Trial reportArteriosclerosis, thrombosis, and vascular biology2018
Homozygous Familial Hypercholesterolemia Patients With Identical Mutations Variably Express the LDLR (Low-Density Lipoprotein Receptor): Implications for the Efficacy of Evolocumab.
Open access · greenAbstract readClinical Trial
In one paragraph
Trial report in Arteriosclerosis, thrombosis, and vascular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 3 pooled it
8.2field-weighted citation impact, top 2% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 3 syntheses or guidelines pooled it, 103 citations in OpenAlex.
- Pooled it
- Exploring research trends and hotspots on PCSK9 inhibitor studies: a bibliometric and visual analysis spanning 2007 to 2023.Frontiers in cardiovascular medicine · 2024Pooled it
- A Systematic Review and Meta-Analysis of Therapeutic Efficacy and Safety of Alirocumab and Evolocumab on Familial Hypercholesterolemia.BioMed research international · 2021 · on this mapPooled it
- Efficacy, Safety, and Tolerability of Inclisiran in Patients With Homozygous Familial Hypercholesterolemia: Results From the ORION-5 Randomized Clinical Trial.Circulation · 2024Trial
- Efficacy and Safety of Alirocumab in Children and Adolescents With Homozygous Familial Hypercholesterolemia: Phase 3, Multinational Open-Label Study.Arteriosclerosis, thrombosis, and vascular biology · 2022Trial
- ANGPTL3 Inhibition With Evinacumab Results in Faster Clearance of IDL and LDL apoB in Patients With Homozygous Familial Hypercholesterolemia-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2021Trial
- Functional Analysis of LDLR (Low-Density Lipoprotein Receptor) Variants in Patient Lymphocytes to Assess the Effect of Evinacumab in Homozygous Familial Hypercholesterolemia Patients With a Spectrum of LDLR Activity.Arteriosclerosis, thrombosis, and vascular biology · 2019Trial
- Safety and Efficacy of Lomitapide in Japanese Patients with Homozygous Familial Hypercholesterolemia (HoFH): Results from the AEGR-733-301 Long-Term Extension Study.Journal of atherosclerosis and thrombosis · 2019Trial
- Article
- Research advances in current drugs targeting hyperlipidemia (Review).Molecular medicine reports · 2025Review
- Gene therapy and genome editing for lipoprotein disorders.European heart journal · 2025Review
- Pediatric Familial Hypercholesterolemia: Targeting Intestinal Absorption and Other Therapeutic Strategies.Nutrients · 2025Review
- Does Genotype Affect the Efficacy of PCSK9 Inhibitors in the Treatment of Familial Hypercholesterolemia?Cardiovascular drugs and therapy · 2025Review
- Homozygous Familial Hypercholesterolemia Treatment: New Developments.Current atherosclerosis reports · 2025Review
- Targeted NGS Revealed Pathogenic Mutation in a 13-Year-Old Patient with Homozygous Familial Hypercholesterolemia: A Case Report.International journal of molecular sciences · 2024Article
- Non-Coding RNA Involved in the Pathogenesis of Atherosclerosis-A Narrative Review.Diagnostics (Basel, Switzerland) · 2024Review
- Evinacumab: Mechanism of action, clinical, and translational science.Clinical and translational science · 2024Review
- Evolocumab Treatment in Pediatric Patients With Homozygous Familial Hypercholesterolemia: Pooled Data From Three Open-Label Studies.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Review of Evolocumab for the Reduction of LDL Cholesterol and Secondary Prevention of Atherosclerotic Cardiovascular Disease.Reviews in cardiovascular medicine · 2024Review
- A machine-learning algorithm using claims data to identify patients with homozygous familial hypercholesterolemia.Scientific reports · 2024Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Aurélie ThedrezFrom the CRNH Ouest, INRA UMR 1280 PhAN (A.T., V.B., M.C., G.L.) and L'institut du thorax, INSERM UMR 1087, CNRS UMR 6291 (A.T., M.P., B.C.), Université de Nantes, France; L'institut du thorax, CHU de Nantes, CIC Endocrino-Nutrition, France (A.T., M.P., B.C.); Lipidology Division of Internal Medicine, University of Cape Town, South Africa (D.J.B.); INSERM UMR 1188 DéTROI, Université de La Réunion, Sainte Clotilde, France (S.R.-M., V.B., K.C., B.N., S.B., G.L.); Amgen, Thousand Oaks, CA (L.T.); CHU Dijon Bourgogne, Point Médical, France (M.F.); and Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa (F.J.R.).
