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Relationship Between Exposure to Prasugrel Active Metabolite and Clinical Outcomes in the TRITON‐TIMI 38 Substudy
Author(s) -
Riesmeyer Jeffrey S.,
Salazar Daniel E.,
Weerakkody Govinda J.,
Ni Lan,
Wrishko Rebecca E.,
Ernest C. Steven,
Luo Junxiang,
Li Ying G.,
Small David S.,
Rohatagi Shashank,
Macias William L.
Publication year - 2012
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270011406280
Subject(s) - prasugrel , timi , medicine , pharmacology , clopidogrel , myocardial infarction , percutaneous coronary intervention
In TRITON‐TIMI 38, levels of the prasugrel active metabolite (pras‐AM) were measured in a population pharmacokinetic substudy that characterized the intrinsic and extrinsic factors influencing exposure. Higher exposure to the pras‐AM was observed in low‐weight or very elderly patients. The authors hypothesized that this higher exposure might explain the higher risk of non—coronary artery bypass graft (CABG)–related TIMI‐related bleeding observed in these 2 patient populations. The relationship between estimated exposure to the pras‐AM and clinical outcomes was assessed in 1159 prasugrel‐treated patients enrolled in the substudy using multivariable logistic regression analysis. There was no relationship between pras‐AM exposure and efficacy through 3 days or after 3 days. Higher estimated pras‐AM exposure was associated with a higher incidence of non‐CABG‐related TIMI major or minor bleeding after 3 days (P < .05) but not through 3 days from start of study drug. Factors associated with increased risk for non‐CABG‐related TIMI bleeding (≥75 years and <60 kg) also identified subgroups with higher exposure to the pras‐AM. Within low body weight and very elderly subgroups, bleeding was largely confined to patients having the highest exposure to the pras‐AM, indicating that a prasugrel lower dose in these subgroups may reduce the risk of bleeding while maintaining efficacy.