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Blood, Vol. 92 No. 5 (September 1), 1998:
pp. 1518-1525
A Double-Blind Randomized Comparison of Combined Aspirin and
Ticlopidine Therapy Versus Aspirin or Ticlopidine Alone on Experimental
Arterial Thrombogenesis in Humans
Jean-Pierre Bossavy,
Claire Thalamas,
Luc Sagnard,
André Barret,
Kjell Sakariassen,
Bernard Boneu, and
Yves Cadroy
From the Laboratoire de Recherche sur l'Hémostase et la
Thrombose, Pavillon Lefèbvre, CHU Purpan, Toulouse; Service de
Chirurgie Générale et Vasculaire, CHU Purpan, Toulouse;
Centre d'Investigation Clinique, CHU Purpan, Toulouse Cedex, France;
Sanofi Recherche, Gentilly Cedex, France; and the Department of
Biology, the Division of Physiology, University of Oslo, Oslo, Norway.
No randomized study comparing the effect of combined ticlopidine and
aspirin therapy versus each drug alone in reducing poststenting thrombotic complications has been performed. To compare these three
antiplatelet regimens versus placebo, we conducted a double-blind randomized study using an ex vivo model of thrombosis. Sixteen healthy
male volunteers were assigned to receive for 8 days the following four
regimens separated by a 1-month period: aspirin 325 mg/d, ticlopidine
500 mg/d, aspirin 325 mg/d + ticlopidine 500 mg/d, and placebo. At
the end of each treatment period, native nonanticoagulated blood was
drawn directly from an antecubital vein over collagen- or tissue factor
(TF)-coated coverslips positioned in a parallel-plate perfusion chamber
at an arterial wall shear rate (2,600 s 1 ) for 3 minutes. Thrombus, which formed on collagen in volunteers treated by
placebo, were rich in platelets and poor in fibrin. As compared with
placebo, aspirin and ticlopidine alone reduced platelet thrombus
formation by only 29% and 15%, respectively (P > .2). In
contrast, platelet thrombus formation was blocked by more than 90% in
volunteers treated by aspirin + ticlopidine (P < .01 v placebo or each treatment alone). Furthermore, the effect of
the drug combination therapy was significantly larger than the sum of
the two active treatments (P < .05). Thrombus, which formed
on TF-coated coverslips in volunteers treated by placebo,
were rich in fibrin and platelets. Neither of the three antiplatelet
treatments significantly inhibited fibrin deposition and platelet
thrombus formation on this surface (P > .2). Thus, the
present study shows that combined aspirin and ticlopidine therapy
dramatically potentiates the antithrombotic effect of each drug alone,
but that the antithrombotic effect of the combined treatment depends on
the nature of the thrombogenic surface.
© 1998 by The American Society of Hematology.
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