Dirk J BlomFrom the CRNH Ouest, INRA UMR 1280 PhAN (A.T., V.B., M.C., G.L.) and L'institut du thorax, INSERM UMR 1087, CNRS UMR 6291 (A.T., M.P., B.C.), Université de Nantes, France; L'institut du thorax, CHU de Nantes, CIC Endocrino-Nutrition, France (A.T., M.P., B.C.); Lipidology Division of Internal Medicine, University of Cape Town, South Africa (D.J.B.); INSERM UMR 1188 DéTROI, Université de La Réunion, Sainte Clotilde, France (S.R.-M., V.B., K.C., B.N., S.B., G.L.); Amgen, Thousand Oaks, CA (L.T.); CHU Dijon Bourgogne, Point Médical, France (M.F.); and Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa (F.J.R.).
Stéphane Ramin-MangataFrom the CRNH Ouest, INRA UMR 1280 PhAN (A.T., V.B., M.C., G.L.) and L'institut du thorax, INSERM UMR 1087, CNRS UMR 6291 (A.T., M.P., B.C.), Université de Nantes, France; L'institut du thorax, CHU de Nantes, CIC Endocrino-Nutrition, France (A.T., M.P., B.C.); Lipidology Division of Internal Medicine, University of Cape Town, South Africa (D.J.B.); INSERM UMR 1188 DéTROI, Université de La Réunion, Sainte Clotilde, France (S.R.-M., V.B., K.C., B.N., S.B., G.L.); Amgen, Thousand Oaks, CA (L.T.); CHU Dijon Bourgogne, Point Médical, France (M.F.); and Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa (F.J.R.).
Valentin BlanchardFrom the CRNH Ouest, INRA UMR 1280 PhAN (A.T., V.B., M.C., G.L.) and L'institut du thorax, INSERM UMR 1087, CNRS UMR 6291 (A.T., M.P., B.C.), Université de Nantes, France; L'institut du thorax, CHU de Nantes, CIC Endocrino-Nutrition, France (A.T., M.P., B.C.); Lipidology Division of Internal Medicine, University of Cape Town, South Africa (D.J.B.); INSERM UMR 1188 DéTROI, Université de La Réunion, Sainte Clotilde, France (S.R.-M., V.B., K.C., B.N., S.B., G.L.); Amgen, Thousand Oaks, CA (L.T.); CHU Dijon Bourgogne, Point Médical, France (M.F.); and Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa (F.J.R.).
Mikaël CroyalFrom the CRNH Ouest, INRA UMR 1280 PhAN (A.T., V.B., M.C., G.L.) and L'institut du thorax, INSERM UMR 1087, CNRS UMR 6291 (A.T., M.P., B.C.), Université de Nantes, France; L'institut du thorax, CHU de Nantes, CIC Endocrino-Nutrition, France (A.T., M.P., B.C.); Lipidology Division of Internal Medicine, University of Cape Town, South Africa (D.J.B.); INSERM UMR 1188 DéTROI, Université de La Réunion, Sainte Clotilde, France (S.R.-M., V.B., K.C., B.N., S.B., G.L.); Amgen, Thousand Oaks, CA (L.T.); CHU Dijon Bourgogne, Point Médical, France (M.F.); and Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa (F.J.R.).
Kévin ChemelloFrom the CRNH Ouest, INRA UMR 1280 PhAN (A.T., V.B., M.C., G.L.) and L'institut du thorax, INSERM UMR 1087, CNRS UMR 6291 (A.T., M.P., B.C.), Université de Nantes, France; L'institut du thorax, CHU de Nantes, CIC Endocrino-Nutrition, France (A.T., M.P., B.C.); Lipidology Division of Internal Medicine, University of Cape Town, South Africa (D.J.B.); INSERM UMR 1188 DéTROI, Université de La Réunion, Sainte Clotilde, France (S.R.-M., V.B., K.C., B.N., S.B., G.L.); Amgen, Thousand Oaks, CA (L.T.); CHU Dijon Bourgogne, Point Médical, France (M.F.); and Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa (F.J.R.).
