Abstract
High-risk dyslipidemia is a treatment problem defined less by an isolated cholesterol value than by the interaction between atherogenic lipoprotein burden and absolute cardiovascular risk. This structured narrative review examines contemporary lipid targets, the role of high-intensity statins, and the place of newer lipid-lowering agents in patients with established or markedly elevated risk of atherosclerotic cardiovascular disease. Searches conducted between August and September 2026 prioritized PubMed/MEDLINE, current 2025 European Society of Cardiology/European Atherosclerosis Society guidance, the 2026 American College of Cardiology/American Heart Association multisociety dyslipidemia guideline, pivotal randomized trials, and major meta-analyses. Current evidence supports intensive and early low-density lipoprotein cholesterol (LDL-C) reduction, with treatment goals that become progressively lower as baseline risk rises. High-intensity statins remain the therapeutic foundation because of extensive outcome evidence, but treatment should not stop at the maximally tolerated statin dose when LDL-C remains above goal. Ezetimibe, PCSK9 monoclonal antibodies, and bempedoic acid have demonstrated cardiovascular benefit in appropriate populations, whereas inclisiran provides potent and durable LDL-C lowering but definitive randomized cardiovascular outcome evidence remains pending as of 2026. Effective care therefore requires target-oriented combination therapy, active management of statin-associated symptoms, and individualized selection of agents according to the magnitude of LDL-C reduction required, prior events, comorbidity, adherence, route of administration, safety, and access.