Novel mineralocorticoid receptor antagonist effective irrespective of HF history

A subgroup analysis of the FIDELIO-DKD trial revealed that the investigative mineralocorticoid receptor antagonist finerenone improved cardiovascular and kidney outcomes irrespective of a pre-existing heart failure status. In addition, finerenone had a reassuring safety profile.

Chronic kidney disease (CKD) and type 2 diabetes (T2D) are highly prevalent among patients with heart failure (HF), and patients suffering from all 3 conditions have an unfavourable prognosis [1–4]. In patients with HF with reduced ejection fraction (HFrEF), guidelines recommend therapy with a steroidal mineralocorticoid receptor antagonist (MRA). However, up to now, a treatment benefit has not been demonstrated in patients with HF and preserved ejection fraction (HFpEF).

Finerenone is a novel, selective, non-steroidal MRA that blocks overactivation of the mineralocorticoid receptor. The latter contributes to inflammation and fibrosis, which are both key drivers of CKD in T2D progression [5]. Finerenone has a balanced distribution between the heart and kidney compared with spironolactone, which is preferentially concentrated in the kidneys. In experimental models, the agent has shown potent anti-inflammatory and anti-fibrotic effects.

“In the FIDELIO-DKD trial (NCT02540993), finerenone demonstrated both kidney and cardiovascular (CV) benefits,” Prof. Gerasimos Filippatos (Attikon University Hospital, Greece) said [6,7]. CKD progression was lowered by 18%, CV morbidity and mortality by 14%. “Our subgroup analysis aimed to evaluate the effect of finerenone on kidney and CV outcomes in CKD and T2D patients with versus without a history of HF. Because we excluded patients with symptomatic HF, we expected patients to have only a mild reduction of ejection fraction or HFpEF,” Prof. Filippatos explained. Of the FIDELIO-DKD trial population, 436 patients (7.7%) had a history of HF at baseline. Compared with those without a history of HF (n=5,238), patients with a history of HF had a lower glomerular filtration rate, a higher BMI, and a larger waist circumference.

The subgroup analysis showed that finerenone reduced the risk of composite CV outcome (i.e. time to CV death, non-fatal myocardial infarction, non-fatal stroke, or hospitalisation for HF) irrespective of history of HF. In patients with a history of HF, the relative risk of the composite CV outcome was lowered by 27% (RR 0.73; 95% CI 0.50–1.06). In patients without a history of HF, it was reduced by 10% (RR 0.90; 95% CI 0.77–1.04). The effect of finerenone on the single components of the composite CV outcome was also consistent across the subgroups. Likewise, finerenone slowed CKD progression in patients with HF history (HR 0.79; 95% CI 0.52–1.20) as well as in patients without HF history (HR 0.83; 95% CI 0.73–0.94). A history of HF did not modify the effect of the novel MRA on all-cause, CV, and non-CV hospitalisation.

“One other very important aspect is safety,” Prof. Filippatos continued. The incidence of overall treatment-emergent side effects was similar between treatment arms, irrespective of HF history. In both subgroups, hyperkalaemia was more frequent in finerenone but did not lead to treatment discontinuation.

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   1. Anker SD, et al. Eur Heart J 2020;22:2383-92.
   2. Solomon SD, et al. Circ Heart Fail 2018:11:e004962.
   3. Seferovic PM, et al. Eur J Heart Fail 2018:20:853-72.
   4. Filippatos G, et al. Eur Heart J 2014;35:416-8.
   5. Agarwal R, et al. Eur Heart J 2021;42:152-61.
   6. Bakris GL, et al. New Engl J Med 2020;383:2219-9.
   7. Filippatos G, et al. Finerenone in patients with chronic kidney disease and type 2 diabetes, with and without a history of heart failure: a secondary analysis of the FIDELIO-DKD trial. LBT 1, Heart Failure and World Congress on Acute Heart Failure 2021, 29 June–1 July.

 

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Posted on 19 August 202117 May 2024