OBJECTIVES: To compare the long-term cost-effectiveness of adding Niaspan® to statin treatment in diabetic and non-diabetic patients with persistently low HDL c. METHODS: Two models were developed to project long-term clinical and economic outcomes. The first model (Monte Carlo simulation) was used to evaluate the impact of simvastatin treatment on lipid levels and identify patients with low HDL-c. Baseline cohort characteristics were taken from the diabetic sub-population of the 4S study. In patients with HDL-c <1 mmol/L, treatment with statin plus add-on Niaspan® was compared to statin monotherapy. Niaspan® treatment effects were taken from several clinical trials as summarized in the European SPC. The second model (Markov) simulated the development of coronary heart disease events based on the Framingham risk formulae. Direct medical costs were accounted from a third-party payer perspective in the UK and expressed in pounds sterling (£). Annual discount rates of 3.5% were applied to clinical and cost outcomes. RESULTS: Niaspan® was associated with improvements in mean discounted life expectancy in diabetic (0.32 years) and non-diabetic cohorts (0.29 years) compared to statin monotherapy. Similarly, improvements in quality-adjusted life expectancy of (diabetic) 0.26 and (non-diabetic) 0.23 quality-adjusted life years (QALYs) were projected. Niaspan® was associated with increases in mean lifetime costs of £4,492 (diabetic) and £4,891 (non-diabetic) versus statin alone. This led to incremental cost-effectiveness ratios of £17,296 per QALY gained in the diabetic cohort and £21,150 in the non-diabetic cohort. CONCLUSIONS: Addition of Niaspan® to statin treatment was cost-effective by generally accepted standards compared to statin monotherapy in patients with persistently low HDL-c in the UK. In patients with type 2 diabetes and an associated high risk of CHD events, add-on therapy with Niaspan® represented better value for money than in non-diabetic patients.