Brice NativelFrom the CRNH Ouest, INRA UMR 1280 PhAN (A.T., V.B., M.C., G.L.) and L'institut du thorax, INSERM UMR 1087, CNRS UMR 6291 (A.T., M.P., B.C.), Université de Nantes, France; L'institut du thorax, CHU de Nantes, CIC Endocrino-Nutrition, France (A.T., M.P., B.C.); Lipidology Division of Internal Medicine, University of Cape Town, South Africa (D.J.B.); INSERM UMR 1188 DéTROI, Université de La Réunion, Sainte Clotilde, France (S.R.-M., V.B., K.C., B.N., S.B., G.L.); Amgen, Thousand Oaks, CA (L.T.); CHU Dijon Bourgogne, Point Médical, France (M.F.); and Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa (F.J.R.).
Matthieu PichelinFrom the CRNH Ouest, INRA UMR 1280 PhAN (A.T., V.B., M.C., G.L.) and L'institut du thorax, INSERM UMR 1087, CNRS UMR 6291 (A.T., M.P., B.C.), Université de Nantes, France; L'institut du thorax, CHU de Nantes, CIC Endocrino-Nutrition, France (A.T., M.P., B.C.); Lipidology Division of Internal Medicine, University of Cape Town, South Africa (D.J.B.); INSERM UMR 1188 DéTROI, Université de La Réunion, Sainte Clotilde, France (S.R.-M., V.B., K.C., B.N., S.B., G.L.); Amgen, Thousand Oaks, CA (L.T.); CHU Dijon Bourgogne, Point Médical, France (M.F.); and Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa (F.J.R.).
Bertrand CariouFrom the CRNH Ouest, INRA UMR 1280 PhAN (A.T., V.B., M.C., G.L.) and L'institut du thorax, INSERM UMR 1087, CNRS UMR 6291 (A.T., M.P., B.C.), Université de Nantes, France; L'institut du thorax, CHU de Nantes, CIC Endocrino-Nutrition, France (A.T., M.P., B.C.); Lipidology Division of Internal Medicine, University of Cape Town, South Africa (D.J.B.); INSERM UMR 1188 DéTROI, Université de La Réunion, Sainte Clotilde, France (S.R.-M., V.B., K.C., B.N., S.B., G.L.); Amgen, Thousand Oaks, CA (L.T.); CHU Dijon Bourgogne, Point Médical, France (M.F.); and Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa (F.J.R.).
Steeve BouraneFrom the CRNH Ouest, INRA UMR 1280 PhAN (A.T., V.B., M.C., G.L.) and L'institut du thorax, INSERM UMR 1087, CNRS UMR 6291 (A.T., M.P., B.C.), Université de Nantes, France; L'institut du thorax, CHU de Nantes, CIC Endocrino-Nutrition, France (A.T., M.P., B.C.); Lipidology Division of Internal Medicine, University of Cape Town, South Africa (D.J.B.); INSERM UMR 1188 DéTROI, Université de La Réunion, Sainte Clotilde, France (S.R.-M., V.B., K.C., B.N., S.B., G.L.); Amgen, Thousand Oaks, CA (L.T.); CHU Dijon Bourgogne, Point Médical, France (M.F.); and Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa (F.J.R.).
Lihua TangFrom the CRNH Ouest, INRA UMR 1280 PhAN (A.T., V.B., M.C., G.L.) and L'institut du thorax, INSERM UMR 1087, CNRS UMR 6291 (A.T., M.P., B.C.), Université de Nantes, France; L'institut du thorax, CHU de Nantes, CIC Endocrino-Nutrition, France (A.T., M.P., B.C.); Lipidology Division of Internal Medicine, University of Cape Town, South Africa (D.J.B.); INSERM UMR 1188 DéTROI, Université de La Réunion, Sainte Clotilde, France (S.R.-M., V.B., K.C., B.N., S.B., G.L.); Amgen, Thousand Oaks, CA (L.T.); CHU Dijon Bourgogne, Point Médical, France (M.F.); and Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa (F.J.R.).
Michel FarnierFrom the CRNH Ouest, INRA UMR 1280 PhAN (A.T., V.B., M.C., G.L.) and L'institut du thorax, INSERM UMR 1087, CNRS UMR 6291 (A.T., M.P., B.C.), Université de Nantes, France; L'institut du thorax, CHU de Nantes, CIC Endocrino-Nutrition, France (A.T., M.P., B.C.); Lipidology Division of Internal Medicine, University of Cape Town, South Africa (D.J.B.); INSERM UMR 1188 DéTROI, Université de La Réunion, Sainte Clotilde, France (S.R.-M., V.B., K.C., B.N., S.B., G.L.); Amgen, Thousand Oaks, CA (L.T.); CHU Dijon Bourgogne, Point Médical, France (M.F.); and Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa (F.J.R.).
