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PCSK9 Inhibitors’ New Users: Analysis of Prescription Patterns and Patients’ Characteristics from an Italian Real-world Study

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Background and Objective

Cardiovascular (CV) diseases represent a major cause of death and severe medical condition worldwide. Different therapeutic options are available to control low-density lipoprotein cholesterol (LDL-C) level in order to prevent CV events. In recent years, two new drugs were approved for patients who are unable to reduce circulating LDL-C with the current therapies: evolocumab and alirocumab (proprotein convertase subtilisin/kexin type nine [PCSK9] inhibitors). This study was aimed to characterise patients who started treatment with PCSK9 inhibitors in the Tuscany region of Italy during the first year of public healthcare service reimbursement and to describe the pattern of PCSK9 inhibitor use in the first 6 months of treatment.


Patients on PCSK9 inhibitor treatment in Tuscany (3.7 million inhabitants) from 07/2017 to 06/2018 were selected from regional healthcare administrative databases. Concomitant use of lipid-lowering therapies (LLTs), adherence and persistence during the 6 months preceding the first PCSK9 inhibitor dispensing, as well as comorbidities since 1996, were described. In the first 6 months of PCSK9 inhibitor treatment, adherence, persistence and concomitant LLTs were assessed.


There were 269 (176 evolocumab, 93 alirocumab) new users of PCSK9 inhibitors. Patients (mean age of 59.1 years) were mainly male (71.0%) in secondary prevention (70.2%) and affected by familial hypercholesterolaemia (53.5%). Sixty-six patients (24.5%) had diabetes mellitus and 12 (4.5%) chronic renal failure. In the 6 months prior to the first PCSK9 inhibitor administration, 61.3% of patients received at least one prescription of ezetimibe or high-intensity statins and 45.7% were persistent to these drugs. During follow-up, 79.9% of patients were adherent to PCSK9 inhibitor and 73.3% were persistent.


During the first year of availability, the rate of prescription of PCSK9 inhibitors appears below expectations. Patients were mainly in secondary prevention and had been slightly persistent to previous LLTs. During follow-up, the PCSK9 inhibitor monotherapy showed high levels of adherence and persistence. This real-world study sets the stage for future longer-term investigations useful to improve our knowledge on the appropriateness, drug access and public healthcare sustainability of PCSK9 inhibitors.

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  1. Ference BA, Ginsberg HN, Graham I, Ray KK, Packard CJ, Bruckert E, 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Catapano AL, Graham I, De Backer G, Wiklund O, Chapman MJ, Drexel H, et al. 2016 ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J. 2016;37(39):2999–3058.

    Article  PubMed  Google Scholar 

  3. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol. Circulation. 2018.

    Article  PubMed  Google Scholar 

  4. Karatasakis A, Danek BA, Karacsonyi J, Rangan BV, Roesle MK, Knickelbine T, et al. Effect of PCSK9 inhibitors on clinical outcomes in patients with hypercholesterolaemia: a meta-analysis of 35 randomized controlled trials. J Am Heart Assoc. 2017.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Schmidt AF, Pearce LS, Wilkins JT, Overington JP, Hingorani AD, Casas JP. PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2017;4:Cd011748.

    Article  PubMed  Google Scholar 

  6. Hlatky MA, Kazi DS. PCSK9 inhibitors: economics and policy. J Am Coll Cardiol. 2017;70(21):2677–87.

    Article  CAS  PubMed  Google Scholar 

  7. Hudson V. The dyslipidaemia market. Nat Rev Drug Discovery. 2014;13(11):807–8.

    Article  CAS  PubMed  Google Scholar 

  8. AIFA (Italian Medicines Agency). Gazzetta Ufficiale n.31 del 07 febbraio 2017. Classificazione del medicinale per uso umano “Repatha”, ai sensi dell’art. 8, comma 10, della legge 24 dicembre 1993, n. 537. (Determina n. 172/2017) (17A01047). 2017.

  9. AIFA (Italian Medicines Agency). Gazzetta Ufficiale n.24 del 06 marzo 2017. Classificazione del medicinale per uso umano “Praluent” ai sensi dell’art. 8, comma 10, della legge 24 dicembre 1993, n. 537. (Determina n. 256/2017) (17A01583). 2017.

  10. Martini N, Arca M, Averna M, Ceconi C, Dondi L, Maggioni AP et al. Concept paper sul Progetto inibitori di PCSK9: accesso e sostenibilità. SPS: i Supplementi di Polirica Sanitaria; 2019.

  11. Zafrir B, Jubran A. Lipid-lowering therapy with PCSK9 inhibitors in the real-world setting: two-year experience of a regional lipid clinic. Cardiovasc Ther. 2018;36(5):e12439.

    Article  CAS  PubMed  Google Scholar 

  12. Stoekenbroek RM, Hartgers ML, Rutte R, de Wijer DD, Stroes ESG, Hovingh GK. PCSK9 inhibitors in clinical practice: delivering on the promise? Atherosclerosis. 2018;270:205–10.

    Article  CAS  PubMed  Google Scholar 

  13. Kaufman TM, Warden BA, Minnier J, Miles JR, Duell PB, Purnell JQ, et al. Application of PCSK9 inhibitors in practice. Circ Res. 2019;124(1):32–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Karalis DG, Mallya UG, Ghannam AF, Elassal J, Gupta R, Boklage SH. Prescribing patterns of proprotein convertase subtilisin-kexin type 9 inhibitors in eligible patients with clinical atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolaemia. Am J Cardiol. 2018;121(10):1155–61.

