Restenosis cilostazol

The PDE3 inhibitor, cilostazol, has been used as an antithrombotic agent and is currently being used in patients being treated for intermittent claudication. Cilostazol is also used for the prevention of restenosis after treatments such as angioplasty. Another PDE3 selective inhibitor, milrinone, has been used in the treatment of congestive heart failure. Milrinone also has been shown to increase the conductance of the CFTR transporter in vitro. 

The restenosis benefit is also intriguing, but, in all likelihood, has nothing to do with the antiplatelet actions of cilostazol, and may relate more to its effects on cytokine release from endothelial cells and smooth muscle cells, There is also preliminary evidence suggesting that cilostazol may speed the process of endothelialization (53). Again, with DES and their well-documented difficulties with endothelialization (54,55), this is a potentially very important future application that will require prospective testing in clinical trials. 

Douglas JS, Holmes DR, Kereiakes DJ, et al. Coronary stent restenosis in patients treated with Cilostazol. Circulation 2005 ... 

Abbreviations CDK, cyclin-dependent kinase CREST, cilostazol for restenosis trial MACE, major adverse cardiac events ORAR, oral rapamycin to prevent restenosis ORBIT, oral rapamune to inhibit restenosis REAR, peroxisome proliferator-activated receptor PRESTO, prevention of restenosis with tranilast and its outcomes SMC. smooth muscle cell ThR, target lesion revascularization tREAT, Tranilast restenosis following angioplasty trials TVR, target vessel failure. ... 

As previously mentioned, for SMC proliferation after coronary angioplasty, cell activation and cell-to-cell interaction of platelets and leukocytes mediated by adhesion molecules are considered to be important. Coronary stenting produces the release of an adhesion molecule, P-selectin, from d-granule of activated platelets. P-selectin-mediated platelet-leukocyte interaction has a crucial role in the development of stent restenosis. Cilostazol is an antiplatelet, antithrombotic, phosphodiesterase III inhibitor that by inhibiting P-selectin release has inhibitory effects on SMC migration. In addition, cilostazol may directly act to inhibit intimal hyperplasia. 

Randomized trials conducted with cilostazol 200 mg daily have shown that it is effective in reducing restenosis (45-47). Douglas et al. undertook the Cilostazol for Restenosis Trial (CREST), a randomized, double-blind, placebo-controlled trial to determine whether cilostazol would reduce renarrowing in patients after stent implantation in native coronary arteries. Seven hundred and five patients who had successful coronary stent implantation received, in addition to... 

Kimishirado H, Inoue T, Mizoguchi K, et al. Randomized comparison of cilostazole versus ticlopdine hydrochloride for antiplatelt therapy after coronary stent implantation for prevention of late restenosis. Am Heart J 2002 144 303-308. 

Tsuchikane E, Fukuhara A, Kobayashi T, et al, Impact of cilostazol on restenosis after percutaneous coronary balloon angioplasty, Circulation 1999 100 21-26,... 

Tanabe Y Ito E, Nakagawa I, Suzuki K. Effect of cilostazol on restenosis after coronary angioplasty and stenting in comparison to conventional coronary artery stenting with ticlopidine, IntJ Cardiol 2001 78(3)285-291. 

Sekiguchi M, Hoshizaki H, Adachi H, Ohshima S, Taniguchi K, Kurabayashi M, Effects of antiplatelet agents on subacute thrombosis and restenosis after successful coronary stenting A randomized comparison of ticlopidine and cilostazol. Circ J 2004 68(7) 6I0-6I4,... 

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