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Interventional Cardiology
Coronary Arteries and Sirolimus-eluting Stents –
Applications, Benefits and Future Potential
a report by
Ricardo Seabra-Gomes
President, Instituto do Coração
It took great courage around 30 years ago to tackle stenotic lesions (DES) era of interventional cardiology. Together with the paclitaxel-
within a diseased coronary artery using the percutaneous approach in eluting stent (PES), approved later, they form the so-called first-
an unanaesthetised human being. Since then, unbelievable progress generation DES. A pivotal randomised controlled trial (RCT) was the
and research have been taking place worldwide in a continuum that Randomized Study with the Sirolimus-coated Bx Velocity Balloon-
never seems to end. Percutaneous coronary intervention (PCI) is, for the Expandable Stent in the Treatment of Patients with De Novo Native
responsible interventional cardiologist, not only an appealing method Coronary Artery Lesions (RAVEL),
1
in which 238 patients were
of coronary revascularisation but also a permanent challenge, as the randomised to a single SES and a BMS. The result was an unexpected
technical progress must be balanced against the perceived and outcome of 0% restenosis in the SES group compared with 26%
foreseeable risks to the patient. Stents were conceived to make balloon restenosis in the BMS group at six months. This was followed by the
angioplasty safer and more effective. They controlled elastic recoil and larger (1,058 patients) Sirolimus-eluting Stent in De Novo Native
negative remodelling, but also stimulated the cellular mechanisms Coronary Lesions (SIRIUS) trial
2
in the US, and the E-SIRIUS
3
(n=352) in
yielding to in-stent restenosis. Restenosis after bare-metal stenting Europe and C-SIRIUS
4
(n=100) in Canada. The combined data from the
(BMS) is mostly due to neointimal proliferation. It was a pure last three studies (NEW-SIRIUS) reported a 5.1% in-lesion restenosis rate.
mechanical solution to an important biological problem. The
development of an antiproliferative drug-coated stent followed The true measure of the efficacy of DES, representing the best angiographic
extensive research on the understanding of vascular biology, surrogate of neointimal proliferation with the unique ability to separate it
pharmacology and experimental and clinical research. Sirolimus from other procedural and intrinsic vessel variables, is in-stent late luminal
(rapamycin) and paclitaxel target the cell cycle, inhibiting the effects of loss (LL). It can reliably predict the restenosis propensity and the clinical
injury-mediated growth factors and cytokines that produce vascular consequence of target lesion revascularisation (TLR).
5
The SES has always
smooth muscle proliferation and intimal hyperplasia. showed the smallest in-stent LL compared with other DES.
The Cypher
®
stent utilises a non-erodable methacrylate co-polymer The on-label indications for the Cypher SES were single de novo lesions
matrix for controlled endovascular delivery of the drug to the arterial in patients with stable coronary artery disease (CAD) in vessels with
tissue. Sirolimus is blended with the polymer and a thin coating is applied reference diameters between 2.5 and 3.5mm and in lesions ≤30mm.
to the surface of the Bx Velocity™ Cordis stent. A second coat of Stimulated by the remarkable results of the initial studies,
drug-free polymers serves as a diffusion barrier. The quantity of sirolimus cardiologists have progressively expanded the use of SES to almost all
loaded onto each stent is approximately 140mg/cm
2
, and the system clinical situations and more complex lesions. The off-label use of DES
provides controlled release of sirolimus over a period of four weeks. is current clinical practice, and may account for as many as 75%
of procedures.
The sirolimus-eluting stent (SES) was the first stent-based
pharmacological therapy approved for the prevention of restenosis and An impressive number of publications have dealt with SES implantation
the first to be approved by the European Community. It was introduced in diabetic patients, patients with acute myocardial infarction (MI), very
into clinical practice in 2002, bringing in the current drug-eluting stent small vessels (<3.0mm), very long lesions (>30mm), multivessel disease,
bifurcation lesions, unprotected left main disease, chronic total
occlusions, saphenous vein grafts and BMS in-stent restenosis. Many of
Ricardo Seabra-Gomes is President of the Instituto do
Coração. He is a former Director of the Department of
the data collected are derived from single or multicentre studies and from
Cardiology at Hospital Santa Cruz, President of the Portuguese
registries, but in some cases RCTs have been performed.
Society of Cardiology and National Co-ordinator for
Cardiovascular Disease. Dr Seabra-Gomes is a Fellow of the
European Society of Cardiology (ESC) and the American
Data from these RCTs have confirmed the efficacy of SES versus BMS
College of Cardiology (ACC), and a Member of the British
and PES in significantly reducing restenosis rates and the need for
Cardiac Society (BCS), the Spanish Society of Cardiology (SEC)
and the Council on Cardiology of the American Heart
further reintervention (TLR). Three RCTs were in acute MI,
6–8
two in small
Association. His areas of interest are coronary artery disease, acute coronary syndromes and vessels
9,10
(the Sirolimus-Eluting and an Uncoated Stent in the Prevention
interventional cardiology. He is the author or co-author of nearly 500 published scientific papers
of Restenosis in Small Coronary Arteries [SES-SMART]
9
trial also showed
and over 1,000 published abstracts. Dr Seabra-Gomes introduced coronary angioplasty (1984)
and several devices, including stents (1990), atherectomy (1991), brachytherapy (2001) and
a decreased incidence of MI comparing SES with BMS, and in the
drug-eluting stents (2002), to Portugal.
Intracoronary Drug-Eluting Stenting to Abrogate Restenosis in Small
E:
seago@esoterica.pt
Arteries-III [ISAR-SMART III]
10
SES was seen to be superior to PES), one in
long lesions (Sirolimus-eluting Stent Versus Paclitaxel-eluting Stent for
102 © TOUCH BRIEFINGS 2008
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