Thromboxane Antagonism with terutroban in Peripheral Arterial Disease: the TAIPAD study.
BACKGROUND
Terutroban is a selective prostaglandin endoperoxide (TP) receptor antagonist with antithrombotic, antivasoconstrictive and antiatherosclerotic properties and is currently in development for long-term cardiovascular secondary prevention.


OBJECTIVE
TAIPAD is an international, double-blind, randomized controlled study comparing the effects of five dosages of oral terutroban vs. aspirin and placebo on platelet aggregation in peripheral arterial disease (PAD) patients.


METHODS
After 10 day's placebo run-in, included patients (n = 435; ankle-brachial pressure index, 0.7 ± 0.1) were randomly allocated to aspirin 75 mg day(-1), terutroban 1, 2.5, 5, 10 or 30 mg day(-1) or placebo. On day 5, the placebo group was reallocated to one of the terutroban groups for the rest of the study (day 83). Ex vivo platelet aggregation induced by the thromboxane analog U46619 (7 μm) was measured 24 h after dosing, as well as platelet aggregation induced by arachidonic acid (AA), collagen and ADP.


RESULTS
Terutroban dose-dependently inhibited U46619-induced platelet aggregation at days 5 and 83. At day 5, the inhibition was significant vs. placebo for all terutroban dosages (P < 0.001). Terutroban (5, 10 and 30 mg day(-1)) was at least as effective as aspirin in inhibiting platelet aggregation induced by arachidonic acid (AA), collagen and adenosine diphosphate (ADP). Terutroban was well tolerated, with a safety profile similar to aspirin.


CONCLUSIONS
In PAD patients, terutroban dose-dependently inhibited platelet aggregation 24 h after dosing, and was at least as effective as aspirin at 5, 10 and 30 mg day(-1). Terutroban was well tolerated.
Fiessinger
J N
JN
Centre d'Investigation Clinique, Hôpital Européen Georges Pompidou, Université Descartes, Paris, France. jean-noel.fiessinger@egp.aphp.fr
Bounameaux
H
H
Cairols
M A
MA
Clement
D L
DL
Coccheri
S
S
Fletcher
J P
JP
Hoffmann
U
U
Turpie
A G G
AG
D000244:Adenosine Diphosphate / Q000737:chemistry; D000328:Adult; D000368:Aged; D001241:Aspirin / Q000627:therapeutic use; D001794:Blood Pressure; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000627:therapeutic use*; D058729:Peripheral Arterial Disease / Q000188:drug therapy*; D010919:Placebos; D010974:Platelet Aggregation; D011422:Propionates / Q000627:therapeutic use*; D013931:Thromboxanes / Q000037:antagonists & inhibitors*; D013997:Time Factors
D009281:Naphthalenes; D010919:Placebos; D011422:Propionates; D013931:Thromboxanes; D000244:Adenosine Diphosphate; C501362:terutroban; D001241:Aspirin