TRIAL OF LOW-DOSE ASPIRIN PLUS DIPYRIDAMOLE VERSUS ANTICOAGULANTS FOR PREVENTION OF AORTOCORONARY VEIN GRAFT OCCLUSION

doi:10.1016/S0140-6736(89)90253-5

The Lancet

Volume 334, Issue 8653, 1 July 1989, Pages 1-7

https://doi.org/10.1016/S0140-6736(89)90253-5 Get rights and content

Abstract

In a prospective randomised trial, 249 patients who had aortocoronary vein bypass surgery were assigned either to a platelet inhibitory drug regimen or to standard anticoagulant therapy. Treatment was replaced by placebo in half of the patients in each group after 3 months. The platelet inhibitory drug regimen—very low-dose aspirin combined with dipyridamole—was as effective as standard anticoagulant therapy to prevent early and late graft occlusion. Death, myocardial infarction, and severe bleeding occurred significantly more often in patients receiving anticoagulants, whereas mild drug-related gastrointestinal and cerebral side-effects were more common in patients taking platelet inhibitory drugs. Antithrombotic treatment should be continued for at least 1 year after coronary artery bypass graft surgery.

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Cited by (60)

The primary and secondary prevention of coronary artery disease: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition)
2008, Chest
Citation Excerpt :
In other studies, VKAs begun from 14 days prior to operation to 2 days after operation (sometimes with heparin) yielded a graft patency comparable to low-dose aspirin (50 mg or 100 mg) or low-dose aspirin in combination with dipyridamole.159,169-172 Fewer bleeding complications occurred with aspirin plus dipyridamole than with oral anticoagulants.169 Warfarin has also been compared to dipyridamole alone (both started 2 or 3 days after surgery).171
The following chapter devoted to antithrombotic therapy for chronic coronary artery disease (CAD) is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh risks, burden, and costs. Grade 2 suggests that individual patient values may lead to different choices (for a full understanding of the grading see the “Grades of Recommendation” chapter by Guyatt et al in this supplement, CHEST 2008; 133[suppl]:123S–131S). Among the key recommendations in this chapter are the following: for patients with non–ST-segment elevation (NSTE)-acute coronary syndrome (ACS) we recommend daily oral aspirin (75–100 mg) [Grade 1A]. For patients with an aspirin allergy, we recommend clopidogrel, 75 mg/d (Grade 1A). For patients who have received clopidogrel and are scheduled for coronary bypass surgery, we suggest discontinuing clopidogrel for 5 days prior to the scheduled surgery (Grade 2A). For patients after myocardial infarction, after ACS, and those with stable CAD and patients after percutaneous coronary intervention (PCI), we recommend daily aspirin (75–100 mg) as indefinite therapy (Grade 1A). We recommend clopidogrel in combination with aspirin for patients experiencing ST-segment elevation (STE) and NSTE-ACS (Grade 1A). For patients with contraindications to aspirin, we recommend clopidogrel as monotherapy (Grade 1A). For long-term treatment after PCI in patients who receive antithrombotic agents such as clopidogrel or warfarin, we recommend aspirin (75 to 100 mg/d) [Grade 1B]. For patients who undergo bare metal stent placement, we recommend the combination of aspirin and clopidogrel for at least 4 weeks (Grade 1A). We recommend that patients receiving drug-eluting stents (DES) receive aspirin (325 mg/d for 3 months followed by 75–100 mg/d) and clopidogrel 75 mg/d for a minimum of 12 months (Grade 2B). For primary prevention in patients with moderate risk for a coronary event, we recommend aspirin, 75–100 mg/d, over either no antithrombotic therapy or vitamin K antagonist (Grade 1A).
Perioperative Blood Transfusion and Blood Conservation in Cardiac Surgery: The Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists Clinical Practice Guideline
2007, Annals of Thoracic Surgery
Citation Excerpt :
Other studies show even higher rates of bleeding complications, at 21.8% to 27.4%, with varying frequency of blood transfusion ranging between 0% and 9.5% [74, 75]. Preoperative antiplatelet and anticoagulant treatment as prophylaxis for coronary occlusive disease is associated with excessive intraoperative and postoperative bleeding as well as resultant transfusion, in most [20, 76–81], but not all situations [82–86]. Therefore, this aspect of patients' preoperative medication regimens must be managed for maximum cardioprotective benefit, while minimizing risk of hemorrhagic complication.
A minority of patients having cardiac procedures (15% to 20%) consume more than 80% of the blood products transfused at operation. Blood must be viewed as a scarce resource that carries risks and benefits. A careful review of available evidence can provide guidelines to allocate this valuable resource and improve patient outcomes.
We reviewed all available published evidence related to blood conservation during cardiac operations, including randomized controlled trials, published observational information, and case reports. Conventional methods identified the level of evidence available for each of the blood conservation interventions. After considering the level of evidence, recommendations were made regarding each intervention using the American Heart Association/American College of Cardiology classification scheme.
Review of published reports identified a high-risk profile associated with increased postoperative blood transfusion. Six variables stand out as important indicators of risk: (1) advanced age, (2) low preoperative red blood cell volume (preoperative anemia or small body size), (3) preoperative antiplatelet or antithrombotic drugs, (4) reoperative or complex procedures, (5) emergency operations, and (6) noncardiac patient comorbidities. Careful review revealed preoperative and perioperative interventions that are likely to reduce bleeding and postoperative blood transfusion. Preoperative interventions that are likely to reduce blood transfusion include identification of high-risk patients who should receive all available preoperative and perioperative blood conservation interventions and limitation of antithrombotic drugs. Perioperative blood conservation interventions include use of antifibrinolytic drugs, selective use of off-pump coronary artery bypass graft surgery, routine use of a cell-saving device, and implementation of appropriate transfusion indications. An important intervention is application of a multimodality blood conservation program that is institution based, accepted by all health care providers, and that involves well thought out transfusion algorithms to guide transfusion decisions.
Based on available evidence, institution-specific protocols should screen for high-risk patients, as blood conservation interventions are likely to be most productive for this high-risk subset. Available evidence-based blood conservation techniques include (1) drugs that increase preoperative blood volume (eg, erythropoietin) or decrease postoperative bleeding (eg, antifibrinolytics), (2) devices that conserve blood (eg, intraoperative blood salvage and blood sparing interventions), (3) interventions that protect the patient's own blood from the stress of operation (eg, autologous predonation and normovolemic hemodilution), (4) consensus, institution-specific blood transfusion algorithms supplemented with point-of-care testing, and most importantly, (5) a multimodality approach to blood conservation combining all of the above.
