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

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

The Lancet

Volume 342, Issue 8866, 31 July 1993, Pages 257-264

https://doi.org/10.1016/0140-6736(93)91815-4 Get rights and content

Abstract

Summary

Aspirin, alone or in combination with dipyridamole, is known to prevent occlusion of aortocoronary vein grafts. The benefit of dipyridamole in addition to aspirin remains controversial, and the efficacy and safety of oral anticoagulants for prevention of vein-graft occlusion have not been established.

We assessed one-year angiographic vein-graft patency after aortocoronary-bypass surgery in 948 patients assigned to receive aspirin, aspirin plus dipyridamole, or oral anticoagulants in a prospective, randomised trial. The design was double-blind and placebo-controlled for the aspirin groups, but open for oral anticoagulant treatment. Dipyridamole (5 mg/kg per 24 h intravenously for 28 h, followed by 200 mg twice daily) and oral anticoagulants (desired prothrombin time range 2·8-4·8 international normalised ratio) were started before surgery, and aspirin (50 mg per day) was started after surgery. Clinical outcome was assessed by the incidence of myocardial infarction, thrombosis, major bleeding, or death. Occlusion rate of distal anastomoses was 11% in the aspirin plus dipyridamole group versus 15% in the aspirin group (relative risk 0·76, 95% Cl 0·54-1·05) and 13% in the oral anticoagulants group. Clinical events occurred in 20·3% of patients receiving aspirin plus dipyridamole compared with 13·9% of the aspirin group (relative risk 1·46, 95% Cl 1·02-2·08) and 16·9% of the oral anticoagulants group. Our data provide no convincing evidence that addition of dipyridamole to 50 mg aspirin per day improves aortocoronary vein-graft patency. Moreover, there is evidence that the combination increases the overall clinical-event rate. Compared with aspirin, oral anticoagulants provided no benefit.

References (28)

Rl Lorenz et al.
Improved aortocoronary bypass patency by low-dose aspirin (100 mg daily). Effects on platelet aggregation and thromboxane formation
Lancet
(1984)
The RISC Group
Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary artery disease
Lancet
(1990)
M. Pfisterer et al.
Trial of low-dose aspirin plus dipyridamole versus anticoagulants for prevention of aortocoronary vein graft occlusion
Lancet
(1989)
F.W. Bär et al.
Prognostic value of Q waves, R/S ratio, loss of R wave voltage, ST-T segment abnormalities, electical axis, low voltage and notching: correlation of electrocardiogram and left ventriculogram.
J Am Coil Cardiol
(1984)
Wg Henderson et al.
The statistical analysis of graft patency data in a clinical trial of antiplatelet agents following coronary artery bypass grafting
Controlled Clin Trials
(1988)
Kh Teoh et al.
Dipyridamole preserved platelets and reduced blood loss after cardiopulmonary bypass
J Thorac Cardiovasc Surg
(1988)
Jh Chesebro et al.
A platelet-inhibitor-drug trial in coronary-artery bypass operations. Benefit of perioperative dipyridamole and aspirin therapy on early postoperative vein-graft patency
N Engl J Med
(1982)
Wg Henderson et al.
Antiplatelet or anticoagulant therapy after coronary artery bypass surgery. A meta-analysis of clinical trials
Ann Intern Med
(1989)
V. Fuster et al.
Drugs interfering with platelet functions: mechanisms and clinical relevance
Jh Chesebro et al.
Effect of dipyridamole and aspirin on late vein-graft patency after coronary bypass operations
N Engl J Med
(1984)

S. Goldman et al.

Improvement in early saphenous vein graft patency after coronary artery bypass surgery with antiplatelet therapy: results of a Veterans Administration cooperative study

Circulation

(1988)

S. Goldman et al.

Saphenous vein graft patency 1 year after coronary artery bypass surgery and effects of antiplatelet therapy. Results of a Veterans Administration cooperative study

Circulation

(1989)

G. Sanz et al.

Prevention of early aortocoronary bypass occlusion by low-dose aspirin and dipyridamole

Circulation

(1990)

