medwireNews: Finerenone modifies the risk for chronic kidney disease (CKD)-associated cardiovascular (CV) events in patients with type 2 diabetes and moderate-to-severe albuminuria, FIDELITY study findings indicate.
The data have “significant implications for clinical practice” because the benefit was apparent even in patients with albuminuria and an estimated normal glomerular filtration rate (eGFR) of 60 mL/min per 1.73m2, write Rajiv Agarwal (Indiana University School of Medicine, Indianapolis, USA) and colleagues in JAMA Cardiology.
Janani Rangaswami (George Washington University School of Medicine, Washington DC, USA) and Roy Mathew (Loma Linda University, California, USA) note in an accompanying commentary that CKD often goes undiagnosed in these patients and they would therefore “miss out on the opportunity for [CV disease] risk attenuation without the quantification of albuminuria.”
Indeed, real-world screening rates for albuminuria in patients with CKD or type 2 diabetes are low even though guidelines recommended that it be done at least annually, explain Agarwal and co-authors. They write: “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.”
The FIDELITY cohort includes patients from two trials – FIDELIO-DKD and FIGARO-DKD – investigating cardiovascular protection with the mineralocorticoid receptor antagonist finerenone versus placebo.
The current, preplanned analysis included 13,026 participants (mean age, 65 years, 70% men) with type 2 diabetes and CKD, defined jointly by eGFR and albuminuria.
During a median 3 years of follow-up, the researchers observed that the incidence of CV events (CV death, nonfatal stroke, nonfatal myocardial infarction, or hospitalization for heart failure) was highest among patients in the lowest category for eGFR and the highest category of albuminuria but this risk was reduced with finerenone versus placebo.
For example, in the placebo group, participants with an eGFR below 30 mL/min per 1.73m2 who had a urine albumin to creatinine ratio (UACR) less than 300 mg/g had a CV event rate of 6.54 per 100 person–years versus 8.74 per 100 person–years in those with a UACR of 300 mg/g or higher.
The corresponding rates among patients given finerenone were 5.85 and 6.89 per 100 person–years.
In those with an eGFR of 90 mL/min per 1.73m2 or greater who received placebo, CV event rates were 2.38 per 100 person–years in the group with a UACR below 300 mg/g and 3.78 per 100 person–years in the participants with a UACR of 300 mg/g or more. With finerenone, the rates in these subgroups were 1.94 and 2.56 per 100 person–years, respectively.
The researchers calculated that, overall, finerenone was associated with a significant 14% reduction in composite CV risk irrespective of eGFR and UACR.
Analysis of US National Health and Nutrition Examination Survey data for 2015–2018 identified approximately 6.4 million individuals with type 2 diabetes and albuminuric CKD who would be eligible for finerenone (approximately 2.6% of the US population). Of these, 75% had CKD with preserved eGFR (ie, >60 mL/min per 1.73m2) and 12.8% had a UACR of 300 mg/g or greater.
Among this group of treatment-eligible individuals, Agarwal and team estimated that finerenone would prevent 38,359 CV events, including approximately 14,000 hospitalizations for heart failure, and that66% of prevented CV events would occur in patients with an eGFR of 60 mL/min per 1.73m2 or greater.
The investigators highlight that “the opportunity to modify the cardiovascular risk is lost” without routine screening of UACR in patients with type 2 diabetes.
They continue: “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.”
Rangaswami and Mathew say: “The cardiovascular benefits seen across a wide eGFR range and albuminuria strata captured in the FIDELITY analysis help minimize the inadvertent exclusion of patients who would benefit from CVD risk-reducing therapies such as finerenone.”
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JAMA Cardiol 2023; doi:10.1001/jamacardio.2023.1505
JAMA Cardiol 2023; doi:10.1001/jamacardio.2023.1512