Finerenone May Lower Cardiovascular Risk in Diabetic Kidney Disease

Finerenone may reduce cardiovascular risk in a wide range of patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) in the United States who have an estimated glomerular filtration rate (eGFR; in mL/min/1.72m²) of 25 or higher and/or a urinary albuminuria to creatinine ratio (UACR) of 30 mg/g or greater, according to investigators.

Rajiv Agarwal, MD, MBBS, MS, of Indiana University School of Medicine in Indianapolis, Indiana, and colleagues pooled data from the FIDELIO-DKD and FIGARO-DKD trials of finerenone (the FIDELITY analysis). Finerenone is a nonsteroidal mineralocorticoid receptor antagonist (MRA). They combined these data with National Health and Nutrition Examination Survey (NHANES) data to project national estimates of finerenone eligibility and potential benefit.

In the FIDELITY analysis, which included data from 13,026 patients, cardiovascular events rates were generally higher among patients with lower eGFR and/or higher albuminuria. Placebo recipients with an eGFR of 90 or greater and UACR less than 300 mg/g or 300 mg/g or more had a cardiovascular events rate of 2.38 and 3.78 per 100 patient-years, respectively. Placebo recipients with an eGFR less than 30 had even higher incidence rates of 6.54 and 8.74 cardiovascular events per 100 patient-years at the respective UACR categories. In the trials, minority groups were underrepresented; patients self-identified as White (68.1%), Asian (22.2%), Hispanic (16.1%), Black (4.0%), and other/unspecified (5.7%).

In both continuous and categorical models, finerenone treatment was significantly associated with a 14% reduction in composite cardiovascular risk compared with placebo, regardless of eGFR and UACR categories, Dr Agarwal’s team reported in JAMA Cardiology.

In 6.4 million treatment-eligible individuals based on NHANES data, 1 year of finerenone treatment was simulated to prevent 38,359 cardiovascular events, including approximately 14,000 heart failure hospitalizations, the investigators reported. Among the components of the composite cardiovascular endpoints, reductions in heart failure hospitalizations were statistically significant, but not reductions in nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death.

The investigators pointed out that 66.1% of events would be prevented in patients with an eGFR of 60 or greater, that is diagnosed with CKD based on albuminuria alone. Despite guideline recommendations, routine albuminuria testing is uncommon in this type 2 diabetes population in real-world settings.

“Although the importance of albuminuria as a risk factor for cardiovascular events is well known, the findings presented here indicate the ability to modify this risk to reduce morbidity and mortality, highlighting the urgency to improve rates of albuminuria testing irrespective of a patient’s eGFR,” according to Dr Agarwal’s team.

Finerenone has been associated with excess hyperkalemia risk. Patients included in these analyses were required to have a maximum serum potassium of less than 5.1 mmoL/L. Patients in the finerenone trials but not necessarily NHANES had background use of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs).

The investigators wrote that “given that the cardiovascular benefits of finerenone occurred on top of optimized use of ACEis or ARBs when prior trials of dual renin-angiotensin blockade alone failed to reduce the number of cardiovascular events in patients with CKD and T2D, the results of this analysis support the notion that MRA activation may be in the causal pathway of cardiovascular disease—especially hospitalization for heart failure— in patients with CKD associated with T2D.”

In an accompanying editorial, Janani Rangaswami, MD, of George Washington University School of Medicine in Washington, DC, and Roy O. Mathew, MD, of the Veterans Administration Medical Center, Loma Linda University in Loma Linda, California, commented that these finerenone findings can be applied to real-world practice.

“Given the cardio-metabolic-kidney protective effects consistently seen with agents such as the sodium-glucose cotransporter-2 inhibitors and the glucagonlike receptor-1 agonists, a multipronged approach using potentially synergistic drug classes will evolve as standard of care in patients with T2D and CKD,” they wrote.

Disclosure: This research was supported by Bayer AG. Please see the original reference for a full list of disclosures.

References

Agarwal R, Pitt B, Rossing P, et al. Modifiability of composite cardiovascular risk associated with chronic kidney disease in type 2 diabetes with finerenone. JAMA Cardiol. Published online June 14, 2023. doi:10.1001/jamacardio.2023.1505

Rangaswami J, Mathew RO. Mitigating cardiovascular disease risk in patients with type 2 diabetes and chronic kidney disease-an unmet need with promising solutions. JAMA Cardiol. Published online June 14, 2023. doi:10.1001/jamacardio.2023.1512