cardiovascular disease

Using Finarenone to Treat CKD and Its Impact on Cardiovascular Disease Risks

AUTHOR:
James Matera, DO
Practicing Nephrologist, Senior Vice President for Medical Affairs, and Chief Medical Officer CentraState Medical Center, Freehold, New Jersey

CITATION:
Matera J. Using finarenone to treat CKD and its impact on cardiovascular disease risks. Consultant360. Published online March 22, 2021.

 

Over expression of the mineralocorticoid receptor (MR) is associated with elevated cardiovascular disease (CVD) risk causing inflammatory issues, fibrosis, and end-organ damage in the kidney and heart, among others.1 The use of mineralocorticoid antagonists has gained a resurgence in the past few years. Spironolactone, the first in its class, has been used for decades. The original RALES study demonstrated the benefit of adding spironolactone to angiotensin-converting enzyme (ACE) inhibitors and loop diuretics in patients with severe heart failure, reducing mortality and morbidity.2

The next agent, eplerenone, is more selective for the MR than spironolactone, thus avoiding some of the major adverse effects seen with spironolactone. The clinical benefits of eplerenone on mortality and morbidity have been demonstrated in several clinical studies as well.3 Both of these agents have become increasingly utilized in the CVD arsenal.

A newer agent, finarenone, has entered into the equation recently. Finerenone is a nonsteroidal, selective MR antagonist (MRA). In patients with decompensating chronic heart failure with low ejection fraction and type 2 diabetes and/or chronic kidney disease (CKD), finarenone reduced the incidence of all-cause mortality and heart failure when compared with eplerenone.4 Patients with CKD and type 2 diabetes are known to be at high risk for cardiovascular morbidity and mortality. The FIDELIO-DKD trial was designed to evaluate cardiac and renal outcomes in this patient population.5

In study participants, finerenone had lowered the risk of cardiovascular events in patients with CKD and type 2 diabetes, whether or not overt CVD was present. Adverse events were similar in the finerenone and placebo groups. The use of finarenone showed benefits in cardiovascular outcomes in patients in diabetic patients and well ad chronic kidney disease patients. Finerenone was used in conjunction with standard care of renin–angiotensin–aldosterone system inhibitors, glycemic control, and targeted blood pressure readings showing control. One important adverse effect often seen with mineralocorticoid antagonists (MCAs) is hyperkalemia, and finarenone was superior to standard treatment, with less hyperkalemia than other MCAs.5 

References

  1.  Aroor AR, Habibi J, Nistala R, et al. Diet-induced obesity promotes kidney endothelial stiffening and fibrosis dependent on the endothelial mineralocorticoid receptor. Hypertension. 2019;73(4):849-858. https://doi.org/10.1161/hypertensionaha.118.12198 
  2. 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(10):709-717. https://doi.org/10.1056/nejm199909023411001  
  3. Zannad F, McMurray JJV, Krum H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364(1):11-21. https://doi.org/10.1056/nejmoa1009492  
  4. Filippatos G, Anker SD, Böhm M, et al. A randomized controlled study of finerenone vs. eplerenone in patients with worsening chronic heart failure and diabetes mellitus and/or chronic kidney disease. Eur Heart J. 2016;37(27):2105-2114. https://doi.org/10.1093/eurheartj/ehw132 
  5. Filippatos G, Anker SD, Agarwal R, et al. Finerenone and cardiovascular outcomes in patients with chronic kidney disease and type 2 diabetes. Circulation. 2021;143(6):540-555. https://doi.org/10.1161/circulationaha.120.051898