INTRAMURAL DELIVERY OF A SPECIFIC TYROSINE KINASE INHIBITOR WITH BIODEGRADABLE STENT SUPPRESSES THE RESTENOTIC CHANGES OF THE CORONARY-ARTERY IN PIGS IN-VIVO

Objectives. This study was designed to examine whether or not intramur al delivery of ST638 (a specific tyrosine kinase inhibitor) with biode gradable stent can suppress the restenotic changes of the coronary art ery in vivo. Background. Clinical and animal studies demonstrated that restenosis after coronary intervention results from a combined effect of neointimal formation and geometric remodeling (decrease in total c ross-sectional area). Thus, the most effective strategy to prevent the restenosis appears to inhibit both the neointimal formation and geome tric remodeling by antiproliferative agent and stent, respectively. We have previously shown that ST638 markedly suppresses the restenotic c hanges of the porcine coronary artery when applied from the adventitia l site. Methods. A poly-L-lactic acid biodegradable stent was coated w ith either ST638 (0.8 mg) or equimolar of its inactive metabolite, ST4 94. A pair of these stents were implanted alternatively in the left an terior descending or circumflex coronary artery in pigs (n = 6). Three weeks after the procedure, coronary stenosis was assessed by angiogra phy followed by histological examination. Results. Coronary stenosis w as significantly less at the ST638 stent site than at the ST494 stent site (47 +/- 5% vs. 25 +/- 4%, p < 0.01), Histological examination als o showed that the extent of neointimal formation and that of geometric remodeling were significantly less at the ST638 stent site than at th e ST494 stent site (p < 0.05). Conclusions. These results indicate tha t intramural delivery of a specific tyrosine kinase inhibitor with bio degradable stent overcomes the proliferative stimuli caused by balloon injury, the stent itself, and the drug coating on the stent, resultin g in the suppression of the restenotic changes of the coronary artery in vivo. This strategy might also be useful in the clinical setting in humans, (J Am Coll Cardiol 1998;32:780-6) (C)1998 by the American Col lege of Cardiology.