Authors
Erlinge D, Ten Berg J, Foley D, et al.
Title
Reduction in platelet reactivity with prasugrel 5 mg in low-body-weight patients is noninferior to prasugrel 10 mg in higher-body-weight patients: results from the FEATHER trial.
References
J Am Coll Cardiol 2012;60: 2032–40
Background
Prasugrel 10 mg reduced ischemic events compared with clopidogrel 75 mg but increased bleeding, particularly in LBW patients.
Purpose
To confirm prior modeling data suggesting that prasugrel 5 mg in low-body-weight (LBW) patients would be noninferior to prasugrel 10 mg in higher-body-weight (HBW) patients as assessed by maximal platelet aggregation (MPA).
Design
  • Blinded, 3-period, crossover study in stable patients with coronary artery disease (CAD)
  • The primary objective of FEATHER was to compare maximal platelet aggregation (MPA) responses to 20 µM adenosine diphosphate (ADP) by light transmission aggregometry in LBW patients receiving prasugrel 5 mg versus HBW patients receiving prasugrel 10 mg
  • In CAD patients takin aspirin, prasugrel 5 and 10 mg and clopidogrel 75 mg were administered to LBW (56.4± 3.7 kg; n = 34) and HBW patients (84.7 ± 14.9 kg; n = 38)
  • Assays included light transmission aggregometry (LTA), VerifyNow P2Y12 (VN), and vasodilator- associated stimulated phosphoprotein (VASP) level measured predose and after each 12-day treatment
Exclusion Criteria
None.
Follow-Up
Each treatment period was 12 days
Treatment Regimen
All patients took aspirin. Prasugrel 5 and 10 mg and clopidogrel 75 mg were administered to LBW and HBW patients.
Results
Primary Endpoints:
  • Median MPA by LTA for prasugrel 5 mg in LBW patients was noninferior to the 75th percentile for prasugrel 10 mg in HBW patients.

Secondary Endpoints:

  • Mean MPA was similar, but active metabolite exposure was lowered by 38%.
  • Within LBW patients, prasugrel 5 mg lowered MPA more than clopidogrel (least squares mean difference [95% confidence interval]: -3.7% [-6.72%, -0.69%]) and resulted in lower rates of high on-treatment platelet reactivity (HPR).
  • Within HBW patients, prasugrel 10 mg lowered MPA more than clopidogrel (-16.9% [-22.3%, -11.5%]). Similar results were observed by VN and VASP.
  • Prasugrel 10 mg in LBW patients was associated with more mild to moderate bleeding (mainly bruising) compared with prasugrel 5 mg and clopidogrel.
Summary
In aspirin-treated patients with CAD, prasugrel 5 mg in LBW patients reduced platelet reactivity to a similar extent as prasugrel 10 mg in HBW patients and resulted in greater platelet inhibition, lower HPR, and similar bleeding rates compared with clopidogrel.
Implications
This is a pharmacodynamic study suggesting low dose prasugrel may be equally effective in patients with low body weight, when compared to regular dose prasugrel in patients with high body weight. The study is hypothesis-generating: Patient trials will need to be done to show that the clinical benefits in the low body-weight population remains preserved with low dose prasugrel.
Related Figures
None.