Clopidogrel 600-mg double loading dose achieves stronger platelet inhibition than conventional regimens: results from the PREPAIR randomized study.
OBJECTIVE
The objective of this study was to compare the level of platelet inhibition achieved by 3 different clopidogrel loading regimens in patients undergoing elective angiography and percutaneous coronary intervention when appropriate.


BACKGROUND
Optimal platelet inhibition is a key therapeutic goal for patients undergoing percutaneous coronary intervention. Although 600 mg has been described as the maximum absorbed dose when given as a single bolus, the effects of 2 boluses given 24 h apart have not been described.


METHODS
Patients (n = 148) were randomly assigned to one of 3 regimens: Group A, clopidogrel 300 mg the day before (>or=15 h) + 75 mg the morning of the procedure; Group B, clopidogrel 600 mg the morning of the procedure (>or=2 h); and Group C, clopidogrel 600 mg the day before (>or=15 h) and 600 mg the morning of the procedure (>or=2 h). Blood samples were obtained at baseline and immediately before angiography. Peak and late platelet aggregation were measured in platelet rich plasma, with researchers blinded to treatment allocation.


RESULTS
There was a consistent difference favoring Group C in all aggregation parameters. Percent inhibition in Groups A, B, and C was 31.4%, 29.0%, and 49.5%, respectively, for peak aggregation (5 micromol/l adenosine diphosphate; p < 0.0001) and 54.1%, 57.7%, and 81.1%, respectively, for late aggregation (p < 0.0001). Similar striking reductions were observed when 20 micromol/l adenosine diphosphate was used. All comparisons between Group C and the other 2 groups were statistically significant, and those between Groups A and B were not.


CONCLUSIONS
Clopidogrel 600-mg double bolus achieves greater platelet inhibition than conventional single loading doses.
L'Allier
Philippe L
PL
Department of Medicine, Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada. philippe.lallier@icm-mhi.org
Ducrocq
Grégory
G
Pranno
Nicolas
N
Noble
Stéphane
S
Ibrahim
Reda
R
Grégoire
Jean C
JC
Azzari
Fabian
F
Nozza
Anna
A
Berry
Colin
C
Doucet
Serge
S
Labarthe
Benoit
B
Théroux
Pierre
P
Tardif
Jean-Claude
JC
D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D001792:Blood Platelets / Q000187:drug effects; D000077144:Clopidogrel; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000628:therapy; D003328:Coronary Thrombosis / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine