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.
OBJECTIVE
The aim of this study was 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).


BACKGROUND
Prasugrel 10 mg reduced ischemic events compared with clopidogrel 75 mg but increased bleeding, particularly in LBW patients.


METHODS
In this blinded, 3-period, crossover study in stable patients with coronary artery disease (CAD) taking 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.


RESULTS
Median MPA by LTA for prasugrel 5 mg in LBW patients was noninferior to the 75th percentile for prasugrel 10 mg in HBW patients (primary endpoint) and 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.


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. (Comparison of Prasugrel and Clopidogrel in Low Body Weight Versus Higher Body Weight With Coronary Artery Disease [FEATHER]; NCT01107925).
Department of Cardiology, Lund University, Lund, Sweden. david.erlinge@med.lu.se
David
D
Erlinge
Jurrien
J
Ten Berg
David
D
Foley
Dominick J
DJ
Angiolillo
Henrik
H
Wagner
Patricia B
PB
Brown
Chunmei
C
Zhou
Junxiang
J
Luo
Joseph A
JA
Jakubowski
Brian
B
Moser
David S
DS
Small
Thomas
T
Bergmeijer
Stefan
S
James
Kenneth J
KJ
Winters
D000293:Adolescent; D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D001835:Body Weight; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000503:physiopathology; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000068799:Prasugrel Hydrochloride; D016037:Single-Blind Method; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D055815:Young Adult
D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine