The Difference Between Cystatin C- and Creatinine-Based eGFR in Heart Failure With Reduced Ejection Fraction: Insights From PARADIGM-HF

The clinical implications of the discrepancy between cystatin C (cysC)- and serum creatinine (Scr)-estimated glomerular filtration rate (eGFR) in patients with heart failure (HF) and reduced ejection fraction (HFrEF) are unknown. Post-hoc analysis of randomized trial data. 1,970 patients with HFrEF enrolled in PARADIGM-HF with available baseline cysC and Scr measurements. Intraindividual differences between eGFR based on cysC (eGFR ) and Scr (eGFR ; eGFRdiff ). Clinical outcomes included the PARADIGM-HF primary end point (composite of cardiovascular [CV] mortality or HF hospitalization), CV mortality, all-cause mortality, and worsening kidney function. We also examined poor health-related quality of life (HRQoL), frailty, and worsening HF (WHF), defined as HF hospitalization, emergency department visit, or outpatient intensification of therapy between baseline and 8-month follow-up. Fine-Gray subdistribution hazard models and Cox proportional hazards models were used to regress clinical outcomes on baseline eGFRdiff . Logistic regression was used to investigate the association of baseline eGFRdiff with poor HRQoL and frailty. Linear regression models were used to assess the association of WHF with eGFR , eGFR , and eGFRdiff at 8-month follow-up. Baseline eGFRdiff was higher than +10 and lower than-10mL/min/1.73m in 13.0% and 35.7% of patients, respectively. More negative values of eGFRdiff were associated with worse outcomes ([sub]hazard ratio per standard deviation: PARADIGM-HF primary end point, 1.18; P=0.008; CV mortality, 1.34; P=0.001; all-cause mortality, 1.39; P