Following bypass surgery to revascularize the lower extremity, patients are at high risk for graft occlusion and other atherosclerotic complications. Oral anticoagulants are routinely prescribed following such surgery, but a substantial proportion of vascular surgeons, up to 60 percent, believe such therapy as low-dose aspirin is more appropriate. The Dutch Bypass Oral anticoagulants or Aspirin Study Group, a consortium of researchers in the Netherlands, compared the efficacy of oral anticoagulation therapy with that of aspirin in preventing ischemic complications following infrainguinal bypass surgery.
All patients undergoing infrainguinal bypass graft surgery for obstructive arterial disease were eligible for the study. Exclusions included substantially shortened life expectancy, coagulation abnormalities, history of recent myocardial infarction or stroke, and contraindications to the study medications. After assessment and within five days of surgery, patients were randomized to receive 80 mg of aspirin daily or oral anticoagulation with a target International Normalized Ratio (INR) range of 3.0 to 4.5. For ethical reasons, the study was not blinded, and surgeons were free to use adjunct treatment, as needed. Follow-up occurred at three and six months, and every six months thereafter, with a mean follow-up period of 21 months. The data collected at follow-up included compliance with study medications, clinical evidence of limb ischemia or hemorrhage, and graft patency, as revealed by clinical examination and Doppler or duplex scanning. The primary outcome of the study was graft occlusion. Secondary first outcomes included vascular death, stroke, myocardial infarction and limb amputation.
Of the 2,690 patients enrolled in the study, 1,339 received oral anticoagulation and 1,351 received aspirin. Baseline characteristics and risk factors were similar between groups. More than one half (54 percent) of the patients were current smokers, 39 percent had hypertension, 26 percent had diabetes and 16 percent had hyperlipidemia. About 14 percent of the patients in each group stopped taking the assigned medication during the study period. In patients taking oral anticoagulants, INR levels were within the target range about one half of the time. Graft occlusion occurred in 308 patients taking anticoagulants and in 322 taking aspirin. While there was no overall difference in effectiveness, the two treatments differed by the type of graft used in surgery. Oral anticoagulants were superior to aspirin in preventing occlusion of autologous venous grafts, while aspirin provided better results in patients with nonvenous grafts. Secondary first outcome events occurred less frequently in patients treated with oral anticoagulants than in those treated with aspirin (248 compared with 275), but this difference was not statistically significant. Major bleeding episodes occurred more frequently (4.7 percent per year) in patients taking oral anticoagulants than in those taking aspirin (2.5 percent per year). Sixteen fatal bleeding episodes occurred in the oral anticoagulant group compared with 12 in the aspirin group.
The authors conclude that oral anticoagulants were superior to aspirin in preventing vein-graft occlusion and more effective in reducing the risk of ischemic events but were associated with more bleeding episodes, while aspirin was superior in preventing nonvenous graft occlusion and was associated with fewer bleeding episodes.