Finerenone reduces kidney and heart risk with CKD and T2D

Anti-mineralocorticoids in clinical trials slowed the progression of chronic kidney disease (CKD) in patients with type 2 diabetes. Phase III FIDELIO-DKD Trial Indicated.

In the trial, 17.8% of 2,833 patients with finelenone experienced major outcome events (renal failure, a persistent reduction of at least 40% of eGFR from baseline, and death from renal causes), but of placebo. 21.1% of 2,841 people (hazard ratio 0.82, 95% CI 0.73-0.93, P= 0.001), reported by George Bakris, MD, and colleagues at the University of Chicago.

People taking Finerenone have significant secondary cardiovascular outcomes (death due to cardiovascular system, non-fatal myocardial infarction, non-fatal stroke, compared to those taking placebo, Or the risk of experiencing hospitalization for heart failure) was also reduced (13% vs. 14.8%, respectively; HR 0.86, 95% CI 0.75-0.99, P= 0.03).

With the exception of non-fatal stroke, which was similar between the two groups, the incidence of all individual cardiovascular outcomes was lower than that of finelenone.

The results of these findings were presented virtually in the American Society of Nephrology. Kidney week Published at the same time New England Journal of Medicine..

“It’s exciting because there were many other unsuccessful discoveries in this high-risk population of diabetes and chronic kidney disease,” said Dr. Rajiv Agarwal, MD, co-author of Indiana University in Indiana Police. It’s a discovery. “

Researchers acting as non-steroidal selective mineralocorticoid receptor antagonists have shown that finelenone has the ability to reduce the urinary albumin to creatinine ratio in CKD patients previously treated with RAS blockers, although Agarwal’s Serum potassium levels higher than spironolactone (Aldactone), a steroidal non-selective inhibitor of the mineralocorticoid receptor, as seen in 2019 Amber trial..

Nonetheless, 2.3% of patients taking finelenone discontinued treatment during the current trial due to hyperkalemia, but 0.9% of patients taking placebo did. .. More than 18% of people taking finelenone experienced adverse events related to hyperkalemia in 9% of people taking placebo, but of fatal hyperkalemia No event has been reported.

However, looking at this, Agarwal found that this 2.3% discontinuation rate (median follow-up of 2.6 years or longer) was 23% due to the hyperkalemia (12 weeks or longer) seen in the patient’s AMBER trial. He emphasized that the discontinuation rate was much lower than that of spironolactone alone, which does not contain ancillary patyromer (Veltassa).

“Ideal drugs will not cause hyperkalemia,” Agarwal said. “But the absolute risks are just a few of what we saw when using spironolactone in this vulnerable population.”

The double-blind study included adults with a confirmed CKD ratio of urinary albumin to creatinine of 30- <300 and eGFR of 25- <60 mL / min / 1.73 m.², And a history of diabetic retinopathy. Patients with an eGFR of 25- <75 mL / min / 1.73 m were also included if albuminuria was severely elevated (urinary albumin to creatinine ratio 300-5,000).²..

In addition, all participants had serum potassium levels below 4.8 mmol / L prior to the start of the study and were treated with the highest doses of ACE inhibitors or angiotensin receptor blockers.

Half of the half allocated to finelenone with eGFR of 25 to <60 mL / min / 1.73 m² At the time of the screening visit, an initial dose of 10 mg was given once daily, but if the eGFR was 60 mL / min / 1.73 m² The above received an initial dose of 20 mg once daily. If serum potassium levels and eGFR were stable after 1 month of treatment, it was recommended to increase the daily dose from 10 mg to 20 mg.

For other secondary outcomes, cause-related death and cause-related hospitalization were not significantly different between the two groups.

so Ancillary editorial, NEJM Deputy Editor-in-Chief Dr. Clifford Rosen and Deputy Editor-in-Chief Julie Ingelfinger said that this benefit to the progression of CKD is completely different from the 2019 SGLT-2 inhibitor canagliflozin (Invocana). I pointed out that I did not CREDENCE trial..

“As Bakris et al. Pointed out, one explanation for the different findings in the two trials is that SGLT2 inhibitors were approved in the current trial, whereas patients treated with mineralocorticoid receptor antagonists were CREDENCE. The fact is that they were excluded from the study, “Rosen and Ingelfinger said, with less than 5% of the total cohort of this study using SGLT-2 inhibitors at baseline.