In patients with moderate to severe chronic kidney disease (CKD) and treatment-resistant hypertension, finerenone is associated with less systolic blood pressure reduction, greater proteinuria reduction, and lower rates of hyperkalemia compared with spironolactone with or without a potassium binder.
The findings are from an indirect posthoc comparison of the placebo-controlled FIDELITY pooled analysis (FIDELIO-DKD and FIGARO-DKD trials) and the uncontrolled AMBER trial evaluating these respective mineralocorticoid receptor antagonists (MRA). Investigators identified a subset of patients with an estimated glomerular filtration rate (eGFR) of 25 to 45 mL/min/1.73 m2, near-normal serum potassium of 4.3 to 5.1 mmol/L, and mean automated office systolic blood pressure (SBP) of 135 to 160 mmHg despite use of 3 or more antihypertensive drugs, including a diuretic at baseline. After matching 624 patients from FIDELITY and 295 patients from AMBER, investigators evaluated the relative efficacy and safety of finerenone, a nonsteroidal MRA, and spironolactone, a steroidal MRA, at approximately 17 weeks and 12 weeks, respectively (the nearest timepoints with data).
Mean office systolic blood pressure declined 1.3 mm Hg in the placebo group, 7.1 mm Hg in the finerenone group, 10.8 mm Hg in the spironolactone group, and 11.7 mm Hg in the spironolactone plus patiromer potassium binder group at 3-4 months, Rajiv Agarwal, MD, of the Richard L. Roudebush VA Medical Center and Indiana University in Indianapolis, and colleagues reported in Clinical Kidney Journal. Although the absolute reduction in urinary albumin to creatinine ratio (UACR) was greater with finerenone, baseline UACR differed among groups, so more data are needed to clarify the relative effects of the drugs on this outcome, the investigators noted.
Rates of eGFR decline and hypotension appeared lower with finerenone than with spironolactone with or without patiromer.
Hyperkalemia (defined as serum potassium of 5.5 mmol/L or more) occurred in 3.3% of a placebo group, 11.6% of the finerenone group, 35.4% of the spironolactone plus patiromer group, and 64.2% of the spironolactone-only group. Treatment discontinuation due to hyperkalemia occurred in 0.3%, 7.0%, and 23% of the MRA groups, respectively. Treatment discontinuation for any reason was lowest with finerenone.
According to Dr Agarwal’s team, these study findings suggest that finerenone may be associated with a lower magnitude of systolic blood pressure reduction and a lower risk of hyperkalemia during the first 4 months of treatment than spironolactone, with or without a potassium-binding agent. The investigators noted that steroidal MRAs such as spironolactone are used infrequently in patients with CKD with or without heart failure, likely because of the increased hyperkalemia risk.
As the aims, dosing, and monitoring protocols of the finerenone and spironolactone studies differed markedly, results should be interpreted cautiously.
Disclosure: This research was supported by Bayer AG. Please see the original reference for a full list of disclosures.
Agarwal R, Pitt B, Palmer BF, et al. A comparative post hoc analysis of finerenone and spironolactone in resistant hypertension in moderate-to-advanced chronic kidney disease. Clin Kidney J February 2023; 16(2):293-302. doi:10.1093/ckj/sfac234