- •PCSK9i have been proven to reduce cardiovascular events in hypercholesterolemia patients.
- •Few studies are available in a real-world setting on the use and effects of PCSK9i.
- •AT-TARGET-IT is the first Italian nation-wide registry on PCSK9i.
- •PCSK9i were very effective, leading to high adherence and persistence to therapy.
- •LDL-C target was reached in most patients, especially when used in combined therapy.
Background and aims
Proprotein Convertase Subtilisin/Kexin type 9 inhibitors (PCSK9i) are recommended in patients at high and very-high cardiovascular (CV) risk, with documented atherosclerotic CV disease (ASCVD), and for very-high risk patients with familial hypercholesterolaemia not achieving LDL-cholesterol (LDL-C) goal while receiving maximally tolerated dose of lipid-lowering therapy (LLT). However, single country real-life data, reporting the use of PCSK9i in clinical practice, are limited. Therefore, we designed AT-TARGET-IT, an Italian, multicenter, observational registry on the use of PCSK9i in clinical practice.
All data were recorded at the time of the first prescription and at the latest observation preceding inclusion in the study.
798 patients were enrolled. The median reduction in LDL-C levels was 64.9%. After stratification for CV risk, 63.8% achieved LDL-C target; of them, 83.3% took LLTs at PCSK9i initiation and 16.7% did not. 760 patients (95.2%) showed high adherence to therapy, 13 (1.6%) partial adherence, and 25 (3.1%) poor adherence. At 6 months, 99.7% of patients enrolled in the study remained on therapy; there were 519 and 423 patients in the study with a follow-up of at least 12 and 18 months, respectively. Persistence in these groups was 98.1% and 97.5%, respectively. Overall, 3.5% of patients discontinued therapy. No differences in efficacy, adherence, and persistence were found between alirocumab and evolocumab.
PCSK9i are safe and effective in clinical practice, leading to very high adherence and persistence to therapy, and achievement of recommended LDL-C target in most patients, especially when used as combination therapy.
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- Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease : consensus Statement of the European Atherosclerosis Society.Eur. Heart J. 2013; 34: 3478-3490https://doi.org/10.1093/eurheartj/eht273
- 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS).Eur. Heart J. 2020; 41: 111-188https://doi.org/10.1093/eurheartj/ehz455
- ESC/EAS guidelines for the management of dyslipidaemias.Eur. Heart J. 2016; 37 (2016): 2999-3058https://doi.org/10.1093/eurheartj/ehw272
- 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. 2018; 73 (2019): e285-e350https://doi.org/10.1016/j.jacc.2018.11.003
- 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: 1-9https://doi.org/10.1001/jamacardio.2021.1810
- Safety and efficacy of alirocumab in a real-life setting: the ODYSSEY APPRISE study.Eur. J. Prev. Cardiol. 2022; 28: 1864-1872https://doi.org/10.1093/eurjpc/zwaa097
- 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: 447-460https://doi.org/10.1093/ehjqcco/qcac009
- Determina AIFA n. 1771/2019. G.U. Serie generale.(n. 291 del 12/12/2019)
- Evaluation of medication adherence in chronic disease at a federally qualified health center.Ther. Adv. Chronic. Dis. 2017; 8: 113-120https://doi.org/10.1177/2040622317714966
- Medication compliance and persistence: terminology and definitions.Value Health. 2008; 11: 44-47https://doi.org/10.1111/j.1524-4733.2007.00213.x
- Implementation of cardiovascular secondary prevention guidelines in clinical practice: a nationwide survey in Italy.Nutr. Metabol. Cardiovasc. Dis. 2012; 22: 149-153https://doi.org/10.1016/j.numecd.2010.05.009
- Adherence to high-intensity statins following a myocardial infarction hospitalization among medicare beneficiaries.JAMA Cardiol. 2017; 2: 890-895https://doi.org/10.1001/jamacardio.2017.0911
