Blood urea nitrogen to creatinine ratio, clinical outcomes, and effect of finerenone in HFmrEF/HFpEF: findings in FINEARTS-HF
R Ono, K Docherty, A D Henderson, B L Claggett, A S Desai, C S P Lam, B Pitt, M Senni, S J Shah, A A Voors, F Zannad, M Vaduganathan, P S Jhund, S D Solomon, J J V McmurrayAbstract
Background
The blood urea nitrogen to creatinine ratio (BUN/Cr) is an established prognostic biomarker in chronic heart failure (HF) with reduced ejection fraction and is thought to reflect neurohumoral activity (especially arginine vasopressin) and renal haemodynamic changes beyond conventional measures of renal function such as estimated glomerular filtration rate (eGFR). However, its prognostic relevance in patients with HF and mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) is less certain, and its potential interaction with the effects of the nonsteroidal mineralocorticoid receptor antagonist (nsMRA) finerenone is unknown.
Purpose
To evaluate the association between BUN/Cr and clinical outcomes in patients with HFmrEF/HFpEF, and to assess the effects of finerenone according to BUN/Cr.
Methods
FINEARTS-HF investigated the efficacy and safety of finerenone compared with placebo in patients with HF and left ventricular ejection fraction (LVEF) ≥40%. The primary outcome was a composite of total (first and recurrent) HF events and cardiovascular (CV) death. We evaluated clinical outcomes and the effects of finerenone versus placebo according to quartiles of BUN/Cr ratio and by continuous BUN/Cr at baseline.
Results
Baseline BUN/Cr was available in 5,861 patients (98%) and was categorised by quartile: Q1 (≤15.97), Q2 (>15.97–≤19.52), Q3 (>19.52–≤23.75), and Q4 (>23.75) (Figure 1A). Patients with higher BUN/Cr were more frequently female and had worse HF symptoms. They also had higher NT-proBNP levels and slightly higher LVEF. Mean (±SD) eGFR (mL/min/1.73m2) did not differ across BUN/Cr quartiles: Q1 62.7±19.3, Q2 61.9±18.9, Q3 62.2±19.6, Q4 61.8±21.1; P=0.19. Patients with higher BUN/Cr had a higher incidence of the primary outcome (Figures 1B and 1C).Compared with placebo, finerenone reduced the primary outcome consistently across baseline BUN/Cr quartiles: rate ratios (95% CI) were 0.92 (0.68-1.24), 0.84 (0.64-1.08), 0.80 (0.61-1.04), and 0.84 (0.67-1.05) for Q1 to Q4, respectively (Pinteraction=0.91). When analysed as a continuous variable, finerenone consistently reduced total HF events and CV death, irrespective of baseline BUN/Cr (Pinteraction=0.26) (Figure 1D).
Conclusion
In a contemporary cohort of patients with HFmrEF/HFpEF, higher BUN/Cr was associated with worse clinical outcomes, while finerenone reduced events regardless of baseline BUN/Cr.For image description, please refer to the figure legend and surrounding text.