The following are key points to remember from this state-of-the-art review on nonsteroidal mineralocorticoid receptor antagonists (MRAs) in cardiorenal disease:

1. Patients with heart failure and chronic kidney disease (CKD) remain at high risk for adverse outcomes and progression to end-stage disease despite contemporary therapies.
2. Steroidal MRAs such as spironolactone and eplerenone reduce mortality but remain underprescribed due to the perceived risk of hyperkalemia and hormonal side effects.
3. The discovery of nonsteroidal MRAs represents a major new dimension in cardiorenal disease therapy. Nonsteroidal MRAs have high affinity and specificity for the mineralocorticoid receptor (MR) and differ from both steroidal agents and each other with respect to important physiochemical, pharmacodynamic, and pharmacokinetic parameters.
4. Similar to their steroidal counterparts, they have beneficial anti-inflammatory, anti-remodeling, and anti-fibrotic properties in the kidneys, heart, and vasculature. There are several nonsteroidal MRAs under development and clinical assessment; of these, only esaxerenone and finerenone are approved for treatment globally.
5. Compared with steroidal MRAs, finerenone more potently inhibits MR co-regulator recruitment and fibrosis and distributes more evenly between the heart and kidneys.
6. The landmark Phase III trials FIGARO-DKD and FIDELIO-DKD demonstrated that finerenone reduced major kidney and cardiovascular events on top of maximally tolerated renin–angiotensin–aldosterone system inhibition in patients with CKD associated with type 2 diabetes.
7. Nonsteroidal MRAs are currently under evaluation in heart failure and for synergistic treatment with sodium–glucose cotransporter 2 inhibitors. These innovative agents could become an important therapy across the spectrum of cardiorenal disease in the future.
8. The recently announced CONFIDENCE trial will investigate finerenone in combination with empagliflozin compared with each medication individually in the setting of diabetes and CKD.
9. For now, steroidal MRAs, which are generic and significantly less expensive, should remain an important role in the treatment of cardiorenal disease. Spironolactone and eplerenone remain the only two MRAs proven to reduce mortality in heart failure with reduced ejection fraction (HFrEF).
10. Additional head-to-head evaluation is also needed to establish whether nonsteroidal MRAs are superior to generic steroidal agents in settings such as HFrEF, as well as whether they are associated with reduced rates of hyperkalemia.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure

Keywords: Anti-Inflammatory Agents, Non-Steroidal, Anti-Inflammatory Agents, Diabetes Mellitus, Type 2, Eplerenone, Fibrosis, Heart Failure, Hyperkalemia, Kidney Diseases, Mineralocorticoid Receptor Antagonists, Receptors, Mineralocorticoid, Renal Insufficiency, Chronic, Renin-Angiotensin System, Secondary Prevention, Sodium-Glucose Transporter 2 Inhibitors, Spironolactone, Stroke Volume

< Back to Listings