Immunosuppression for human saphenous vein allograft bypass surgery: A prospective randomized trial

Purpose: Vein allografts are an alternative bypass conduit for patients who lack adequate autogenous vein. Animal studies have demonstrated that patency can be augmented by low-dose immunosuppression with azathioprine. Methods: In a prospective trial, 40 patients (20 men, 20 women) were randomly assigned to receive (17) or to not receive (23) azathioprine (1 mg/kg/day) after cryopreserved vein allograft bypass grafting. Patients had pain or tissue loss that required bypass grafting to pedal or crural outflow and lacked adequate autogenous saphenous vein. Anti-HLA antibody screens were obtained before and after surgery. Biopsies of allografts were performed at implantation and at all subsequent opportunities. Postoperative physical and vascular laboratory examinations occurred every 3 months. Results: During the 31-month follow-up interval (mean, 15.7 months) there were 10 deaths (none immunosuppression-related). The primary graft patency rate at 12 months was 13%, and the limb salvage rate was 42%. No significant difference (p > 0.05) was noted between immunosuppressed and control groups for mortality rate, primary graft patency rate, or limb salvage rate. As a predictor of graft failure, positive preoperative anti-HLA antibody screen (8 patients) approached significance (p = 0.09). Of 22 explanted grafts, 13 (59%) had histologic evidence of rejection (six immunosuppressed, seven control). Seven patients who had negative results of preoperative anti-HLA antibody screens converted after surgery, and six patients had positive results of preoperative screens that became more strongly positive. Conclusion: Vein allograft failure is in part mediated by rejection, which is not eliminated by low-dose azathioprine. Both humoral (antibody) and cellular responses to vein allografts develop. The poor patency rates of vein allograft bypass grafts may be improved by more potent immunosuppression as well as improvement in allograft procurement, preservation, and matching.