Coronary Arteries and Sirolimus-eluting Stents – Applications, Benefits and Future Potential

Coronary Arteries and Sirolimus-eluting Stents – Applications, Benefits and Future Potential

Seabra-Gomes Ricardo
European Cardiology - Volume 4 - Issue I
Published: August 2008
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It took great courage around 30 years ago to tackle stenotic lesions within a diseased coronary artery using the percutaneous approach in an unanaesthetised human being. Since then, unbelievable progress and research have been taking place worldwide in a continuum that never seems to end. Percutaneous coronary intervention (PCI) is, for the responsible interventional cardiologist, not only an appealing method of coronary revascularisation but also a permanent challenge, as the technical progress must be balanced against the perceived and foreseeable risks to the patient. Stents were conceived to make balloon angioplasty safer and more effective. They controlled elastic recoil and negative remodelling, but also stimulated the cellular mechanisms yielding to in-stent restenosis. Restenosis after bare-metal stenting (BMS) is mostly due to neointimal proliferation. It was a pure mechanical solution to an important biological problem. The development of an antiproliferative drug-coated stent followed extensive research on the understanding of vascular biology, pharmacology and experimental and clinical research. Sirolimus (rapamycin) and paclitaxel target the cell cycle, inhibiting the effects of injury-mediated growth factors and cytokines that produce vascular smooth muscle proliferation and intimal hyperplasia.

The Cypher® stent utilises a non-erodable methacrylate co-polymer matrix for controlled endovascular delivery of the drug to the arterial tissue. Sirolimus is blended with the polymer and a thin coating is applied to the surface of the Bx Velocity™ Cordis stent. A second coat of drug-free polymers serves as a diffusion barrier. The quantity of sirolimus loaded onto each stent is approximately 140mg/cm2, and the system provides controlled release of sirolimus over a period of four weeks.

The sirolimus-eluting stent (SES) was the first stent-based pharmacological therapy approved for the prevention of restenosis and the first to be approved by the European Community. It was introduced into clinical practice in 2002, bringing in the current drug-eluting stent (DES) era of interventional cardiology. Together with the paclitaxeleluting stent (PES), approved later, they form the so-called firstgeneration DES. A pivotal randomised controlled trial (RCT) was the Randomized Study with the Sirolimus-coated Bx Velocity Balloon-Expandable Stent in the Treatment of Patients with De Novo Native Coronary artery Lesions (RAVEL),1 in which 238 patients were randomised to a single SES and a BMS. The result was an unexpected outcome of 0% restenosis in the SES group compared with 26% restenosis in the BMS group at six months. This was followed by the larger (1,058 patients) Sirolimus-eluting Stent in De Novo Native Coronary Lesions (SIRIUS) trial2 in the US, and the E-SIRIUS3 (n=352) in Europe and C-SIRIUS4 (n=100) in Canada. The combined data from the last three studies (NEW-SIRIUS) reported a 5.1% in-lesion restenosis rate.

The true measure of the efficacy of DES, representing the best angiographic surrogate of neointimal proliferation with the unique ability to separate it from other procedural and intrinsic vessel variables, is in-stent late luminal loss (LL). It can reliably predict the restenosis propensity and the clinical consequence of target lesion revascularisation (TLR).5 The SES has always showed the smallest in-stent LL compared with other DES.

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