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2023, American Heart Journal
To provide data guiding long-term antithrombotic therapy after coronary artery by-pass grafting (CABG) in patients with preoperative atrial fibrillation (AF).
From the SWEDEHEART registry, we included all patients, between January 2006 and September 2016, with preoperative AF and CHA₂DS₂-VASC score ≥2, undergoing CABG. Based on dispensed prescriptions 12 to 18 months after CABG, patients were divided in 3 groups: use of platelet inhibitors (PI) only, oral anticoagulant (OAC) only or a combination of OAC + PI. Outcomes were: Major adverse cardiac and cerebrovascular events (MACCE, [all-cause death, myocardial infarction, or stroke]), net adverse clinical events (NACE, [MACCE or bleeding]) and the individual components of NACE. Inverse probability of treatment weighting was used to adjust for the non-randomized study design.
Among 2,564 patients, 1,040 (41%) were treated with PI alone, 1,064 (41%) with OAC alone, and 460 (18%) with PI + OAC. Treatment with PI alone was associated with higher risk for MACCE (adjusted HR 1.43, 95% CI 1.09-1.88), driven by higher risk for stroke and MI, compared with OAC alone. Treatment with PI + OAC, was associated with higher risk for NACE (adjusted HR 1.40, 95% CI 1.06-1.85), driven by higher risk for bleeds, compared with OAC alone.
In this real-world observational study, a high proportion of patients with AF, undergoing CABG, did not receive a long-term OAC therapy. Treatment with OAC alone was associated with a net clinical benefit, compared with PI alone or PI + OAC.
Efforts to improve bypass graft patency have not been "in vein"
2015, Journal of Thoracic and Cardiovascular Surgery
Continuing antiplatelet therapy before cardiac surgery with cardiopulmonary bypass: A meta-analysis on the need for reexploration and major outcomes
2014, Journal of Cardiothoracic and Vascular Anesthesia
Citation Excerpt :
The number needed to harm (NNTH) is 87 (95% CI 390, 44), calculated from an expected rate of reexploration of 2.4%.16 There was no statistical difference for death at 30 days4,5,15 and 1 year,15 myocardial infarction at 30 days,4,6,8,12,15 and stroke at 30 days (Table 2).6,15 There were no data available for renal insufficiency.
To determine major adverse outcomes, including the risk of mediastinal reexploration, death, stroke and myocardial infarction, associated with continuing antiplatelet therapy in patients undergoing surgery with cardiopulmonary bypass.
A meta-analysis of parallel randomized, controlled trials published in English.
A university-based electronic search.
Patients undergoing surgery with cardiopulmonary bypass (CPB).
Continuing antiplatelet therapy versus stopping antiplatelet therapy before the surgery.
A search was conducted in PubMed, EMBASE, MEDLINE(R), and the Cochrane Central Register of Controlled Trials. Twelve studies were retained for analysis. Continuing antiplatelet drugs for CPB increases the rate of reexploration by a standardized mean difference (SMD) 0.22, 95% confidence interval (CI) 0.06, 0.39; I-square 0%; p value 0.01; classical fail-safe number 5. The number needed to harm (NNTH) is 87 (95% CI 390, 44). There was no statistical difference for death at 30 days and 1 year, myocardial infarction at 30 days, and stroke at 30 days. Continuing antiplatelet drugs increases blood loss, SMD 0.27 (95% CI 0.09, 0.45), I-square 73.1%; p = 0.003.
Continuing antiplatelet therapy for patients undergoing surgery with CPB is associated with a low risk for reexploration.
Prehospitalization antiplatelet therapy and outcomes after saphenous vein graft intervention
2013, American Journal of Cardiology
Antiplatelet therapy is recommended after coronary artery bypass grafting, because it improves saphenous vein graft (SVG) patency and clinical outcomes. We investigated the association between prehospital antiplatelet regimens and outcomes after SVG intervention. Patients who underwent SVG intervention from 2003 to 2008 were divided into 3 groups: (1) no antiplatelet therapy, (2) the use of aspirin or clopidogrel, and (3) the use of dual antiplatelet therapy (DAPT) at admission. Clinical follow-up examinations were performed at 30 days and 1 year. The primary outcome was the composite of all-cause mortality, myocardial infarction, the need for revascularization, and stroke at 30 