OBJECTIVES: Statin-treated patients at low-density lipoprotein cholesterol (LDL-C) goal continue to be at risk for cardiovascular disease (CVD) events; treating multiple lipid targets, such as high density lipoprotein cholesterol and triglycerides may result in further CVD risk reduction. The annual cost per patient treated to LDL-C goal (<100 mg/dL) with a statin ranges from $1343-$3025.  Niaspan® and Zetia® are two add-on therapies used in statin-treated patients.  A cost-effectiveness analysis was conducted to estimate the incremental cost of simultaneously achieving multiple lipid targets with Niaspan versus Zetia.  METHODS: A model was used to predict changes in lipid levels (total-C, LDL-C, HDL-C, and TG) and associated costs over 1 year among hypothetical cohort of 1000 statin-treated patients with a history of CVD in a US managed care population.  Baseline CVD risk factors and lipid parameters, along with their distributions, were based on NHANES data  Efficacy was based on product labeling, and adjusted to reflect mean days with combination therapy on-hand per published studies.  Prices were based on wholesale acquisition costs (WAC); daily WAC for Niaspan was weighted to reflect a 12-week dose-titration period.  RESULTS: When combined with simvastatin, Crestor®, Lipitor®, or Pravachol® the percentage of statin patients attaining three lipid targets was higher for Niaspan in comparison to Zetia (range, 98%-100% versus 87%-95%, respectively).  Annualized per patient treatment costs for Zetia were lower than Niaspan (difference, range: $3-$77).  Niaspan had the lowest annualized cost per patient attaining three lipid targets compared to Zetia (range, $681-$1379 versus $681-$1441, respectively).  The incremental cost of one additional patient attaining three lipid targets with Niaspan over Zetia, ranged from $59-$678.  CONCLUSIONS: The addition of Niaspan relative to Zetia in patients receiving on-going statin therapy results in more patients attaining three lipid targets and the cost per patient attaining three lipid targets is lower.