Affiliation:
1. Department of Cardiovascular Medicine, Mayo Clinic, 5777 E Mayo Blvd, Phoenix, AZ 85054, USA
2. Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN 55905, USA
Abstract
Lipoprotein(a) [Lp(a)] is a lipid molecule with atherogenic, inflammatory, thrombotic, and antifibrinolytic effects, whose concentrations are predominantly genetically determined. The association between Lp(a) and cardiovascular diseases (CVDs) has been well-established in numerous studies, and the ability to measure Lp(a) levels is widely available in the community. As such, there has been increasing interest in Lp(a) as a therapeutic target for the prevention of CVD. The impact of the currently available lipid-modifying agents on Lp(a) is modest and heterogeneous, except for the monoclonal antibody proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), which demonstrated a significant reduction in Lp(a) levels. However, the absolute reduction in Lp(a) to significantly decrease CVD outcomes has not been definitely established, and the magnitude of the effect of PCSK9i seems insufficient to directly reduce the Lp(a)-related CVD risk. Therefore, emerging therapies are being developed that specifically aim to lower Lp(a) levels and the risk of CVD, including RNA interference (RNAi) agents, which have the capacity for temporary and reversible downregulation of gene expression. This review article aims to summarize the effects of Lp(a) on CVD and to evaluate the available evidence on established and emerging therapies targeting Lp(a) levels, focusing on the potential reduction of CVD risk attributable to Lp(a) concentrations.
Subject
Drug Discovery,Pharmaceutical Science,Molecular Medicine
Reference122 articles.
1. Cholesterol Treatment Trialists Collabtion (2019). Efficacy and safety of statin therapy in older people: A meta-analysis of individual participant data from 28 randomised controlled trials. Lancet, 393, 407–415.
2. Ezetimibe for the prevention of cardiovascular disease and all-cause mortality events;Zhan;Cochrane Database Syst. Rev.,2018
3. Fibrates for primary prevention of cardiovascular disease events;Jakob;Cochrane Database Syst. Rev.,2016
4. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events;Robinson;N. Engl. J. Med.,2015
5. The Evolving Understanding and Approach to Residual Cardiovascular Risk Management;Dhindsa;Front. Cardiovasc. Med.,2020
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