- Underutilization of high-intensity statin therapy after hospitalization for coronary heart disease.J. Am. Coll. Cardiol. 2015; 65: 270-277https://doi.org/10.1016/j.jacc.2014.09.088
- The Medicines Utilisation Monitoring Centre. National Report on Medicines Use in Italy.vol. 202. Italian Medicines Agency, 2020 (Year, Rome)
- An expert opinion paper on statin adherence and implementation of new lipid-lowering medications by the ESC Working Group on Cardiovascular Pharmacotherapy: barriers to be overcome.Eur. Heart J. Cardiovasc. Pharmacother. 2020; 6 (Erratum in: Eur Heart J Cardiovasc Pharmacother): 115-121
- Real-world insights into evolocumab use in patients with hyperlipidemia: Canadian analysis from the ZERBINI study.CJC Open. 2022; 4: 558-567https://doi.org/10.1016/j.cjco.2022.03.003
- Application of PCSK9 inhibitors in practice.Circ. Res. 2019; 124: 32-37https://doi.org/10.1161/CIRCRESAHA.118.314191
- Treatment patterns and patient characteristics among early initiators of PCSK9 inhibitors.Vasc. Health Risk Manag. 2018; 14: 409-418https://doi.org/10.2147/VHRM.S180496
- Pro-protein subtilisin kexin-9 (PCSK9) inhibition in practice: lipid clinic experience in 2 contrasting UK centres.Int. J. Clin. Pract. 2017; 71https://doi.org/10.1111/ijcp.13032
- Effectiveness of proprotein convertase subtilisin/kexin-9 monoclonal antibody treatment on plasma lipoprotein(a) concentrations in patients with elevated lipoprotein(a) attending a clinic.Clin. Cardiol. 2021; 44: 805-813https://doi.org/10.1002/clc.23607
- Evolocumab and clinical outcomes in patients with cardiovascular disease.N. Engl. J. Med. 2017; 376: 1713-1722https://doi.org/10.1056/NEJMoa1615664
- Alirocumab and cardiovascular outcomes after acute coronary syndrome.N. Engl. J. Med. 2018; 379: 2097-2107https://doi.org/10.1056/NEJMoa1801174
- Long-Term evolocumab in patients with established atherosclerotic cardiovascular disease.Circulation. 2022; 146: 1109-1119https://doi.org/10.1161/CIRCULATIONAHA.122.061620
- Long-term low-density lipoprotein cholesterol-lowering efficacy, persistence, and safety of evolocumab in treatment of hypercholesterolemia: results up to 4 Years from the open-label OSLER-1 extension study.JAMA Cardiol. 2017; 2: 598-607https://doi.org/10.1001/jamacardio.2017.0747
- Effectiveness and safety of PCSK9 inhibitors in real-world clinical practice. An observational multicentre study. The IRIS-PCSK9I study.Atherosclerosis Plus. 2021; 45: 32-38https://doi.org/10.1016/j.athplu.2021.08.009
- PCSK9 inhibitors revisited: effectiveness and safety of PCSK9 inhibitors in a real-life Spanish cohort.Biomed. Pharmacother. 2022; 146112519https://doi.org/10.1016/j.biopha.2021.112519
- PCSK9 inhibitors in real-world practice: analysis of data from 314 patients and 2 Years of experience in a center of preventive cardiology.Curr. Atherosclerosis Rep. 2022; 24: 357-363https://doi.org/10.1007/s11883-022-01008-8
- Very high-risk familial hypercholesterolaemia patients in real life: the remaining gap in achieving the current LDL-C targets despite the use of PCSK9 inhibitors.Atherosclerosis. 2020; 309: 67-69https://doi.org/10.1016/j.atherosclerosis.2020.07.018
- Two phase 3 trials of inclisiran in patients with elevated LDL cholesterol.N. Engl. J. Med. 2020; 382: 1507-1519https://doi.org/10.1056/NEJMoa1912387
- Evinacumab in patients with refractory hypercholesterolemia.N. Engl. J. Med. 2020; 383: 2307-2319https://doi.org/10.1056/NEJMoa2031049
- Safety and efficacy of bempedoic acid to reduce LDL cholesterol.N. Engl. J. Med. 2019; 380: 1022-1032https://doi.org/10.1056/NEJMoa1803917
- EU-wide cross-sectional observational study of lipid-modifying therapy use in secondary and primary care: the DA VINCI study.Eur. J. Prev. Cardiol. 2021; 28: 1279-1289https://doi.org/10.1093/eurjpc/zwaa047
Published online: January 11, 2023
Accepted: January 10, 2023
Received in revised form: December 17, 2022
Received: November 12, 2022
© 2023 Elsevier B.V. All rights reserved.