Superior efficacy of clopidogrel plus acetylsalicylic acid compared with extended-release dipyridamole plus acetylsalicylic acid in preventing arterial thrombogenesis in healthy volunteers.
BACKGROUND
Recent ex vivo platelet aggregometry data indicate that clopidogrel 75 mg/day plus acetylsalicylic acid (ASA) 75 mg/day is a more potent antiplatelet regimen than the marketed combination of dipyridamole+ASA. The present study was designed to assess the antithrombotic effect of both dual antiplatelet regimens using a human ex vivo model of arterial thrombosis.


METHODS
This was a randomized, double-blind, placebo-controlled, crossover study. During two 10-day treatment periods separated by a 14-day washout period, 23 healthy male volunteers received once-daily clopidogrel 75 mg plus acetylsalicylic acid 75 mg, or twice-daily extended-release dipyridamole 200 mg plus acetylsalicylic acid 25 mg. Assessments were made at baseline and on Day 10 of each period. Arterial thrombus formation was induced ex vivo by exposing a collagen-coated surface in a parallel-plate perfusion chamber to native blood for 3 min (arterial wall shear rate 2600 s(-1)). Total platelet and fibrin deposition was determined by immunoenzymatic methods.


RESULTS
Compared with baseline values, the mean inhibition of total platelet deposition was 63.9+/-5.9% with clopidogrel plus acetylsalicylic acid, compared with 18.4+/-5.6% for extended-release dipyridamole plus acetylsalicylic acid (67% reduction; 95% CI, 49-79%; p<0.0001). Corresponding figures for fibrin deposition were 64.9+/-4.8% and 18.3+/-9.7%, respectively (58% reduction; 95% CI, 45-67%; p<0.0001). Both treatments were well tolerated.


CONCLUSIONS
Clopidogrel plus acetylsalicylic acid showed significantly superior antithrombotic efficacy compared with extended-release dipyridamole plus acetylsalicylic acid in preventing arterial thrombogenesis in humans.
Cadroy
Yves
Y
Laboratoire de Recherche sur l'Hémostase et la Thrombose, EA2049, CHU Rangueil, TSA 50032, 31059 Toulouse Cedex 9, France. y.cadroy@medibridge.fr
Thalamas
Claire
C
Sakariassen
Kjell
K
Boneu
Bernard
B
D000293:Adolescent; D000328:Adult; D001158:Arteries; D001241:Aspirin / Q000008:administration & dosage*; D000077144:Clopidogrel; D003094:Collagen; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004176:Dipyridamole / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D010477:Perfusion; D010973:Platelet Adhesiveness / Q000187:drug effects; D010979:Platelet Function Tests; D013927:Thrombosis / Q000188:drug therapy / Q000191:economics / Q000517:prevention & control*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D003692:Delayed-Action Preparations; D004176:Dipyridamole; D005337:Fibrin; D003094:Collagen; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin