Finerenone reduces incident atrial fibrillation/flutter in patients with CKM syndrome

In a large FINE-HEART pooled analysis, finerenone lowered the risk of new-onset atrial fibrillation/flutter compared with placebo in HF patients and patients with CKD and T2D.

This summary is based on the publication of Pabon MA, Filippatos G, Claggett BL, et al. - Finerenone Reduces New-Onset Atrial Fibrillation Across the Spectrum of Cardio-Kidney-Metabolic Syndrome: The FINE-HEART Pooled Analysis. J Am Coll Cardiol. 2025 May 6;85(17):1649-1660. doi: 10.1016/j.jacc.2025.03.42.

Introduction and methods

Background

Cardiovascular-kidney-metabolic (CKM) syndrome is a progressive condition in which pathophysiological interactions between the CV system, kidney dysfunction, and metabolic risk factors, such as obesity and diabetes, can lead to multiorgan dysfunction, excess morbidity, and premature mortality [1]. Clinical CVD (including CHD, HF, and atrial fibrillation or flutter (AFF)) is apparent in the final stage (stage 4) [1]. It is important to identify therapies that are effective across all CKM stages and that prevent progression to late stages [1].

Recently, the nonsteroidal MRA finerenone reduced the risk of new-onset AFF in patients with CKD and T2D [2] and prevented or delayed adverse CV and kidney outcomes in patients with CKM syndrome [3] compared with placebo. However, it is unknown whether MRAs mitigate the risk of AFF in patients with this syndrome.

Aim of the study

The authors investigated the effect of finerenone on the occurrence of new-onset AFF in patients across the CKM spectrum.

Methods

This was a prespecified FINE-HEART analysis, a prospectively planned and registered participant-level pooled analysis of 3 phase 3 RCTs on the efficacy and safety of finerenone versus placebo: 2 trials in patients with CKD and T2D (FIDELIO-DKD (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease; n=5674) and FIGARO-DKD (Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease; n=7437)) and 1 trial in patients with HFmrEF or HFpEF (FINEARTS-HF (FINerenone trial to investigate Efficacy and sAfety superioR to placebo in paTientS with Heart Failure; n=6001)) [4-6].

In the current analysis, data of 14,581 participants with no history of AFF or presence of AFF on baseline ECG were pooled. Median follow-up duration was 2.9 years, during which 631 patients (4.3%) experienced new-onset AFF.

Outcomes

The primary endpoint was new-onset AFF as prospectively adjudicated by blinded clinical event committees in all 3 trials. Other key endpoints included CV death, HF hospitalization, MACE (a composite outcome of nonfatal MI, nonfatal stroke, HF hospitalization or CV death), a kidney composite endpoint (defined as sustained eGFR decline ≥50% from baseline, sustained eGFR decline to <15 mL/min/1.73 m², kidney failure, or death due to kidney failure), and all-cause mortality.

Main results

Effect of finerenone on new-onset atrial fibrillation/flutter

• The incidence rate of AFF was lower in patients treated with finerenone (n=7267) than those receiving placebo (n=7314) (1.4 vs. 1.6 per 100 patient-years; HR: 0.83; 95%CI: 0.71–0.97; P=0.019).
• Subgroup analysis showed generally consistent results across subgroups stratified by, among others, age, sex, number of CKM conditions (HF, CKD, T2D; P for interaction=0.87), or trial (P for interaction=0.57). The treatment effect of finerenone versus placebo did appear to be greater in Asian participants, whereas Black participants seemed to experience a higher AFF rate with finerenone compared with placebo (P for interaction for race=0.004), although the confidence intervals in the latter subgroup were wide.

Predictors of new-onset atrial fibrillation/flutter

• Independent predictors of new-onset AFF included older age, history of HF, higher BMI, geographical region, and higher urinary albumin-to-creatinine ratio.
• On the contrary, female sex and finerenone treatment were independently associated with lower rates of new-onset AFF.

Associations of new-onset atrial fibrillation/flutter with CV and kidney outcomes

• Patients who developed AFF during follow-up had a higher risk of HF hospitalization or CV death (adjusted HR (aHR): 3.7; 95%CI: 2.9–4.6; P<0.001), MACE (aHR: 2.8; 95%CI: 2.2–3.5; P<0.001), the kidney composite endpoint (aHR: 2.0; 95%CI: 1.4–2.7; P<0.001), and all-cause mortality (aHR: 4.3; 95%CI: 3.6–5.2; P<0.001) compared with patients with no AFF.

Conclusion

In this prespecified FINE-HEART pooled analysis, encompassing 3 RCTs and 14,581 participants, finerenone reduced the risk of incident AFF compared with placebo in patients across the CKM spectrum (HF, CKD, T2D). Patients who did experience new-onset AFF during follow-up were at increased risk of adverse CV and kidney outcomes compared with those who remained AFF free.

Find this article online at J Am Coll Cardiol.

References

1. Ndumele CE, Rangaswami J, Chow SL, et al. Cardiovascular-kidney-metabolic health: a presidential advisory from the American Heart Association. Circulation. 2023;148(20):1606–1635. https://doi.org/10.1161/CIR.0000000000001184
2. Wang N, Yu Y, Sun Y, et al. Acquired risk factors and incident atrial fibrillation according to age and genetic predisposition. Eur Heart J. 2023;44(47):4982–4993. https://doi.org/10.1093/eurheartj/ehad615
3. Vaduganathan M, Filippatos G, Claggett BL, et al. Finerenone in heart failure and chronic kidney disease with type 2 diabetes: FINE-HEART pooled analysis of cardiovascular, kidney and mortality outcomes. Nat Med. 2024;30(12):3758–3764. https://doi.org/10.1038/s41591-024-03264-4
4. Bakris GL, Agarwal R, Anker SD, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med. 2020;383(23):2219–2229. https://doi.org/10.1056/NEJMoa2025845
5. Pitt B, Filippatos G, Agarwal R, et al. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med. 2021;385(24):2252–2263. https://doi.org/10.1056/NEJMoa2110956
6. Solomon Scott D, McMurray John JV, Vaduganathan M, et al. Finerenone in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. 0(0). https://doi.org/10.1056/NEJMoa2407107