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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
Study Questions:
Does 5 mg of prasugrel in low-body-weight (LBW) patients achieve an equivalent antiplatelet effect as 10 mg in higher-body-weight (HMW) patients?
Methods:
In the FEATHER (Comparison of Prasugrel and Clopidogrel in Low Body Weight Versus Higher Body Weight With Coronary Artery Disease) trial, prasugrel 5 and 10 mg and clopidogrel 75 mg were administered to LBW (56.4 ± 3.7 kg; n = 34) and HBW (84.7 ± 14.9 kg; n = 38) patients with coronary artery disease (CAD) on aspirin. Endpoints were light transmission aggregometry, VerifyNow P2Y12 (VN), and vasodilator-associated stimulated phosphoprotein (VASP) level measured pre and post each 12-day treatment.
Results:
Mean maximal platelet aggregation (MPA) for prasugrel 5 mg in LBW patients was similar to prasugrel 10 mg in HBW patients, but active metabolite exposure was lowered by 38%. Within LBW patients, prasugrel 5 mg lowered MPA more than clopidogrel (-3.7%) 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%). 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.
Conclusions:
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.
Perspective:
Suboptimal platelet inhibition leads to increased risk of complications such as stent thrombosis, whereas high doses lead to increased bleeding risk. In the TRITON–TIMI 38 trial, patients with LBW were at increased risk for bleeding complications when treated with 10 mg of prasugrel. Analyses of prasugrel metabolites indicated that this increased bleeding risk was due to high drug exposure and that 5 mg should be sufficient for patients with body weight <60 kg. Using measures of platelet reactivity, this study confirms that 5 mg of prasugrel will likely be effective and safer in LBW patients. Effects on clinical outcomes will be evaluated in the TRILOGY-ACS trial, which will compare 75 mg clopidogrel to 5 mg prasugrel in LBW patients.
Keywords: Coronary Artery Disease, Microfilament Proteins, Platelet Aggregation Inhibitors, Platelet Function Tests, Thiophenes, Ticlopidine, Blood Platelets, Piperazines, Stents, Biomarkers, Coronary Angiography, Troponin I, Thrombosis, Platelet Aggregation, Phosphoproteins, Cell Adhesion Molecules
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