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430 Cardio Diabetes Medicine 2017

New Armamentarium In Combined Dyslipidemia

Management - Current Evidences

Dr. Sudhir Mehta, MD., MNAMS., FACP., FICP
Senior Professor, Department of Medicine,
SMS Medical College, Jaipur

ABSTRACT EZETIMIBE
Hypercholesterolemia, and in particular, an elevated Ezetimibe is a non-statin drug that decreases cho-
level of serum low density lipoprotein cholesterol lesterol level by inhibiting its absorption in the in-
(LDL-C), is associated with an increased risk of ad- testine. Ezetimibe was approved in 2003 for use in
verse cardiovascular events. Lipid lowering drug ther- management of dyslipidemia and prevention of CVD
apy, particularly with statins, is indicated to decrease as monotherapy in patients intolerant of statins or
the risk of cardiovascular events in most individu- as add on therapy to statins in high risk or refracto-
als with established atherosclerotic cardiovascular ry patients. Ezetimibe when added to statin therapy
disease and in many who are at high risk. Statins reduced LDL by 24% and CVD by 6%. 1,2
are the preferred therapy for most patients requir-
ing treatment of dyslipidemia and in particular those Proprotein convertase subtilisin/kexin type
with an elevated LDL-C. If after treatment with the 9 (PCSK9) inhibitors [PCSK9 inhibitors]:
maximal tolerated dose of statin the patient has not
achieved the LDL-C goal, a number of other agents Proprotein convertase subtilisin/kexin type 9 (PCSK9)
are available with varying levels of evidence for clini- is a serine protease which binds to the LDL receptors
cal benefits. These individuals remain at high risk for on the hepatocyte surface and take it into lysosomes
cardiovascular events. This topic will discuss newer for degradation, thereby reducing the hepatic uptake
3
therapies beyond statins and their status in current of LDL. Inhibition of PCSK9 results in decreased LDL
clinical practice. receptor degradation, increased hepatic LDL uptake
and subsequently reduction in serum LDL. PCSK9
3
also enhances inflammation and endothelial dys-
INTRODUCTION
function thus accelerate atherosclerosis. 3
Dyslipidemia including hypercholesterolemia and
raised low density lipoprotein (LDL) is one of the The genetic studies document that loss-of-function
common risk factors for cardiovascular morbidity mutations of PCSK9 are associated with lower serum
and mortality. Many factors influence individual’s LDL and a reduction in cardiovascular risk while a
lipid levels including life style, endocrine/ metabolic gain of function mutation (as occurs in autosomal
status, genetic predisposition and drugs. With life- dominant familial hypercholesterolemia) is associat-
5
style modification, up to 37% reduction in LDL can ed with increased serum LDL.
be achieved.Though statins (HMG CoA reductase in- Several PCSK9 inhibitors have been developed in-
hibitors) are the most commonly used drug in man- cluding evolocumab, alirocumab, LY3015014 and in-
agement of dyslipidemia, some patients are unable clisiran. Evolocumab and alirocumab are fully human
to tolerate them and some fail to respond up to the monoclonal antibodies. LY3015014 is a humanized
desired level. To overcome these challenges, newer immunoglobulin G4 monoclonal antibody. Bococi-
therapies are being developed for management of zumab is a humanized antibody that inhibits PCSK9
dyslipidemia. This review will focus on the drugs be- and was discontinued because of higher incidence
yond statins. of antidrug antibodies formation that decreased its
6
efficacy in reduction of LDL. Inclisiran is a small in-

GCDC 2017