Lomitapide affects HDL composition and function

Yahya, R.; Favari, Elda; Calabresi, Laura; Verhoeven, Adrie J.M.; Zimetti, F.; Adorni, Maria Pia; Gomaraschi, Monica; Averna, Maurizio; Cefalù, Angelo Baldassare; Bernini, Franco; Sijbrands, Eric J.G.; Mulder, Monique; Lennep, Jeanine E. Roeters van

doi:10.1016/j.atherosclerosis.2016.05.005

Cited by 11 publications

(13 citation statements)

References 23 publications

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“… 299 However, the follow-up clinical studies determined that lomitapide not only reduced the level of LDL-C, but also resulted in a reduction in plasma HDL-C and ApoAI. 300 , 301 Owing to the combined benefits and risks, lomitapide is currently only available as an adjunctive orphan therapy to treat homozygous familial hypercholesterolemia.…”

Section: Atherosclerosis Therapiesmentioning

confidence: 99%

Inflammation and atherosclerosis: signaling pathways and therapeutic intervention

Kong

Cui

Huang

et al. 2022

Sig Transduct Target Ther

436

173

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Atherosclerosis is a chronic inflammatory vascular disease driven by traditional and nontraditional risk factors. Genome-wide association combined with clonal lineage tracing and clinical trials have demonstrated that innate and adaptive immune responses can promote or quell atherosclerosis. Several signaling pathways, that are associated with the inflammatory response, have been implicated within atherosclerosis such as NLRP3 inflammasome, toll-like receptors, proprotein convertase subtilisin/kexin type 9, Notch and Wnt signaling pathways, which are of importance for atherosclerosis development and regression. Targeting inflammatory pathways, especially the NLRP3 inflammasome pathway and its regulated inflammatory cytokine interleukin-1β, could represent an attractive new route for the treatment of atherosclerotic diseases. Herein, we summarize the knowledge on cellular participants and key inflammatory signaling pathways in atherosclerosis, and discuss the preclinical studies targeting these key pathways for atherosclerosis, the clinical trials that are going to target some of these processes, and the effects of quelling inflammation and atherosclerosis in the clinic.

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Section: Atherosclerosis Therapiesmentioning

confidence: 99%

Inflammation and atherosclerosis: signaling pathways and therapeutic intervention

Kong

Cui

Huang

et al. 2022

Sig Transduct Target Ther

436

173

View full text Add to dashboard Cite

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“…1 while baseline characteristics of patients are presented in Table 1 (Ref. [19,21,[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]).…”

Section: Resultsmentioning

confidence: 99%

“…CVD complications, lomitapiderelated adverse events (AEs) were evaluated as safety outcomes (Table 4, Ref. [19,21,[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]).…”

Section: Efficacy and Safety Outcomesmentioning

confidence: 99%

“…In this study, HoFH patients treated with the maximum tolerable dose of lipid-lowering agents and LA and who did not achieve normal LDL-C levels were subjected to a combination therapy of lomitapide to decrease LDL-C levels. In 2016, Yahya et al [29] conducted a study involving on 4 HoFH patients treated with increasing lomitapide doses. They found that lomitapide reduced LDL-C levels (range -34--89%), and all patients presented with gastrointestinal symptoms during treatment.…”

Section: Fig 3 Overall Quality Assessment Of Case Series According To...mentioning

confidence: 99%

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Efficacy and Safety of Lomitapide in Homozygous Familial Hypercholesterolaemia: A Systematic Review

Wei¹,

Hu²,

Li³

et al. 2022

Rev. Cardiovasc. Med.

