Is HPS2-THRIVE the death knell for niacin?

•Low serum levels of high-density lipoprotein cholesterol (HDL-C) and high levels of non-HDL-C are frequent phenotypic features of patients with acute coronary syndromes and contribute significantly to residual risk after low-density lipoprotein cholesterol lowering with statin therapy.•Adjuvant therapy with niacin in patients with stable ischemic heart disease and well-controlled atherogenic lipoprotein burden was shown not to be efficacious in both the AIM-HIGH and HPS2-THRIVE trials. Niacin does, however, favorably alter atherosclerotic plaque architecture.•Low HDL-C is a reliable predictor of risk for recurrent events in patients who have sustained an acute coronary syndrome. Raising HDL-C with niacin does not appear to contribute to risk reduction. HDL-C is not currently a target of therapy, and niacin should not be used to raise low HDL-C levels.•There is renewed interest in the atherogenicity of triglyceride (TG)-enriched remnant lipoproteins. Non-HDL-C encompasses TG-enriched lipoproteins such as very low-density lipoprotein cholesterol remnants and intermediate-density lipoprotein cholesterol.•Recent meta-analyses and one post hoc analysis suggest that niacin therapy contributes to risk reduction in patients with mixed dyslipidemia characterized by elevated levels of TG-enriched lipoproteins.•Consistent with guidelines from around the world (including those of the NLA) that emphasize risk stratified non-HDL-C goal attainment, niacin therapy can be considered in patients with established coronary disease on statin therapy but whose non-HDL-C still exceeds 100 mg/dL.

Niacin is a lipid-modifying therapy with proven efficacy for reducing cardiovascular events as monotherapy and when used in combination with other lipid-modifying medications impacts rates of atherosclerotic disease progression. Large outcome trials using niacin against a background of statin therapy with optimal control of atherogenic lipoprotein burden in serum were unable to demonstrate incremental benefit of niacin beyond statin therapy. We address 2 key questions: (1) Can the results from randomized clinical trials performed in stable ischemic heart disease populations (AIM-HIGH and HPS2-THRIVE) be applied to patients who sustain an acute coronary syndrome or myocardial infarction? (2) Are patients with very low baseline levels of high-density lipoprotein cholesterol (<30 mg/dL) at particularly high risk for subsequent cardiac events?