Safety and efficacy of limited-dose tissue plasminogen activator in acute vascular occlusion

Objective: The purposes of this study were to evaluate the safety and effic acy of limited-close tissue plasminogen activator (t-PA) in patients with a cute vascular occlusion and to compare these results with those obtained in equivalent patients receiving urokinase. Methods: We compared the results of 60 patients receiving catheter-directed urokinase from November 1997 to November 1998 (240,000 units/h x 4 h, 120, 000 units/h thereafter for a maximum of 48 li) with those of 45 patients re ceiving catheter-directed t-PA from November 1998 to August 2000 (2 mg/h, t otal dose less than or equal to 100 mg) for acute arterial occlusion (AAO) and acute venous occlusion (AVO). Interventional approaches such as cross-c atheter and coaxial techniques were used to reduce the dose of lyric agent needed to achieve pre-lysis-treatment goals (eg, complete lysis of all thro mbus/unmasking graft stenosis or establishing outflow target). Statistical analysis was performed using Student t test and Fisher exact test. Results: The urokinase and t-PA groups were comparable with regard to age, comorbidities (coronary artery disease, hypertension, diabetes, renal insuf ficiency, smoking), duration of ischemic or occlusive symptoms, location of occlusive process, pretreatment with warfaxin, and thrombotic versus embol ic and native versus graft occlusion in patients with AAO. In patients with AAO and in those with AVO, t-PA was equivalent to or better than urokinase with regard to percent of clot lysis, incidence of major bleeding complica tions, limb salvage, and mortality. Achievement of pretreatment goals (arte rial patients only) was 50% for urokinase patients and 76% for t-PA patient s (P =.02). Analysis of success in individual pretreatment-goal achievement showed urokinase and t-PA to be equivalent in unmasking stenoses (85% and 84%, respectively; P = NS), whereas t-PA was superior to urokinase in the m ore critical task of establishing run-off (39% versus 81% for urokinase and t-PA, respectively; P =.001). Additional interventions, either endovascula r or surgical, were required in 60% and 51% (P = NS) of patients receiving urokinase and t-PA, respectively, for AAO, and in 54% and 62% (P = NS) of p atients receiving urokinase and t-PA, respectively, for AVO. onclusions: Limited-close t-PA is a safe and effective therapy for AAO and AVO when administered by experienced teams using innovative but well-establ ished interventional techniques.