Antithrombotic therapy in patients with saphenous vein and internal mammary artery bypass grafts: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy
2004, Chest
Citation Excerpt :
In other studies, VKAs begun from 14 days prior to operation to 2 days after operation (sometimes with heparin) yielded a graft patency comparable to low-dose aspirin (50 mg or 100 mg) or low-dose aspirin in combination with dipyridamole.9434445 Fewer bleeding complications occurred with aspirin plus dipyridamole than with oral anticoagulants.43 Warfarin has also been compared to dipyridamole alone (both started 2 or 3 days after surgery).46
This chapter about prevention of coronary artery bypass occlusion is part of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126:179S–187S). Among the key recommendations in this chapter are the following: For patients undergoing coronary artery bypass grafting (CABG), we recommend aspirin, 75 to 162 mg/d, starting 6 h after operation over preoperative aspirin (Grade 1A). In patients in whom postoperative bleeding prevents the administration of aspirin at 6 h after CABG, we recommend starting aspirin as soon as possible thereafter (Grade 1C). For patients undergoing CABG, we recommend against addition of dipyridamole to aspirin therapy (Grade 1A). For patients with coronary artery disease undergoing CABG who are allergic to aspirin, we recommend clopidogrel, 300 mg, as a loading dose 6 h after operation followed by 75 mg/d po (Grade 1C+). In patients who undergo CABG for non–ST-segment elevation acute coronary syndrome (ACS), we recommend clopidogrel, 75 mg/d for 9 to 12 months following the procedure in addition to treatment with aspirin (Grade 1A). For patients who have received clopidogrel for ACS and are scheduled for CABG, we recommend discontinuing clopidogrel for 5 days prior to the scheduled surgery (Grade 2A). For patients undergoing CABG who have no other indication for vitamin K antagonists (VKAs), we suggest clinicians to not administer VKAs (Grade 2B). For patients undergoing CABG in whom oral anticoagulants are indicated, such as those with heart valve replacement, we suggest clinicians administer VKA in addition to aspirin (Grade 2C). For all patients with coronary artery disease who undergo internal mammary artery (IMA) bypass grafting, we recommend aspirin, 75 to 162 mg/d, indefinitely (Grade 1A). For all patients undergoing IMA bypass grafting without other indication for VKA, we suggest clinicians not use VKA (Grade 2C).
Nitric oxide synthase gene transfer inhibits biological features of bypass graft disease in the human saphenous vein
2004, Journal of Thoracic and Cardiovascular Surgery
Bypass graft disease is related to proliferation and migration of vascular smooth muscle cells and to platelet activation with thrombus formation. Nitric oxide inhibits these biological responses; it has never been demonstrated, however, whether this occurs in intact human vascular tissue after endothelial nitric oxide synthase gene transfer.
We examined whether endothelial nitric oxide synthase overexpression inhibits biological features of bypass graft disease in saphenous vein tissue.
The nitric oxide donor diethylenetriamineNONOate inhibited proliferation (P < .001) and migration (P < .001) of human saphenous vein vascular smooth muscle cells in response to 20% serum in a concentration-dependent manner. A similar effect on proliferation (P < .05) and migration (P < .05) without any cytotoxicity was observed after adenoviral endothelial nitric oxide synthase transfection. Staining of saphenous vein tissue for placental alkaline phosphatase demonstrated that adenoviral transfection was efficient. Consistent with this observation, endothelial nitric oxide synthase protein expression and nitric oxide release were enhanced in transfected tissue. Further, endothelial nitric oxide synthase overexpression inhibited vascular smooth muscle cell outgrowth from saphenous vein explants over 21 days; 48% ± 12% of explants exhibited outgrowth after treatment with endothelial nitric oxide synthase adenovirus as compared with 69% ± 10% in those infected with control adenovirus and 90% ± 5% in uninfected tissue (P < .05). Similarly, platelet adhesion to human saphenous vein tissue was inhibited by endothelial nitric oxide synthase overexpression; adhesion was reduced in segments infected with endothelial nitric oxide synthase adenovirus (58% ± 6%) as compared with those infected with control adenovirus (107% ± 8%) or uninfected saphenous vein (100%; P < .05).
These data demonstrate that endothelial nitric oxide synthase gene transfer inhibits biological features of bypass graft disease in intact human saphenous vein tissue. Therefore, endothelial nitric oxide synthase transfection represents a promising gene transfer approach to prevent venous bypass graft disease.
Antithrombotic therapy in patients with saphenous vein and internal mammary artery bypass grafts
2001, Chest
Citation Excerpt :
Only one study showedincreased graft patency in comparison with placebo.32 Oralanticoagulant therapy, with starting times ranging from 14 dayspreoperatively to the day of operation (sometimes with heparin) gave agraft patency comparable to low-dose aspirin or low-dose aspirin incombination with dipyridamole therapy.33, 34, 35, 36 Nocomparisons were made with placebo.33, 34, 35, 36
Haemostatic function in patients undergoing coronary artery bypass grafting peroperative perturbations and relations to saphenous vein graft closure
2000, Thrombosis Research
Vein graft failure remains a major problem after coronary artery bypass grafting. Occlusion in the first weeks usually is caused by thrombosis, whereas intimal hyperplasia and eventually atherosclerotic changes with superimposed thrombus formation underlie subsequent closure. The present investigation was conducted as a pilot study to examine whether perturbations of haemostatic function predispose to early saphenous vein graft occlusion after coronary artery bypass grafting. Pre- and postoperative determinations (performed on the first, third, and sixth postoperative days) of haemostatic factors and inhibitors were related to the presence of graft occlusion assessed by angiography at 3 months after surgery in 100 men undergoing elective coronary artery bypass grafting for stable angina pectoris. Occlusion of one or more vein grafts within three months of surgery occurred in 23 of the 100 patients examined. The percentage increase in plasma plasminogen activator inhibitor-1 activity on the first postoperative day was significantly higher in patients who subsequently were found to have vein graft occlusion (p<0.05). Otherwise no postoperative haemostatic measurements were found to predict early vein graft closure. A perturbed plasma plasminogen activator inhibitor-1 response to coronary artery bypass grafting tentatively could be added to the vessel-specific factors that remain the main determinants of early vein graft closure.

