As blogged previously, finerenone is a nonsteroidal and highly selective mineralocorticoid receptor antagonist (MRA), meaning that it blocks the activation of the mineralocorticoid receptor. As part of its mechanism of action, finerenone has been shown to reduce chronic inflammation and fibrosis (scarring) in the kidney. It also has anti-inflammatory and anti-fibrotic effects in heart muscle and blood vessel (endothelial and vascular smooth muscle) cells.
Finerenone (trade name Kerendia) is now approved in Canada, for adults with type 2 diabetes (T2DM) and chronic kidney disease (CKD), to reduce the risk of:
- End-stage kidney disease and a sustained decrease in GFR (kidney function); and
- Cardiovascular death, non fatal myocardial infarction (heart attack) and hospitalization for heart failure.
The data for this approval comes from two large trials called FIDELIO and FIGARO. As blogged previously, the FIDELIO trial randomized 5,734 patients with chronic kidney disease and type 2 diabetes (on maximally tolerated dose of ACEi or ARB) to receive finerenone vs placebo. At baseline, the mean GFR was 44, and mean urine albumin was about 850 mg/g (about 96mg/mmol, or 1.4 g/day). The primary endpoint was a composite of time to kidney failure, ≥40% decrease in GFR, or renal death. After a median of 2.6 years, the primary endpoint was reduced by 18%. Said another way, treating 29 people for 3 years resulted in one less kidney event. The benefit was seen to emerge after about a year of treatment. The study also found (as a secondary CV composite endpoint) a 14% reduction in time to CV death, non fatal MI, non fatal stroke or hospitalization for heart failure. The number needed to treat to prevent one of these cardiovascular events was 42 after 3 years, and the benefit was seen as soon as a month after starting treatment.
In the FIGARO-DKD trial, the goal was to examine the effect of finerenone vs placebo on cardiovascular outcomes in people with type 2 diabetes (T2DM) and chronic kidney disease. The investigators randomized 7,437 patients with CKD and T2DM (on maximally tolerated dose of ACEi or ARB). The primary endpoint was a composite of CV death, non-fatal MI, non-fatal stroke, or hospitalization for heart failure. At baseline, the mean eGFR was 68, and importantly, 62% of patients had albuminuric CKD with preserved kidney function (GFR ≥60). They found that people in the finerenone group had a reduction in the primary endpoint of 13%, which was driven by a 29% reduction in hospitalization for heart failure. None of CV death, nonfatal MI, nor nonfatal stroke were significantly reduced. In this study, the main prespecified renal outcome was not reduced, possibly because this population had healthier kidneys than in the FIDELIO renal study.
In the pooled analysis of FIDELIO and FIGARO, called the FIDELITY analysis, there was a 14% reduction in the composite cardiovascular endpoint (non fatal heart attack, non fatal stroke, CV death, or hospitalization for heart failure), and a 23% reduction in the composite kidney outcome (kidney failure, ≥57% decrease in GFR, or renal death).
In terms of side effects, in the FIDELITY pooled analysis, potassium levels were slightly higher (0.21 mmol/L) with finerenone vs placebo. They found that 8.8% of patients had elevated potassium related to finerenone, vs 3.8% with placebo (baseline potassium had to be ≤4.8 mmol/L to qualify for these studies). In the FIDELIO renal study, where patients had sicker kidneys, potassium levels were slightly higher (0.23 mmol/L) with finerenone vs placebo, and the risk of elevated potassium requiring discontinuation of medication was higher than placebo (2.3% vs 0.9%). There was no increased risk of gynecomastia (male breast enlargement) with finerenone (which is a common side effect of spironolactone, an older steroidal MRA).
A common question on the minds of many doctors may be: Can you get the same benefits with the older steroidal MRAs, spironolactone and eplerenone? Data on hard renal outcomes are lacking for these medications, and both have a higher risk of high potassium, which can be a limiting factor for use of these medications in people with CKD, because CKD patients are more susceptible to high potassium. It is important to note that spironolactone and eplerenone are standard of care treatments in people with heart failure with reduced ejection fraction (HFrEF), and as such, these patients were excluded from the finerenone studies.
BOTTOM LINE: Finerenone is a new and important treatment that provides cardiorenal (heart and kidney) protection for people with type 2 diabetes and chronic kidney disease.
Disclaimer: I receive honoraria as a continuing medical education speaker and consultant from the makers of finerenone (Bayer).
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