days. The relation between antiplatelet therapy and outcomes was adjusted for factors associated with the outcomes. A total of 225 patients underwent SVG intervention, 87% were men, and the mean age was 70 years. Of the 225 patients, 21 (9.4%) were not receiving antiplatelet therapy, 102 (45.3%) were receiving aspirin/clopidogrel, and 102 (45.3%) were receiving DAPT. The patients without antiplatelet therapy were more frequently women, had presented earlier after coronary artery bypass grafting, and were less frequently taking other cardiac-related medications. The patients taking aspirin or DAPT were more often smokers and had a greater peripheral vascular burden. The incidence of the 30-day and 1-year primary outcomes was greater in patients without preadmission antiplatelet use (38.1% vs 14.9% and 13.9%, overall p = 0.01; 52.4% vs 29.5% and 28.3%, overall p = 0.03). After adjustment, antiplatelet use remained associated with the primary outcome. In conclusion, prehospital use of antiplatelet therapy was associated with a lower occurrence of major adverse cardiac events after SVG intervention. We did not find that DAPT improved outcomes compared to single antiplatelet therapy.
Fourteen-year follow-up from CABADAS: Vitamin K antagonists or dipyridamole not superior to aspirin
2010, Annals of Thoracic Surgery
Citation Excerpt :
Although differences in the separate components of MACE are well recognized [11, 13–15], in our study, this finding is intriguing. Firstly, 1-year angiographic results from the CABADAS study showed comparable graft occlusion in the three treatment groups, which is not consistent with the observed difference already present within the second year of follow-up [8, 16]. Secondly, when evaluating the quality of VKA therapy (ie, percentage of time spent below the target range and the stability of the international normalized ratio) during the first year, no difference in repeat revascularization was observed for patients with optimal VKA and patients with nonoptimal VKA (data not shown).
Secondary prophylaxis using aspirin is standard of care after coronary artery bypass graft surgery. Limited data are available for long-term results. We evaluated the effect of aspirin, aspirin with dipyridamole, and vitamin K antagonists (VKA) on 14-year clinical outcome of patients included in the Prevention of Coronary Artery Bypass Graft Occlusion by Aspirin, Dipyridamole, and Acenocoumarol/Phenprocoumon Study (CABADAS).
All 726 Dutch patients for whom antithrombotic therapy with aspirin (n = 248), aspirin with dipyridamole (n = 234), or VKA (n = 244) was randomly allocated were included. The primary endpoint was occurrence of major adverse cardiac events (MACE). Outcomes were retrospectively evaluated during 14-year follow-up.
Cumulative incidences for MACE over 14 years were 49%, 50%, and 59% for patients treated with aspirin, aspirin with dipyridamole, and VKA, respectively. Although the overall occurrence of MACE did not significantly differ among the three treatment groups (p = 0.12), patients treated with VKA were at higher risk of MACE than patients treated with aspirin with dipyridamole (hazard ratio 1.3, 95% confidence interval: 1.0 to 1.8, p = 0.041) and patients treated with aspirin alone (hazard ratio 1.1, 95% confidence interval: 0.86 to 1.5, p = 0.37). This difference was attributed to an increased risk of repeat revascularization in patients treated with VKA, without any differences in cardiac death and myocardial infarction among the three treatment groups. However, the observed high rate of repeat revascularization in patients treated with VKA could reflect an a priori increased probability for repeat revascularization due to the specific conditions surrounding VKA therapy (ie, more intense patient–doctor contacts).
This study with 14-year clinical outcome provides further evidence for the use of aspirin as secondary prophylaxis after coronary artery bypass graft surgery.
Coronary vein graft disease: Pathogenesis and prevention
2009, Canadian Journal of Cardiology
