Nonsteroidal MRA reduces new-onset AF in DKD patients
Finerenone And New Onset Of Atrial Fibrillation Or Flutter In Patients With Chronic Kidney Disease And Type 2 Diabetes
Presented at ACC.21 by Gerasimos Filippatos (Athens, Greece)
Introduction and methods
Patients with CKD and T2DM have an increased risk of atrial fibrillation (AF). Subsequently, patients with AF are at increased risk of heart failure and stroke. Overactivation of the mineralocorticoid receptor (MR) may result in structural cardiac remodeling, shown in preclinical studies. Also, MR overactivation is a key driver of chronic kidney disease progression and a potential contributing factor of AF.
Finerenone is a novel, nonsteroidal, selective MR antagonist (MRA) with anti-inflammatory and anti-fibrotic properties in animal model studies. Recently, it was demonstrated that finerenone reduces risk of CVD and CKD progression in patient with CKD and T2D in the FIDELIO-DKD trial.
In the FIDELIO-DKD trial, 5734 patients were enrolled and during a run-in period of 4-16 weeks standard medication (including RAASi) was optimized and uptitrated to maximally tolerated dose.
The trial enrolled T2DM patients with eGFR ≥25 and ≤75 mL/min/1.73m2. Patients with HRrEF with NYHA Class II-IV and uncontrolled arterial hypertension were excluded.
In this study, the effect of finerenone compared to placebo on the prespecified outcome of new-onset AF was examined. In addition, kidney and CV composite outcomes were analyzed in patients with and without history of AF.
- Risk of new-onset AF was 29% lower in patients on finerenone compared to those on placebo (3.2% vs. 4.5%, HR 0.71, 95%CI: 0.53-0.94, P=0.0164. Separation of the curves started after 6 months, followed by a consistent divergence throughout the trial.
- Reduced risk of new-onset AF by finerenone was consistent across patient subgroups.
- The effect of finerenone on kidney and CV outcomes was consistent in patients with and without history of AF.
In a subanalysis of the FIDELIO-DKD trial, treatment with finerenone in optimally treated patients with T2DM and CKD resulted in a reduction of new-onset AF compared to placebo. Cardiorenal production by finerenone in patients with CKD and T2DM was independent of history of AF.
The discussant Anne Curtis, MD (Buffalo, NY, USA) said it is important to know whether there are benefits other than for the primary outcome because patients may benefit of these side effects. But because of the small benefit and these were initial results she wouldn’t treat patients with this drug to reduce AF risk per se. She concluded by saying that drugs for treatment of diabetes, heart failure, etc. may have pleotropic effects, such as benefits on AF. It is important to look for these effects and implement the therapies where it makes sense.
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