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Therapeutics

Dipyridamole in addition to aspirin or oral anticoagulants compared with aspirin alone did not improve 1-year-graft potency after coronary bypass surgery

ACP J Club. 1994 Jan-Feb;120:7. doi:10.7326/ACPJC-1994-120-1-007

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Source Citation

van der Meer J, Hillege HL, Kootstra GJ, et al. Prevention of one-year vein-graft occlusion after aorto-coronary-bypass surgery: a comparison of low-dose aspirin, low-dose aspirin plus dipyridamole, and oral anticoagulants. Lancet. 1993 Jul 31;342:257-64.


Abstract

Objective

To compare low-dose aspirin, low-dose aspirin plus dipyridamole, and anticoagulants for prevention of vein-graft occlusion 1 year after coronary bypass surgery.

Design

Randomized, double-blind trial of aspirin and dipyridamole compared with aspirin; open trial of oral anticoagulants.

Setting

10 hospitals in the Netherlands, Germany, and Switzerland.

Patients

948 patients (mean age 58 y, 87% men) with disabling angina who had had elective aortocoronary bypass surgery. Exclusion criteria were age > 70 years, unstable angina for < 2 days, myocardial infarction (MI) within 7 days, previous or concurrent cardiac surgery, need for continued antithrombotic therapy, history of bleeding disorders, gastrointestinal bleeding or peptic ulcer, known allergy or intolerance to study drugs or contrast media, impaired renal or hepatic function, concomitant systemic diseases, malignancy, or recent use of antiplatelet drugs or anticoagulants. Angiographic follow-up was 86%.

Intervention

Aspirin was started at midnight the day of surgery; other treatments were started before surgery. 309 patients were allocated to receive aspirin, 50 mg/d, and placebo; 296 patients to receive aspirin, 50 mg/d, and dipyridamole, 200 mg twice daily; and 307 to receive oral anticoagulants that were adjusted to keep the international normalized ratio between 2.8 and 4.8. Saphenous vein grafts were implanted (single, sequential, or branched) and coronary endarterectomy was done at the surgeon's discretion. Acetaminophen was used by all patients as a substitute for aspirin.

Main outcome measures

The primary end point was graft occlusion. Primary clinical outcomes included mortality, MI, thromboembolism, or major bleeding. Secondary end points were angina, heart failure, or arrhythmias.

Main results

The graft-occlusion rate was 11% for the aspirin combination group compared with 15% for the aspirin alone group (relative risk reduction 24%, 95% CI -5% to 45%). The rate for the oral anti-coagulated group was 18%. Patients with occluded grafts were 26%, 27%, and 27% for the aspirin combination, aspirin alone, and anticoagulant groups, respectively. The groups did not differ for mortality, MI, thromboembolic events, or major bleeding (15% in the aspirin alone group, 22% for aspirin plus dipyridamole group, and 18% for the oral anticoagulant group).

Conclusions

No evidence existed that the addition of dipyridamole to aspirin improved 1-year vein-graft patency after coronary bypass surgery. Compared with aspirin, oral anticoagulants provided no benefit.

Sources of funding: The Netherlands Heart Foundation; Dr. Karl Thomae GmbH; Boehringer Ingleheim; Interuniversity Cardiology Institute of the Netherlands.

For article reprint: Dr. J. van der Meer, Thoraxcentre, University Hospital, 9713 EZ Groningen, the Netherlands. FAX 31-50-633-113.


Commentary

Aortocoronary bypass surgery is recommended to relieve angina and reduce mortality in subsets of patients with coronary artery disease. Aspirin is recommended to maintain patency of the vein grafts by preventing platelet-dependent thrombosis. Because the side effects of aspirin are dose related, a need exists to establish the lowest effective dose. Without antithrombotic therapy, 25% of grafts will be occluded at 1 year (1).

The report by van der Meer and colleagues compares the results of low-dose aspirin (50 mg/d) with aspirin plus dipyridamole and with oral anticoagulants. No difference in the incidence of graft occlusion existed with oral anticoagulants or with the combination of dipyridamole and aspirin when compared with aspirin alone. The incidence of graft occlusion at 1 year with aspirin alone was 20%, which is consistent with the 18% incidence found in the Veterans Administration Cooperative Study that used higher doses of aspirin (2). The van der Meer study also showed no difference in clinical outcomes of death, stroke, and bleeding when dipyridamole was taken with the aspirin.

Therefore, aspirin, 50 mg/d, is beneficial after bypass surgery without the addition of dipyridamole. It has not been directly compared with higher doses of aspirin. Physicians should be aware that the benefits of antithrombotic therapy are greater when the drugs are started preoperatively or within 24 hours postoperatively. Benefits diminish with longer delays between surgery and the start of the antithrombotic agents.

Moira Cruickshank MD, MSc
University HospitalLondon, Ontario, Canada


References

1. Chesebro JH, Fuster V, Elveback LR, et al. Effect of dipyridamole and aspirin on late vein-graft patency after coronary bypass operations.N Engl J Med. 1984;310:209-14.

2. Goldman S, Copeland J, Moritz T, 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;80:1190-7.