1. 1 Efficacy of a novel anti-inflammatory drug-eluting balloon coated with genistein before stent implantation in porcine coronary arteries I. Sheiban, C. Moretti, M. Anselmino, G. Biondi-Zoccai, P. Omedé, F. Sciuto, M. Galloni, and G. P. Trevi University of Turin, Turin, Italy (gbiondizoccai@gmail.com)

2. 2 BACKGROUND Drug-eluting stents using cytostatic drugs significantly reduce restenosis after percutaneous coronary intervention, but may be associated with persistent local inflammation. Coating coronary devices with potent anti- inflammatory agents such as the flavonoid genistein may provide significant benefits, without unduly promoting inflammation.

3. 3 BACKGROUND A novel genistein-eluting balloon has been developed by Sahajanand (Gujarat, India), with promising in vitro data, but no in vivo/preclinical data. We thus aimed to test in a porcine model the safety and efficacy of a novel genistein-eluting balloon before coronary stent implantation.

4. 4 METHODS Female piglets underwent PCI in 25 coronary segments in a randomized fashion with either a genistein-eluting balloon or a standard balloon, followed by bare-metal stent implantation at 1.1:1.0 balloon to artery ratio. Pigs were then sacrificed at different time points to appraise safety (i.e. endothelialization) and efficacy (i.e. anti-inflammatory and anti- proliferative effects): 1, 4, and 6 to 8 weeks after PCI.

5. 5 STUDY PROFILE DEB=drug-eluting balloon SB=standard balloon

6. 6 RESULTS Overall analysis was conducted on 14 piglets treated with 25 standard bare-metal stents were implanted, of which 13 with conventional angioplasty balloon and 12 with the genistein- eluted angioplasty balloon. The genistein-eluting balloon proved safe, as no untoward effects were found in any of the animals, including those sacrificed as early as 1 week post-PCI, with healing and endothelialization appearing almost universal in all stent struts within four weeks.

7. 7 RESULTS The drug-eluting balloon also showed significant biologic efficacy, as at 4 weeks animals treated with this device had a significant reduction in peri-stent inflammatory cells (39±32 vs 96±29, p= 0.019). This statistically significant anti-inflammatory effect translated into non-significant trends towards reduced neointimal hyperplasia (measured as neointimal thickness) at eight weeks (0.13±0.11 mm vs. 0.15±0.09 mm, p>0.05).

8. 8 RESULTS 46N = Drug-eluting balloon yesno % stenosis 35 28 21 14 7 46N = Drug-eluting balloon yesno Neointimal thickness (mm),3,2,1 0,0 p=0,788 p=0,319

9. 9 RESULTS 46N = Drug-eluting balloon yesno Injury score 1,2 1,0,8,6,4,2 0,0 46N = Drug-eluting balloon yesno MNCs x mm2 160 120 80 40 0 p=0,630 p=0,019

10. 10 HISTOLOGY OF GENISTEIN-ELUTING BALLOON (A) VERSUS CONVENTIONAL ANGIOPLASTY BALLOON (B) FOLLOWED BY CORONARY STENTING AT FOUR WEEKS

11. 11 4-WEEK PERI-STENT CELLULARITY AFTER CONVENTIONAL BALLOON (TOTAL CELLULARITY IN A, MNC IN B) VS GENISTEIN-ELUTING BALLOON (TOTAL CELLULARITY IN C, MNC IN D) WITH ARROWS INDICATING MNC.

12. 12 CONCLUSIONS This study provides the first in vivo demonstration of the anti-inflammatory effects of a novel genistein-eluting balloon in percutaneous coronary stenting. Further research is warranted to appraise whether the combination of a genistein- eluting balloon with standard drug-eluting stent can provide both anti-restenotic and anti-inflammatory effects.

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