Direct Oral Anticoagulants Started After Infrageniculate Bypass Reduces Two-Year Mortality, Amputation, and Loss of Primary Patency Compared With Warfarin

Abstract

Despite numerous studies of antiplatelet and/or anticoagulation regimens after lower extremity bypass, no consensus has been reached regarding the optimal regimen for a particular combination of conduit and target. A 2017 Vascular Quality Initiative study reported that anticoagulation therapy had no effect on primary patency of infrainguinal bypass grafts but had some benefit in secondary patency of infrageniculate targets. Clinically, many patients who undergo below the knee bypass will start anticoagulation therapy, which, historically, has been with warfarin. However, more and more patients have been discharged with a prescription for direct oral anticoagulants (DOACs). The goal of our study was to evaluate whether DOACs are equivalent or superior to warfarin after infrageniculate bypass. The Vascular Quality Initiative infrainguinal bypass database was queried for all anticoagulation-naive patients who had undergone infrageniculate bypass and had been subsequently discharged with anticoagulant therapy. A survival analysis was performed after following up patients for ≤2 years to determine whether discharge with warfarin vs a DOAC affected overall mortality, loss of primary patency, or the risk of amputation. A multivariate Cox proportional hazards analysis was performed to help control for differences in important baseline demographic factors between the groups. Overall, 57,890 patients had undergone infrageniculate bypass. Of these patients, 1909 were anticoagulation naive and had been discharged with either warfarin (n = 1323) or a DOAC (n = 586). Discharge with a DOAC resulted in a significantly reduced hazard ratio (HR) for overall mortality (HR, 0.66; 95% confidence interval [CI], 0.47-0.92), loss of primary patency (HR, 0.75; 95% CI, 0.62-0.91), or amputation (HR, 0.73; 95% CI, 0.71-0.90) on multivariate regression analysis. A separation in the improved outcomes began <1 year after bypass and persisted for ≤2 years after the initial procedure on Kaplan-Meier analysis (Fig). The patients who were anticoagulation naive and had undergone infrageniculate bypass had experienced an unexpected mortality benefit, decrease in amputation, and increased patency when discharged with a DOAC compared with discharge with warfarin. The mechanism for this benefit requires further investigation.