Reduction of indium-111 platelet deposition on Dacron vascular grafts in humans by aspirin plus dipyridamole.

Abstract

Aspirin plus dipyridamole reduces platelet accumulation on short-term Dacron vascular grafts in man. To determine whether drug inhibition of platelet deposition is sustained on older grafts, we studied 18 men aged 41 to 87 years who had Dacron aortic bifurcation grafts in place a mean of 43.4 months (range 9.8 to 121.0) before and during short-term therapy with aspirin (325 mg tid) plus dipyridamole (75 mg tid). During both the baseline and drug studies, indium-111 (1'In) platelet deposition was quantitated by two techniques, standard planar imaging performed at 24, 48, and 72 hr after injection of platelets and single photon emission computed tomographic imaging performed at 24 and 72 hr after injection. All analyses were performed in a blinded fashion. On both the planar and tomographic images, platelet accumulation on the graft was quantitated by a graft/blood ratio that compared activity in the graft to simultaneously collected whole blood 1 'In platelet activity. Aspirin plus dipyridamole reduced the tomographic graft/blood ratio at 24 hr (20.6 + 3.5 vs 17.3 + 2.5) (±+ SEM) and at 72 hr (29.0 ± 4.8 vs 25.0 ± 4.1) after injection of platelets (p = .02). Similarly, the planar graft/blood ratio was reduced at 24 hr (2.7 ± 0.5 vs 2.4 ± 0.5), 48 hr (3.7 ± 0.9 vs 3.1 ± 0.7), and 72 hr (4.0 ± 0.9 vs 3.6 ± 0.8) (p = .04). We conclude that aspirin (325 mg tid) plus dipyridamole (75 mg tid) reduces platelet accumulation on long-term Dacron vascular grafts. Circulation 73, No. 2, 325-330, 1986. AFTER PROSTHETIC ARTERIAL GRAFT placement, occlusion is a common complication, particularly for grafts of smaller caliber. Although the mechanisms of occlusion are multifactorial,' many studies in animals and in humans suggest that platelet accumulation may play a prominent role, either directly by the formation of occlusive thrombus or indirectly by stimulation of intimal hyperplasia. Studies of indium-i 1 1 ("'In)-labeled platelets have documented that platelet deposition is greatest early after arterial graft placement.2' 3 Although deposition decreases in the subsequent 6 months, platelet accumulation remains readily detectable for periods of up to 10 years.4 5 Aspirin plus dipyridamole, used early postoperatively when deposition is maximal, reduces "'In-labeled platelet uptake on Dacron or polytetrafluoroethylene arterial grafts in humans6' 7 and has been associated with improved short-term patency compared with placebo ther-6, [8][9][10] apy.Whether aspirin plus dipyridamole reduces platelet uptake on older grafts that have a lesser rate of platelet deposition, but a continued risk of occlusion, remains unclear. Prior studies have documented that other platelet inhibitory agents, including ticlopidine," suloctidil,'2 and sulfinpyrazone'3 do not reduce platelet accumulation on grafts greater than 9 months old. With two methods of platelet imaging, the hypothesis tested in this study was that aspirin (325 mg tid) plus dipyridamole (75 mg tid) would reduce "'In-labeled platelet deposition on Dacron grafts that ha...

A Specific Thromboxane Receptor Blocking Drug, AH23848, Reduces Platelet Deposition on Vascular Grafts in Man

“…Possibly, the lack of effect of aspirin plus dipyridamole in our present study may have been due to a reduction in prostacyclin generation by the pseudointima resulting from aspirin therapy at this dose. Interestingly, in a recent study involving greater numbers of patients, aspirin plus dipyridamole has been reported to marginally, but significantly, inhibit platelet deposition onto mature Dacron grafts (39). The 10% reduction in platelet deposition reported is much less than that observed with the combination of drugs in freshly implanted grafts (17,18) and is less impressive than the mean 40% reduction in TI of the mature grafts seen with AH23848 in the present study.…”

Antithrombotic Activity of Bay u3405, a Thromboxane A2-Antagonist, in Patients with Dacron Aortic Grafts: a Random Controlled Clinical Trial

“…The increase in bleeding time is regarded as both statistically and clinically insignificant. [36][37][38][39][40][41]. Activated platelets also accelerate the generation of thrombin about 280,000-fold by enabling the formation of the prothrombinase complex on the membrane surface (42).…”

“…Aspirin, ticlopidine and prostacyclin nevertheless reduce the initial accumulation of platelets on freshly implanted grafts (38,40). One study has shown that the only drug regimen that diminishes platelet deposition on mature grafts (>9 months old) in humans is a combination of aspirin and dipyridamole (39). This remains a controversial issue, because in a recent clinical trial it was shown that aspirin/dipyridamole is not effective in the reduction of platelet deposition on mature Dacron grafts (45).…”

Antithrombotic Therapy in Peripheral Arterial Occlusive Disease

“…139 -142 Other studies in patients with Dacron aortofemoral bypass prostheses show continued uptake of labeled platelets on these prostheses when studied years after implantation. 142,143 This points out the difference in healing responses between man and experimental animals, which develop an endothelialized neointima that completely covers the luminal surface of large aortic and iliac prostheses within months to years after implantation. 144 -146…”