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Multicenter Study
. 2024 Jun 3;31(8):1038-1047.
doi: 10.1093/eurjpc/zwae036.

Contemporary lipid-lowering management and risk of cardiovascular events in homozygous familial hypercholesterolaemia: insights from the Italian LIPIGEN Registry

Laura D'Erasmo  1 , Simone Bini  1 , Manuela Casula  2   3 , Marta Gazzotti  4 , Stefano Bertolini  5 , Sebastiano Calandra  6 , Patrizia Tarugi  7 , Maurizio Averna  8   9 , Gabriella Iannuzzo  10 , Giuliana Fortunato  11   12 , Alberico L Catapano  2   3 , Marcello Arca  1   13 ; LIPIGEN HoFH group
Collaborators, Affiliations
Multicenter Study

Contemporary lipid-lowering management and risk of cardiovascular events in homozygous familial hypercholesterolaemia: insights from the Italian LIPIGEN Registry

Laura D'Erasmo et al. Eur J Prev Cardiol. .

Abstract

Aims: The availability of novel lipid-lowering therapies (LLTs) has remarkably changed the clinical management of homozygous familial hypercholesterolaemia (HoFH). The impact of these advances was evaluated in a cohort of 139 HoFH patients followed in a real-world clinical setting.

Methods and results: The clinical characteristics of 139 HoFH patients, along with information about LLTs and low-density lipoprotein cholesterol (LDL-C) levels at baseline and after a median follow-up of 5 years, were retrospectively retrieved from the records of patients enrolled in the LIPid transport disorders Italian GEnetic Network-Familial Hypercholesterolaemia (LIPIGEN-FH) Registry. The annual rates of major atherosclerotic cardiovascular events (MACE-plus) during follow-up were compared before and after baseline. Additionally, the lifelong survival free from MACE-plus was compared with that of the historical LIPIGEN HoFH cohort. At baseline, LDL-C level was 332 ± 138 mg/dL. During follow-up, the potency of LLTs was enhanced and, at the last visit, 15.8% of patients were taking quadruple therapy. Consistently, LDL-C decreased to an average value of 124 mg/dL corresponding to a 58.3% reduction (Pt < 0.001), with the lowest value (∼90 mg/dL) reached in patients receiving proprotein convertase subtilisin/kexin type 9 inhibitors and lomitapide and/or evinacumab as add-on therapies. The average annual MACE-plus rate in the 5-year follow-up was significantly lower than that observed during the 5 years before baseline visit (21.7 vs. 56.5 per 1000 patients/year; P = 0.0016).

Conclusion: Our findings indicate that the combination of novel and conventional LLTs significantly improved LDL-C control with a signal of better cardiovascular prognosis in HoFH patients. Overall, these results advocate the use of intensive, multidrug LLTs to effectively manage HoFH.

Keywords: Cardiovascular risk; Evinacumab; Homozygous familial hypercholesterolaemia; Lipid-lowering therapies; Lomitapide; PCSK9 inhibitors; Real-world.

Plain language summary

Contemporary real-world data from the Italian cohort of patients affected by homozygous familial hypercholesterolaemia demonstrated that the addition of novel, low-density lipoprotein receptor (LDLR)-independent medications to conventional therapies allowed the achievement of unprecedented low-density lipoprotein cholesterol (LDL-C) values with a trend towards a reduction of cardiovascular risk.

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Conflict of interest statement

Conflict of interest: Mar.A. received research grant support from Amryt Pharmaceutical, Amgen, IONIS, Akcea Therapeutics, Daiichi-Sankyo, Novartis, Pfizer, and Regeneron; served as a consultant for Amgen, Akcea Therapeutics, Daiichi-Sankyo, and Ultragenyx; and received fees for lecturing, congress participation, and advisory board participation from Amgen, Amryt Pharmaceutical, Daiichi-Sankyo, Regeneron, Sanofi, Amarin, and Ultragenyx. R.A. received consulting fees from GSK-Galaxosmithline. Si.B. received fees for lectures from SOBI; detains stock options of Eli Lilly, UnitedHealth, Novo Nordisk, Merck, and Thermo Fisher Scientific; and received grants for meeting participation from Novartis. M.B. received fees for lectures from Menarini, Servier, Alfasigma, Neopharmed, Aurora, Biopharma, Amryt, Novartis, Sanofi, and Viatris and received fees for participations in meeting from Ultragenyx, Daiichi-Sankyo, Lusofarmaco, and Sanofi. Carubbi F received grants for lectures and meeting participation from Amgen and Amryt, received funding for grants from Sanofi and Amgen, and received funding for data monitoring and lectures from Sanofi. A.L.C. received funding for consulting, lectures, and meeting attendance from Amgen, AstraZeneca, Aegerion, Amryt, Daiichi-Sankyo, Esperion, Kowa, Ionis Pharma, Mylan, Merck, Menarini, Novartis, Recordati, Regeneron, Sandoz, Sanofi, and Viatris and also received research grants from Sanofi, Eli Lilly, Amgen, Menarini, Sanofi-Regeneron, and Mylan. L.D. received personal fees for public speaking or consultancy or grant support from Amryt Pharmaceutical, Akcea Therapeutics, SOBI, AuroraBiopharma, Novartis, Amarin, Daiichi-Sankyo, Bayer, and Sandoz. F.F. received consulting funds from Merck. G.I. received funds for research grants from Amryt and Ultragenix; lecture fees from Novartis, Sanofi, Lusofarmaco, and Agaton; funds for meeting attendance from Ultragenix; and funds for data monitoring from Novartis, Agaton, and Sanofi; G.M. received research grants from Daiichi-Sankyo and Novartis; lecture fees from Amgen, Eli Lilly, and Neopharmed; fund for meeting attendance from Amgen; and funds for data monitoring from Sanofi-Aventis, Daiichi-Sankyo, Amrin, and Novo Nordisk. F.N. received fees for consulting, lectures, and data monitoring from Sanofi. C.P. received fees for lectures from SOBI. L.P. received fees for lectures from Amgen, Sanofi, and Amryt and received funding for meeting attendance from Sanofi, Ultragenyx, and Daiichi-Sankyo; D.T. received fees for lectures from SOBI. J.P.W. received fees for lectures from Servier, Novartis, Daiichi-Sankyo, Sanofi, and Amgen and received funding for meeting attendance from Daiichi-Sankyo, Amgen, and MSD. A.Z. received fees for lectures from Amgen, Sanofi, Amarin, Amryt, Abbott, Viatris, Novartis, Daiichi-Sankyo, Alfasigma, and Servier. The other authors have no conflicts of interest to declare.

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