Question: Are oral anticoagulants (target INR 3.0-4.5) more effective than aspirin (80 mg) in the prevention of infrainguinal bypass-graft occlusion?
Population: Patients who required infrainguinal bypass graft surgery (venous or synthetic grafts) for obstructive arterial disease.
Design and methods: Randomized, open, clinical trial. A total of 1339 patients randomized to oral anticoagulants (target INR = 3.0-4.5) and 1351 to aspirin (80 mg/day). Treatment was started within 5 days of surgery. Primary outcome was graft occlusion defined as clinical examination and Doppler or duplex ultrasound evaluation and angiography when indicated. Mean length of follow-up was 21 months. Blinded adjudication of primary and secondary outcomes. Intention to treat analysis. Pre-specified subgroup analysis of primary outcome by graft type.
Results: In all, 182/1326 (13.7%) discontinued oral anticoagulants and 190/1324 (14.3%) discontinued aspirin. A total of 308/1326 (23.2%) on oral anticoagulants vs 322/1324 (24.3%) on aspirin had graft occlusion; relative risk = 0.95 (95% CI: 0.82-1.11). Secondary outcome composite of cardiovascular death, myocardial infarction, stroke, and amputation was 248/1326 (18.7%) on oral anticoagulants vs 275/1324 (20.8%) on aspirin; relative risk = 0.89 (95% CI: 0.75-1.06). Major hemorrhage was 108/1326 (8.1%) on oral anticoagulants vs 56/1324 (4.2%) on aspirin; relative risk = 1.96 (95% CI: 1.42-2.71). For vein grafts (n = 1546) the relative risk of occlusion was 0.69 (95% CI: 0.54-0.88) on oral anticoagulants vs aspirin. For non-vein grafts (n = 1104) the relative risk of occlusion was 1.26 (95% CI: 1.03-1.55) on oral anticoagulants vs aspirin. The statistical test for interaction between these subgroups was significant (p = 0.002).
Conclusion: High intensity warfarin (INR: 3-4.5) does not significantly reduce graft occlusion after infrainguinal bypass compared with aspirin. Oral anticoagulants are associated with a significant increase in major bleeding episodes. Oral anticoagulants and aspirin may alter the pathogenesis of graft re-occlusion differently depending on graft type.