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Target achievement and cardiovascular event rates with Lomitapide in homozygous Familial Hypercholesterolaemia

BACKGROUND: Homozygous familial hypercholesterolaemia (HoFH) is characterized by a markedly increased risk of premature cardiovascular (CV) events and cardiac death. Lomitapide reduces low-density lipoprotein cholesterol (LDL-C) levels; however, the probable impact on LDL-C goals and CV events is un...

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Autores principales: Blom, Dirk J., Cuchel, Marina, Ager, Miranda, Phillips, Helen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6011273/
https://www.ncbi.nlm.nih.gov/pubmed/29925433
http://dx.doi.org/10.1186/s13023-018-0841-3
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author Blom, Dirk J.
Cuchel, Marina
Ager, Miranda
Phillips, Helen
author_facet Blom, Dirk J.
Cuchel, Marina
Ager, Miranda
Phillips, Helen
author_sort Blom, Dirk J.
collection PubMed
description BACKGROUND: Homozygous familial hypercholesterolaemia (HoFH) is characterized by a markedly increased risk of premature cardiovascular (CV) events and cardiac death. Lomitapide reduces low-density lipoprotein cholesterol (LDL-C) levels; however, the probable impact on LDL-C goals and CV events is unknown. METHODS: We used data collected in the first 26 weeks of the lomitapide pivotal phase 3 study (NCT00730236) to evaluate achievement of European Atherosclerosis Society (EAS) LDL-C targets. We used publicly available data reporting major adverse CV events (MACE) rates from other cohorts of HoFH patients to compare event rates for an equivalent number of patient years of exposure (98) in the lomitapide extension trial (NCT00943306). RESULTS: Twenty-nine patients were included in the phase 3 study. During the first 26 weeks, 15 (51%) and eight (28%) reached LDL-C targets of 100 mg/dL and 70 mg/dL, respectively, at least once. Fourteen (74%) and 11 (58%) of the 19 patients who remained in the extension study after week 126 reached LDL-C targets of 100 mg/dL and 70 mg/dL at least once during the entire study period. Only two MACE were reported in the lomitapide trials (one cardiac death and one coronary artery bypass graft (CABG)) – equivalent to 1.7 events per 1000 patient months of treatment. MACE rates were 21.7, 9.5 and 1.8 per 1000 patient-months respectively in cohorts of HoFH patients pre- and post-mipomersen, and receiving evolocumab. On treatment LDL-C levels were 166, 331 and 286 mg/dL for lomitapide, mipomersen and evolocumab, respectively. CONCLUSIONS: Approximately three quarters and half of patients who took lomitapide for at least 2 years reached LDL-C goals of 100 mg/dL and 70 mg/dL, respectively. There were fewer major CV events per 1000 patient months of treatment in patients taking lomitapide, mipomersen or evolocumab than reported in the mipomersen cohort prior to starting mipomersen. These results support the hypothesis that novel lipid-lowering therapies may reduce CV events in HoFH patients by lowering LDL-C further. TRIAL REGISTRATION: NCT00730236 (registered 8 Aug 2008) and NCT00943306 (registered 22 July 2009).
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spelling pubmed-60112732018-06-27 Target achievement and cardiovascular event rates with Lomitapide in homozygous Familial Hypercholesterolaemia Blom, Dirk J. Cuchel, Marina Ager, Miranda Phillips, Helen Orphanet J Rare Dis Research BACKGROUND: Homozygous familial hypercholesterolaemia (HoFH) is characterized by a markedly increased risk of premature cardiovascular (CV) events and cardiac death. Lomitapide reduces low-density lipoprotein cholesterol (LDL-C) levels; however, the probable impact on LDL-C goals and CV events is unknown. METHODS: We used data collected in the first 26 weeks of the lomitapide pivotal phase 3 study (NCT00730236) to evaluate achievement of European Atherosclerosis Society (EAS) LDL-C targets. We used publicly available data reporting major adverse CV events (MACE) rates from other cohorts of HoFH patients to compare event rates for an equivalent number of patient years of exposure (98) in the lomitapide extension trial (NCT00943306). RESULTS: Twenty-nine patients were included in the phase 3 study. During the first 26 weeks, 15 (51%) and eight (28%) reached LDL-C targets of 100 mg/dL and 70 mg/dL, respectively, at least once. Fourteen (74%) and 11 (58%) of the 19 patients who remained in the extension study after week 126 reached LDL-C targets of 100 mg/dL and 70 mg/dL at least once during the entire study period. Only two MACE were reported in the lomitapide trials (one cardiac death and one coronary artery bypass graft (CABG)) – equivalent to 1.7 events per 1000 patient months of treatment. MACE rates were 21.7, 9.5 and 1.8 per 1000 patient-months respectively in cohorts of HoFH patients pre- and post-mipomersen, and receiving evolocumab. On treatment LDL-C levels were 166, 331 and 286 mg/dL for lomitapide, mipomersen and evolocumab, respectively. CONCLUSIONS: Approximately three quarters and half of patients who took lomitapide for at least 2 years reached LDL-C goals of 100 mg/dL and 70 mg/dL, respectively. There were fewer major CV events per 1000 patient months of treatment in patients taking lomitapide, mipomersen or evolocumab than reported in the mipomersen cohort prior to starting mipomersen. These results support the hypothesis that novel lipid-lowering therapies may reduce CV events in HoFH patients by lowering LDL-C further. TRIAL REGISTRATION: NCT00730236 (registered 8 Aug 2008) and NCT00943306 (registered 22 July 2009). BioMed Central 2018-06-20 /pmc/articles/PMC6011273/ /pubmed/29925433 http://dx.doi.org/10.1186/s13023-018-0841-3 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Blom, Dirk J.
Cuchel, Marina
Ager, Miranda
Phillips, Helen
Target achievement and cardiovascular event rates with Lomitapide in homozygous Familial Hypercholesterolaemia
title Target achievement and cardiovascular event rates with Lomitapide in homozygous Familial Hypercholesterolaemia
title_full Target achievement and cardiovascular event rates with Lomitapide in homozygous Familial Hypercholesterolaemia
title_fullStr Target achievement and cardiovascular event rates with Lomitapide in homozygous Familial Hypercholesterolaemia
title_full_unstemmed Target achievement and cardiovascular event rates with Lomitapide in homozygous Familial Hypercholesterolaemia
title_short Target achievement and cardiovascular event rates with Lomitapide in homozygous Familial Hypercholesterolaemia
title_sort target achievement and cardiovascular event rates with lomitapide in homozygous familial hypercholesterolaemia
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6011273/
https://www.ncbi.nlm.nih.gov/pubmed/29925433
http://dx.doi.org/10.1186/s13023-018-0841-3
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