Emerging RNA Therapeutics to Lower Blood Levels of Lp(a) JACC Focus Seminar 2/4

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

卷:77

Article

Tsimikas, Sotirios¹  Moriarty, Patrick M.²  Stroes, Erik S.³ 

[1] Univ Calif San Diego, Sulpizio Cardiovasc Ctr, Div Cardiovasc Med, La Jolla, CA 92093 USA

[2] Univ Kansas, Med Ctr, Div Clin Pharmacol, Dept Internal Med, Kansas City, MO USA

[3] Acad Med Ctr, Dept Vasc Med, Amsterdam, Netherlands

关键词: aortic stenosis;    antisense;    cardiovascular disease;    lipoprotein(a);    lipoproteins;   

DOI  :  10.1016/j.jacc.2021.01.051

来源: Elsevier

【 摘 要 】

Lipoprotein(a) [Lp(a)] has risen to the level of an accepted cardiovascular disease risk factor, but final proof of causality awaits a randomized trial of Lp(a) towering. Inhibiting apotipoprotein(a) production in the hepatocyte with ribonucleic add therapeutics has emerged as an elegant and effective solution to reduce plasma Lp(a) levels. Phase 2 clinical trials have shown that the antisense oligonucleotide petacarsen reduced mean Lp(a) levels by 80%, allowing 98% of subjects to reach on-treatment levels of <125 nmol/l (similar to 50 mg/dl). The phase 3 Lp(a)HORIZON (Assessing the Impact of Lipo-protein(a) Lowering With TQJ230 on Major Cardiovascular Events in Patients With CVD) outcomes trial is currently enrolling approximately 7,680 patients with history of myocardial infarction, ischemic stroke, and symptomatic peripheral arterial disease and controlled tow-density lipoprotein cholesterol to petacarsen versus placebo. The co-primary endpoints are major adverse cardiovascular events in subjects with Lp(a) >70 mg/dl and >90 mg/dl, in which either of the two being positive will lead to a successful trial. Additional ribonucleic acid-targeted therapies to tower Lp(a) are in preclinical and clinical development. The testing of the Lp(a) hypothesis will provide proof whether Lp(a)-mediated risk can be abolished by potent Lp(a) lowering. (C) 2021 by the American College of Cardiology Foundation.

【 授权许可】

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