Consistent benefit with non-steroidal MRA in CKD and T2DM patients with and without HF
Finerenone in patients with CKD and T2D with and without heart failure: A prespecified subgroup analysis of the FIDELIO-DKD trial
Literature - Filippatos G, Pitt B, Agarwal R, et al., - Eur J Heart Fail 2022, doi: 10.1002/ejhf.2469.Introduction and methods
Background
In the FIDELIO-DKD trial, treatment with the non-steroidal MRA finerenone resulted in improvement of kidney function and reduction of CV morbidity and mortality in patients with CKD and T2DM without HFrEF [1,2]. Phase II studies with finerenone showed benefits in patients with HFrEF, with T2DM and/or CKD [3-5]. And mechanistic studies have suggested that MRAs may improve LV diastolic function, but clear benefit has not been shown in patients with HFmrEF or HFpEF in randomized trials [6-8].
In this prespecified analysis of the FIDELIO-DKD trial, the effects of finerenone on CV, kidney, and HF outcomes was examined in patients with and without a history of HF (HFpEF or HFmrEF) at baseline.
Methods
FIDELIO-DKD was a multicenter, phase III, randomized, double-blind, placebo-controlled trial. Patients with a clinical diagnosis of T2DM and CKD were included, and patients had to be treated ≥4 weeks with either ACEi or ARB for the screening visit. Patients with HFrEF were excluded.
For this prespecified subgroup analysis, patients with categorized by presence or absence of HF. Of 5674 patients, 436 (7.7%) had a history of HF at baseline.
Median follow-up was 2.6 years (IQR: 2.0-3.4 years).
Outcomes
The composite CV outcome was defined as time to first occurrence of CV death, non-fatal MI, non-fatal stroke or hospitalization for HF. The composite kidney outcome was time to first occurrence of kidney failure, a sustained decrease of ≥40% in eGFR from baseline to at least 4 weeks, or death from renal causes.
Main results
Effect of finerenone on CV outcomes
- The effect of finerenone compared with placebo on the composite CV outcomes was consistent across patients with (HR 0.73, 95%CI:0.50-1.06) or without (HR 0.90, 95%CI:0.77-1.04) history of HF (Pinteraction=0.33).
- There was no clear difference of the effect of finerenone vs. placebo on hospitalization for HF, all-cause CV or non-CV hospitalization in patients with or without a history of HF.
Effect of finerenone on kidney outcomes
- The effect of finerenone compared with placebo on the composite kidney outcome was consistent across patients with (HR 0.79, 95%CI:0.52-1.20) or without (HR 0.83, 95%CI: 0.73-0.94) history of HF (Pinteraction=0.83).
Effect of finerenone on HF outcomes
- The effect of finerenone compared with placebo on the composite of CV death or hospitalization for HF was consistent across patients with (HR 0.78, 95%CI:0.51-1.19) or without (HR 0.89, 95%CI:0.74-1.07) history of HF (Pinteraction=0.63).
Safety outcomes
- There were fewer serious adverse events in patients receiving finerenone compared with placebo, most notably in patients with a history of HF (31.8% vs. 40.2%).
- There was a higher incidence of hyperkalemia with finerenone than with placebo, which was consistent in patients with (19.5% vs. 7.9%) or without (18.2% vs. 9.1%) history of HF.
Conclusion
There was no difference in benefit with finerenone with regard to CV and kidney outcomes in patients with CKD and T2DM between those with and without a history of HF. Also, finerenone was well tolerated both in patients with and without a history of HF.
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