An update on trials of novel lipid-lowering drugs.

Abstract

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.

• Authors: Anthony S Wierzbicki, Timothy M Reynolds, Adie Viljoen
• Journal: Current opinion in cardiology (Curr Opin Cardiol) Vol. 33 Issue 4 Pg. 416-422 (07 2018) ISSN: 1531-7080 [Electronic] United States
• PMID: 29561321 (Publication Type: Journal Article, Review)

Chemical References

• Cholesterol Ester Transfer Proteins
• Hypolipidemic Agents
• PCSK9 Inhibitors
• Ezetimibe

Topics

• Cardiovascular Diseases (prevention & control)
• Cholesterol Ester Transfer Proteins (antagonists & inhibitors)
• Clinical Trials as Topic
• Ezetimibe (therapeutic use)
• Humans
• Hypolipidemic Agents (pharmacology, therapeutic use)
• PCSK9 Inhibitors