Frederick J RaalFrom the CRNH Ouest, INRA UMR 1280 PhAN (A.T., V.B., M.C., G.L.) and L'institut du thorax, INSERM UMR 1087, CNRS UMR 6291 (A.T., M.P., B.C.), Université de Nantes, France; L'institut du thorax, CHU de Nantes, CIC Endocrino-Nutrition, France (A.T., M.P., B.C.); Lipidology Division of Internal Medicine, University of Cape Town, South Africa (D.J.B.); INSERM UMR 1188 DéTROI, Université de La Réunion, Sainte Clotilde, France (S.R.-M., V.B., K.C., B.N., S.B., G.L.); Amgen, Thousand Oaks, CA (L.T.); CHU Dijon Bourgogne, Point Médical, France (M.F.); and Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa (F.J.R.).
Gilles LambertFrom the CRNH Ouest, INRA UMR 1280 PhAN (A.T., V.B., M.C., G.L.) and L'institut du thorax, INSERM UMR 1087, CNRS UMR 6291 (A.T., M.P., B.C.), Université de Nantes, France; L'institut du thorax, CHU de Nantes, CIC Endocrino-Nutrition, France (A.T., M.P., B.C.); Lipidology Division of Internal Medicine, University of Cape Town, South Africa (D.J.B.); INSERM UMR 1188 DéTROI, Université de La Réunion, Sainte Clotilde, France (S.R.-M., V.B., K.C., B.N., S.B., G.L.); Amgen, Thousand Oaks, CA (L.T.); CHU Dijon Bourgogne, Point Médical, France (M.F.); and Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa (F.J.R.). gilles.lambert@univ-reunion.fr.
Amgen (United States) · USUniversity of Cape Town · ZA
Funding
Intramural NIH HHS NIH0010513932
Abstract
objectiveEvolocumab, a PCSK9 (proprotein convertase subtilisin kexin type 9)-neutralizing antibody, lowers low-density lipoprotein cholesterol (LDL-C) in homozygous familial hypercholesterolemic (HoFH) patients with reduced LDLR (low-density lipoprotein receptor) function. However, their individual responses are highly variable, even among carriers of identical LDLR genetic defects. We aimed to elucidate why HoFH patients variably respond to PCSK9 inhibition. APPROACH AND
resultsLymphocytes were isolated from 22 HoFH patients enrolled in the TAUSSIG trial (Trial Assessing Long Term Use of PCSK9 Inhibition in Subjects With Genetic LDL Disorders). Ten patients were true homozygotes (FH1/FH1) and 5 identical compound heterozygotes (FH1/FH2). Lymphocytes were plated with or without mevastatin, recombinant PCSK9 (rPCSK9), or a PCSK9-neutralizing antibody. Cell surface LDLR expression was analyzed by flow cytometry. All HoFH lymphocytes had reduced cell surface LDLR expression compared with non-FH lymphocytes, for each treatment modality. Lymphocytes from FH1/FH2 patients (LDLR defective/negative) displayed the lowest LDLR expression levels followed by lymphocytes from FH1/FH1 patients (defective/defective). Mevastatin increased, whereas rPCSK9 reduced LDLR expression. The PCSK9-neutralizing antibody restored LDLR expression. Lymphocytes displaying higher LDLR expression levels were those isolated from patients presenting with lowest levels of LDL-C and apolipoprotein B, before and after 24 weeks of evolocumab treatment. These negative correlations remained significant in FH1/FH1 patients and appeared more pronounced when patients with apolipoprotein E3/E3 genotypes were analyzed separately. Significant positive correlations were found between the levels of LDLR expression and the percentage reduction in LDL-C on evolocumab treatment.
conclusionsResidual LDLR expression in HoFH is a major determinant of LDL-C levels and seems to drive their individual response to evolocumab.
Indexed as
HomozygoteMutationPCSK9 InhibitorsAdolescentAdultAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAnticholesteremic AgentsApolipoprotein B-100Cells, CulturedCholesterol, LDLDrug Therapy, CombinationEzetimibeFemaleGenetic Predisposition to DiseaseHeterozygoteAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAnticholesteremic AgentsAPOB protein, humanApolipoprotein B-100Cholesterol, LDLevolocumabEzetimibeHydroxymethylglutaryl-CoA Reductase InhibitorsLDLR protein, humanLovastatinmevastatinPCSK9 InhibitorsPCSK9 protein, humanProprotein Convertase 9Receptors, LDLSerine Proteinase Inhibitorsheterozygotehomozygotelipidsmetabolismmutation
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