Brian Kolski1, Sotirios Tsimikas. 1. Division of Cardiology, Department of Medicine, University of California San Diego, La Jolla, California 92093-0682, USA.
Abstract
PURPOSE OF REVIEW: Recent epidemiological and genetic studies have suggested that lipoprotein (a) [Lp(a)] is a causal mediator of cardiovascular disease (CVD). There is now interest in evaluating Lp(a) as a therapeutic target. This review will summarize emerging therapeutic agents to lower Lp(a). RECENT FINDINGS: Apheresis is the most efficacious method to lower Lp(a). Currently, there are no approved drugs to specifically lower Lp(a). However, recent data has demonstrated that Lp(a) can be significantly lowered, along with reductions in other apolipoprotein B-100 (apoB) containing lipoproteins, with antisense oligonucleotides to apoB, monoclonal antibodies to proprotein convertase subtilisin/kexin type 9, cholesterol ester transfer protein inhibitors, and thyromimetics. The farnesoid X receptor/fibroblast growth factor axis and interleukin-6 also influence Lp(a) levels and may be targets of therapy. Finally, specific apolipoprotein (a) [apo(a)] inhibitors apo(a) have been developed and reduce apo(a) mRNA and protein levels up to 86% without significantly affecting other lipoproteins. SUMMARY: Lp(a) remains the last major lipoprotein disorder without any specific therapy. With the strong and accumulating data on its role as a causal risk factor for CVD, a rationale exists to develop novel agents to reduce Lp(a) and test the hypothesis that this will lead to reduced CVD events.
PURPOSE OF REVIEW: Recent epidemiological and genetic studies have suggested that lipoprotein (a) [Lp(a)] is a causal mediator of cardiovascular disease (CVD). There is now interest in evaluating Lp(a) as a therapeutic target. This review will summarize emerging therapeutic agents to lower Lp(a). RECENT FINDINGS: Apheresis is the most efficacious method to lower Lp(a). Currently, there are no approved drugs to specifically lower Lp(a). However, recent data has demonstrated that Lp(a) can be significantly lowered, along with reductions in other apolipoprotein B-100 (apoB) containing lipoproteins, with antisense oligonucleotides to apoB, monoclonal antibodies to proprotein convertase subtilisin/kexin type 9, cholesterol ester transfer protein inhibitors, and thyromimetics. The farnesoid X receptor/fibroblast growth factor axis and interleukin-6 also influence Lp(a) levels and may be targets of therapy. Finally, specific apolipoprotein (a) [apo(a)] inhibitors apo(a) have been developed and reduce apo(a) mRNA and protein levels up to 86% without significantly affecting other lipoproteins. SUMMARY:Lp(a) remains the last major lipoprotein disorder without any specific therapy. With the strong and accumulating data on its role as a causal risk factor for CVD, a rationale exists to develop novel agents to reduce Lp(a) and test the hypothesis that this will lead to reduced CVD events.
Authors: Fleur M van der Valk; Siroon Bekkering; Jeffrey Kroon; Calvin Yeang; Jan Van den Bossche; Jaap D van Buul; Amir Ravandi; Aart J Nederveen; Hein J Verberne; Corey Scipione; Max Nieuwdorp; Leo A B Joosten; Mihai G Netea; Marlys L Koschinsky; Joseph L Witztum; Sotirios Tsimikas; Niels P Riksen; Erik S G Stroes Journal: Circulation Date: 2016-08-05 Impact factor: 29.690