559 SACUBITRIL/VALSARTAN IN “REAL WORLD“ HEART FAILURE PATIENTS: FOCUS ON RENAL FUNCTION AND DRUG TITRATION
Authors: Bonini Niccolo , Albini Alessandro , Venturelli Andrea , Maisano Anna , Luli Jozef , Vitolo Marco , Imberti Jacopo Francesco , Valenti Anna Chiara , Righelli Ilaria , Cataldo Paolo , Muto Federico , Tosetti Alberto , Boriani Giuseppe 
Published: December 2022

Abstract

Background and aim of the study
There is a rising interest in real-world data about Sacubitril/Valsartan (Sa/Va) treatment, especially for the renal outcomes in patients treated with low (24/26 mg bid), mid (49/51 mg bid) and high (97/103 mg bid) dosages. Our aim was to assess the changes of the estimated glomerular filtration rate (eGFR) and the association of chronic kidney disease (CKD) with the titration of Sa/Va in a cohort of ambulatory HF patients with reduced ejection fraction (HFrEF) enrolled in a monocentric registry.

Methods
CKD was defined with an eGFR &lt; 60ml/min, and the patients were stratified according to the CKD stage with the CKD-EPI formula. After one year of follow-up, Sa/Va titration was defined as the passage from a lower to a higher dose. We performed a descriptive analysis assessing the improvement or worsening of the eGFR, defined as ≥ or ≤ 20% from the eGFR baseline, and the association of CKD status and other clinical factors (age, male biological sex, BMI, systolic blood pressure, NYHA≥2) with Sa/Va titration.

Results
Among the original 158 patients, 139 (87.9%) patients with serial creatinine values were included in this analysis. Patients had a median age of 66 years [IQR 56-71], 16.5% were female, with a median EF of 30% [IQR 28-35], median NYHA class was 2 [IQR 2-3], 73 (52.5%) had an ischemic aetiology, and 77 (55.4%) and 39 (28.1%) patients had a prior ICD and CRT-P/D implantation, respectively. Prescribed dosages of Sa/Va were low for 96 (69.1%) patients, mid for 36 (25.9%) and high for 6 (4.3%) patients. Fifty-eight (41.7%) patients had CKD with an eGFR median of 48.1 [IQR 41.8-53.0]; forty of them (28.8%) were in stage IIIA, and eighteen of them (12.9%) were in stage IIIB. Among this group, the prescribed dosage of Sa/Va was low for thirty-nine (67.2%) patients, mid for seventeen (29.3%) patients, and high for two (3.4%) patients. After one year of follow-up, in the whole cohort, clinicians titrated the dose of Sa/Va in twenty-two (15.8%) patients, and in a multivariable logistic regression analysis, CKD was inversely associated with the titration of the Sa/Va [Figure]. Five (3.6%) patients improved renal function, while twenty-two (15.8%) patients experienced decreased renal function. Among those who tolerated the titration, none had an improvement of the eGFR ≥20%. Among the CKD patients’ subgroup, seven (12.1%) received a titrated dose of Sa/Va; two (3.4%) patients improved renal function, and twelve (20.7%) patients worsened it, but no Sa/Va discontinuations were detected. As with the whole cohort, in this group no patients improved their renal function and titrated the Sa/Va dose.

Conclusions
After one year of follow-up, in a contemporary cohort of HFrEF Italian patients treated with Sa/Va, CKD was a predictor of no-titration of Sa/Va. Improved eGFR ≥ 20% from the baseline occurred in around 4% of patients in the general cohort and CKD subgroup, but not in conjunction with Sa/Va titration. Although 20.7% of CKD patients worsened their renal function, this did not result in Sa/Va discontinuation.
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