Page 102 - HA Convention 2016 [Full Version]

HOSPITAL AUTHORITY CONVENTION 2016 Masterclasses

M2.3 Recent Advances in Internal Medicine 13:15 Theatre 2

Tuesday, 3 May Treatment of Hypercholesterolaemia: Statins and Beyond
Luk A

Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong

High level of low density-lipoprotein (LDL) cholesterol leading to cardiovascular morbidity and mortality is well established.
Although the updated lipid treatment guideline by the American College of Cardiology and American Heart Association
abandoned using LDL-cholesterol target as a surrogate endpoint in cardiovascular risk management, clinical trials on statin
have unanimously demonstrated that vascular benefits are directly related to magnitude of LDL-cholesterol reduction, and
that risk reduction persists in very low LDL-cholesterol ranges. Until recently, statin has been the most potent lipid-lowering
agent in the market and was superior to fibrate, ezetimibe and bile acid sequestrants in LDL-cholesterol reduction. Making
it less favourable is that a substantial proportion of patients failed to achieve adequate LDL-cholesterol reduction with
statin alone, partially related to intolerance or genetic factors that limit drug response. Furthermore, patients with familial
hypercholesterolaemia respond only partially to statin and still at high risk of cardiovascular diseases in their lifetime. A
recently completed randomised clinical trial comparing statin-ezetimibe combination against statin monotherapy reported
significant risk reduction of fatal or non-fatal cardiovascular events in patients assigned to combination therapy, providing
robust evidence for the use of dual agents in maximising lipid control. Inhibitors of the proprotein convertase subtilisin kexin
type 9 (PCSK9), a protein secreted by hepatocyte facilitating degradation of LDL-receptors has shown remarkable LDL-
cholesterol lowering efficacy in phase two and phase three studies, with post-hoc analyses suggesting outcome benefits.
Drug authorities in both the United States and Europe recently approved the use of two PCSK9 inhibitors, alirocumab and
evolocumab, in selected subjects. Cholesterylester transfer protein inhibitors which raise high density-lipoprotein cholesterol
in addition to decreasing LDL-cholesterol, are being investigated in late phase studies. The landscape of cholesterol
management is seeing revolutionary changes, and new additions to the therapeutic armamentarium hold great promise in
targeting residual cardiovascular risks after statins.

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