title: Unmet Needs in LDL-C Lowering: When Statins Won't Do!
abstract: The use of low-density lipoprotein cholesterol (LDL-C)-lowering medications has led to a significant reduction of cardiovascular risk in both primary and secondary prevention. Statin therapy, one of the cornerstones for the prevention and treatment of cardiovascular disease (CVD), has been demonstrated to be effective in lowering LDL-C levels and in reducing the risk for CVD and is generally well-tolerated. However, compliance with statins remains suboptimal. One of the main reasons is limitations by adverse events, notably myopathies, which can lead to non-compliance with the prescribed statin regimen. Reducing the burden of elevated LDL-C levels is critical in patients with CVD as well as in patients with very high baseline levels of LDL-C (e.g. patients with familial hypercholesterolaemia), as statin therapy is insufficient for optimally reducing LDL-C below target values. In this review, we discuss alternative treatment options after maximally tolerated doses of statin therapy, including ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and cholesteryl ester transfer protein (CETP) inhibitors. Difficult-to-treat patients may benefit from combination therapy with ezetimibe or a PCSK9 inhibitor (evolocumab or alirocumab, which are now available). Updates of treatment guidelines are needed to guide the management of patients who will best benefit from these new treatments.
authors.affiliation: Division of Clinical Pharmacology and Toxicology, University Hospital, Basel, Switzerland. stephan.kraehenbuehl@usb.ch.|Department of Clinical Research, University of Basel, Basel, Switzerland. stephan.kraehenbuehl@usb.ch.
authors.forename: Stephan
authors.initials: S
authors.lastname: Krähenbühl
authors.affiliation: Amgen Switzerland AG, Dammstrasse 21, 6301, Zug, Switzerland.
authors.forename: Ivana
authors.initials: I
authors.lastname: Pavik-Mezzour
authors.affiliation: Institute of Clinical Chemistry, University Hospital Zürich, Zurich, Switzerland.|Zürich Center for Integrative Human Physiology, University of Zürich, Zurich, Switzerland.
authors.forename: Arnold
authors.initials: A
authors.lastname: von Eckardstein
mesh_terms: D002318:Cardiovascular Diseases / Q000097:blood / Q000517:prevention & control; D008078:Cholesterol, LDL / Q000097:blood*; D000069438:Ezetimibe / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy; D012307:Risk Factors; D020860:Subtilisin / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D020860:Subtilisin; D000069438:Ezetimibe