Local Delivery of Paclitaxel to Inhibit Re-Stenosis During Angioplasty of the Leg

Abstract

Conclusion: Performance of percutaneous angioplasty of the superficial femoral artery (SFA) using Paclitaxel-coated angioplasty balloons results in significant reductions in late lumen loss and target lesion revascularization. Summary: A previous trial of a sirolimus-coated stents for SFA angioplasty failed to reveal benefit when compared to un-coated stents (Circ 2002;106:1505-9). There have, however, been animal trials that the use of Paclitaxel as a coating on angioplasty balloons and also when added to contrast media, can reduce vascular smooth muscle cell proliferation and therefore decrease intimal hyperplasia. In this study the authors investigated the use of Paclitaxel-coated angioplasty balloons and the addition of Paclitaxel to contrast media on lower extremitiy angioplasty. This trial randomly assigned 154 patients with stenosis or occlusion of the femoral/popliteal artery to treatment with standard balloon catheters coated with Paclitaxel, treatment with uncoated balloons but with Paclitaxel dissolved in the contrast medium, or to treatment with uncoated balloons without Paclitaxel in the contrast medium (control group). Three centers in Germany participated in the study. The study was sponsored by Bavaria Medizintecnologie and Schering, Germany. The primary end point was lumen loss at six months. Mean age of the patients was 68 ± 8 years. Forty nine percent of the patients had diabetes. Of the lesions treated, 27% were total occlusions and 36% were restenotic lesions. Mean lesion length was 7.4 ± 6.5 cm. The study groups had no significant demographic differences. All patients received 75 mg of Clopidogril daily for four weeks after intervention, and 100 mg of aspirin daily indefinitely. Plasma Paclitaxel concentrations were determined immediately and two hours after intervention, using high performance liquid choromatography. Residual Paclitaxel on the balloon after use was also determined. Fifty four patients were assigned to the control group, 48 to treatment with Paclitaxel-coated balloons, and 52 to treatment with Paclitaxel in the contrast medium. Mean ankle-brachial index prior to intervention was 0.5 ± 0.3. Late lumen loss was determined by angiography and 83% of the patients underwent angiography at six months of follow-up. At six months, mean late lumen loss in the control group was 1.7 ± 1.8 mm. In the group treated with Paclitaxel-coated balloons it was 0.4 ± 1.2 mm (P < 0.001). In the group treated with Paclitaxel only in the contrast medium mean late lumen loss at six months was 2.2 ± 1.6 mm (P = 0.11 compared to the control group). Revascularization of target lesions at six months was 37% in the control group, 4% in the group treated with Paclitaxel-coated balloons (P < 0.001), and 29% in the group treated with Paclitaxel only in the contrast medium (P = 0.41). At 24 months, revascularization rates increased to 52% in the control group, 15% in the group treated with Paclitaxel-coated balloons, and 40% in the group treated with Paclitaxel in the contrast medium. Maximum plasma Paclitaxel concentration remained below detectable limits in 40 of 42 patients treated with coated balloons. The majority of patients with Paclitaxel in the contrast medium had measurable plasma concentrations immediately after the procedure. Comment: The results of this study seem almost too good to be believed. Nevertheless, based on the animal data, they are not inconceivable. The investigators, however, were not fully blinded to the treatment arm of the individual patients. Some also served as consultants and received grant support from the industry sponsors or are involved in patent applications with respect to the techniques used in the trial. Fully blinded studies with non-potentially biased investigators will be required.