Recovery of platelet function after discontinuation of prasugrel or clopidogrel maintenance dosing in aspirin-treated patients with stable coronary disease: the recovery trial.
OBJECTIVE
The goal of this study was to assess the offset of the antiplatelet effects of prasugrel and clopidogrel.


BACKGROUND
Guidelines recommend discontinuing clopidogrel at least 5 days and prasugrel at least 7 days before surgery. The pharmacodynamic basis for these recommendations is limited.


METHODS
Aspirin-treated patients with coronary artery disease were randomly assigned to either prasugrel 10 mg or clopidogrel 75 mg daily for 7 days. Platelet reactivity was measured before study drug administration and for up to 12 days during washout. The primary endpoint was the cumulative proportion of patients returning to baseline reactivity after study drug discontinuation.


RESULTS
A total of 56 patients were randomized; 54 were eligible for analysis. Platelet reactivity was lower 24 h after the last dose of prasugrel compared with clopidogrel. After prasugrel, ≥75% of patients returned to baseline reactivity by washout day 7 compared with day 5 after clopidogrel. Recovery time was dependent on the level of platelet reactivity before study drug exposure and the initial degree of platelet inhibition after study drug discontinuation but not on treatment assignment.


CONCLUSIONS
Recovery time after thienopyridine discontinuation depends on the magnitude of on-treatment platelet inhibition, resulting, on average, in a more delayed recovery with prasugrel compared with clopidogrel. The offset of prasugrel was consistent with current guidelines regarding the recommended waiting period for surgery after discontinuation. (Prasugrel/Clopidogrel Maintenance Dose Washout Study; NCT01014624).
Scripps Clinic and Scripps Translational Science Institute, La Jolla, California, USA. price.matthew@scrippshealth.org
Matthew J
MJ
Price
James S
JS
Walder
Brian A
BA
Baker
Darell E
DE
Heiselman
Joseph A
JA
Jakubowski
Douglas K
DK
Logan
Kenneth J
KJ
Winters
Wei
W
Li
Dominick J
DJ
Angiolillo
D000328:Adult; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects*; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D001792:Blood Platelets / Q000187:drug effects*; D000077144:Clopidogrel; D015986:Confounding Factors, Epidemiologic; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D017410:Practice Guidelines as Topic; D000068799:Prasugrel Hydrochloride; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects*; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine; D001241:Aspirin