Therapeutic Agents Targeting Cardiometabolic Risk for Preventing and Treating Atherosclerotic Cardiovascular Diseases

Abstract

Targeting atherogenic lipoprotein levels with statins remains the current cornerstone of atherosclerotic cardiovascular disease (ACVD) management. In patients at high ACVD risk who cannot achieve the desired low-density lipoprotein (LDL) cholesterol target, the addition of compounds such as ezetimibe and proprotein subtilisin/kexin type-9 (PCSK9) inhibitors incrementally lowers cardiovascular risk. New glucose-lowering drugs such as glucacon-like peptide-1 receptor (GLP1R) agonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors were also shown to improve cardiometabolic risk factors and provide cardiovascular benefits in patients with type 2 diabetes. Our objective is to review the role of these agents in the management of patients at high ACVD risk and introduce new and (re)-emerging drugs targeting atherogenic lipoproteins such as LDL (inclisiran, bempedoic acid, etc.), remnant-like particles (fibrates, volanesorsen, and angiopoietin-like protein-3 (ANGPTL3) inhibitors), and lipoprotein(a) (AKCEA-APO[A]L ). The potential role of drugs targeting inflammation (canakinumab, methotrexate, and colchicine) in ACVD risk prevention/management will also be discussed.

Pterostilbene Increases LDL Metabolism in HL-1 Cardiomyocytes by Modulating the PCSK9/HNF1α/SREBP2/LDLR Signaling Cascade, Upregulating Epigenetic hsa-miR-335 and hsa-miR-6825, and LDL Receptor Expression

“…Epigenetic modulation using oligonucleotides to regulate disease gene expression through a variety of processes, such as RNAi, splicing modulation, target degradation by RNase H-mediated cleavage, non-coding RNA inhibition, programmed gene editing, and gene activation, has opened new opportunities for therapy development [ 46 ]. Inclisiran is a double-stranded small interfering RNA designed to target PCSK9 mRNA and subsequently inhibit PCSK9 synthesis and secretion of both free and lipoprotein-bound forms [ 47 ]. It has the potential benefit of much lower dose frequency than treatment with PCSK9 monoclonal antibodies.…”

A Review on Clinical Outcomes of Bempedoic Acid as Add-on Therapy With Ezetimibe for the Treatment of Hyperlipidemia

“…Bempedoic acid is a non-statin, small molecule inhibitor of ATP citrate (MW 344.5g/mol). BA offers a safe and effective oral therapeutic option for lipid-lowering in patients who cannot tolerate statins by lowering LDL-C 6,7 . Ezetimibe is in a class of lipid-lowering compounds that selectively inhibit the intestinal absorption of cholesterol (MW413.4 g/mol) 8 .…”

The Relationship between Compound Danshen Dripping Pills with Isosorbide Mononitrate in the Treatment of Elderly Patients with Unstable Angina Pectoris

“…UAP [ 1 ] is a common coronary syndrome between stable angina and acute myocardial infarction, which could lead to myocardial infarction or sudden death [ 2 ]; it is a clinically common cardiovascular disease (CVD) [ 3 ]. The pain can be induced; UAP is accompanied by accidental pains which would be induced even in the resting state [ 4 ].…”