NOVEL DIRECTIONS IN LIPID-LOWERING THERAPY FOR THE PREVENTION OF CARDIOVASCULAR DISEASES

Beyond the Pill – The Future of LipidLowering Therapy: A 2026 Review of Novel Lipid-Lowering Agents

These agents have expanded treatment options for patients with familial dyslipidaemia, severe hypertriglyceridaemia, and persistent residual cardiovascular risk while paving the way for precision medicine.

Targeting Residual Inflammation in Cardiovascular Disease: Beyond LDL Cholesterol Toward Precision Cardiometabolic Prevention

Cardiovascular disease remains the leading cause of mortality worldwide despite substantial advances in lipid-lowering therapies. Although achieving recommended low-density lipoprotein cholesterol (LDL-C) targets significantly reduces cardiovascular risk, many patients continue to experience recurrent cardiovascular events, a phenomenon known as residual cardiovascular risk. Increasing evidence indicates that chronic low-grade inflammation is a major contributor to this persistent risk. This review analyzes current scientific evidence regarding the biological mechanisms, inflammatory biomarkers, and emerging therapeutic strategies associated with residual inflammatory risk beyond LDL cholesterol. The literature demonstrates that activation of the NLRP3 inflammasome and the interleukin-1β/interleukin-6 pathway plays a central role in endothelial dysfunction, plaque progression, and atherosclerotic instability. High-sensitivity C-reactive protein (hs-CRP) remains the most widely validated biomarker for identifying persistent inflammatory activity in clinical practice. Landmark clinical trials, including CANTOS, COLCOT, and LoDoCo2, have demonstrated that selective anti-inflammatory therapies reduce recurrent cardiovascular events independently of additional LDL-C lowering, whereas nonspecific anti-inflammatory approaches have shown limited benefit. Furthermore, obesity, type 2 diabetes mellitus, metabolic syndrome, and chronic kidney disease substantially amplify residual inflammatory risk through shared pathophysiological mechanisms. Current evidence supports a transition toward comprehensive cardiometabolic prevention integrating lipid management, lifestyle modification, metabolic optimization, and targeted anti-inflammatory therapy. Future precision medicine strategies incorporating inflammatory biomarkers and individualized risk assessment may further improve cardiovascular outcomes and reduce the global burden of atherosclerotic disease.

Targeting Dyslipidemia in Ischemic Stroke: Pathophysiology, Clinical Evidence, and Future Perspectives.

Dyslipidemia is a major risk factor for atherosclerosis, and high low-density lipoprotein (LDL) cholesterol is closely associated with the onset of atherosclerotic cardiovascular disease (ASCVD), including coronary artery disease. Numerous large-scale clinical trials have demonstrated that LDL cholesterol-lowering therapy, primarily involving statins, reduces not only coronary events, but also stroke, and has been established as a cornerstone of cardiovascular prevention. However, ischemic stroke is a group of diseases comprising different pathologies, such as atherothrombotic stroke, cardioembolic stroke, and small-vessel disease; the involvement of dyslipidemia and the efficacy of lipid-lowering therapy vary significantly depending on the subtype. Therefore, the evidence established for coronary artery disease cannot necessarily be applied directly to stroke management, and establishing lipid management strategies tailored to each subtype has become a critical challenge in stroke management. Furthermore, in recent years, in addition to LDL cholesterol-lowering therapy, treatments targeting hypertriglyceridemia, lipoprotein(a) [Lp(a)], and residual inflammatory risk have advanced, and the development of new therapeutic agents-such as PCSK9 inhibitors, selective PPARα modulators, and ATP citrate lyase inhibitors-is progressing, thus raising expectations for their application in stroke prevention. This article provides an overview of domestic and international guidelines for dyslipidemia and summarizes the association between dyslipidemia and ischemic stroke from the perspectives of pathophysiology, pathological findings, and imaging and blood biomarker. In addition, it outlines the latest evidence from large-scale clinical trials, new lipid-lowering therapies, acute-phase lipid management, and interventions targeting residual risk, and discusses the current status and future prospects of lipid management tailored to specific stroke subtypes.

Current Trends in Lipid-Lowering Target Therapy

Lipoprotein(a) as a Cardiovascular Risk Factor: Clinical Significance and Therapeutic Perspectives

Lipoprotein(a) (Lp(a)) is an elusive yet powerful cardiovascular risk factor, largely independent of LDL cholesterol. Elevated Lp(a) increases the risk of coronary artery disease, stroke, peripheral arterial disease, calcific aortic valve disease, heart failure, and abdominal aortic aneurysm. The challenge is that conventional lipid-lowering therapies have minimal impact on Lp(a), leaving patients with substantial residual risk. While observational and genetic studies generally support Lp(a) as a driver of cardiovascular events, results are not entirely consistent, and risk may differ between primary and secondary prevention. Novel therapies—including antisense oligonucleotides, siRNA therapeutics, CETP inhibitors, and experimental gene-editing approaches—show promising potential, reducing Lp(a) levels by up to 90%. Ongoing phase III trials will clarify whether these reductions translate into meaningful decreases in cardiovascular morbidity and mortality. This review critically examines the current evidence, highlights gaps in knowledge, and discusses emerging therapeutic strategies, emphasizing the need for individualized risk assessment. Lp(a) may soon shift from a “silent threat” to a precise, actionable target in cardiovascular prevention.

Contemporary non-statin therapies for dyslipidemia management: achieving current lipid targets

This expert position paper proposes practical algorithms for a precision medicine approach in Latin America, matching treatment intensity to individual risk profiles for the primary and secondary prevention of atherosclerotic cardiovascular disease.