Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, may improve CV risk among patients with type 2 diabetes and kidney disease and those with albuminuria, according to a FIDELITY substudy published in JAMA Cardiology.
Rajiv Agarwal, MD, MBBS, MS, professor of medicine at the Indiana University School of Medicine and physician scientist at the Richard L. Roudebush VA Medical Center, and colleagues posited that urine albumin-to-creatinine ratio screening could improve outcomes among finerenone-eligible patients.
“The modifiability of cardiovascular risk among patients with chronic kidney disease has been demonstrated with the use of simvastatin-ezetimibe in the Study of Heart and Renal Protection (SHARP) trial. However, the study considered kidney function (as assessed by estimated glomerular filtration rate) but not kidney damage (albuminuria) in the recruitment strategy. Thus, the modifiability of chronic kidney disease-associated cardiovascular risk in patients with type 2 diabetes in a broader population — even with estimated glomerular filtration rate of 60 or greater and defined by albuminuria — remains unknown,” the researchers wrote. “In patients with type 2 diabetes, we tested whether the cardiovascular disease risk associated with chronic kidney disease, as defined jointly by estimated glomerular filtration rate and albuminuria, was modifiable with finerenone treatment. We then estimated the population-wide benefit in the U.S. if all eligible patients were treated with finerenone.”
For the present study, Agarwal and colleagues used data from the FIDELITY pooled analysis of patients from the FIDELIO-DKD and FIGARO-DKD trials of finerenone (Kerendia, Bayer) on top of maximized renin-angiotensin system inhibition.
As Healio previously reported, results from the FIDELIO-DKD trial showed that finerenone delayed chronic kidney disease (CKD) progression among adult patients with type 2 diabetes compared with placebo, and results of the FIGARO-DKD trial showed that finerenone reduced CV event risk by 13%, a finding driven by significant reduction in HF hospitalization.
In this subanalysis of 13,026 participants (mean age, 65 years; 70% men), Agarwal and colleagues combined FIDELITY data with data from the National Health and Nutrition Examination Survey to simulate the population-level number of CV events prevented per year with finerenone among patients with type 2 diabetes and CKD.
The primary outcome was a composite of CV events including CV death, nonfatal stroke, nonfatal MI or HF hospitalization during a median of 3 years.
Among participants in the placebo group with an estimated glomerular filtration rate (eGFR) of 90 mL/min/1.73 m2 or more and urine albumin-to-creatinine ratio less than 300 mg/g, the CV event rate was 2.38 per 100 patient-years (95% CI, 1.03-4.29) and 3.78 CV events per 100 patient-years (95% CI, 2.91-4.75) among participants with a urine albumin-to-creatinine ratio of 300 mg/g or greater.
Among participants with an eGFR of less than 30 mL/min/1.73 m2 and urine albumin-to-creatinine ratio less than 300 mg/g, the CV event rate was 6.54 per 100 patient-years (95% CI, 4.19-9.4) compared with 8.74 CV events per 100 patient-years (95% CI, 6.78-10.93) among participants with a urine albumin-to-creatinine ratio of 300 mg/g or greater.
Moreover, finerenone was associated with a lower composite risk for CV events irrespective of eGFR and urine albumin-to-creatinine ratio (HR = 0.86; 95% CI, 0.78-0.95; P = .002; P for interaction = .66), according to the study.
Using nationally representative data from 6.4 million finerenone-eligible people, the researchers estimated that treatment for 1 year could prevent approximately 38,359 CV events (95% CI, 31,741-44,852), including 14,000 HF hospitalizations, of which approximately 66% could be prevented in patients with eGFR of 60 mL/min/1.73 m2 or more.
“The observation of an elevated, but modifiable, composite cardiovascular risk in patients with eGFR of 60 or greater but with moderately to severely increased albuminuria has significant implications for clinical practice,” the researchers wrote. “Despite recommendations in guidelines to screen both eGFR and albuminuria at least annually in patients with type 2 diabetes, real-world evidence indicates that levels of screening for albuminuria in patients with CKD or type 2 diabetes in clinical practice are very low. 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.
“Given that treatment with finerenone also reduces the risk of CKD progression, including end-stage kidney disease, in patients with CKD and type 2 diabetes, the health impact of screening for albuminuria in people with type 2 diabetes is substantial,” the researchers wrote.