Eligibility for pharmacological therapies in heart failure with reduced ejection fraction: implications of the new Chronic Kidney Disease Epidemiology Collaboration creatinine equation for estimating glomerular filtration rate

Abstract

Aims: The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for estimating glomerular filtration rate (eGFR), based on serum creatinine, that does not incorporate race may reclassify individuals, irrespective of race, from one eGFR category to another, with implications for eligibility for treatments in patients with heart failure and reduced ejection fraction (HFrEF).

Methods and results: A total of 43 138 ambulatory patients with HFrEF from 12 clinical trials were included (mean age 64.3 years; 9580 [22.2%] women). Mean eGFR was 67 (standard deviation [SD] 21) ml/min/1.73 m² and 70 (SD 21) ml/min/1.73 m² using the original and new CKD-EPI equations, respectively (mean difference 3.20 ml/min/1.73 m² , 95% confidence interval [CI] 3.17-3.23, p < 0.001). Of the 935 patients with chronic kidney disease (CKD) stages 4 or 5, identified using the original equation, 309 (33.0%) were reclassified to CKD stages 1-3 (eGFR ≥30 ml/min/1.73 m² ) with the new equation. However, the opposite was observed among the 2521 Black patients (5.8%) included, with a reduction in mean eGFR from 75 to 68 ml/min/1.73 m² using the original and new equations, respectively (mean difference 6.94 ml/min/1.73 m² , [95% CI 6.82-7.06], p < 0.001). The number of Black patients with an eGFR <30 ml/min/1.73 m² increased from 49 (1.9%) using the original equation to 71 (2.8%) with the new equation.

Conclusions: The new CKD-EPI creatinine equation reclassified CKD stage in a large proportion of patients with HFrEF enrolled in clinical trials. As eGFR is an essential determinant of eligibility for several key pharmacological therapies in HFrEF, this reclassification could result in a substantial change in the proportion of patients considered eligible for such therapies and reduce the proportion of eligible Black patients.

Figure 1

Estimated glomerular filtration rate (eGFR) according to the original and new Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equation based on creatinine. (A) Changes in eGFR categories. (B) Histogram and frequency distribution curves.