Massimiliano Ruscica1, Nicola Ferri2, Raul D Santos3,4, Cesare R Sirtori5, Alberto Corsini6,7. 1. Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy. massimiliano.ruscica@unimi.it. 2. Department of Pharmaceutical and Pharmacological Sciences, Università degli Studi di Padova, Padova, Italy. 3. Lipid Clinic, Heart Institute (InCor), University of Sao Paulo, São Paulo, Brazil. 4. Hospital Israelita Albert Einstein, São Paulo, Brazil. 5. Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy. 6. Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy. alberto.corsini@unimi.it. 7. IRCCS MultiMedica, Sesto S. Giovanni, Milan, Italy. alberto.corsini@unimi.it.
Abstract
PURPOSE OF REVIEW: Based on the recent data of the DA VINCI study, it is clear that, besides utilization of statins, there is a need to increase non-statin lipid lowering approaches to reduce the cardiovascular burden in patients at highest risk. RECENT FINDINGS: For hypercholesterolemia, the small synthetic molecule bempedoic acid has the added benefit of selective liver activation, whereas inclisiran, a hepatic inhibitor of the PCSK9 synthesis, has comparable effects with PCSK9 monoclonal antibodies. For hypertriglyceridemia, cardiovascular benefit has been achieved by the use of icosapent ethyl, whereas results with pemafibrate, a selective agonist of PPAR-α, are eagerly awaited. In the era of RNA-based therapies, new options are offered to dramatically reduce levels of lipoprotein(a) (APO(a)LRX) and of triglycerides (ANGPTL3LRX and APOCIII-LRx). Despite the demonstrated benefits of statins, a large number of patients still remain at significant risk because of inadequate LDL-C reduction or elevated blood triglyceride-rich lipoproteins or lipoprotein(a). The area of lipid modulating agents is still ripe with ideas and major novelties are to be awaited in the next few years.
PURPOSE OF REVIEW: Based on the recent data of the DA VINCI study, it is clear that, besides utilization of statins, there is a need to increase non-statin lipid lowering approaches to reduce the cardiovascular burden in patients at highest risk. RECENT FINDINGS: For hypercholesterolemia, the small synthetic molecule bempedoic acid has the added benefit of selective liver activation, whereas inclisiran, a hepatic inhibitor of the PCSK9 synthesis, has comparable effects with PCSK9 monoclonal antibodies. For hypertriglyceridemia, cardiovascular benefit has been achieved by the use of icosapent ethyl, whereas results with pemafibrate, a selective agonist of PPAR-α, are eagerly awaited. In the era of RNA-based therapies, new options are offered to dramatically reduce levels of lipoprotein(a) (APO(a)LRX) and of triglycerides (ANGPTL3LRX and APOCIII-LRx). Despite the demonstrated benefits of statins, a large number of patients still remain at significant risk because of inadequate LDL-C reduction or elevated blood triglyceride-rich lipoproteins or lipoprotein(a). The area of lipid modulating agents is still ripe with ideas and major novelties are to be awaited in the next few years.
Entities:
Keywords:
ANGPTL3LRX; APOCIII-LRx; Inclisiran; Lipoprotein(a); Proprotein convertase subtilisin/kexin type 9
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