Addition of Niacin to Statin Increases HDL Cholesterol but Does Not Reduce Cardiovascular Events in Patients with Cardiovascular Disease and Well-Controlled LDL Cholesterol

DynaMed Weekly Update - Volume 6, Issue 46

High levels of LDL cholesterol and low levels of HDL cholesterol are independent risk factors for coronary artery disease. Statins for lowering LDL cholesterol levels have been shown to be effective for both primary and secondary prevention of cardiovascular events (Cochrane Database Syst Rev 2011 Jan 19;(1):CD004816, Arch Intern Med 2004 Jul 12;164(13):1427). Niacin increases HDL cholesterol concentrations, but clinical benefits from combined use of niacin and a statin drug have not been demonstrated.

The AIM-HIGH trial evaluated the addition of niacin for secondary CAD prevention in 3,414 patients with well-controlled LDL cholesterol levels. Patients with stable cardiovascular disease (mean age 64 years, 85% men) were randomized to niacin 1,500-2,000 mg/day vs. placebo. All patients received simvastatin 40-80 mg/day as needed to maintain LDL cholesterol target level of 40-80 mg/dL (1.03-2.07 mmol/L). Ezetimibe 10 mg/day could be added as necessary to reach LDL targets. Most patients had already been taking a statin for at least 1 year at baseline. Patients were excluded for recent stroke, revascularization procedure, or hospitalization for acute coronary syndrome (ACS) or acute myocardial infarction (MI). Patients who could not tolerate niacin 1,500 mg/day during an open-label run-in period were also excluded. The primary clinical outcome was first occurrence of any cardiovascular event (death from coronary heart disease, nonfatal MI, ischemic stroke, hospitalization for ACS, or symptom-driven coronary or cerebral revascularization).

At 2-year follow-up, the niacin group had significantly increased HDL cholesterol levels (median increase 25% vs. 9.8%, p < 0.001) and decreased levels of triglycerides and LDL cholesterol (p values not reported). However, there was no significant difference in the primary outcome (16.4% vs. 16.2%), or in any specific cardiovascular events or all-cause mortality (level 1 [likely reliable] evidence). The trial was terminated early for lack of efficacy after mean follow-up of 3 years (N Engl J Med 2011 Nov 15 early online).

For more information, see the Niacin topic in DynaMed.