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TRIAL OF LOW-DOSE ASPIRIN PLUS DIPYRIDAMOLE VERSUS ANTICOAGULANTS FOR PREVENTION OF AORTOCORONARY VEIN GRAFT OCCLUSION

Abstract

Ann Thorac Surg

Am J Cardiol

Lancet

Am J Cardiol

Chest

Am J Cardiol

Improved graft patency with oral anticoagulant therapy after aortocoronary bypass surgery: a prospective randomized study

Circulation

A platelet-inhibitor-drug trial in coronary-artery bypass operations. Benefit of penoperative dipyridamole and aspirin therapy on early postoperative vein-graft patency

N Engl J Med

Effect of ticlopidine on saphenous vein bypass patency rates: a double blind study

Ann Thorac Surg

Evaluation of antiplatelet agents in the prevention of aorta-coronary bypass occlusion

Eur Heart J

Noninvasive radioisotopic technique for detection of platelet deposition in coronary artery bypass grafts in dogs and its reduction with platelet-inhibitors

Circulation

Antikoagulantien versus niedrigdosierte Aggregationshemmer zur Verhinderung des perioperativen Verschlusses von aortokoronaren Bypassgrafts. Preliminare Resultate einer prospektiven randomisierten Untersuchung

Helv Chir Acta

Eine Untersuchung uber Wechselwirkungen zwischen Pirprofen und Phenprocoumon

Fortschr Med

Morphological studies m saphenous vein grafts for aorto-coronary bypass surgery

Thorax Cardiovasc Surg

Beziehung zwischen intraoperativen Blutflussmessungen und Graft-Verschlussen nach aortokoronarer Bypass-Operation

Schweiz Med Wochenschr

Accuracy of serial myocardial perfusion scintigraphy with thallium-201 for prediction of graft patency early and late after coronary artery bypass surgery. A controlled prospective study

Circulation

Statistische methoden. 3