Abstract 11291: No Difference in Active Metabolite Exposure Between Very Elderly and Non-elderly Coronary Artery Disease Patients Treated With Prasugrel 5 mg or 10 mg in the GENERATIONS Trial
Background: Prasugrel 10 mg reduced ischemic events compared to clopidogrel 75 mg in the TRITON trial. The notable increase in bleeding over clopidogrel in the very elderly prompted the recommendation of a lower prasugrel 5 mg maintenance dose in patients ≥75 years, but pharmacokinetic (PK) data for this dose-adjustment is limited. We therefore performed a blinded, three-period cross-over study in very elderly and non-elderly patients with stable CAD, examining active metabolite (AM) PK for prasugrel (5 and 10 mg) and clopidogrel 75 mg.
Methods: After a run-in on daily low-dose aspirin, very elderly (≥75 years) and non-elderly (≥45 to <65 years) patients were randomized to prasugrel (5 or 10 mg) or clopidogrel 75 mg during three 12-day periods. PK was measured at the end of each period.
Results presented here were based on statistical linear models using log-transformed AUC data from the first study period. Results: The mean body weight was 85.4 kg (SD 11.2 kg) and 93.1 kg (SD 18.6 kg) in very elderly and non-elderly, respectively. Levels of prasugrel AM (geometric mean AUC(0-tlast)) were slightly higher in very elderly than in non-elderly (Table). With prasugrel 10 and 5 mg, levels of AM were 9% and 18% higher in very elderly compared to non-elderly (40.12 vs. 36.69 and 18.88 vs. 16.06 ng•hr/mL, respectively). In very elderly with prasugrel 5 mg the ratio of AM was 51% of that in non-elderly on prasugrel 10 mg (18.88 vs. 36.69 ng•hr/mL, respectively). After adjusting for body weight, exposures in the very elderly group were similar to the non-elderly group within each treatment (Table). Exposure of AM based on Cmax were similar to those based on AUC(0-tlast) (data not shown).
Conclusion: In aspirin-treated patients with CAD ≥75 years of age, the AM exposure to prasugrel 10 mg and 5 mg was similar to that of patients ≥45 to <65 years when adjusted for the modestly lower body weight in very elderly patients.
- © 2012 by American Heart Association, Inc.