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Cited by 35Lipoproteins and Cardiovascular HealthLipid metabolism and disordersCholesterol and Lipid Metabolism

Real-world effectiveness of PCSK9 inhibitors in reducing LDL-C in patients with familial hypercholesterolemia in Italy: a retrospective cohort study based on the AIFA monitoring registries

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Arca, Marcello, Celant, Simone, Olimpieri, Pier Paolo, Colatrella, Antonietta, Tomassini, Luca, D'Erasmo, Laura, Averna, Maurizio, Zambon, Alberto +2 more·2023·Journal of the American Heart Association
DOI 10.1161/jaha.122.026550PMC PMC10727418
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Abstract

Background Information on the real-world use of proprotein convertase subtilisin kexin 9 inhibitors (PCKS9is) in familial hypercholesterolemia are limited. We evaluated the pattern of prescription and the long-term efficacy of alirocumab and evolocumab in Italian patients with familial hypercholesterolemia in clinical practice. Methods and Results The data set for analysis was extracted from the PCKS9i Italian Medicines Agency (AIFA) registry and included 2484 patients with heterozygous familial hypercholesterolemia (HeFH) and 62 patients with homozygous familial hypercholesterolemia (HoFH) who were prescribed PCKS9is from February 2017 to December 2021. As the follow-up schedules were not prespecified and could vary, persistence and adherence as well as low-density lipoprotein cholesterol (LDL-C) changes during 2 years of treatment were analyzed in a final cohort of 1299 patients with familial hypercholesterolemia. At baseline, 53.8% of patients with HeFH and 69.4% of patients with HoFH were receiving maximally tolerated lipid-lowering therapies, while 45.9% of patients with HeFH and 30.7% of patients with HoFH reported statin intolerance; mean LDL-C was 197.7±52.3 mg/dL in HeFH and 252.0±106.2 mg/dL in HoFH. The 6-month persistence and adherence to therapy were >85%, and LDL-C reduction reached 58.6% (to 79.7 mg/dL) in HeFH and 57.6% (to 95.1 mg/dL) in HoFH after 24 months of treatment. The European Atherosclerosis Society/European Society of Cardiology LDL-C goals were achieved in 43.3% of patients with HeFH and 37.5% of patients with HoFH. Conclusions PCKS9i prescribed to patients with familial hypercholesterolemia in clinical practice showed LDL-C-lowering efficacy similar to that observed in controlled trials. However, 2 of 5 HeFH cases and 2 of 6 HoFH cases achieved the recommended LDL-C goals. The full achievement of European Atherosclerosis Society/European Society of Cardiology LDL-C goals should require a lower threshold for PCKS9i initiation and a combination of multiple therapies.

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  • First-year discontinuation of PCSK9 inhibitor monoclonal antibodies can lead to suboptimal LDL cholesterol reduction compromising prevention of cardiovascular events.

    “Studies of PCSK9 inhibitor moAbs have reported first-year discontinuation rates approaching 50%, which can lead to suboptimal LDL cholesterol reduction compromising prevention of cardiovascular events.5, 6, 7, 8, 9, 10, 11, 12, 13”

    From Adherence to PCSK9 Inhibitors in Clinical Practice (2026) · cites this paper as [6]

    In Results, the paper reports 85.83% persistence at 12 months among the HeFH patients analyzed, rather than first-year discontinuation approaching 50%. In Discussion, it explicitly excludes lack of adherence as an explanation for patients not reaching LDL-C targets and instead points to high LDL-C at treatment initiation. The paper does not assess whether discontinuation compromised prevention of cardiovascular events. (LLM, conf=0.85)

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  • Studies of PCSK9 inhibitor monoclonal antibodies have reported first-year discontinuation rates approaching 50%.

    “Studies of PCSK9 inhibitor moAbs have reported first-year discontinuation rates approaching 50%, which can lead to suboptimal LDL cholesterol reduction compromising prevention of cardiovascular events.5, 6, 7, 8, 9, 10, 11, 12, 13”

    From Adherence to PCSK9 Inhibitors in Clinical Practice (2026) · cites this paper as [6]

    The Results (Adherence to and Effectiveness of PCSK9i Therapy in HeFH; page unavailable) report 85.83% persistence at 12 months, rather than first-year discontinuation approaching 50%. The Discussion describes persistence and adherence as remarkably high in practice. (LLM, conf=0.84)

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Sorted by citations

Authors
Arca, M., Celant, S., Olimpieri, P. P., Colatrella, A., Tomassini, L., D'Erasmo, L., Averna, M., Zambon, A., Catapano, A. L., & Russo, P.
Affiliations
  • Sapienza University of Rome (IT)
  • Italian Medicines Agency (IT)
  • Department of Translational and Precision Medicine Sapienza University of Rome Rome Italy
  • University of Palermo (IT)
  • University of Padua (IT)
  • University of Milan (IT)
Corresponding author
Arca, Marcello
ORCID
Venue
Journal of the American Heart Association
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2023-11-07
Volume
12
Issue
21
Pages
e026550-e026550
ISSN
2047-9980 (ISSN-L)
DOI
10.1161/jaha.122.026550
PMC
PMC10727418
OpenAlex
W4387729374
Cited by
35
References
1
Citations by year
2026: 11 · 2025: 9 · 2024: 14 · 2023: 1
FWCI
9.38
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Journal of the American Heart Association (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Padua Research Archive (University of Padova) (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Keywords
PCSK9 inhibitors, familial hypercholesterolemia, heterozygous familial hypercholesterolemia, homozygous familial hypercholesterolemia, alirocumab, evolocumab, LDL cholesterol lowering, LDL cholesterol targets, treatment persistence, medication adherence, statin intolerance, real-world effectiveness, prescribing patterns, Italian patients
MeSH terms
Proprotein Convertase 9, Homozygous Familial Hypercholesterolemia, PCSK9 Inhibitors, Anticholesteremic Agents, Humans, Hypercholesterolemia, Hyperlipoproteinemia Type II, Cholesterol, LDL, Retrospective Studies, Atherosclerosis

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