Critical review of non-statin treatments for dyslipoproteinemia

Abstract

Statins are the cornerstone of lipid-modifying therapy for dyslipidemias and reducing cardiovascular events. Recent US guidelines have shifted away from the concept of cholesterol targets and are encouraging moderate-to-high statin intensity. However, residual risk and statin intolerance remains a significant challenge. Therapies beyond the statins, for combination or monotherapy, include fibrates, ezetimibe, bile acid sequestrants, n-3 fatty acids and niacin. Both the antisense oligonucleotide, mipomersen, and the microsomal triglyceride transfer protein inhibitor, lomitapide, have been approved by the US FDA for use in homozygous familial hypercholesterolemia. The first gene replacement therapy for lipoprotein lipase deficiency has also been approved. The cardiovascular benefit of treating elevated lipoprotein(a) in cardiovascular disease risk prevention remains unproven.

Keywords::

• dyslipidemia
• familial combined hyperlipidemia
• familial hypercholesterolemia
• hypertriglyceridemia
• lipoprotein(a)
• metabolic syndrome
• new therapy
• statin intolerance
• treatment
• Type 2 diabetes

Financial & competing interests disclosure

GF Watts has received honoraria for lectures and advisory boards from Sanofi, Amgen and Abbott. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Statins are the frontline therapy for dyslipidemias, and high-risk patients are likely to require intensive statin therapy.

• Patients with residual dyslipidemia and statin intolerance will necessitate LDL cholesterol lowering beyond the statins.

• Fibrates, ezetimibe, bile acid sequestrants and n-3 fatty acids may be beneficial for atherogenic dyslipidemias.

• Mipomersen and lomitapide are now both approved by the US FDA for use in homozygous familial hypercholesterolemia as orphan drugs.

• Gene therapy for severe hypertriglyceridemia is on the horizon.

• The underlying role of lipoprotein(a)-lowering in cardiovascular disease risk prevention remains unclear with difficulties to ascertain whether the independent effect is beneficial.

• Several trials of emerging therapies are currently underway and are highly anticipated, in particular, cholesteryl ester transfer protein inhibitors, pure eicosapentaenoic acid and proprotein convertase subtilisin/kexin type 9 inhibitors.