OBJECTIVES: To evaluate the long-term clinical and cost outcomes of adding Niaspan® to statin treatment in patients with persistently low HDL-c on statin monotherapy. METHODS: Two models were developed to project long-term clinical and economic benefits of treatment. The first simulated the evolution of lipid levels with treatment utilising second order Monte Carlo methodology, and the second was designed to calculate the risk of coronary heart disease (CHD) events each subsequent year using standard Markov modelling techniques. Transition probabilities for CHD events were derived from the Framingham risk formulae. Baseline cohort characteristics and Niaspan® treatment effects were taken from the ARBITER II study. Patients with persistently low HDL-c (<1.03 mmol/L) on statin treatment received either add-on Niaspan® 1g daily or continued statin monotherapy. Direct costs (2004 Euros) were accounted (cardiovascular disease and treatment costs). Annual discount rates of 5% (Germany) and 3.5% (UK) were applied to clinical outcomes and costs. Undiscounted life expectancy (LE) was also calculated. Sensitivity analyses were performed. RESULTS: A total of 53.75% of patients were projected to have persistently low HDL-c levels after statin treatment. In these patients mean undiscounted LE of 16.12 years and 15.85 years were projected for the Niaspan® and statin monotherapy arms respectively. Lifetime direct medical costs were higher by €3,563 in Germany and by £2,820 in the UK with addition of Niaspan®. Incremental cost-effectiveness ratios based on discounted LE were €26,624 per life year gained in Germany and £17,262 in the UK for statin plus Niaspan® versus statin monotherapy. Results were most sensitive to the gender distribution, as women have a lower risk of CHD events. CONCLUSIONS: In patients with dyslipidemia and persistently low HDL-c, addition of Niaspan® to statin therapy was projected to be cost-effective compared to statin monotherapy in Germany and the UK.