Factors associated with NT-proBNP reduction in acute heart failure: a secondary analysis of the PREMIER trial
Y Nabeshima, A Tanaka, T Imai, Y Matsue, K Kida, K NodeAbstract
Background/Introduction
N-terminal pro-B-type natriuretic peptide (NT-proBNP) reduction is a key surrogate for heart failure (HF) outcomes. The PREMIER trial showed that in-hospital sacubitril/valsartan (Sac/Val) initiation yielded a greater 8-week NT-proBNP reduction than angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (ACEi/ARB) in Japanese patients with acute heart failure (AHF). However, clinical characteristics associated a clinically meaningful NT-proBNP reduction remain undefined. Notably, atrial fibrillation (AF) can elevate the natriuretic peptide levels via atrial structural remodelling, complicating the interpretation of NT-proBNP changes.
Purpose
To identify independent predictors of ≥ 50% NT-proBNP reduction by Week 8 in patients with AHFand to further explore if they differed by baseline AF status (non-AF vs AF).
Methods
This post-hoc analysis of the multicentre, randomised PREMIER trial included 376 (Sac/Val n=183, ACEi/ARB n=193) patients haemodynamically stabilised after an AHF event. Independent predictors of achieving the reduction in NT-proBNP were identified using multivariable logistic regression in the AF-stratified cohorts. Interaction tests within the AF cohort tested treatment effect modification by baseline characteristics.
Results
Overall, 39.7% of patients achieved a ≥ 50% NT-proBNP reduction by Week 8. Its independent predictors included Sac/Val use (adjusted odds ratio [aOR] 2.21, 95% confidence interval [CI] 1.32 to 3.67), younger age (aOR 1.98 per 10-year decrease, 95% CI 1.29 to 3.04), de novo HF (aOR 2.40, 95% CI 1.41 to 4.10), higher baseline NT-proBNP (aOR 3.06 per 2-fold increase), and higher systolic blood pressure (aOR 1.44 per 10 mm Hg increase, 95% CI 1.03 to 2.02) (Figure 1). Stratified by AF status (non-AF n=214, AF n=162), 43.4% of non-AF and 34.6 % of AF cohorts achieved the reduction in NT-proBNP. In the non-AF cohort, Sac/Val use remained an independent predictor of response (aOR 3.12, 95% CI 1.57 to 6.21). Conversely, in the AF cohort, Sac/Val use was not a significant predictor (aOR 1.33, 95% CI 0.53 to 3.33). Instead, higher baseline NT-proBNP (aOR 4.07, 95% CI 2.09 to 7.93) and lower left ventricular ejection fraction (LVEF) (aOR 3.38 per 10% decrease, 95% CI 1.23 to 9.29) were significant predictors (Figures 1 and 2). Interaction analysis in the AF cohort showed that HF chronicity modified treatment effect (P=0.026): Sac/Val tended to favour NT-proBNP change (−25% [95% CI −43 to 10%]) in patients with de novo HF, but not in those with a history of HF (+36% [95% CI −3 to 91%]).
Conclusions
Predictors of NT-proBNP response in stabilised patients after an AHF event differed by AF status. In non-AF, Sac/Val was the primary driver of NT-proBNP reduction, whereas in AF, NT-proBNP response depended on some background HF status. Our findings highlight a need for a patient-centric therapeutic approach for this population.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.