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An update on trials of novel lipid-lowering drugs

Wierzbicki, Anthony, S.a; Reynolds, Timothy, M.b; Viljoen, Adiec

Current Opinion in Cardiology: July 2018 - Volume 33 - Issue 4 - p 416–422
doi: 10.1097/HCO.0000000000000518
LIPIDS AND EMERGING RISK FACTORS: Edited by Dimitri P. Mikhailidis and Anthony S. Wierzbicki

Purpose of review A number of novel trials have assessed the efficacy of new lipid-lowering therapies in cardiovascular disease (CVD).

Recent findings Proprotein convertase subtilisin kexin-9 inhibitors reduce low-density lipoprotein cholesterol (LDL-C) by 50–55%. A CVD outcome trial in patients with acute coronary syndromes with evolocumab achieved a LDL-C of 0.8 mmol/l (31 mg/dl) and a 20% relative risk reduction in CVD events in 2.2 years. Cholesterol ester transfer protein inhibitors raise high-density lipoprotein cholesterol and can lower LDL-C. Anacetrapib reduced coronary artery disease events by 7%, but not wider composite CVD outcomes, in a population with chronic CVD with pretreatment LDL-C of 1.6 mmol/l (62 mg/dl). The conflicting outcomes of cholesterol ester transfer protein inhibitor trials means these compounds are not being developed further. Trials using lipid drugs targeting inflammation have previously been generally unsuccessful, but recent data on the interleukin-1B receptor antagonist canakinumab has proven the concept of intervention on inflammation in atherosclerosis by showing a reduction in acute coronary interventions, but at the predictable cost of increased infections.

Summary Despite the success of proprotein convertase subtilisin kexin-9 inhibition, the ability to achieve low LDL-C with off-patent medications and the costs of novel therapies will limit their use even in high-risk patients and confine them to the highest-risk sub-groups of patients.

aDepartment of Metabolic Medicine/Chemical Pathology; Guy's & St Thomas’ Hospitals, London

bDepartment of Metabolic Medicine/Chemical Pathology, Queen's Hospital, Burton-on-Trent

cDepartment of Metabolic Medicine/Chemical Pathology, East & North Hertfordshire Hospitals, Lister Hospital, Stevenage, UK

Correspondence: Professor Anthony S. Wierzbicki, DM, DPhil, FRCPath, Department of Chemical Pathology, St. Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, UK. Tel: +44 207 188 1256; fax: +44 207 188 7325; e-mail: Anthony.wierzbicki@kcl.ac.uk

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