Thromboxane Antagonism with terutroban in Peripheral Arterial Disease: the TAIPAD study
| Autor: | J N, Fiessinger, H, Bounameaux, M A, Cairols, D L, Clement, S, Coccheri, J P, Fletcher, U, Hoffmann, A G G, Turpie, R, Koppensteiner |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Time Factors Adenosine Diphosphate/chemistry Platelet Aggregation medicine.drug_class Thromboxane Naphthalenes/*therapeutic use Blood Pressure Naphthalenes Pharmacology Placebo Placebos Peripheral Arterial Disease chemistry.chemical_compound Double-Blind Method Antithrombotic medicine Humans Aged ddc:616 Aspirin business.industry Thromboxanes Hematology Middle Aged Propionic Acids/*therapeutic use Receptor antagonist Peripheral Arterial Disease/*drug therapy Adenosine Diphosphate chemistry Terutroban Anesthesia Aspirin/therapeutic use Arachidonic acid Female Propionates business Thromboxanes/*antagonists & inhibitors Ex vivo medicine.drug |
| Zdroj: | Journal of Thrombosis and Haemostasis, Vol. 8, No 11 (2010) pp. 2369-2376 |
| ISSN: | 1538-7836 |
| Popis: | 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. OBJECTIVES: 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. 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. |
| Databáze: | OpenAIRE |
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