The need for combination drug therapies in patients with complex dyslipidemia.

Statins are first line therapy for the prevention of cardiovascular disease (CVD). Only 30 %-70 % of high risk patients will attain standard low-density lipoprotein cholesterol targets. Patients with familial hypercholesterolemia and genetic mixed hyperlipidemias do not meet goals with standard therapy. Patients with mixed hyperlipidemia secondary to the metabolic syndrome, diabetes, renal, or HIV infection are at high residual risk due to low HDL-cholesterol or high triglycerides. Newer therapies can be added to statins. The use of ezetimibe has CVD outcomes evidence in chronic renal disease. Adding omega-3 fatty acids, fibrates, or niacin to statins has failed to show any benefit except possibly with fibrates in patients with diabetes and low HDL-C/high triglycerides. Additional benefits on lipid profiles have been shown with pro-protein convertase subtilisin/kexin-9 (PCSK9), mipomersen, lomitapide, and cholesterol ester transfer protein inhibitors (CETPIs). Two CETPIs have failed to show benefit in hard outcomes trials but others remain under investigation. It remains unclear whether additional therapies add to statins for the prevention of CVD in most patients. They may have some added benefit in patients with complex dyslipidemias.