Paclitaxel coating on the terminal portion of hemodialysis grafts effectively suppresses neointimal hyperplasia in a porcine model.

OBJECTIVE: The local delivery of paclitaxel onto a graft has been reported to prevent neointimal hyperplasia. Because more than half of vascular stenoses occur within 3 cm of the venous anastomosis, this study tested the effectiveness of a paclitaxel coating restricted to both ends of the expanded polytetrafluoroethylene (ePTFE) graft to reduce the amount of drug delivered.

METHODS: Both ends of ePTFE grafts were coated with paclitaxel at a dose of 0.58 μg/mm(2); the total amount of paclitaxel per graft was 0.66 mg. Paclitaxel-coated hemodialysis grafts 15 cm in length were surgically implanted between the common carotid artery and external jugular vein in female Landrace pigs. The animals were sacrificed 6 weeks after graft placement. Cross sections of the anastomosis sites were analyzed histomorphometrically to measure the ratio of neointimal hyperplasia to the graft area (H/G ratio) and the percentage of luminal stenosis. The experimental results were compared between grafts coated with paclitaxel at the ends only (n = 8), grafts coated over the entire length (n = 6), and uncoated control grafts (n = 6).

RESULTS: The mean ± standard error values of the H/G ratios for the arterial anastomosis were 0.82 ± 0.13 (control), 0.41 ± 0.09 (terminal coating), and 0.21 ± 0.04 (whole coating). The values for the venous anastomosis were 0.82 ± 0.12 (control), 0.39 ± 0.11 (terminal coating), and 0.12 ± 0.03 (whole coating). Compared with the uncoated grafts, neointimal hyperplasia was suppressed effectively in the vascular grafts coated terminally with paclitaxel (artery, P = 050; vein, P < .001). However, the suppressive effect was less than that of grafts coated with paclitaxel over the entire length. The percentages of luminal stenosis showed similar tendency to the H/G ratios.

CONCLUSIONS: Despite a reduced amount of the drug, paclitaxel coating applied to both ends of the ePTFE hemodialysis grafts effectively suppressed neointimal hyperplasia at the sites of anastomosis.