OBJECTIVES: Randomized controlled trials (RCTs) provide the most robust evidence source for making patient healthcare decisions. When RCT data are lacking, however, complementary evidence sources may also be needed. As an example of this, three clinical trials comparing rosuvastatin with atorvastatin were simulated using the Archimedes model, a validated, individual-based simulation of human pathophysiology and behaviours, treatment interventions and healthcare systems.  METHODS: Comparison A assessed clinical outcomes in patients receiving available doses of the two drugs. Comparison B assessed the impact of initial treatment decisions, with individuals randomized to receive various doses of either rosuvastatin or atorvastatin and eligible for treatment intensification for up to 5 years if target lipid levels were not met. Comparison C assessed the effect of switching patients’ treatment from rosuvastatin to atorvastatin. RESULTS: In comparison A, rosuvastatin was estimated to result in greater reductions than atorvastatin in major adverse cardiac events (MACEs) at 5 and 20 years at all doses examined (relative risk [RR]: 0.907, 0.892 and 0.931 at 20 years for rosuvastatin 20 mg versus atorvastatin 40 mg, rosuvastatin 40 mg versus atorvastatin 80 mg, and rosuvastatin 20 mg versus atorvastatin 80 mg, respectively; P<0.05 in all cases). In comparison B, outcomes were significantly better in patients initially prescribed rosuvastatin relative to atorvastatin (RR of MACE at 10 years: 0.919; P<0.001). In comparison C, risk of MACE was significantly greater in patients who switched from rosuvastatin to atorvastatin, relative to those who remained on rosuvastatin (RR at 10 years: 1.115; P<0.001). CONCLUSIONS: In this example using the well-validated Archimedes model, better outcomes were predicted in patients receiving rosuvastatin than in those receiving atorvastatin in a variety of different settings. This provides an example of the utility of robust modelling approaches to generating evidence that is not available from clinical trials.