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Background: Homozygous familial hypercholesterolaemia (HoFH) patients have little or no low-density lipoprotein receptor (LDLR) function. HMG-CoA (3-hydroxy-3-methyl glutaryl coenzyme A) reductase inhibitors (statins) and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have limited lipid-lowering effects, therefore, there is an urgent need to develop new HoFH treatments. In 2012, the US Food and Drug Administration (FDA) approved the administration of lomitapide for lowering low-density lipoprotein cholesterol (LDL-C) levels. However, lomitapide is associated with various gastrointestinal disorders, elevated hepatic alanine aminotransferase (ALT) levels and other adverse reactions, thus, its long-term efficacy and safety in pediatrics and adults should be evaluated. A systematic review conducted in 2017 reported the efficacy and safety of lomitapide in Family hypercholesterolaemia (FH) patients. In this systematic review, we elucidate on the efficacy and safety of lomitapide in HoFH patients. Methods: A search was conducted in PubMed, Embase, Web of Science and Cochrane library databases to identify valid studies involving lomitapide-treated HoFH patients published before 11th August 2021. Results: A total of 18 clinical studies involving 120 lomitapide-treated HoFH patients were identified. Lomitapide significantly suppressed LDL-C levels in HoFH patients. Clinical manifestations for lomitapide in children were comparable to those in adults. The most common adverse events were gastrointestinal disturbances and elevated ALT levels. However, most patients tolerated the treatment-associated adverse reactions. Low-fat diets and drug dose adjustments were appropriate measures for controlling the treatment-associated adverse reactions. Conclusions: In pediatric and adult HoFH patients, lomitapide significantly suppresses LDL-C levels, therefore, it is an important option for HoFH treatment. The most common adverse events of lomitapide treatment include gastrointestinal disorders and elevated hepatic ALT levels. Despite the limitations, lomitapide is feasible for long-term treatment of HoFH patients, with dietary and safety monitoring. Registration Number in PROSPERO: CRD42021284425.

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“…Based on the data from a phase III clinical study, lomitapide treatment was associated with a moderate decrease in HDL-C levels [45]. However, Yahya et al [50] showed that such a reduction in HDL-C was followed by the shift of the HDL subclass distribution toward more extensive, more buoyant HDL 2 particles, without significant impact on cholesterol efflux capacity (i.e., HDL functionality). Currently, no available data have demonstrated the effects of lomitapide on the sdLDL particles.…”

Section: Lomitapidementioning

confidence: 99%

Novel Pharmaceutical and Nutraceutical-Based Approaches for Cardiovascular Diseases Prevention Targeting Atherogenic Small Dense LDL

et al. 2022

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Compelling evidence supports the causative link between increased levels of low-density lipoprotein cholesterol (LDL-C) and atherosclerotic cardiovascular disease (CVD) development. For that reason, the principal aim of primary and secondary cardiovascular prevention is to reach and sustain recommended LDL-C goals. Although there is a considerable body of evidence that shows that lowering LDL-C levels is directly associated with CVD risk reduction, recent data shows that the majority of patients across Europe cannot achieve their LDL-C targets. In attempting to address this matter, a new overarching concept of a lipid-lowering approach, comprising of even more intensive, much earlier and longer intervention to reduce LDL-C level, was recently proposed for high-risk patients. Another important concern is the residual risk for recurrent cardiovascular events despite optimal LDL-C reduction, suggesting that novel lipid biomarkers should also be considered as potential therapeutic targets. Among them, small dense LDL particles (sdLDL) seem to have the most significant potential for therapeutic modulation. This paper discusses the potential of traditional and emerging lipid-lowering approaches for cardiovascular prevention by targeting sdLDL particles.

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Lomitapide affects HDL composition and function

Abstract: Background: Lomitapide reduces low-density lipoprotein-cholesterol (LDL-C) but also high-

Cited by 11 publications

References 23 publications

Inflammation and atherosclerosis: signaling pathways and therapeutic intervention

Inflammation and atherosclerosis: signaling pathways and therapeutic intervention

Efficacy and Safety of Lomitapide in Homozygous Familial Hypercholesterolaemia: A Systematic Review

Novel Pharmaceutical and Nutraceutical-Based Approaches for Cardiovascular Diseases Prevention Targeting Atherogenic Small Dense LDL

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