(Circulation. 2000;101:2823.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Early Potent Antithrombotic Effect With Combined Aspirin and a Loading Dose of Clopidogrel on Experimental Arterial Thrombogenesis in Humans
From Laboratoire de Recherche sur l’Hémostase et la Thrombose, Pavillon Lefèbvre, CHU Purpan, 31059 Toulouse CEDEX, France (Y.C., J.-P.B., B.B.); Service de Chirurgie Générale et Vasculaire CHU Purpan, 31059 Toulouse CEDEX, France (J.-P.B.); Centre d’Investigation Clinique, CHU Purpan, 31059 Toulouse CEDEX, France (C.T.); Sanofi Recherche, 94255 Gentilly CEDEX, France (L.S.); and University of Oslo, Norway (K.S.).
Correspondence to Yves Cadroy, MD, PhD, Laboratoire de Recherche sur l’Hémostase et la Thrombose, Pavillon Lefèbvre, CHU Purpan, 31059 Toulouse CEDEX, France. E-mail cadroy.y{at}chu-toulouse.fr
Background—We conducted a double-blind, randomized, crossover study to assess the antithrombotic effects of the combination of aspirin (acetylsalicylic acid, ASA) and clopidogrel, with or without a loading dose, versus ASA alone in a model of arterial thrombosis in humans.
Methods and Results—Eighteen male volunteers received the
following 3 regimens for 10 days separated by a 1-month period: (1) 325
mg ASA daily, (2) 325 mg ASA+75 mg clopidogrel daily, (3) 325 mg ASA
daily+300-mg clopidogrel loading dose on day 1 and +75 mg clopidogrel
per day on days 2 to 10. The antithrombotic effect was measured 1.5, 6,
and 24 hours after drug intake on day 1 and 6 hours after drug intake
on day 10. Arterial thrombus formation was induced ex vivo
by exposing a collagen-coated coverslip in a parallel-plate perfusion
chamber to native blood for 3 minutes at an arterial wall
shear rate. Without a loading dose, clopidogrel+ASA developed an
antithrombotic effect within 6 hours after the first intake. It was
superior to that produced by ASA, but it was moderate
(P
0.03). However, with the loading dose, the
antithrombotic effect of clopidogrel+ASA appeared within 90 minutes,
and after 6 hours it was comparable to that on day 10. On day 10,
clopidogrel+ASA decreased platelet thrombus formation by 
70%,
and the effect was significantly more potent than that produced by ASA
alone (P<0.001).
Conclusions—This study confirms the synergistic antithrombotic effects of a combined ASA and clopidogrel therapy and shows the early benefit obtained with a loading dose of clopidogrel.
Key Words: aspirin • blood flow • collagen • platelets • thrombosis
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