    Article  CAS  PubMed  Google Scholar 

  15. Fairman KA, Davis LE, Sclar DA. Real-world use of PCSK-9 inhibitors by early adopters: cardiovascular risk factors, statin co-treatment, and short-term adherence in routine clinical practice. Ther Clin Risk Manag. 2017;13:957–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Razek O, Cermakova L, Armani H, Lee T, Francis GA, Mancini GBJ, et al. Attainment of recommended lipid targets in patients with familial hypercholesterolaemia: real-world experience with PCSK9 inhibitors. Can J Cardiol. 2018;34(8):1004–9.

    Article  PubMed  Google Scholar 

  17. Virani SS, Kennedy KF, Akeroyd JM, Morris PB, Bittner VA, Masoudi FA, et al. Variation in lipid-lowering therapy use in patients with low-density lipoprotein cholesterol ≥ 190 mg/dL: insights from the national cardiovascular data registry-practice innovation and clinical excellence registry. Circ Cardiovasc Qual Outcomes. 2018;11(5):e004652.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Tai MH, Shepherd J, Bailey H, Williams N, Hatz M, Campos Tapias I, et al. Real-world treatment patterns of PCSK9 inhibitors among patients with dyslipidemia in Germany, Spain, and the United Kingdom. Curr Med Res Opin. 2018.

    Article  PubMed  Google Scholar 

  19. Hines DM, Rane P, Patel J, Harrison DJ, Wade RL. Treatment patterns and patient characteristics among early initiators of PCSK9 inhibitors. Vasc Health Risk Manag. 2018;14:409–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Rane PB, Patel J, Harrison DJ, Shepherd J, Leith A, Bailey H, et al. Patient characteristics and real-world treatment patterns among early users of PCSK9 inhibitors. Am J Cardiovasc Drugs. 2018;18(2):103–8.

    Article  PubMed  Google Scholar 

  21. Regione Toscana. Bollettino Ufficiale Regione Toscana n. 29 del 19.7.2017. Individuazione Centri Specialistici per la diagnosi, il rilascio del piano terapeutico e/o la prescrizione di medicinali a carico del Servizio Sanitario Regionale. 2017. p. 113–4.

  22. Trifiro G, Gini R, Barone-Adesi F, Beghi E, Cantarutti A, Capuano A, et al. The role of european healthcare databases for post-marketing drug effectiveness, safety and value evaluation: where does Italy stand? Drug Saf. 2019;42(3):347–63.

    Article  PubMed  Google Scholar 

  23. Gini R, Roberto G, Biagini S, Volpi E, Maggioni AP. Farmaci ipolipemizzanti. In: Gini R, Roberto G, editors. Secondo rapporto sui farmaci in Toscana: ARS Toscana; 2017.

  24. Maggioni AP, Calabria S, Rossi E, Martini N. Use of lipid lowering drugs in patients at very high risk of cardiovascular events: an analysis on nearly 3,000,000 Italian subjects of the ARNO Observatory. Int J Cardiol. 2017;246:62–7.

    Article  PubMed  Google Scholar 

  25. Catapano AL, Graham I, De Backer G, Wiklund O, Chapman MJ, Drexel H, et al. 2016 ESC/EAS guidelines for the management of dyslipidaemias. Revista espanola de cardiologia (English ed). 2017;70(2):115.

    Article  Google Scholar 

  26. Lubloy A. Factors affecting the uptake of new medicines: a systematic literature review. BMC Health Serv Res. 2014;14:469.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Sbrana F, Del Pino B, Bigazzi F, Ripoli A, Volpi E, Fogliaro M, et al. A large Italian cohort on proprotein convertase subtilisin/kexin type 9 inhibitors. Eur J Prev Cardiol. 2019.

    Article  PubMed  Google Scholar 

  28. Corrao G, Monzio Compagnoni M, Franchi M, Cantarutti A, Pugni P, Merlino L, et al. Good adherence to therapy with statins reduces the risk of adverse clinical outcomes even among very elderly. Evidence from an Italian real-life investigation. Eur J Intern Med. 2018;47:25–31.

    Article  PubMed  Google Scholar 

  29. Sampietro T, Bigazzi F, Sbrana F, Toma M, Dal Pino B, Ripoli A, et al. Personalized regimen for PCSK9 inhibitors: a therapeutic option that maintains efficacy and reduces costs. J Clin Lipidol. 2018;12(5):1324–5.

    Article  PubMed  Google Scholar 

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Authors and Affiliations



CP, ICA, APM and RG conceived the study. RG, ICA and GR conducted the analyses. CP and ICA wrote the first version of the article. AP, SC, GR, LD, NM, TS, FS, BDP, FB, GLS, EV and SB contributed to the interpretation of the results and revised manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Carlo Piccinni.

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No funding was received to conduct this study.

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

This is an observational, non-interventional database study, re-utilising administrative data for the purpose of addressing a research question. The Agenzia regionale di Sanità della Toscana has general legal and ethical frameworks that allow conducting research by making secondary use of administrative data, upon approval of an internal governance board. Permission to contribute to this study was granted by the governance boards of the Agenzia regionale di Sanità della Toscana.

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Piccinni, C., Antonazzo, I.C., Maggioni, A.P. et al. PCSK9 Inhibitors’ New Users: Analysis of Prescription Patterns and Patients’ Characteristics from an Italian Real-world Study. Clin Drug Investig 40, 173–181 (2020).

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