Optimal pharmacotherapy to combat the atherogenic lipid triad

Abstract

Purpose of review: 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.

Recent findings: 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.

Summary: 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.