Finerenone Reduces Onset of Atrial Fibrillation in Patients With Chronic Kidney Disease and Type 2 Diabetes
abstract
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Access this abstract now Full Text Available for ClinicalKey SubscribersBACKGROUND
Patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) are at risk of atrial fibrillation or flutter (AFF) due to cardiac remodeling and kidney complications. Finerenone, a novel, selective, nonsteroidal mineralocorticoid receptor antagonist, inhibited cardiac remodeling in preclinical models.
OBJECTIVES
To examine the effect of finerenone on new-onset AFF and cardiorenal effects by history of AFF in FIDELIO-DKD.
METHODS
Patients with CKD and T2D were randomized (1:1) to finerenone or placebo. Eligible patients had a urine albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g, an estimated glomerular filtration rate (eGFR) ≥25 to <75 ml/min/1.73 m2 and received optimized doses of renin-angiotensin system blockade. Effect on new-onset AFF was evaluated as a prespecified outcome adjudicated by an independent cardiologist committee. The primary composite outcome (kidney failure, sustained ≥40% decrease in eGFR from baseline, or renal death) and key secondary outcome (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) were analyzed by history of AFF.
RESULTS
Of 5,674 patients, 461 (8.1%) had a history of AFF. New-onset AFF occurred in 82 (3.2%) patients on finerenone and 117 (4.5%) on placebo (hazard ratio: 0.71; 95% confidence interval: 0.53 to 0.94; p = 0.016). The effect of finerenone on primary and key secondary kidney and cardiovascular outcomes was not significantly impacted by baseline AFF (interaction p value: 0.16 and 0.85, respectively).
CONCLUSIONS
In patients with CKD and T2D, finerenone reduced the risk of new-onset AFF. The risk of kidney or cardiovascular events was reduced irrespective of history of AFF at baseline.
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Additional Info
Finerenone Reduces Onset of Atrial Fibrillation in Patients With Chronic Kidney Disease and Type 2 Diabetes
J Am Coll Cardiol 2021 May 04;[EPub Ahead of Print], G Filippatos, GL Bakris, B Pitt, R Agarwal, P Rossing, LM Ruilope, J Butler, CSP Lam, P Kolkhof, L Roberts, C Tasto, A Joseph, SD AnkerFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Chronic kidney disease (CKD) and type 2 diabetes (T2D) are capable of inducing atrial structural or electrical remodeling that may be responsible for the increased risk of atrial fibrillation (AF) found in both diseases. Upregulation of aldosterone and mineralocorticoid receptor overactivation may contribute to structural atrial remodeling predisposing to AF. Therefore, it was reasonable to test whether mineralocorticoid receptor antagonists (MRAs) might reduce the risk of AF in patients with CKD and T2D.
Finerenone, a selective, nonsteroidal MRA, was found to reduce mineralocorticoid receptor-mediated myocardial remodeling and prevent left atrial dilatation and left atrial fibrosis in rats. Clinically, in a randomized, double-blind, placebo-controlled study, finerenone reduced the risk of cardiovascular events in patients with CKD and T2D in the FIDELIO-DKD (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease) phase III trial. The present report, a secondary analysis of the FIDELIO-DKD trial, found that finerenone also reduced the risk of new-onset AF or flutter vs placebo (HR = 0.71, 95% CI: 0.53–0.94; P = .016) at 6 months and for the length of the study and improved cardiovascular and kidney outcomes.
Eplerenone, a steroidal MRA, exerted a similar effect in patients with symptomatic heart failure with reduced ejection fraction in the EMPHASIS-HF trial. Interestingly, in the TOPCAT trial, spironolactone did not reduce the risk of either new-onset atrial fibrillation or atrial fibrillation recurrence in patients with symptomatic heart failure with preserved ejection fraction, perhaps due to the different patient population. Finerenone is now being tested in this population in the FINEARTS trial.
The take-home message for clinicians is that patients with AF have increased atrial mineralocorticoid receptor expression compared with those with normal sinus rhythm and MRAs may be useful in this broader group to prevent atrial remodeling and reduce the risk of AF.