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ANGIOPLASTY: minimally invasive & relatively inexpensive
Evolving as one of the most prevalent causes of death, the epidemic of coronary heart disease (CHD) has taken deep roots in India. One method of dealing with it constitutes unblocking the coronary artery through percutaneous coronary interventions (PCI). PCI can be used to mechanically improve myocardial perfusion without resorting to surgery.
The most common procedure, percutaneous transluminal coronary angioplasty (PTCA), helps to achieve revascularisation of myocardium in patients with symptomatic CHD and suitable stenoses (narrowing) of coronary arteries. In PTCA a guide wire is inserted through an artery in the groin and advanced through aortic arch into the stenosed coronary artery over which a miniature balloon catheter is advanced. When inflated, the balloon exerts circumferential pressure and compresses the accumulated plaque. Inflation is repeated until stenosis is relieved.
Even though primary success rates are high, 1/3rd to 1/2 of patients with successful angioplasty return in 3 to 6 months due to renarrowing or blockage at same site (restenosis). Restenosis represents an extreme form of healing response, which occurs in all interventional sites due to neointimal hyperplasia (rapid cell proliferation in angioplasty region) and thrombosis (clot formation due to lesions created by angioplasty). This condition is difficult to treat and limits the value of coronary interventions. Restenosis of dilated vessels occurs in 40 to 50% cases within 6 months of procedure, and angina occurs within 6 to 12 months in 25% cases. Hence, coronary stenting emerged as a new procedure in conjunction with angioplasty.
In coronary stenting, a stent is placed in coronary artery to prevent closure after angioplasty. This article describes the importance of coronary stenting and focuses on the latest advances in stenting: drug-eluting stents.

CORONARY STENTING: Most frequent pCI
Coronary stenting represents over 80% of interventions done worldwide. It offers same degree of protection against death, stroke and myocardial infarction as bypass surgery. Compared to balloon angioplasty, coronary stenting has a more favourable outcome, and it reduces restenosis in coronary artery by eliminating negative remodelling and elastic recoil. Neointimal hyperplasia is less common.
Coronary stents are miniature mesh tubes, implanted in coronary arteries to keep blocked portions open after angioplasty procedures. Stents must be flexible yet strong and easy to deliver. They are usually made of stainless steel, tantalum and nitinol. But these bare metallic stents are unable to cover entire surface of lesions. Exposure of lesions to flowing blood leads to thrombosis. Further, bare metal itself instigates thrombosis and neointimal hyperplasia.
Even better methods of stent implantation failed to get rid of factors causing restenosis. Hence, modifications were made in stent design: Fibrin film stents provide uniform coverage, maintain vascular integrity. Autologous graft stents combinations of metal stent and vascular tissue. Polymeric stents provide mechanical support to maintain lumen gain and allow endothelialization of the diseased arterial segment. Radioactive stents emit b particles to inhibit neointimal proliferation and thrombosis.
However, use of stents has not completely eliminated the risk of restenosis and need for re-intervention. Stents carry a risk of two long term-complications, restenosis and blood clot (0.5%). The risk of restenosis after stent implantation (in-stent restenosis) is 10 to 20% within 6 months of stent placement. In-stent restenosis occurs in up to 60% of patients with diabetes, diffuse lesions, lesions in small vessels or at a bifurcation. Research in the field of interventional cardiology is focused on minimising the problems of stent implantation. One area of ongoing research is drug-eluting stents.

DRUG-ELUTING STENTS: Precursor to a new era
Development of drug-eluting stents (DES), delivering antiproliferative agents, is a promising approach to prevent restenosis. DES is designed to control the release of drug into the surrounding tissue. The intention of this time-release process is to slow down growth of unwanted cells and allow the vessel to heal. DES address negative remodelling and intimal hyperplasia. Doctors have begun to use drug-eluting or medicated stents in clinical trials to prevent restenosis.
Sirolimus-eluting stents (SES):
Sirolimus, an immunosupp-ressive agent, is a potent inhibitor of growth-factor-mediated cell prolifera-tion. Studies with SES have shown virtually no re-growth of tissue for at least a year, and in some up to 2 years. The RAVEL study (RAndomized study with the sirolimus-eluting VELocity balloon-expandable stent) evaluated the efficacy of sirolimus-coated stents. At six months, there was 0% restenosis in sirolimus group compared with 26% in bare stents group. Event-free survival at 7 months was 97% versus 73% in control group. It significantly reduced the need for revascularisation procedures. In the SIRIUS study, 8 month angiographic follow-up showed 94% reduction in in-stent restenosis versus control arm. At 9-month follow-up, event-free survival rate was 91% vs. 81% in control group. In April 2002, the European Union gave clearance to commercial use of CYPHER, (SES).

Paclitaxel-eluting stents (PES): Pacli-taxel, a derivative of taxol, is a potent antineoplastic agent with long-lasting antiproliferative effects. It allows normal endothelialisation of arterial wall, thereby being better than radioactive stents. It was found that though release of paclitaxel by
coated stent stopped within two months, it prevented cell proliferation and restenosis for 6 months, which indicate its persistent efficacy. The ELUTES study (EvaLUation of pacliTaxel Eluting Stent) supported the efficacy of paclitaxel-coated stent in reducing restenosis with no short-term adverse events. It evaluated and identified a minimally effective paclitaxel dose using polymer-free stent. At 6 months, angiographic restenosis occurred in 21% of patients receiving bare stent and 3% of patients treated with 2.7 mg/mm2 paclitaxel-coated stent. Percent diameter stenosis was 34% with control stent and 14% with 2.7 mg/mm2 PES. The TAXUS program is a series of clinical studies on PES. The restenosis rate was 0% in the coated stent group. There were no major adverse cardiac events and no incidence of thrombosis. Taxus II, III and IV are in progress. QuaDS-QP2, a derivative of paclitaxel, is being tested in new DES. The antiproliferative effect of this stent was evident at 6 months but was not maintained at 12 months. Heparin-coated stents have been clinically studied for six months, but do not provide any angiographic benefits in coronary arteries. Other drugs currently in trials are actinomycin-D and titanium nitric oxide.

THE FUTURE: Is it the Holy Grail?
It is a simple adaptation of known stent technology, because it is deployed in the same fashion, as a conventional metal stent. The technology of DES has matured and established itself as a promising method to further reduce the incidence of restenosis. New methods of stent production are being designed and modifications are being made frequently. To date, no major adverse event has been observed in clinical studies. The cost of treatment in India with stent angioplasty is around Rs. 2 lacs.
Latest data continue to sustain hope that DES represent a major breakthrough in the battle against restenosis. That sense is conveyed by ELUTES and RAVEL study. However, these studies are small and long-term potential is yet to be evaluated. If these data are confirmed, drastic changes in policy and strategy of revascularisation will occur. The future goal is a drug-coated ‘smart’ biodegradable stent that the physician dips in a preferred cocktail of antiproliferative drugs just prior to deployment.