Restenosis prevention

Clinical efficacy of anti-inflammatory properties has been shown in several trials independent of their lipid-lowering effects (18,19). Statins reduce CRP levels and it is known that elevated CRP levels are associated with restenosis. Counter intuitively, however, several trials tested statins for restenosis prevention and were disappointing (20-23). The only trial that showed reduction in restenosis was the REGRESS trial (24), which used pravastatin 40 mg once daily for a period of two years. In this study, the binary restenosis assessed at two... 

Hausleiter J, Kastrati A, Mehilli J, et al. Randomized, double blind, placebo controlled trial of oral sirolimus for restenosis prevention in patients with in-stent restenosis. The oral sirolimus to inhibit recurrent in-stent stenosis trial (OSIRIS). Circulation 2004 I 10 790. 

In parallel to catheter-based delivery, stent-based approaches, such as passive stent coatings (diamond-like carbon, phosphorylcholine, and silicon carbide coatings) and immobilized drug coatings (heparin-coated stents), were evaluated for their ability to inhibit restenosis. Although animal studies demonstrated some promise, none of these technologies were clinically successful for restenosis prevention. The failure of these surface modification technologies further added to the need for the development of DES based on the principles of sustained CDD,... 

Waksman R, Robinson KA, Crocker IR, et al. Endovascular low-dose irradiation inhibits neointima formation after coronary artery balloon injury in swine a possible role for radiation therapy in restenosis prevention. Circulation 1995 91 1533-1539. 

Serruys FW, Rutsch W Heyndrickx GR, et al. Prevention of restenosis after percutaneous transluminal coronary angioplasty with thromboxane A2-receptor blockade. A randomized, double-blind, placebo-controlled trial. Coronary Artery Restenosis Prevention on Repeated Thromboxane-Antagonism Study (CARPORT). Circulation 1991 84(4) 1568-1580. 

At therapeutic dosimetries in vivo, the main photodynamic mechanism for vascular SMC depletion is apoptosis (10). Re-endothelialization appears to be accelerated after PDT and may contribute to the sustained inhibition of neointimal formation (26,45-47). If so, this would be an important advantage over other restenosis prevention strategies such as brachytherapy or certain drug-eluting stents. 

The next step in this approach to restenosis prevention is to implant a device, fabricated from such a polymer, at the site of injury to determine whether vascular smooth muscle cell proliferation and platelet attachment... 

Waksman, R., Intracoronaiy radiation therapy for restenosis prevention Status of the clinical trials, Cardiovasc. Radial. Med., 1999 l(l) 20-29. 

The calcification of atherosclerotic plaques may be induced by osteopontin expression, since osteopontin is a protein with a well-characterized role in bone formation and calcification. Vascular smooth muscle cell migration on osteopontin is dq endent on the integrin av 33 and antagonists of av 33 prevent both smooth muscle cell migration and restenosis in some animal model [8]. 

Due to the pivotal role of platelets in thrombus formation, especially in the arterial system, inhibition of platelet function has become a central pharmacological approach. Antiplatelet drugs are given in order to prevent and treat thromboembolic diseases such as coronary heart disease, peripheral and cerebrovascular disease. They have also revolutionized the procedures of invasive coronary interventions as they reduce the risk of restenosis and thrombosis. 

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. 

Percutaneous coronary intervention A minimally invasive procedure whereby access to the coronary arteries is obtained through the femoral artery up the aorta to the coronary os. Contrast media is used to visualize the coronary artery stenosis using a coronary angiogram. A guidewire is used to cross the stenosis and a small balloon is inflated and/or stent is deployed to break up atherosclerotic plaque and restore coronary artery blood flow. The stent is left in place to prevent acute closure and restenosis of the coronary artery. Newer stents are coated with antiproliferative drugs, such as paclitaxel and sirolimus, which further reduce the risk of restenosis of the coronary artery. 

Initial tests in the rat revealed a high degree of tissue compatibility of Dat-Tyr-Hex derived polymers. More detailed tests are now in progress. In addition, tyrosine derived polymers are currently being evaluated in the formulation of an intracranial controlled release device for the release of dopamine, in the design of an intraarterial stent (to prevent the restenosis of coronary arteries after balloon angioplasty), and in the development of orthopedic implants. The use of tyrosine derived polymers in these applications will provide additional data on the biocompatibility of these polymers. 

Tardif, J., Probucol and multivitamins in the prevention of restenosis after coronary angioplasty, N. Engl. Med., 337,365-372,1997. 

Hypothesis Systemic Depletion of Macrophages to Prevent Restenosis... 

As mentioned, Fukuda et al. (46) have recently shown that circulating monocytes count increased and reached its peak two days after human stent implantation (from 350 167 to 515 149/mm ). These data support the correlation between monocytes depletion and prevention of restenosis. Inactivation of systemic monocytes immediately after injury suppresses... 

Garas SM, Huber P, Scott NA. Overview of therapies for prevention of restenosis after coronary interventions. Pharmacol Therapeut 2001 92 165-178. 

Babapulle MN, Eisenberg MJ. Coated stents for the prevention of restenosis Part II. Circulation 2002 106 2859-2866. 

Pepine CJ, Hirshfeld JW, Macdonald RG, et al. A controlled trial of corticosteroids to prevent restenosis after coronary angioplasty. M-HEART Group. Circulation 1990 81 1753-1761. 

Stone GW, Rutherford BD, McConahay DR, et al. A randomized trial of corticosteroids for the prevention of restenosis in 102 patients undergoing repeat coronary angioplasty. Cathet Cardiovasc Diagn 1989 18 227-231. 

Versaci F, Gaspardone A, Tomai F, et al. Immunosuppressive therapy for the prevention of restenosis after coronary artery stent implantation (IMPRESS Study). J Am Coll Cardiol 2002 40 1935-1942. 

Zotarolimus (53 Endeavor stent) Sirolimus (33) Macrolide antibiotic Semi-synthetic NP Microbial Cardiovascular surgery Inhibits cell proliferation, preventing scar tissue formation and minimizes restenosis in angioplasty patients 467 74... 

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