Greater cardioprotective effects of nonsteroidal MRA in CKD and T2D patients with anemia

ESC Congress 2023 A post-hoc analysis of FIDELITY showed that baseline anemia status modifies the effect of finerenone on cardiovascular outcomes, but not renal outcomes, in patients with CKD and T2D.

Presented at the ESC Congress 2023 by: Ajay Singh, MD - Boston, MA, USA

Introduction and methods

The FIDELITY (FInerenone in chronic kiDney diseasE and type 2 diabetes: Combined FIDELIO-DKD and FIGARO-DKD Trial programme analYsis) prespecified pooled analysis previously showed that the selective, nonsteroidal MRA finerenone reduces the risk of CV outcomes and slows CKD progression compared with placebo in patients with CKD and T2D. Anemia is a common complication in patients with CKD and diabetes. Previous observational studies have associated anemia with increased risk of adverse CV and renal outcomes in patients with CKD. The aim of this post-hoc analysis of FIDELITY was to investigate the effect of finerenone on CV and renal outcomes in patients with anemia compared with patients without anemia.

A total of 13,026 patients with CKD and T2D were included in the FIDELITY dataset. Patients on a maximum tolerated dose of single RAASi and serum potassium level of ≤4.8 mmol/l were included. Patients with symptomatic HFrEF were excluded in this analysis. Anemia was defined as an Hb<12 g/dl in women and Hb <13 g/dl in men. Moderate to severe anemia was defined as an Hb ≤10 g/dl. In the FIDELITY dataset, 4293 patients had anemia, whereas 8714 patients had no anemia.

The primary outcomes were: (1) a CV composite consisting of time to CV death, non-fatal MI, non-fatal stroke or hospitalization for HF; (2) a kidney composite consisting of time to kidney failure, sustained ≥57% decrease in eGFR from baseline, or kidney death; (3) hospitalization for HF; and (4) all-cause mortality.

Main results

• Finerenone reduced the risk of the CV composite outcome in patients with anemia at baseline compared with placebo (HR: 0.76; 95%CI: 0.65-0.89). However, these effects of finerenone were not seen in patients without anemia at baseline (HR: 0.93; 95%CI: 0.82-1.04). The effect of finerenone on the CV composite outcome was modified by anemia status (P for interaction=0.04).
• Finerenone reduced the risk of the primary kidney composite outcome compared with placebo in patients with anemia (HR: 0.78; 95%CI: 0.65-0.95) and in patients without anemia (HR: 0.75; 95%CI: 0.61-0.92). The treatment effect of finerenone on the primary kidney composite outcome was not modified by anemia status (P for interaction=0.85).
• The effect of finerenone on the other key outcomes were not modified by baseline anemia status.
• When patients were stratified in groups based on severity of anemia (with anemia, with moderate-severe anemia, or without anemia), comparable trends were detected.
• The benefit of finerenone on the CV and renal composite outcomes was observed across a broad range of Hb levels.
• Treatment with finerenone vs. placebo led to a higher incidence of hyperkalemia in patients with anemia (24.6% vs. 9.8%, respectively) and in patients without anemia (12.9% vs. 6.2%, respectively). The incidence of other adverse events were mostly balanced between treatment arms, with generally a higher number of adverse events in patients with anemia.

Conclusion

This post-hoc analysis of FIDELITY showed that finerenone has beneficial effects on CV and renal outcomes compared with placebo in patients with anemia, CKD and T2D. The effect of finerenone on the primary CV composite outcome was significantly greater in patients with anemia vs. no anemia at baseline. Treatment with finerenone increased the number of hyperkalemia events in patients with and without anemia. “The take-home message is that the cardioprotective effect of finerenone observed in the FIDELTY dataset is likely to be preserved and more pronounced in patients with anemia versus those who do not have anemia.” , according to Ajay Singh.

- Our reporting is based on the information provided at the ESC Congress 2023 -