Not long after coronary artery bypass grafting surgery was described, several reports presented follow-up angiographic data on large cohorts of patients, demonstrating that approximately one-half of saphenous vein grafts fail within 10 to 15 years of surgery and that graft failure is associated with worse clinical outcomes. Three processes are responsible for vein graft failure. Thrombosis, intimal hyperplasia and accelerated atherosclerosis contribute to graft failure in the acute, subacute and late postoperative periods, respectively. Studies have shown that perioperative antiplatelet therapy can reduce early thrombosis and graft failure. As in native coronaries, intensive lipid lowering can attenuate the process of atherosclerosis in vein grafts. Intimal hyperplasia in the vein graft is thought to be an adaptation of the vein to higher pressures in the arterial circulation. This process is further promoted by the loss of inhibition from the endothelial layer, which is injured during surgery. A new ‘no-touch’ technique for harvesting grafts may be effective in preventing disruption to the endothelial layer, and subsequent intimal hyperplasia and graft loss. Off-pump surgery and endoscopic vein harvesting, which are known to reduce surgical morbidity, have been shown to be no worse than on-pump surgery and open vein harvesting, respectively, in terms of vein graft patency. Various gene therapies can prevent intimal hyperplasia in animal models, but human data obtained so far have been disappointing. Placing an external stent around a vein graft may reduce tangential wall stress and subsequent intimal hyperplasia.
Peu après la description du pontage aortocoronarien, plusieurs rapports ont porté sur les données angiographiques de suivi de vastes cohortes de patients, démontrant qu’environ la moitié des greffons veineux saphènes échouent dans les dix à 15 ans suivant l’opération et que l’échec des greffons s’associe à des issues cliniques encore plus négatives. Trois processus sont responsables de l’échec des greffons veineux. La thrombose, l’hyperplasie intimale et l’athérosclérose accélérée contribuent à l’échec du greffon pendant les périodes postopératoires aiguë, subaiguë et tardive, respectivement. Les études démontrent qu’une thérapie antiplaquettaire périopératoire peut réduire le risque de thrombose précoce et d’échec du greffon. Tout comme dans les artères coronaires originales, une diminution lipidique intensive peut atténuer le processus d’athérosclérose dans les greffons veineux. On pense que l’hyperplasie intimale dans le greffon veineux est une adaptation de la veine à de plus fortes pressions de la circulation artérielle. Ce processus est favorisé par la perte d’inhibition de la couche endothéliale, blessé pendant l’opération. Une nouvelle méthode sans contact de prélèvement du greffon pourrait être efficace pour prévenir la perturbation de la couche endothéliale, l’hyperplasie intimale qui s’ensuit et la perte du greffon. Il est démontré que le pontage à cœur battant et le prélèvement veineux par endoscopie, dont l’effet sur la réduction de la morbidité chirurgicale est connu, ne sont pas plus néfastes que le pontage avec circulation extracorporelle et le prélèvement veineux ouvert, respectivement, pour ce qui est de la perméabilité du greffon veineux. Plusieurs thérapies géniques peuvent prévenir l’hyperplasie intimale dans les modèles animaux, mais les données humaines obtenues jusqu’à présent sont décevantes. L’installation d’une endoprothèse externe autour d’un greffon veineux peut réduire la contrainte tangentielle exercée sur la paroi et l’hyperplasie intimale qui s’ensuit.

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

Abstract

Lancet

Lancet

Lancet

J Am Coil Cardiol

Controlled Clin Trials

J Thorac Cardiovasc Surg

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

N Engl J Med

Antiplatelet or anticoagulant therapy after coronary artery bypass surgery. A meta-analysis of clinical trials

Ann Intern Med

Drugs interfering with platelet functions: mechanisms and clinical relevance

Effect of dipyridamole and aspirin on late vein-graft patency after coronary bypass operations

N Engl J Med

Improvement in early saphenous vein graft patency after coronary artery bypass surgery with antiplatelet therapy: results of a Veterans Administration cooperative study

Circulation

Saphenous vein graft patency 1 year after coronary artery bypass surgery and effects of antiplatelet therapy. Results of a Veterans Administration cooperative study

Circulation

Prevention of early aortocoronary bypass occlusion by low-dose aspirin and dipyridamole

Circulation

Articles
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