Effect of Ticlopidine on the Long-Term Patency of Saphenous-Vein Bypass Grafts in the Legs

Becquemin, Jean‐Pierre

doi:10.1056/nejm199712113372404

Cited by 118 publications

(30 citation statements)

References 21 publications

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“…Control endarterectomized aortic segments produced substantial thrombus by 60 minutes, ie, platelet deposition averaged 1.6Ϯ0.39ϫ10 9 platelets/cm, and mean fibrin accumulation was 1.1Ϯ0.3 mg/cm.…”

Section: Pͼ02)mentioning

confidence: 99%

Clopidogrel Inhibition of Stent, Graft, and Vascular Thrombogenesis With Antithrombotic Enhancement by Aspirin in Nonhuman Primates

et al. 1998

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Background-A recent study showed that clopidogrel reduces thrombo-occlusive complications in patients with symptomatic atherosclerosis more effectively than aspirin. Methods and Results-The effects of clopidogrel and aspirin have been compared, singly and in combination, for measurements of 111 In-labeled platelets and 125 I-labeled fibrin deposition in baboon models of arterial thrombosis and related to platelet aggregation and expression of activation epitopes induced by ADP, collagen, and thrombin receptor agonist peptide (TRAP) and to template bleeding times (BTs). Low-dose oral clopidogrel (0.2 mg ⅐ kgIn-platelet and 125 I-fibrin deposition for segments of prosthetic vascular graft, deployed endovascular metallic stents, and endarterectomized aorta (PϽ0.009 in all cases); (2) elimination of ADP-induced platelet aggregation (PϽ0.001); (3) modest inhibition of collagen-induced platelet aggregation (PϽ0.01); (4) no reduction in TRAP-induced platelet aggregation; and (5) minimal prolongation of BTs (Pϭ0.03). High-dose oral clopidogrel (Ն2 mg/kg) produced the same effects within 3 hours. The effects of clopidogrel dissipated over 5 to 6 days. Aspirin 10 mg ⅐ kg Ϫ1 ⅐ d Ϫ1 alone did not decrease 111 In-platelet and 125 I-fibrin deposition on segments of vascular graft but detectably decreased 111 In-platelet and 125 I-fibrin accumulation on stents (PϽ0.01), minimally inhibited ADP-and collagen-induced platelet aggregation (PϽ0.05 in both cases), and minimally prolonged BTs (Pϭ0.004). Within 3 hours of aspirin administration, the antithrombotic effects of acute high-dose or chronic low-dose clopidogrel were substantially enhanced, and BTs were modestly prolonged without inhibiting platelet aggregation induced by TRAP (PϽ0.001 in all cases compared with clopidogrel alone). Conclusions-Clopidogrel produces irreversible, dose-dependent, intermediate reduction in thrombosis that is substantially enhanced by the addition of aspirin. The effects of combining aspirin and clopidogrel need to be evaluated in patients at risk of vascular thrombosis. (Circulation. 1998;98:2461-2469.)

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Section: Pͼ02)mentioning

confidence: 99%

Clopidogrel Inhibition of Stent, Graft, and Vascular Thrombogenesis With Antithrombotic Enhancement by Aspirin in Nonhuman Primates

et al. 1998

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“…In this study, 243 participants were randomized to ticlopidine versus placebo. A strong statistically significant effect of ticlopidine was demonstrated on venous bypass patency: ORs of 0.26 (95% CI 0.11-0.63) at six months; 0.38 (95% CI 0.19 -0.75) at 12 months; and 0.37 (95% CI 0.21 -0.64) at 24 months [31]. For early occlusion rates, within one month after operation, ticlopidine did not have any advantage (OR 3.00; 95% CI 0.…”

Section: B Ticlopidinementioning

confidence: 90%

A Critical Analysis on the Impact of Antiplatelet Therapy in the Patency of Infrainguinal Bypass Grafts

Sfyroeras¹,

Saleptsis²,

Argyriou³

et al. 2013

Current Vascular Pharmacology

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Antiplatelet therapy plays an important role in the management of atherosclerotic disease and numerous studies have shown their efficacy in the reduction of cardiovascular mortality and morbidity. Antiplatelets are given in patients subjected to lower limb bypass aiming not only to reduce cardiovascular mortality and morbidity but also improve graft patency. Various antiplatelet agents have been used for this purpose. The aim of this review article is to critically evaluate the existing evidence on the impact of antiplatelet therapy for maintaining infrainguinal graft patency and highlight the mechanisms involved along these lines.

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“…The greater efficacy of aspirin in preventing occlusion of prosthetic grafts may be due to the greater thrombogenicity of prosthetic grafts. In contrast to the trial results with aspirin, a recent trial in femorodistal vein bypass grafts with a different type of inhibitor of platelet aggregation, ticlopidine, has shown a significant effect of the drug in reducing vein bypass occlusion [19]. Ticlopidine is thought to act by reducing ADP‐induced platelet aggregation, whereas in vitro tests indicate a greater effect of aspirin on collagen and arachidonic acid‐induced platelet aggregation than on that induced by ADP.…”

Section: Discussionmentioning

confidence: 99%

Graft material and results of platelet inhibitor trials in peripheral arterial reconstructions: reappraisal of results from a meta‐analysis

Watson¹,

Skene²,

Belcher³

2000

Brit J Clinical Pharma

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Aims To investigate the characteristics of published trials in order to establish the origin of the differing results obtained in trials of platelet inhibitors after peripheral bypass procedures. Methods Analysis of the information from 11 randomised, controlled trials of platelet inhibitors after peripheral bypass procedures published up until 1999 and involving 2302 patients undergoing peripheral bypass operations, 1250 of whom were treated with platelet inhibitors. Results There is a signi®cant treatment bene®t of platelet inhibitors on meta-analysis of the trials, but a signi®cant heterogeneity amongst the individual trial results. The proportion of patients in a trial with prosthetic grafts was a signi®cant factor in explaining the heterogeneity. Proportion of prosthetic grafts was associated with sample size and with the proportion of grafts above the knee, but these were not found to make an independent contribution to the heterogeneity observed. The platelet inhibitor regimen used, the severity of ischaemic symptoms and the proportion of smokers included were also not found to be important. Conclusions The improvement of graft patency by aspirin and related platelet inhibitors in clinical trials in peripheral bypass procedures can be attributed to an effect on patients with prosthetic grafts. There is little evidence that these agents prevent occlusion of vein grafts. The conclusion of an earlier meta-analysis that antiplatelet agents should be used for all bypasses is not supported.

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Effect of Ticlopidine on the Long-Term Patency of Saphenous-Vein Bypass Grafts in the Legs

Abstract: Ticlopidine significantly improved the long-term patency of saphenous-vein bypass grafts in the legs. Since the drug was well tolerated, its use can be recommended after peripheral-vein bypass surgery.

Cited by 118 publications

References 21 publications

Clopidogrel Inhibition of Stent, Graft, and Vascular Thrombogenesis With Antithrombotic Enhancement by Aspirin in Nonhuman Primates

Clopidogrel Inhibition of Stent, Graft, and Vascular Thrombogenesis With Antithrombotic Enhancement by Aspirin in Nonhuman Primates

A Critical Analysis on the Impact of Antiplatelet Therapy in the Patency of Infrainguinal Bypass Grafts

Graft material and results of platelet inhibitor trials in peripheral arterial reconstructions: reappraisal of results from a meta‐analysis

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