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

dc.contributor.authorBlom, Dirk J
dc.contributor.authorCuchel, Marina
dc.contributor.authorAger, Miranda
dc.contributor.authorPhillips, Helen
dc.date.accessioned2018-07-11T12:31:28Z
dc.date.available2018-07-11T12:31:28Z
dc.date.issued2018-06-20
dc.date.updated2018-06-24T03:28:08Z
dc.description.abstractBackground 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).
dc.identifier.apacitationBlom, D. J., Cuchel, M., Ager, M., & Phillips, H. (2018). Target achievement and cardiovascular event rates with Lomitapide in homozygous Familial Hypercholesterolaemia. <i>Orphanet Journal of Rare Diseases</i>, http://hdl.handle.net/11427/28293en_ZA
dc.identifier.chicagocitationBlom, Dirk J, Marina Cuchel, Miranda Ager, and Helen Phillips "Target achievement and cardiovascular event rates with Lomitapide in homozygous Familial Hypercholesterolaemia." <i>Orphanet Journal of Rare Diseases</i> (2018) http://hdl.handle.net/11427/28293en_ZA
dc.identifier.citationOrphanet Journal of Rare Diseases. 2018 Jun 20;13(1):96
dc.identifier.ris TY - Journal Article AU - Blom, Dirk J AU - Cuchel, Marina AU - Ager, Miranda AU - Phillips, Helen AB - 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). DA - 2018-06-20 DB - OpenUCT DP - University of Cape Town J1 - Orphanet Journal of Rare Diseases LK - https://open.uct.ac.za PB - University of Cape Town PY - 2018 T1 - Target achievement and cardiovascular event rates with Lomitapide in homozygous Familial Hypercholesterolaemia TI - Target achievement and cardiovascular event rates with Lomitapide in homozygous Familial Hypercholesterolaemia UR - http://hdl.handle.net/11427/28293 ER - en_ZA
dc.identifier.urihttps://doi.org/10.1186/s13023-018-0841-3
dc.identifier.urihttp://hdl.handle.net/11427/28293
dc.identifier.vancouvercitationBlom DJ, Cuchel M, Ager M, Phillips H. Target achievement and cardiovascular event rates with Lomitapide in homozygous Familial Hypercholesterolaemia. Orphanet Journal of Rare Diseases. 2018; http://hdl.handle.net/11427/28293.en_ZA
dc.language.isoen
dc.publisherBioMed Central
dc.publisher.departmentDivision of Lipidologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rights.holderThe Author(s).
dc.sourceOrphanet Journal of Rare Diseases
dc.source.urihttps://ojrd.biomedcentral.com/
dc.subject.other(3–10): Homozygous familial hypercholesterolemia
dc.subject.otherLomitapide
dc.subject.otherNumber needed to treat
dc.subject.otherTarget
dc.subject.otherLow-density lipoprotein cholesterol
dc.subject.otherMajor adverse cardiovascular event
dc.titleTarget achievement and cardiovascular event rates with Lomitapide in homozygous Familial Hypercholesterolaemia
dc.typeJournal Article
uct.type.filetypeText
uct.type.filetypeImage
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