Optimal pharmacotherapy to combat the atherogenic lipid triad

Abstract

A lipid triad involving an atherogenic dyslipidemia characterized by moderate/high LDL-C, low HDL-C, and elevated triglyceride (TG) occurs in numerous clinical settings associated with high cardiovascular risk. This article focuses on optimizing treatment of atherogenic dyslipidemias involving this lipid triad, emphasizing niacin-based or fibrate-based therapies. Niacin-based therapies comprehensively improve the atherogenic lipid profile, lead to atherosclerosis regression, and exert benefits across a spectrum of cardiovascular endpoints in studies based on limited patient numbers. Fibrates impact TG, HDL-C, and LDL-C according to lipid phenotype and underlying metabolic abnormality. In a recent meta-analysis, fibrates significantly reduced major cardiovascular events (-10%) and coronary events (-13%) across a wide range of lipid phenotypes, but had no impact on stroke, sudden death, or mortality. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial in type 2 diabetic patients similarly showed no significant effect of fenofibrate + simvastatin (vs. simvastatin) on nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death; a subgroup (17%) with marked atherogenic dyslipidemia trended toward benefit. Both niacin and fibrates attenuate vascular inflammation but the potential clinical relevance is indeterminate. Optimal cardiovascular risk reduction in patients exhibiting the lipid triad requires integrated pharmacotherapy to normalize LDL-C, HDL-C, TGs, and potentially lipoprotein(a). Ongoing studies may provide definitive evidence of the impact of niacin plus statins on cardiovascular outcomes.