A specific thromboxane receptor blocking drug, AH23848, reduces platelet deposition on vascular grafts in man.
The antithrombotic effect of a specific thromboxane A2 receptor blocking drug, AH23848, on radio-labelled platelet deposition in mature Dacron aorto-bifemoral grafts has been evaluated in patients. Thirty patients were randomly allocated to AH23848 70 mg, aspirin 300 mg plus dipyridamole 75 mg or placebo 8-hourly for 9 days. AH23848 inhibited platelet aggregation induced by the thromboxane A2 mimetic U-46619; no such effect was observed with aspirin plus dipyridamole. 111In-platelet uptake was measured as the thrombogenicity index (TI) which is a measure of the daily rate of accumulation of platelets by the graft. The mean (s.e. mean) value of 0.193 (0.029) on placebo was significantly reduced to 0.115 (0.022) by AH23848 (p less than 0.05) but only to 0.175 (0.028) by aspirin plus dipyridamole. There was no difference in mean platelet life span between the three treatment groups. The pronounced antithrombotic effect of AH23848 implicates thromboxane A2 in the process of platelet deposition in arterial prostheses and demonstrates the considerable promise of thromboxane receptor blocking drugs as antithrombotic therapy.
Lane
I F
IF
Department of Surgery, Charing Cross Hospital, London, U.K.
Lumley
P
P
Michael
M F
MF
Peters
A M
AM
McCollum
C N
CN
D000368:Aged; D001241:Aspirin / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000009:adverse effects / Q000494:pharmacology*; D001807:Blood Vessel Prosthesis / Q000009:adverse effects*; D002470:Cell Survival / Q000187:drug effects; D004176:Dipyridamole / Q000494:pharmacology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors; D011093:Polyethylene Terephthalates; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D017482:Receptors, Thromboxane
D001713:Biphenyl Compounds; D010975:Platelet Aggregation Inhibitors; D011093:Polyethylene Terephthalates; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D004176:Dipyridamole; C046926:AH 23848; D001241:Aspirin