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Clinical Trial
. 2018 Jun 20;13(1):96.
doi: 10.1186/s13023-018-0841-3.

Target Achievement and Cardiovascular Event Rates With Lomitapide in Homozygous Familial Hypercholesterolaemia

Free PMC article
Clinical Trial

Target Achievement and Cardiovascular Event Rates With Lomitapide in Homozygous Familial Hypercholesterolaemia

Dirk J Blom et al. Orphanet J Rare Dis. .
Free PMC article


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).

Keywords: (3–10): Homozygous familial hypercholesterolemia; Lomitapide; Low-density lipoprotein cholesterol; Major adverse cardiovascular event; Number needed to treat; Target.

Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the competent regulatory authorities and the ethics committee or independent review board at each site.

Consent for publication

All authors consent to the publication of this paper in accordance with the guidance set out by the ICMJE.

Competing interests

MA and HP are paid employees contracted by Aegerion Pharmaceuticals. DB and MC receive honoraria for consultancy and speaking engagements from Aegerion and other companies that produce therapeutics in the field of HoFH.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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