Abstract
KEY POINTS: Whether the effect of finerenone on eGFR slope differs according to baseline urine albumin-to-creatinine ratio or eGFR is not clear. Finerenone caused a greater initial decline in eGFR (acute slope) than placebo across all categories of baseline urine albumin-to-creatinine ratio and eGFR. Although without clear heterogeneity (P interaction = 0.09), finerenone appeared to slow the chronic eGFR slope more than placebo in those with urine albumin-to-creatinine ratio ≥300 mg/g. BACKGROUND: Finerenone did not modify the risk of kidney outcomes or eGFR decline among patients with heart failure in the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure (FINEARTS-HF) trial, who were generally at low risk for kidney disease progression. However, whether the effect of finerenone on eGFR slope differs according to baseline urine albumin-to-creatinine ratio (UACR) or eGFR is not clear. METHODS: FINEARTS-HF was a global, randomized clinical trial of finerenone versus placebo among patients with heart failure with mildly reduced or preserved ejection fraction (N=6001). In this post hoc analysis, we used mixed models repeated measures approaches to explore treatment effects on changes in eGFR slope from baseline to month 3 (acute slope), month 3 to end of follow-up (chronic slope), and baseline to end of follow-up (total slope) according to categories of baseline UACR (<30, 30 to <300, and ≥300 mg/g) and eGFR (<45, 45 to <60, and ≥60 ml/min per 1.73 m(2)). RESULTS: Among 5797 participants with available data, the mean baseline eGFR was 62±20 ml/min per 1.73 m(2) and the median UACR was 18 (7–67) mg/g (UACR <30 mg/g: 61%; 30 to <300 mg/g: 30%; and ≥300 mg/g: 10%). Finerenone caused a greater initial decline in eGFR (acute slope) than placebo across all categories of baseline UACR and eGFR. Although there was no clear heterogeneity of treatment effects (P interaction = 0.09), finerenone appeared to slow the decline in chronic eGFR slope more than placebo among those with UACR ≥300 mg/g (difference, 1.2; 95% confidence interval, 0.1 to 2.2 ml/min per 1.73 m(2) per year). The association of finerenone versus placebo on chronic eGFR slope was consistent across baseline eGFR categories (P interaction = 0.48). CONCLUSIONS: Among patients with heart failure and macroalbuminuria (a subgroup of patients at higher risk of kidney disease progression), finerenone was associated with slower decline in chronic eGFR slope to a clinically relevant greater extent than placebo. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Funded by Bayer; FINEARTS-HF ClinicalTrials.gov number, NCT04435626.