT, sST2, and CRP levels and those with lower GDF-15 levels (Figure 2). The effect of the Sac/Val on NT-proBNP was significantly modified by the baseline CRP level (p = 0.020), and this effect was more pronounced in patients with LVEF <40%.
Conclusions
Sac/Val did not reduce the cardio-inflammatory biomarkers more than ACEI/ARB over eight weeks in patients with AHF after haemodynamic stabilisation within the PREMIER study. However, Sac/Val was associated with a greater NT-proBNP reduction in patients with a higher inflammatory status and an LVEF <40%, suggesting a potential benefit in this subpopulation.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.