Abstract 243: Comparing the Major Adverse Cardiovascular Event Risk of Treatment and Titration Sequences Using Atorvastatin and Rosuvastatin: a Simulated Study

Objective: Using simulation modeling, we compared the effects of initiating statin therapy with atorvastatin and rosuvastatin on a population of patients with LDL-C levels above goal. Methods: Using the Archimedes Model, a clinically detailed simulation model of human physiology, disease progression, and healthcare delivery, two treatment scenarios were simulated in which patients initiated atorvastatin (10, 20, 40, or 80 mg) or rosuvastatin (10, 20, or 40 mg), and then periodically intensified treatment at rates determined from US pharmacy claims. Simulated individuals (derived from NHANES 1999-2006) were aged 45 to 70 years and had LDL-C exceeding Adult Treatment Panel (ATP) III goal. Initial statin doses were conservatively assigned based on each individual's LDL-C, their LDL-C goal, and the expected treatment effect. Patients not reaching goal either intensified the current statin dose or switched to an appropriate rosuvastatin dose. Occurrence of major adverse cardiovascular event (MACE), comprising MI, stroke, or cardiovascular (CV) death, was tracked for 10 years for all patients and several high-risk subpopulations, including those with diagnosed diabetes and with prior CV disease (CVD). Statin effects were modeled using biomarker results from the STELLAR trial and outcomes data from the JUPITER trial (rosuvastatin) and the CARDS, ASCOT, and TNT trials (atorvastatin). Results: At baseline, the study population (n=50,025) had a mean age of 57.3 [SD: 6.9] years, were 56% male, and had average LDL-C of 166.6 [41.3] mg/dL, HDL-C 49.3 [13.7] mg/dL, total cholesterol 252.0 [50.2] mg/dL, BMI 30.2 [6.6] kg/m2, 26% had diagnosed diabetes, 58% had hypertension, and 25% were current smokers. Initiating treatment with rosuvastatin versus atorvastatin provided a significant reduction in MACE: the 5- and 10-year relative risk of MACE for the overall population was 0.92 (95% CI: 0.90[[Unsupported Character - ]]0.94) and 0.92 (95% CI: 0.91-0.93), respectively; with prior diabetes, 0.90 (95% CI: 0.86[[Unsupported Character - ]]0.94) and 0.91 (95% CI: 0.88-0.93); and with prior CVD, 0.93 (95% CI: 0.90[[Unsupported Character - ]]0.97) and 0.95 (95% CI: 0.93-0.97); all p<0.05. Conclusion: In this simulation model, initial treatment with rosuvastatin versus atorvastatin lowered the incidence of MACE across the overall study population and in patients with prior diabetes or CVD.