Looking into the Crystal Ball—Upcoming Drugs for Dyslipidemia

Abstract

Dyslipidaemia is a critical risk factor for the development of cardiovascular complications such as ischemic heart disease and stroke. Although statins are effective anti-dyslipidemic drugs, their usage is fraught with issues such as failure of adequate lipid control in 30% of cases and intolerance in select patients. The limited potential of other alternatives such as fibrates, bile acid sequestrants and niacin has spurred the search for novel drug molecules with better efficacy and safety. CETP inhibitors such as evacetrapib and anacetrapib have shown promise in raising HDL besides LDL lowering property. Microsomal triglyceride transfer protein (MTP) inhibitors such as lomitapide and Apo CIII inhibitors such as mipomersen have recently been approved in Familial Hypercholesterolemia but experience in the non-familial setting is pretty much limited. One of the novel anti-dyslipidemic drugs which is greatly anticipated to make a mark in LDL-C control is the PCSK9 inhibitors. Some of the anti-dyslipidemic drugs which work by PCSK9 inhibition include evolocumab, alirocumab and ALN-PCS. Other approaches that are being given due consideration include farnesoid X receptor modulation and Lp-PLA2 inhibition. While it may not be an easy proposition to dismantle statins from their current position as a cholesterol reducing agent and as a drug to reduce coronary and cerebro-vascular atherosclerosis, our improved understanding of the disease and appropriate harnessing of resources using sound and robust technology could make rapid in-roads in our pursuit of the ideal anti-dyslipidemic drug.

Microsomal Transfer Protein Inhibitors, New Approach for Treatment of Familial Hypercholesterolemia, Review of the Literature, Original Findings, and Clinical Significance

“…Severe and resistant cases are treated with LDL apheresis in combination with drug therapy. Also, new therapy such as PSCK9 inhibitors, mipomersen, and finally the lomitapide may help these patients in the future [21]. This review is focused on lomitapide treatment and particularly presents the original findings.…”

Current Treatment of Familial Hypercholesterolaemia

“…3,35 and lomitapide (a microsomal transfer protein inhibitor) (Juxtapid-Aegerion). 39 These agents interfere with the production and secretion of apoB-containing lipoproteins respectively, independent of the LDL receptor. These agents are used after statins, cholesterol absorption inhibitors and bile acid sequestrants have been considered.…”

Acanthaster planci Inhibits PCSK9 Gene Expression via Peroxisome Proliferator Response Element (PPRE) and Activation of MEK and PKC Signaling Pathways in Human Liver Cells

“…In addition, statins also increase the expression of low-density lipoprotein receptor (LDLR) on the cell surface, which induces the clearance of LDL-C from the bloodstream [ 5 ]. However, failure to reach normal levels of cholesterol (despite patients consuming the maximum dosage of statins) and non-compliance due to potential adverse side effects (such as musculoskeletal disorders, abdominal pain, headaches, numbness, and skin rashes) are two primary causes for the discontinuation of statin therapy in some patients, which has raised debate regarding the potential risks and benefits of statin therapy [ 6 , 7 , 8 , 9 , 10 ]. It has also been reported that statins may induce oxidative stress in patients with chronic heart failure, diabetes, and myopathy, as statin drugs interfere with the synthesis of coenzyme Q10 [ 11 , 12 , 13 ].…”