Physicians' Academy for Cardiovascular Education

New non-steroidal MRA safely reduced NT-proBNP in phase IIb study

Filippatos G et al., Eur Heart J 2016

A randomized controlled study of finerenone vs. eplerenone in patients with worsening chronic heart failure and diabetes mellitus and/or chronic kidney disease

Filippatos G, Anker SD, Böhm M, et al.
Eur Heart J 2016; published online ahead of print


Guidelines recommend the use of steroidalmineralocorticoid receptor antagonists (MRAs) spironolactone and eplerenone for symptomatic heart failure patients with reduced ejection fraction (HFrEF), which is based on data showing a reduction of mortality and morbidity in these patients [1-4]. However, prescription for patients with worsening HF is limited by the high risk of adverse events (AEs) caused by these agents, and by the particular risk of developing hyperkalaemia in patients with DM or chronic kidney disease (CKD) [5-7]. These patients need medical care that cannot be achieved with the currently available MRAs.
Finerenone, a novel non-steroidal MRA, may provide improved cardio-renal protection, particularly in high-risk patients with impaired kidney function, due to its higher potency and selectivity towards the mineralocorticoid receptor, as well as its balanced tissue distribution into heart and kidney, compared with spironolactone or eplerenone [8-10].
The phase IIa ARTS trial showed that in patients with HFrEF and mild CKD, finerenone had comparable efficacy with spironolactone, with lesser increases in serum potassium levels and smaller decreases in estimated glomerular filtration rate (eGFR), while the phase IIb ARTS-Diabetic Nephropathy study confirmed the safety of finerenone in patients with diabetic kidney disease [11,12].
In the randomised, double-blind ARTS-HF study, the 90 days efficacy and safety of five treatment regimens of finerenone (once-daily oral administration, dose uptitrated at day 30) compared with eplerenone was evaluated, in 1066 patients with worsening HFrEF and T2DM and/or CKD.

Main results


  • Decreases in plasma NT-proBNP of >30% from baseline towards day 90 (responder) were similar in the finerenone and eplerenone groups, and occurred in: 37.2% of patients in the eplerenone group, 30.9% in the 2.5→5 mg finerenone group, 32.5% in the 5→10 mg finerenone group, 37.3% in the 7.5→15 mg finerenone group, 38.8% in the 10→20 mg finerenone group and 34.2% in the 15→20 mg finerenone group (P = 0.42–0.88).  
  • Except for the 2.5→5 mg finerenone group, the composite clinical endpoint (death from any cause, cardiovascular hospitalization, or emergency presentation for worsening chronic HF until Day 90;) occurred numerically less frequently in finerenone-treated patients compared with eplerenone. This difference reached nominal statistical significance in the 10→20 mg group (HR: 0.56; 95% CI: 0.35-0.90; nominal P = 0.02).


Based on biomarker levels for organ injury, vital signs, laboratory parameters and incidence of AEs:
  • All doses of finerenone had a similar safety profile to that of eplerenone
  • AEs showed a balanced distribution among all treatment groups. A potassium level increase to ≥5.6 mmol/L at any time point occurred in 4.3% of patients. The mean eGFR was comparable to this of eplerenone and increased slightly in the two lowest finerenone groups but decreased in the other groups.


In a phase IIb study in patients with worsening HFrEF requiring hospitalisation and with concomitant DM and/or CKD, finerenone, a novel non-steroidal MRA, showed a comparable safety and efficacy profile to this of eplerenone.
Find this article online at Eur Heart J

Editorial comment [13]

Naegele et al encourage the translation of scientific data towards the clinic. ‘Without incorporating new science into medicine, we will be faced forever with old therapies for patients while new advances are left in the lab or worse on the shelf’. To this end, they mentioned the planned large confirmatory multicenter phase III trial of finerenone in HFrEF patients (FINESSE-HF; EUCTR2015-002168-17-SE), as the benefit of finerenone in relation to MRAs in heart failure treatment requires definitive outcome assessment. Furthermore, they highlighted the exclusion of severe CDK patients (eGFR <30 mL/min) in the ARTS-HF trial but also other studies. These patients are at an even higher risk for hyperkalaemia and AEs and this lack of information causes a gap in clinical information that is needed in the clinic. Also regarding the high activation of the renin-angiotensin-aldosterone system and the high mortality rate in these patients, there is a significant need for the validation of finerenone in these patients.


1. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999;341:709–717.
2. Zannad F, McMurray JJ, Krum H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 2011;364:11–21.
3. McMurray JJ, Adamopoulos S, Anker SD, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J 2012;33:1787–1847.
4. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2013;128:1810–1852.
5. Juurlink DN, Mamdani MM, Lee DS, et al. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med 2004;351:543–551.
6. Eschalier R, McMurray JJ, Swedberg K, et al. Safety and efficacy of eplerenone in patients at high risk for hyperkalemia and/or worsening renal function: analyses of the EMPHASIS-HF study subgroups (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure). J Am Coll Cardiol 2013;62:1585–1593.
7. Loutradis C, Tolika P, Skodra A, et al. Prevalence of hyperkalemia in diabetic and non-diabetic patients with chronic kidney disease: A Nested Case-Control Study. Am J Nephrol 2015;42:351–360.
8. Liu LC, Schutte E, Gansevoort RT, et al. Finerenone: third generation mineralocorticoid receptor antagonist for the treatment of heart failure and diabetic kidney disease. Expert Opin Investig Drugs 2015;24:1123–1135.
9. Bärfacker L, Kuhl A, Hillisch A, et al. Discovery of BAY 94-8862: a nonsteroidal antagonist of the mineralocorticoid receptor for the treatment of cardiorenal diseases. ChemMedChem 2012;7:1385–1403.
10. Kolkhof P, Delbeck M, Kretschmer A, et al. Finerenone, a novel selective nonsteroidal mineralocorticoid receptor antagonist protects from rat cardiorenal injury. J Cardiovasc Pharmacol 2014;64:69–78.
11. Pitt B, Kober L, Ponikowski P, et al. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial. Eur Heart J 2013;34:2453–2463.
12. Bakris GL, Agarwal R, Chan JC, et al. Mineralocorticoid Receptor Antagonist Tolerability Study-Diabetic Nephropathy (ARTS-DN) Study Group. Effect of finerenone in patients with diabetic nephropathy. JAMA 2015;314:884–894.
13. Naegele M, Hernandez AF, Ruschitzka F. Finerenone in heart failure: walking a fine line. Eur Heart J 2016; April 29, published online ahead of print