Dyslipidemia treatment: current considerations and unmet needs

Abstract

Monumental evidence from clinical trials indicates an approximately 30% reduction in atheroslcerotic cardiovascular disease (ASCVD) risk using monotherapy with lipid-regulating drugs in dyslipidemic patients. In order to achieve greater reductions in risk, other approaches are necessary, including improvements in technology designed to assess ASCVD risk. Recent preliminary, but encouraging evidence indicates that by combining drugs that have different mechanisms of action on lipid metabolism yields not only an additive effect on the lipoprotein spectrum, but also reduces ASCVD events. New studies indicate that niacin potently increases high-density lipoproteins (HDL) by inhibiting HDL catabolism and decreases hepatic production of atherogenic very-low- and low-density lipoproteins by inhibiting the key enzyme for triglyceride synthesis (diacylglycerol acyltransferase). Statins, fibrates, bile acid sequestrants and ezetimibe have mechanisms that are different. Combination therapy using statins and niacin not only safely corrects dyslipidemia, but also yields ASCVD risk reduction significantly in excess of the 30% seen with monotherapy. Newer drugs with different mechanisms of action or combinations of new formulations have recently become available. Drug discovery research is likely to yield additional agents. Clinical trials focused on combination therapies to reduce ASCVD risk well beyond 30% need to be conducted to establish the rationale for further reducing the incidence of the primary cause of death today.