THERAPY AND CLINICAL TRIALS: Edited by Erik S.G. Stroes and Gerald F. WattsRecent lipoprotein(a) trialsWei, Trent; Cho, Leslie Author Information Department of Preventive Cardiology and Rehabilitation, Women's Cardiovascular Center, Cleveland Clinic, Cleveland, Ohio, USA Correspondence to Leslie Cho, MD, FACC, FSCAI, FESC, Section Head, Preventive Cardiology and Rehabilitation, Director, Women's Cardiovascular Center, Cleveland Clinic, 9500 Euclid Ave JB-1, Cleveland, OH 44195, USA. Tel: +1 216 445 6320; fax: +1 216 444 8856; e-mail: [email protected] Current Opinion in Lipidology 33(6):p 301-308, December 2022. | DOI: 10.1097/MOL.0000000000000856 Buy Metrics Abstract Purpose of review Lipoprotein(a) (Lp(a)) is a genetically determined independent risk factor for cardiovascular disease and calcific aortic stenosis; thus, serum levels are minimally affected by conventional treatments for hypercholesterolemia and hypertriglyceridemia. New RNA therapies directly targeting Lp(a) have demonstrated efficacy in decreasing serum levels. Several recent trials have demonstrated efficacy and safety of these RNA therapeutics. Recent findings Single-stranded antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) are two classes of RNA-targeted therapeutics that specifically target the LPA gene, which encodes for apolipoprotein(a), a dominant and rate-limiting component in the hepatic synthesis of Lp(a) particle. Pelacarsen (ASO), olpasiran (siRNA) and SLN360 (siRNA) are novel drugs that have demonstrated efficacy in lowering Lp(a) levels and excellent safety profiles. Summary Lp(a) is an independent risk factor for cardiovascular disease. RNA-directed therapies, pelacarsen, olpasiran and SLN360, have shown efficacy in dramatically lowering serum Lp(a) levels. Outcomes data will be the next frontier of Lp(a) trials. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.