P0260CLINICAL PROFILE OF PATIENTS INITIATING EVOLOCUMAB IN SPANISH NEPHROLOGY UNITS: A RESTROSPECTIVE, OBSERVATIONAL STUDY IN CLINICAL PRACTICE (RETOSS-NEPHRO)
Authors: Goicoechea Marian , Álvarez Vicente , Segarra Alfonso , Polaina Manuel , Martín Guillermo , Robles-Perez Nicolas-Roberto , Escudero Quesada Veronica , Orellana Cristhian , Gorriz Jose Luis , Villamayor Santiago 
Published: June 2020

Abstract

Background and Aims
Cardiovascular disease is the primary cause of morbidity and mortality in patients with chronic kidney disease (CKD). Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers serum low density lipoprotein cholesterol (LDL-C) levels. Evolocumab is indicated for adult patients with hypercholesterolaemia or mixed dyslipidaemia who are unable to reach LDL-C goals with the maximum tolerated dose of statin or are statin intolerant. This study was conducted to describe clinical characteristics, reasons for therapy initiation and treatment effects in patients treated with evolocumab in Spanish Nephrology units.

Method
Retrospective, observational, chart review of consecutive patients initiating evolocumab (Feb-2016 to Aug-2018) in 15 Spanish Nephrology Units. Patient characteristics, lipid modifying therapies and lipid profiles over time were retrospectively collected at 24 weeks pre- and 12±4 weeks post-evolocumab initiation.

Results
60 patients were enrolled: 53.3% women; mean (SD) age, 56.9 (12.8) years; mean (SD) body mass index, 28.0 (4.7) kg/m2; 45.0% had familial hypercholesterolemia (FH) (5.0% homozygous, 23.3% heterozygous, 16.7% undetermined FH); from the total population, 35% were in primary prevention and 65.0% started evolocumab after previous Atherosclerotic Cardiovascular Disease [ASCVD]. Regarding renal function, mean (SD) eGFR was 62.6 (30.0) ml/min/1.73m2; 51.7% of patients had eGFR &lt;60 ml/min/1.73m2 (CKD stage&gt;2), 50.0% had proteinuria (&gt;300 mg/g) and 10.0% had nephrotic syndrome. Other CV risk factors were hypertension (75.0%), diabetes (25.0%), and smoking (21.7%); 40.0% of patients were statin intolerant. At evolocumab initiation, 41.7% of patients were on a high intensity statin, 18.3% on moderate intensity statin and 50.0% were receiving ezetimibe. Mean (SD) LDL-C at evolocumab initiation was 179.7 (62.9) mg/dL (53.4% of patients with LDL-C≥160; 29.3% ≥190). Mean (SD) baseline HDL-C and total cholesterol were 48.5 (15.0) mg/dL and 273.1 (82.7) mg/dL, respectively. After 12 weeks, evolocumab resulted in LDL-C reductions of 60.1%, to a mean (SD) of 72.7 (80.3) mg/dL, with similar results observed in patients in primary/secondary prevention, with CKD stage &gt;2/≤2 or with/without proteinuria. Conversely, patients with/without FH showed significant differences between their reductions (46.6% vs 76.6%, respectively, p=0.0276). At week 12, 90.0% of patients reached LDL-C levels &lt;100 mg/dL, 70.0% &lt;70 mg/dL, and 55.0% &lt;55mg/dL, while eGFR levels and statin use remained stable.

Conclusion
In Spanish Nephrology Units, evolocumab was predominantly prescribed in patients with FH, ASCVD and/or CKD stage &gt;2. Initial evolocumab use was aligned with ESC/EAS dyslipidaemia guidelines, but with higher baseline LDL-C levels than the recommended thresholds. After 12 weeks of evolocumab treatment, LDL–C levels were more than halved and the majority of patients achieved both the 2016 and 2019 EAS/ESC targets of LDL-C control.