Prevention of one-year vein-graft occlusion after aortocoronary- bypass surgery: a comparison of low-dose aspirin, low-dose aspirin plus dipyridamole, and oral anticoagulants

Meer, Jan van der; Hillege, Hans L.; Kootstra, G. J.; Ascoop, C. A. P. L.; Pfisterer, Matthias; Gilst, Wiek H. van; Lie, Ki

doi:10.1016/0140-6736(93)91815-4

Cited by 99 publications

(33 citation statements)

References 24 publications

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“…[13][14][15][16] The disappointing results of some of these trials, with respect to graft patency, emphasize the gaps in our understanding of how the antithrombotic surface of saphenous vein endothelium is altered when vein is implanted in the arterial circulation. Here, we show that the concentration of thrombomodulin on saphenous vein endothelium is downregulated rapidly in response to arterial flow conditions, whereas the changes in tissue factor expression are either slower or much more subtle.…”

Section: Discussionmentioning

confidence: 99%

Arterial Flow Conditions Downregulate Thrombomodulin on Saphenous Vein Endothelium

et al. 1999

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Background —The antithrombogenic properties of venous endothelium may be attenuated when vein is implanted in the arterial circulation. Such changes may facilitate thrombosis, which is the final common pathway for saphenous vein arterial bypass graft occlusion. Methods and Results —Using human saphenous vein in a validated ex vivo flow circuit, we investigated (1) the possibility that arterial flow conditions (mean pressure, 100 mm Hg, 90 cpm, ≈200 mL/min) alter the concentration of proteins involved in regulating thrombosis at the vessel wall and (2) the influence of ion channel blockade on such effects. Concentrations of thrombomodulin and tissue factor were quantified by Western blotting (ratio of von Willebrand factor staining) and immunohistochemistry (as a percentage of CD31-staining area). Thrombomodulin concentrations after 90 minutes of venous and arterial flow conditions were quantified by immunostaining (68.9±4.8% and 41.0±3.0% CD31, respectively; P <0.01) and by Western blotting (1.35±0.20 and 0.15±0.03 ratio of von Willebrand factor, respectively; P <0.01). The ability of endothelial cells to generate activated protein C also decreased from 62±14 to 19±10 ng · min −1 · 1000 cells −1 ( P =0.01). The significant reduction in thrombomodulin was attenuated if calcium was removed from the perfusate but not by external vein stenting. Inclusion in the vein perfusate of drugs that reduce calcium entry (including Gd 3+ , to block stretch-activated ion channels, and nifedipine) abolished the reduction in thrombomodulin concentration observed after arterial flow conditions. In freshly excised vein, negligible concentrations of tissue factor were detected on the endothelium and concentrations did not increase after 90 minutes of arterial flow conditions, although the inclusion of nifedipine caused the immunostaining to increase from 3.0±0.4% to 8.5±0.7% CD31 ( P <0.02). Conclusions —In saphenous vein endothelium exposed to arterial flow conditions, there is rapid downregulation of thrombomodulin, sufficient to limit protein C activation, by a calcium-dependent mechanism.

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Section: Discussionmentioning

confidence: 99%

Arterial Flow Conditions Downregulate Thrombomodulin on Saphenous Vein Endothelium

et al. 1999

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“…The prevention of Coronary Artery Bypass graft occlusion by Aspirin, Dipyridamole, and Acenocoumarol/phenoprocoumon Study (CABADAS) (22) demonstrated that the addition of dipyridamole to aspirin does not significantly improve graft patency, although it results in higher chest tube drainage and the need for transfusion.…”

Section: Prevention Antiplatelet Therapymentioning

confidence: 99%

Coronary vein graft disease: Pathogenesis and prevention

Parang

Arora

2009

Canadian Journal of Cardiology

155

109

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“…The efficacy of aspirin in the prevention of death and myocardial infarction in patients with unstable angina has been well documented, as has the efficacy of aspirin in maintaining venous graft patency when initiated at the time of surgery. [5][6][7][8][9][10][11][12] However, long-term benefits to maintain graft patency are less well documented. Warfarin used alone can prevent recurrence of unstable angina 13 but has not been shown to be more effective than aspirin in maintaining graft patency.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4] Aspirin prevents graft closure during the first year after surgery, [5][6][7][8][9][10][11][12] but its long-term benefit in this specific setting has not been documented. Warfarin had been evaluated in unstable angina, 13 but no studies have addressed the specific population of patients with unstable coronary syndromes without ST elevation developing late after CABG.…”

mentioning

confidence: 99%

Aspirin, Warfarin, or the Combination for Secondary Prevention of Coronary Events in Patients With Acute Coronary Syndromes and Prior Coronary Artery Bypass Surgery

et al. 2001

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Background —Patients with a non–ST-elevation acute coronary syndrome and prior CABG are at high risk of a recurrent ischemic event despite aspirin therapy. This trial investigated the potential benefit of secondary prevention with warfarin. Methods and Results —In a double-blind randomized trial, 135 patients with unstable angina or non–ST-segment elevation myocardial infarction, with prior CABG, and who were poor candidates for a revascularization procedure received therapy with aspirin and placebo+warfarin, warfarin and placebo+aspirin, or aspirin and warfarin for 12 months. Warfarin was titrated to an international normalized ratio of 2.0 to 2.5. The primary end point (death or myocardial infarction or unstable angina requiring hospitalization 1 year after randomization) occurred in 14.6% of the patients in the warfarin-alone group, in 11.5% of patients in the aspirin-alone group, and in 11.3% of patients randomized to the combination therapy ( P =0.76). Subgroup analyses by risk features provided no indications that warfarin alone or in combination with aspirin could be of benefit over aspirin alone. Bleeding was more frequent in the 2 groups of patients administered warfarin. Conclusions —Moderate-intensity oral anticoagulation alone or combined with low-dose aspirin does not appear to be superior to low-dose aspirin in the prevention of recurrent ischemic events in patients with non–ST-elevation acute coronary syndromes and previous CABG.

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Prevention of one-year vein-graft occlusion after aortocoronary- bypass surgery: a comparison of low-dose aspirin, low-dose aspirin plus dipyridamole, and oral anticoagulants

Cited by 99 publications

References 24 publications

Arterial Flow Conditions Downregulate Thrombomodulin on Saphenous Vein Endothelium

Arterial Flow Conditions Downregulate Thrombomodulin on Saphenous Vein Endothelium

Coronary vein graft disease: Pathogenesis and prevention

Aspirin, Warfarin, or the Combination for Secondary Prevention of Coronary Events in Patients With Acute Coronary Syndromes and Prior Coronary Artery Bypass Surgery

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