Advanced Medical Therapeutic Approaches to Treat Chronic Coronary Syndromes: A Narrative Review

Chronic coronary syndromes (CCSs) encompass obstructive and non-obstructive coronary artery disease, including epicardial atherosclerosis, coronary microvascular dysfunction, and coronary vasospasm, which may lead to angina pectoris, myocardial infarction, heart attack, and sudden death. Understanding the pathophysiology of CCS has led to targeted therapeutic approaches aimed at managing dyslipidemia, inflammation, and thrombus formation to reduce cardiovascular burden and mortality risk. This review aimed to explore advanced and emerging therapeutic strategies for the treatment of CCS, including advanced lipid-lowering therapies, Lp(a)-lowering RNA agents, novel anti-inflammatory agents, including interleukin-6 (IL-6)-targeted therapy, Factor XIa-targeted antithrombotic therapy, cholesteryl ester transfer protein inhibitors (CETP), angiopoietin-like protein 3 (ANGPTL3) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), nanoparticle-based targeted therapies, and microbiome-modifying therapies. This review situates each therapeutic agent within the 2024 ESC and 2023 ACC/AHA chronic coronary syndrome guidelines and, because regulatory approval, guideline recommendations, and cardiovascular outcome evidence are distinct concepts, considers each separately: high-intensity statins, ezetimibe, PCSK9 inhibitors, low-dose colchicine, and semaglutide are approved and guideline-recommended for defined populations with outcome-trial support; inclisiran and bempedoic acid are approved and guideline-endorsed as add-on lipid-lowering therapies, although inclisiran's dedicated cardiovascular outcomes trial remains ongoing; and pelacarsen, olpasiran, lepodisiran, zerlasiran, ziltivekimab, and obicetrapib remain investigational, with regulatory approval and guideline recommendations contingent on cardiovascular outcomes trial (CVOT) data. Nanomedicine- and microbiome-based approaches remain preclinical or early-phase and are considered hypothesis-generating. Despite promising advances, long-term safety, optimal patient selection, and cardiovascular outcome benefits remain uncertain. Future research should prioritize outcome-driven trials and personalized therapeutic strategies to address residual cardiovascular risk.

Keywords: Advanced therapeutic approaches, atherosclerosis, chronic coronary syndromes, ESC guidelines, lipoprotein (a).