KEYWORDS: Ticlopidine, acenocoumarol, platelet inhibitors, anticoagulants, coronary bypass patency rate. Introduction platelet aggregation and prolonging bleeding time; Long standing patency of aorto-coronary a P otent antithrombotic activity has also been bypass grafts is essential for good subjective and shown in animal models" 8 '. In mongrel dogs objective results of surgical myocardial pretreatment with ticlopidine reduced adhesion revascularization" 21 . About 10% of bypass grafts and aggregation of platelets on arterial dacron become occluded within days of insertion and g rafts and significantly increased their patency rate 16-26% during the first postoperative year"-61 .U P t0 6 weeks after implantation" 91 . In a Thrombosis plays an important role in early graft randomized blinded clinical trial reported preocclusion. while later obstruction is caused mainly viously from this institution, ticlopidine or placebo by intimal proliferation and atherosclerosis 13 " 5) . were started 3 da y s before b yP ass surgery and were For prevention of thrombosis, oral anticoagulants continued until angiography 3 months postand platelet active drugs, namely aspirin, alone or operatively; in addition all patients postoperatively in combination with dipyridamole as well as received acenocoumarol as an oral anticosulfinpyrazone have been tested in animal experagulant 1201 . When very severe bleeding occurred in iments [781 and in clinical trials 169 " 171 .

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In a prospective study (238 men, mean age 53 years) the changes of the native vessels were studied 3 months after a-c-bypass operation and 5 months after preop. angiography. Progression was defined as increase of stenoses of at least 20% or new total occlusion. Progression was significantly more frequent in vessels with than without bypass and was located proximally to the anastomoses in most cases, less frequently at the anastomoses and very rarely distally to the anastomoses. Proximal progression was significantly more frequent with patent than with occluded bypasses. Stenoses at the anastomoses were significantly more frequent with occluded than with patent bypasses. Stenoses of higher degrees had a stronger tendency for progression than slighter stenoses. Regression was rare and nearly always caused by surgery.

It is generally believed that calcium ions play a key role in regulation of platelet functions. One of the main storage pool of calcium in the platelet is the dense tubular system. A platelet membrane fraction which actively sequesters calcium has been isolated and characterized. Phenothiazine analogues have been tested on the characterized calcium uptake into platelet membrane vesicles. The drugs are competitive inhibitors of calcium transport and a relationship between structure-activity has been established. Evidence for two analogues with an apparent Ki of the same order of magnitude than chlorpromazine and trifluoperazine was found. Furthermore a strong correlation was found between the inhibition of the calcium uptake and the inhibition of the ionophore-induced platelet activation which confirms the role of intracellular calcium movements in the regulation of the ionophore-induced platelet activation. The possible action mechanism of these phenothiazine analogues namely on the involvement of calmodulin within the platelet system is discussed. Aorto-coronary bypass graft occlusion during the early weeks after surgery is caused mainly by thrombosis and oral anticoagulant therapy has been shown to improve graft patency. To compare the effect of Ticlopidine (T) an antiaggregant drug to that of oral anticoagulation by Acenocoumarol (A) in a prospective randomized trial 76 patients (p) received T 2x250 mg daily and 72 p received A according to prothrombine time for the first 3 postoperative months. Graft patency was then tested by angiography. The two p groups were comparable in respect to age, symptoms, ejection fraction, coronary anatomy and number of bypass grafts implanted.The occlusion rate was 16 % in p with T and 20 % in p with A (n.s.). In small arteries (1-1,5mm) the occlusion rate was 20 % with T and 24 % with A, in larger arteries (2mm or more) occlusion rates were 12 % with T and 16 % with A.In conclusion the effect of Ticlopidine is at least equal to that of oral anticoagulation of out-patients for the prevention of graft thrombosis during the first 3 postoperative months.

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