A 66-year-old man presents to your general cardiology clinic for routine follow-up. His medical history includes type 2 diabetes mellitus (T2DM) since the age of 45 with mild retinopathy, hypertension, chronic kidney disease (CKD) stage 3, hyperlipidemia, and obstructive sleep apnea. His medications are metformin 1000 mg twice daily, dapagliflozin 10 mg daily, lisinopril 40 mg daily, aspirin 81 mg daily, and atorvastatin 40 mg daily. His most recent laboratory results from his primary care physician visit the previous week follow:
He has an extensive family history of atrial fibrillation (AF), with both his parents and his older sister requiring multiple electrical cardioversions and catheter ablations. Today he has no complaints and denies any palpitations. The electrocardiograms performed at previous visits all showed normal sinus rhythm. The most recent transthoracic echocardiogram 6 months ago showed a left ventricular ejection fraction of 60% and no valvular abnormalities. He inquires if there are ways to decrease his risk of developing AF in the future.
Which one of the following medications has been shown to reduce the risk of new-onset AF in patients like this one?
Show Answer
The correct answer is: B. Finerenone
Finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, has been shown in a recent pre-specified analysis of a randomized controlled trial to reduce the risk of new-onset AF and flutter in patients with CKD and T2DM.1 Previous heart failure trials studying steroidal mineralocorticoid receptor antagonists such as eplerenone and spironolactone have shown variable effects. EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) observed a decrease in the incidence of new-onset AF in patients with heart failure with reduced ejection fraction, whereas the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial did not show this trend in patients with heart failure with preserved ejection fraction.2,3
The FIDELIO-DKD (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease) trial included adult patients with T2DM and CKD (estimated glomerular filtration rate 25-60 mL/min/1.73m2, moderately elevated albuminuria 30-300 mg/g, and diabetic retinopathy or severe albuminuria 300-5000 mg/g) on maximally tolerated renin angiotensin blockers and serum potassium <4.8 mmol/L and excluded patients with heart failure with reduced ejection fraction, uncontrolled hypertension, and diabetes (hemoglobin A1C >12%). A total of 5,734 patients was randomized in a 1:1 fashion to finerenone and placebo. In the pre-specified analysis of new-onset AF or atrial flutter over 2.6 years, finerenone was 3.2%, and placebo was 4.5% (hazard ratio 0.71; 95% confidence interval, 0.53-0.94; p = 0.016). The proposed mechanism of finerenone involves the attenuation of aldosterone receptor-mediated adverse atrial remodeling associated with T2DM and CKD. This patient has normal cardiac function, long-standing T2DM and CKD, with moderate albuminuria and retinopathy and has tolerated the maximum dose of lisinopril with normal serum potassium levels. His significant family history of AF and personal history of obstructive sleep apnea puts him at risk for new-onset AF. Based on the results of the FIDELIO-DKD trial, he may benefit from finerenone to reduce his risk of new-onset AF in the future.
References
Filippatos G, Bakris GL, Pitt B, et al. Finerenone Reduces New-Onset Atrial Fibrillation in Patients With Chronic Kidney Disease and Type 2 Diabetes. J Am Coll Cardiol 2021;78:142-52.
Swedberg K, Zannad F, McMurray JJV, et al. Eplerenone and atrial fibrillation in mild systolic heart failure: results from the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure) study. J Am Coll Cardiol 2012;59:1598-603.
Neefs J, van den Berg NWE, Krul SPJ, Boekholdt SM, de Groot JR. Effect of Spironolactone on Atrial Fibrillation in Patients with Heart Failure with Preserved Ejection Fraction: Post-Hoc Analysis of the Randomized, Placebo-Controlled TOPCAT Trial. Am J Cardiovasc Drugs 2020;20:73-80.
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