RESULTS OF A PROSPECTIVE RANDOMIZED TRIAL EVALUATING SURGERY VERSUS THROMBOLYSIS FOR ISCHEMIA OF THE LOWER-EXTREMITY - THE STILE TRIAL

Purpose This study was designed to evaluate intra-arterial thrombolyti c therapy as part of a treatment strategy for patients requiring revas cularization for lower limb ischemia caused by nonembolic arterial and graft occlusion. Materials and Methods Patients with native arterial or bypass graft occlusion were randomized prospectively to either opti mal surgical procedure or intra-arterial, catheter-directed thrombolys is with recombinant tissue plasminogen activator (rt-PA) or urokinase (UK). Thrombolysis patients required successful catheter placement int o the occlusion before infusion of either rt-PA at 0.05 mg/kg/hr for u p to 12 hours or UK of 250,000 units bolus followed by 4000 units/min X 4 hours, then 2000 units/min for up to 36 hours. A composite clinica l outcome of death, ongoing/recurrent ischemia, major amputation, and major morbidity was the primary endpoint. Additional endpoints were re duction in surgical procedure, clinical outcome classification, length of hospitalization, and outcome by duration of ischemia. Results Rand omization was terminated at 393 patients because a significant primary endpoint occurred by the first interim analysis. Failure of catheter placement occurred in 28% of patients who were randomized to lysis, an d thus, were considered treatment failures, Thirty-day outcomes demons trated significant benefit to surgical therapy compared with thromboly sis (p < 0.001), primarily because of a reduction in ongoing/recurrent ischemia (p < 0.001). However, clinical outcome classification at 30 days was similar. Stratification by duration of ischemia indicated tha t patients with ischemic deterioration of 0 to 14 days had lower amput ation rates with thrombolysis (p = 0.052) and shorter hospital stays ( p < 0.04), Patients with ischemic deterioration of > 14 days who who w ere were treated surgically had less ongoing/recurrent ischemia (p < 0 .001) and trends toward lower morbidity (p = 0.1). At B-month follow-u p, there was improved amputation-free survival in acutely ischemic pat ients treated with thrombolysis (p = 0.01); however, chronically ische mic patients who were treated surgically had significantly lower major amputations rates (p = 0.01). More than half of thrombolysis patients (55.8%) had a reduction in magnitude of their surgical procedure (p < 0.001). There was no difference in efficacy or safety between rt-PA a nd UK; however, in the thrombolysis group as a whole, fibrinogen deple tion predicted hemorrhagic complications (p < 0.01). Conclusions Surgi cal revascularization of patients with < 6 months of ischemia is more effective and safer than catheter-directed thrombolysis. Although ongo ing/recurrent ischemia is greater in the patients undergoing thromboly sis, 30-day clinical outcomes are similar, probably because of cross-o ver treatment to surgery. There is no difference in efficacy or safety between rt-PA and UK, although bleeding occurs in patients with great er fibrinogen depletion. A significant reduction in planned surgical p rocedure is observed after thrombolysis. Patients with acute ischemia (0-14 days) who were treated with thrombolysis had improved amputation -free survival and shorter hospital stays. However, for patients with chronic ischemia (> 14 days), surgical revascularization was more effe ctive and safer than thrombolysis. Combining a treatment strategy of c atheter-directed thrombolysis for acute limb ischemia with surgical re vascularization for chronic limb ischemia offers the best overall resu lts.