Advances in Pharmacologic Strategies to Reduce Atheroma Plaque Size in Atheromatosis: A Comprehensive Review

Atheromatosis, characterized by the accumulation of atheromatous plaques within the arterial walls, is a major contributor to cardiovascular diseases, including myocardial infarction and ischemic stroke. Recent therapeutic advancements have shifted from merely preventing plaque progression to actively reducing plaque size and improving stability to lower the risk of cardiovascular events. This narrative review examines established and emerging pharmacologic strategies for plaque management. Traditional lipid-lowering therapies, including statins and fibrates, remain foundational. Recent agents such as PCSK9 inhibitors, bempedoic acid, and anti-inflammatory drugs like canakinumab and colchicine have introduced new mechanisms for addressing atherosclerotic burden. Novel classes such as GLP-1 receptor agonists and SGLT2 inhibitors, initially developed for diabetes management, have demonstrated cardiovascular benefits with potential implications for plaque reduction. PCSK9 inhibitors reduce LDL-C by 50–60%, exceeding the 30–40% typically achieved with statins. This review is the first comprehensive synthesis of lipid-lowering and anti-inflammatory strategies focused on atheroma regression rather than just stabilization. This review synthesizes evidence from major clinical trials, highlights mechanistic insights, and discusses future directions in this rapidly evolving field. A multifaceted, personalized approach integrating these therapies offers the promise of improved outcomes for patients with atheromatosis.