Real-World Insights into Evolocumab Use in Patients with Hyperlipidemia Across Five Countries: Analysis from the ZERBINI Study
Tóm tắt
This study characterizes patients receiving evolocumab in clinical practice and assesses treatment effectiveness, safety and persistence outcomes across five countries. This retrospective and prospective observational study enrolled patients initiated on evolocumab during August 2017 to July 2019 at 49 sites across Canada, Mexico, Colombia, Saudi Arabia and Kuwait. Medical records data were extracted within 6 months prior to (baseline) and every 3 months for 12 months post evolocumab initiation and reported as available. A total of 578 patients were enrolled (40.1% female, median age 60 [interquartile range (IQR) 51–68] years); 83.7% had atherosclerotic cardiovascular disease and/or familial hypercholesterolemia. Median low-density lipoprotein cholesterol (LDL-C) at baseline was 3.4 (IQR 2.7–4.2) mmol/L (131.5 [IQR 104.4–162.4] mg/dL), with 75.6% of patients receiving a statin (59.2% high intensity). Compared to baseline, the median lowest LDL-C was reduced by 70.2% and remained stable over 12 months of treatment. Guideline-recommended LDL-C thresholds < 1.8, < 1.4 and < 1.0 mmol/L (< 70, < 55 and < 40 mg/dL) were achieved by 75.3%, 63.6% and 47.4% of patients. LDL-C outcomes were consistent across high- and very high-risk patients. Background lipid-lowering therapy remained relatively stable. No serious treatment-emergent adverse events were reported, and persistence to evolocumab was 90.2% at 12 months. These findings provide real-world evidence that evolocumab use is in accordance with its international guideline-recommended place in dyslipidemia therapy, as well as confirmation of its effectiveness and safety in a heterogeneous population. Evolocumab can address a healthcare gap in the management of dyslipidemia by increasing the proportion of patients achieving LDL-C goals recommended to lower cardiovascular risk.
Tài liệu tham khảo
World Health Organization. Cardiovascular diseases. https://www.who.int/health-topics/cardiovascular-diseases#tab=tab_1. Accessed Aug 26, 2021.
Silverman MG, Ference BA, Im K, et al. Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis. JAMA. 2016;316(12):1289–97.
Ference BA, Ginsberg HN, Graham I, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017;38(32):2459–72.
Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73(24):e285–350.
Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111–88.
Pearson GJ, Thanassoulis G, Anderson TJ, et al. 2021 Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol. 2021;37(8):1129–50.
Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 Suppl 2):S1-45.
Allen JM, Arnold SV, Lohr NL, et al. Assessing low-density lipoprotein cholesterol risk in secondary prevention patients within the PINNACLE National Outpatient Registry. Circulation. 2019;140:A12904.
Gitt AK, Lautsch D, Ferrières J, et al. Cholesterol target value attainment and lipid-lowering therapy in patients with stable or acute coronary heart disease: results from the Dyslipidemia International Study II. Atherosclerosis. 2017;266:158–66.
Al Sifri SN, Almahmeed W, Azar S, et al. Results of the Dyslipidemia International Study (DYSIS)-Middle East: clinical perspective on the prevalence and characteristics of lipid abnormalities in the setting of chronic statin treatment. PLoS One. 2014;9(1): e84350.
Ezetimibe Product Monograph. Sandoz Canada. March 14, 2017. https://www.sandoz.ca/sites/www.sandoz.ca/files/Ezetimibe%20Product%20Monograph.pdf.
Cannon CP, de Lemos JA, Rosenson RS, et al. Use of lipid-lowering therapies over 2 years in GOULD, a registry of patients with atherosclerotic cardiovascular disease in the US. JAMA Cardiol. 2021;6(9):1–9.
Toth PP, Worthy G, Gandra SR, et al. Systematic review and network meta-analysis on the efficacy of evolocumab and other therapies for the management of lipid levels in hyperlipidemia. J Am Heart Assoc. 2017;6(10): e005367.
Ray KK, Dhalwani N, Sibartie M, et al. Low-density lipoprotein cholesterol levels exceed the recommended European threshold for PCSK9i initiation: lessons from the HEYMANS study. Eur Heart J Qual Care Clin Outcomes. 2022;8(4):447–60.
Nanchen D, Carballo D, Bilz S, et al. Effectiveness, adherence, and safety of evolocumab in a Swiss multicenter prospective observational study. Adv Ther. 2022;39(1):504–17.
Gupta M, Mancini GBJ, Wani RJ, et al. Real-world insights into evolocumab use in patients with hyperlipidemia: Canadian analysis from the ZERBINI study. CJC Open. 2022;4(6):558–67.
