Toward an international consensus-Integrating lipoprotein apheresis and new lipid-lowering drugs

Background: Despite advances in pharmacotherapy of lipid disorders, many dyslipidemic patients do not attain sufficient lipid lowering to mitigate risk of atherosclerotic cardiovascular disease. Several classes of novel lipid-lowering agents are being evaluated to reduce atherosclerotic cardiovascular disease risk. Lipoprotein apheresis (LA) is effective in acutely lowering the plasma concentrations of atherogenic lipoproteins including low-density lipoprotein cholesterol and lipoprotein(a), and novel lipid-lowering drugs may dampen the lipid rebound effect of LA, with the possibility that LA frequency may be decreased, in some cases even be discontinued. Sources of material: This document builds on current American Society for Apheresis guidelines and, for the first time, makes recommendations from summarized data of the emerging lipid-lowering drug classes (inhibitors of proprotein convertase subtilisin/kexin type 9 or microsomal triglyceride transfer protein, high-density lipoprotein mimetic), including the available evidence on combination therapy with LA with respect to the management of patients with dyslipidemia. Abstract of findings: Recommendations for different indications are given based on the latest evidence. However, except for lomitapide in homozygous familial hypercholesterolemia and alirocumab/evolocumab in heterozygous familial hypercholesterolemia subjects, limited data are available on the effectiveness and safety of combination therapy. More studies on combining LA with novel lipid-lowering drugs are needed. Conclusion: Novel lipid-lowering agents have potential to improve the performance of LA, but more evidence is needed. The Multidisciplinary International Group for Hemapheresis TherapY and Metabolic DIsturbances Contrast scientific society aims to establish an international registry of clinical experience on LA combination therapy to expand the evidence on this treatment in individuals at high cardiovascular disease risk

Zusammensetzung der Lipoproteinfraktionen VLDL, LDL und HDL bei Hyperlipämikern der Typen IIa, IIb, III, IV und V im Vergleich zu Stoffwechselgesunden

Peer Reviewe

Short term effects of dietary medium-chain fatty acids and n-3 long-chain polyunsaturated fatty acids on the fat metabolism of healthy volunteers

Abstract Background The amount and quality of dietary fatty acids can modulate the fat metabolism. Objective This dietary intervention is based on the different metabolic pathways of long-chain saturated fatty acids (LCFA), which are mostly stored in adipocytic triacylglycerols, medium-chain fatty acids (MCFA) which are preferentially available for hepatic mitochondrial β-oxidation and n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) suggested to modulate fat oxidation and storage by stimulating the peroxisomal β-oxidation. Combined dietary MCFA and n-3 LCPUFA without LCFA may synergistically stimulate fatty acid oxidation resulting in blood lipid clearance and LCFA release from adipocytes. Design In a short term, parallel, randomized, double-blind trial effects on the fatty acid metabolism of 10 healthy volunteers (Body Mass Index 25–30) of a formula containing 72% MCFA and 22% n-3 LCPUFA without LCFA (intake: 1.500 kcal/day; fat: 55.5% of energy) were measured in comparison to an isoenergetic formula with equal fat amount and LCFA dominated lipid profile. Results The plasma triacylglycerol (p Conclusion Combined dietary 72% MCFA and 22% n-3 LCPUFA without LCFA stimulate the fatty acid oxidation and release from adipocytes without affecting any safety parameters measured.</p

The cardiovascular safety of oral alitretinoin. A population-based cohort study involving 19,513 patients exposed to oral alitretinoin

International audienceBACKGROUND: Oral alitretinoin is a retinoid used for severe chronic hand eczema. Although caution is recommended for patients with uncontrolled dyslipidaemia or cardiovascular risk factors, the actual atherothrombotic risk has not been investigated thus far. OBJECTIVES: Our aim was to detect any excess of atherothrombotic events among patients exposed to alitretinoin, during the treatment or in the 2 years following initiation. METHODS: Using the French Health Insurance database, we compared the number of patients having had an atherothrombotic event (coronary artery disease, ischemic stroke or peripheral artery disease requiring revascularisation) in the population exposed to oral alitretinoin versus the general population of the same age, gender and baseline cardiovascular risk, using standardized morbidity ratios (SMRs). RESULTS: Between 2009 and 2017, 19,513 patients were exposed to oral alitretinoin in France. Sixty-four (0.3%) patients had an atherothrombotic event while on alitretinoin. Patients receiving alitretinoin experienced no more atherothrombotic events than the general population: patients without cardiovascular risk factors or previous atherothrombotic events reached a SMR of 0.65, 95%CI [0.26-1.34] during alitretinoin treatment, and 1.21, 95%CI [0.90-1.59] in the 2 years following initiation; patients with cardiovascular risk factors or previous atherothrombotic events reached a SMR of 0.82, 95%CI [0.60-1.08] during alitretinoin treatment, and 0.95, 95%CI [0.82-1.09] in the 2 years following initiation. Taken separately, SMRs for each outcome did not increase either. CONCLUSIONS: These data from an exhaustive nationwide population-based study did not support an increase in the incidence of atherothrombotic events under alitretinoin, regardless of the baseline cardiovascular risk of the patient