Improvement of Outcome for Treatment of 'Restenosis-prone' Vascular Lesions? Potential Impact of the Paclitaxel dose on Late Lumen Loss in Porcine Peripheral Arteries

Purpose Clinical data indicate that the drug density on drug-coated balloons (DCBs) might have a role on treatment effect and durability. The aim of the current study was to investigate inhibition of neointimal formation and potential adverse effects after treatment with a novel double-dose DCB in swine. Material and methods A four-week study was performed in peripheral arteries of 12 domestic pigs after vessel injury and stent implantation. The novel double-dose DCB with 6-mu g paclitaxel (Ptx)/mm(2) balloon surface (1 x 6) was compared to a standard DCB with 3.5 mu g Ptx/mm(2) (3.5) and uncoated balloons (POBA). Potential adverse effects were stimulated by using three fully overlapping DCBs with 6 mu g Ptx/mm(2) each (3 x 6). Quantitative angiography, histomorphometry and histopathological analyses were performed. Results Higher paclitaxel doses per square millimeter of treated arteries were associated with reduced late lumen loss (LLL) in quantitative angiography 4 weeks after treatment (POBA: 0.91 +/- 0.75 mm; 3.5: 0.45 +/- 0.53 mm; 1 x 6: 0.21 +/- 0.41 mm; 3 x 6: - 0.38 +/- 0.65 mm). In histomorphometry, maximal neointimal thickness and neointimal area were the lowest for the 1 x 6 group (0.15 +/- 0.06 mm/1.5 +/- 0.4 mm(2)), followed by 3 x 6 (0.20 +/- 0.07 mm/1.8 +/- 0.4 mm(2)), 3.5 (0.22 +/- 0.12 mm/2.2 +/- 1.1 mm(2)) and POBA (0.30 +/- 0.07 mm/3.2 +/- 0.7 mm(2)). Downstream tissue showed histopathological changes in all groups including POBA, in larger number and different quality (e.g., edema, inflammation, vessel wall necrosis, vasculitis and perivasculitis) in the 3 x 6 group, which did not cause clinical or functional abnormalities throughout the study. Conclusion Treatment with the double-dose DCB (6 mu g Ptx/mm(2)) tended to increase inhibition of in-stent neointimal formation and to diminish LLL after peripheral intervention in the porcine model compared to a market-approved DCB with 3.5 mu g Ptx/mm(2).