Thrombolytic therapy with use of alteplase (rt-PA) in peripheral arterial occlusive disease: Review of the clinical literature

PURPOSE: The clinical literature describing the use of alteplase in the treatment of peripheral arterial occlusive (PAO) disease is reviewed. MATERIALS AND METHODS: The literature database was acquired by a MEDLINE search using the Boolean keyword string: tissue plasminogen activator and/or rt-PA and peripheral not animal. A review was performed to identify the dose range of alteplase, technique of infusion, use of anticoagulation, clinical success rates, and risk of complications. RESULTS: Forty-six clinical studies were identified. There are few prospective, randomized clinical trials and a lack of standardized protocols and endpoints. Use of catheter-directed infusions of recombinant tissue plasminogen activator (rt-PA) may be beneficial versus surgery in the initial management of acute limb ischemia (< 14 days) and in reducing the magnitude of subsequent surgical or percutaneous revascularization. For patients with chronic limb ischemia (> 14 days), irreversible acute limb ischemia, or advanced diabetic arteriopathy, catheter-directed infusion of rt-PA or other plasminogen activators may be unsuitable. The risk of adverse bleeding appears related to the overall dose and duration of infusion. These risks appear similar to those of urokinase. The role of heparin in increasing adverse bleeding during rt-PA therapy is unclear. CONCLUSIONS: There is no generally accepted dose or technique for administering catheter-directed thrombolysis using alteplase; however, several studies have demonstrated its clinical safety and efficacy. Formal studies will be required to determine the optimal dose, technique of infusion, the role of anticoagulation, and complication rates when alteplase is used for PAO disease.