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Finerenone Reduces New-Onset Atrial Fibrillation Across the Spectrum of Cardio-Kidney-Metabolic Syndrome: The
Maria A Pabon1, Gerasimos Filippatos2, Brian L Claggett1
1Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Background:
Mineralocorticoid receptor antagonists (MRA) modulate cardiac and systemic pathways such as fibrosis and inflammation, which may contribute to the onset of atrial fibrillation (AF) or atrial flutter (AFL).
Objectives:
In this participant-level pooled analysis of 3 large clinical trials, the authors evaluated the effect of the nonsteroidal MRA finerenone on incident AF/AFL across the cardio-kidney-metabolic (CKM) spectrum.
Methods:
In this prespecified analysis, we pooled participants from 2 trials of chronic kidney disease and type 2 diabetes (FIDELIO-DKD and FIGARO-DKD) and a trial of heart failure (HF) with mildly reduced or preserved ejection fraction (FINEARTS-HF). Patients were randomized 1:1 to finerenone or placebo. New-onset AF/AFL was prospectively adjudicated in all trials by blinded clinical event committees. The risk of new-onset AF/AFL was evaluated using Cox regression models stratified by region and trial.
Results:
Among 14,581 patients who were free of AF/AFL at trial enrollment, 631 (4.3%) experienced new-onset AF/AFL during follow-up. Predictors of new-onset AF/AFL included older age, history of HF, higher body mass index, geographic region, and higher levels of urine albumin-to-creatinine ratio. During 2.9 years of median follow-up, new-onset AF/AFL occurred in 286 (3.9%) participants receiving finerenone and 345 (4.7%) assigned to placebo (HR: 0.83; 95% CI: 0.71-0.97; P = 0.019). Risk reductions were consistent irrespective of number of CKM conditions (Pinteraction = 0.87) and by trial (Pinteraction = 0.57). Participants with new-onset AF/AFL were at significantly higher subsequent risk of cardiovascular death, HF hospitalization, and adverse kidney outcomes.
Conclusions:
The nonsteroidal MRA finerenone reduced the risk of new-onset AF/AFL across the CKM spectrum.
Insights
Finerenone, a nonsteroidal mineralocorticoid receptor antagonist (MRA), significantly reduced the risk of new-onset atrial fibrillation (AF) or atrial flutter (AFL) in patients across the cardio-kidney-metabolic spectrum. This finding highlights finerenone
Area of Science:
- Cardiology
- Nephrology
- Endocrinology
Background:
- Mineralocorticoid receptor antagonists (MRAs) influence cardiac and systemic pathways implicated in atrial fibrillation (AF) and atrial flutter (AFL), including fibrosis and inflammation.
- Understanding the impact of MRAs on AF/AFL incidence is crucial for managing patients with cardio-kidney-metabolic (CKM) conditions.
Purpose of the Study:
- To evaluate the efficacy of the nonsteroidal MRA finerenone in preventing new-onset AF/AFL.
- To assess finerenone's effect on incident AF/AFL across the diverse cardio-kidney-metabolic (CKM) spectrum using a pooled analysis of clinical trials.
Main Methods:
- A participant-level pooled analysis of 14,581 patients from FIDELIO-DKD, FIGARO-DKD, and FINEARTS-HF trials.
- Patients were randomized to receive either finerenone or placebo.
- New-onset AF/AFL was prospectively adjudicated, and risk was analyzed using Cox regression models.
Main Results:
- A total of 631 (4.3%) patients developed new-onset AF/AFL during a median follow-up of 2.9 years.
- Finerenone use was associated with a reduced risk of new-onset AF/AFL compared to placebo (HR: 0.83; 95% CI: 0.71-0.97; P=0.019).
- The risk reduction was consistent across different numbers of CKM conditions and within individual trials.
Conclusions:
- The nonsteroidal MRA finerenone demonstrated a significant reduction in the risk of new-onset atrial fibrillation/atrial flutter.
- This benefit was observed across the spectrum of cardio-kidney-metabolic conditions, suggesting a broad therapeutic role for finerenone.
- New-onset AF/AFL independently predicted increased subsequent risk of cardiovascular death, heart failure hospitalization, and adverse kidney outcomes.
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