Abstract 12470: Sacubitril/Valsartan in Patients With Heart Failure and Deterioration of Kidney Function to Estimated Glomerular Filtration Rate Less Than 30ml/min/1.73m 2 : Insights From PARAGON-HF and PARADIGM-HF

Abstract

Background: Sacubitril/valsartan is a foundational therapy for patients with heart failure (HF). Although current US FDA labeling does not identify threshold kidney function below which initiation or continuation of sacubitril/valsartan is precluded, guidelines generally identify eGFR<30mL/min/1.73m 2 as a contraindication to therapy. Methods: The RCTs PARAGON-HF and PARADIGM-HF assessed sacubitril/valsartan versus valsartan or enalapril in patients with HF. Patients with eGFR <30 (PARADIGM) or <25 mL/min/1.73 m 2 (PARAGON) at randomization were excluded. Discontinuation below this eGFR during follow-up was not mandated. We examined the effects of sacubitril/valsartan on efficacy and safety in patients experiencing progression of CKD to eGFR<30mL/min/1.73m 2 in follow-up. Results: Among 4,746 patients in PARAGON-HF and 8,346 patients in PARADIGM-HF (with eGFR>30ml/min/1.73m 2 at randomization), 613 (12.9%) and 691 (8.3%), respectively, had an eGFR<30mL/min/1.73m 2 at least once in follow-up. Patients with CKD progression had higher rates of study drug discontinuation and hyperkalemia (>5.5 mmol/L); however, rates remained similar between treatment groups. Patients with deterioration in kidney function to eGFR<30ml/min/1.73m 2 were at a higher risk of the primary composite outcome in both PARAGON-HF (RR 2.08; 95% CI: 1.72-2.52) and PARADIGM-HF (HR 2.32; 95% CI: 1.94-2.76). The incidence of the primary composite outcome was lower in patients treated with sacubitril/valsartan irrespective of deterioration in kidney function to eGFR<30mL/min/1.73m 2 in both PARAGON-HF (P int =0.74) and PARADIGM-HF (P int =0.50); Figure 1 . Conclusion: HF patients with progression of CKD to eGFR<30ml/min/1.73m 2 experience high risk of CV outcomes and continuation of sacubitril/valsartan was associated with persistent benefit. These data support potential continuation of sacubitril/valsartan, even among patients experiencing progression to advanced CKD.