Hemorrhagic complications during long-term postoperative warfarin administration in patients undergoing lower extremity arterial bypass surgery.

Lower extremity bypass procedures restore function and prevent amputation in many patients with severe peripheral arterial occlusive disease. The regular postoperative use of aspirin offers the dual benefit of extending bypass patency and patient survival. Previous trials of adjunctive oral anticoagulant therapy with warfarin have infrequently combined warfarin with aspirin. We hypothesized that the addition of oral anticoagulant therapy would further enhance the benefits of aspirin but may increase the risk of clinically important bleeding. Eligible patients (N = 831) scheduled for elective lower extremity arterial bypass surgery were randomized to receive either warfarin plus aspirin (WA) (n = 418) or aspirin alone (n = 413). At monthly intervals, the warfarin dose was adjusted to a target international normalized ratio (INR) of 1.4 to 2.8; both groups received aspirin (325 mg/d). The end point of major hemorrhagic events, defined as intracranial hemorrhage or bleeding that required intervention, is reported, and INR values and compliance with warfarin therapy are presented. Major hemorrhagic events occurred more frequently in the WA group (35 in the WA group vs 15 in the aspirin group; p = .02) during a mean follow-up of 38 months. In the WA group, an intracranial hemorrhage occurred in six patients (two had an INR > 3.0), of whom four died; one subdural hemorrhage occurred in the aspirin group. Transfusions and interventions for bleeding were more frequent in the WA group, as were minor bleeding events. Of the 8,946 INR determinations, 58% were in the target range, whereas a higher value occurred in 10% and a lower value in 32%. Compliance with warfarin was maintained in 65% of the patients after the first year of observation. In patients with elective lower extremity bypass procedures, the postoperative adjunctive use of warfarin with aspirin increased the risk of major hemorrhagic events. Most of these events occurred when the INR was in the target range.