Desai NR, Wade RL, Xiang P, et al. Low-density lipoprotein cholesterol lowering in real-world patients treated with evolocumab. Clin Cardiol. 2021;44(5):715–22.
Al Faraidy K, Akbar M, Shehri M, et al. Multizonal observational study conducted by clinical practitioners on evolocumab use in subjects with hyperlipidemia in Saudi Arabia and Kuwait: results from the ZERBINI study. PLoS One. 2023;18(1):e0278821.
Benchimol EI, Smeeth L, Guttmann A, et al. The reporting of studies conducted using observational routinely-collected health data (RECORD) statement. PLoS Med. 2015;12(10): e1001885.
Repatha (evolocumab) Product Monograph. Amgen Canada Inc. December 9, 2021. https://www.amgen.ca/-/media/Themes/CorporateAffairs/amgen-ca/amgen-ca/documents/products/en/repatha_pm.pdf.
International Diabetes Federation. Diabetes Atlas 10th Edition. Middle East and North Africa. Diabetes Report 2000–2045. https://diabetesatlas.org/data/en/region/4/mena.html. Accessed July 2, 2021.
Schludi B, Giugliano RP, Sabatine MS, et al. Time-averaged low-density lipoprotein cholesterol lowering with evolocumab: pooled analysis of phase 2 trials. J Clin Lipidol. 2022;16(4):538–43.
O’Donoghue ML, Giugliano RP, Wiviott SD, et al. Long-term evolocumab in patients with established atherosclerotic cardiovascular disease. Circulation. 2022;146(15):1109–19.
Qamar A, Giugliano RP, Keech AC, et al. Interindividual variation in low-density lipoprotein cholesterol level reduction with evolocumab: an analysis of FOURIER trial data. JAMA Cardiol. 2019;4(1):59–63.
Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376(18):1713–22.
Gencer B, Mach F, Murphy SA, et al. Efficacy of evolocumab on cardiovascular outcomes in patients with recent myocardial infarction: a prespecified secondary analysis from the FOURIER trial. JAMA Cardiol. 2020;5(8):952–7.
Sabatine MS, De Ferrari GM, Giugliano RP, et al. Clinical benefit of evolocumab by severity and extent of coronary artery disease: analysis from FOURIER. Circulation. 2018;138(8):756–66.
Nissen SE, Stroes E, Dent-Acosta RE, et al. Efficacy and tolerability of evolocumab vs ezetimibe in patients with muscle-related statin intolerance: the GAUSS-3 randomized clinical trial. JAMA. 2016;315(15):1580–90.
Zhang L, McCabe T, Condra JH, et al. An anti-PCSK9 antibody reduces LDL-cholesterol on top of a statin and suppresses hepatocyte SREBP-regulated genes. Int J Biol Sci. 2012;8(3):310–27.
Koren MJ, Sabatine MS, Giugliano RP, et al. Long-term efficacy and safety of evolocumab in patients with hypercholesterolemia. J Am Coll Cardiol. 2019;74(17):2132–46.
Colantonio LD, Huang L, Monda KL, et al. Adherence to high-intensity statins following a myocardial infarction hospitalization among Medicare beneficiaries. JAMA Cardiol. 2017;2(8):890–5.
Guglielmi V, Bellia A, Pecchioli S, et al. Effectiveness of adherence to lipid lowering therapy on LDL-cholesterol in patients with very high cardiovascular risk: a real-world evidence study in primary care. Atherosclerosis. 2017;263:36–41.
Khunti K, Danese MD, Kutikova L, et al. Association of a combined measure of adherence and treatment intensity with cardiovascular outcomes in patients with atherosclerosis or other cardiovascular risk factors treated with statins and/or ezetimibe. JAMA Netw Open. 2018;1(8):e185554.
Bates TR, Connaughton VM, Watts GF. Non-adherence to statin therapy: a major challenge for preventive cardiology. Expert Opin Pharmacother. 2009;10(18):2973–85.
Wouters H, Van Dijk L, Geers HC, et al. Understanding statin non-adherence: knowing which perceptions and experiences matter to different patients. PLoS One. 2016;11(1): e0146272.
Toth PP, Descamps O, Genest J, et al. Pooled safety analysis of evolocumab in over 6000 patients from double-blind and open-label extension studies. Circulation. 2017;135(19):1819–31.
Robinson JG, Nedergaard BS, Rogers WJ, et al. Effect of evolocumab or ezetimibe added to moderate- or high-intensity statin therapy on LDL-C lowering in patients with hypercholesterolemia: the LAPLACE-2 randomized clinical trial. JAMA. 2014;311(18):1870–82.