Declining-dose study of reteplase treatment for lower extremity arterial occlusions

Abstract

Purpose: To prospectively determine the technical success and complication rates of three different reteplase dosing regimens during catheter-directed arterial thrombolysis.

Materials and methods: Prospective data were obtained from three groups of patients who underwent lower extremity arterial thrombolysis with three different regimens of reteplase: 0.5 U/h, 0.25 U/h, and 0.125 U/h. A total of 101 thrombosed lower extremity arterial occlusions in 87 patients were treated. A subtherapeutic intravenous heparin dose of 400-500 U/h was administered. All limbs were viable at presentation. Thrombolytic success was defined as 95% thrombolysis of the occluded artery or graft with restored distal antegrade flow. Thirty-day mortality and amputation rates were calculated. Bleeding complications and need for transfusions were recorded. Laboratory values recorded included fibrinogen level, platelet count, hematocrit level, hemoglobin level, and prothrombin time.

Results: Thrombolytic success was achieved in 86.7% of patients in the 0.5-U/h dose group, 83.8% of patients in the 0.25-U/h dose group, and 85.3% of patients in the 0.125-U/h dose group. The major bleeding and transfusion rates were 13.3% in the 0.5-U/h dose group, 5.4% in the 0.25-U/h dose group, and 2.9% in the 0.125-U/h dose group. The 30-day amputation-free survival rates were 90% in the 0.5-U/h dose group, 97.3% in the 0.25-U/h dose group, and 94.1% in the 0.125-U/h dose group. Pre- and postprocedural fibrinogen levels and the fibrinogen nadir were not statistically different between the groups. No differences in total infusion times were found between the 0.5-U/h dose and 0.25-U/h dose groups. However, the infusion time in the 0.125-U/h dose group was significantly longer than in the other two groups (42 h vs 30 h; P <.05).

Conclusion: All dosing regimens were equally effective in the treatment of acute lower extremity occlusions. The infusion times were longer with the 0.125-U/h dose. Significantly fewer major bleeding complications were encountered with the 0.25-U/h and 0.125-U/h dose regimens than with the 0.5-U/h dose regimen.