What Would Be the Ideal Drug-eluting Stent for Managing Patients with Long Lesions?

What Would Be the Ideal Drug-eluting Stent for Managing Patients with Long Lesions?

Daniel J Blackman, Rhidian J Shelton
Interventional Cardiology Volume 4 Issue 1
Published: November 2009
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Drug-eluting stents (DES) substantially reduce the risk of restenosis, particularly in complex coronary disease. Their use is now standard in demanding anatomy, including in long lesions, which represent an increasing proportion of percutaneous coronary intervention (PCI) cases. However, long lesions pose a number of procedural and clinical challenges for DES, specifically stent deliverability, stent overlap and an increased risk of restenosis, peri-procedural myocardial infarction, geographical miss and stent thrombosis. The ideal DES for long lesions would incorporate a number of specific design characteristics to meet these challenges, including low late loss to minimise restenosis risk, thin struts to enhance deliverability and minimise risk of peri-procedural infarction and the availability of long lengths to minimise overlap and avoid geographical miss. It is clear from a knowledge of their properties, and from available data on DES performance in long lesions, that some currently available DES have superior design characteristics and clinical outcomes in the setting of diffuse disease. An awareness of these issues is essential for the practising interventional cardiologist in treating long lesions in routine clinical practice.

The introduction of coronary stents in the late 1980s improved outcome over balloon angioplasty via a reduction in acute vessel losure, prevention of vessel recoil, increase in acute gain and a lower rate of clinical restenosis.1,2 However, in-stent restenosis (ISR), caused by smooth-muscle cell proliferation and migration, leading to neointimal hyperplasia, remains the Achilles’ heel of bare-metal stents (BMS). The development of drug-eluting stents (DES), which release antiproliferative drugs into the vessel wall to inhibit neointimal hyperplasia, has revolutionised percutaneous coronary intervention (PCI), dramatically reducing the incidence of ISR and target lesion revascularisation (TLR)3 and permitting the treatment of more complex and extensive coronary artery disease, including diffuse or long lesions.

Long lesions account for approximately 20% of contemporary PCI cases, and present specific challenges for drug-eluting stenting. In this article we describe the difficulties encountered in the treatment of long lesions using DES. We discuss how the characteristics and design of DES could be adapted to overcome these challenges and to deliver an optimal outcome. Finally, we relate these observations to contemporary DES, and discuss the vidence for the performance of the different commercially available DES in the setting of long lesions. For the purposes of thisarticle we will focus on those DES with pivotal phase III randomised controlled trial data at the time of writing, namely the CYPHER sirolimus-eluting stent (SES) (Cordis, Johnson & Johnson, Miami Lakes, FL, US), the TAXUS paclitaxel-eluting stent (PES) (Boston Scientific, Natick, MA, US), the Endeavor Sprint zotarolimus-eluting stent (ZES) (Medtronic, Santa Rosa, CA, US), the Xience V (Abbott Vascular, IL, US)/Promus (Boston Scientific) everolimus-eluting stent (EES) and the Biomatrix biolimus-eluting stent (BES) (Biosensors Interventional, Singapore), although emerging technologies will also be discussed.

The Role of Drug-eluting Stents in Long Lesions
Together with vessel diameter, lesion length is the most powerful factor influencing the risk of ISR. For BMS, lesion length is an independent predictor of late lumen loss, binary angiographic ISR, TLR and major adverse cardiac events (MACE: death, non-fatal myocardial infarction [MI] or target vessel revascularisation [TVR]).4–7 The increased incidence of clinical and angiographic restenosis with longer lesions relates simply to the greater degree of arterial wall injury and consequent neointimal proliferation, and significantly limits the clinical utility of BMS in the treatment of long lesions. The dramatic reduction in restenosis associated with DES is greatest in complex disease settings in which BMS fare poorly, including long lesions. Data from randomised controlled trials and large observational registries highlight the increased risk of restenosis with longer lesions, and demonstrate a significant reduction in restenosis and TVR rates with DES use.8–13 As a consequence, use of DES in long lesions has become standard clinical practice, supported by international guidelines.14–17

The Challenges of Long Lesions forDrug-eluting Stenting
Even with DES use, treatment of long lesions poses a number of specific challenges to the interventional cardiologist, including an increased risk of restenosis, peri-procedural MI, stent deliverability, geographical miss (GM) and stent thrombosis (ST). The ideal DES for long lesions needs to offer optimal performance with regard to each of these factors.

Restenosis
Although significantly lower than with BMS, angiographic and clinical restenosis rates with DES use also increase progressively with lesion length (see Figure 1).18 The ideal DES in long lesions must ameliorate restenosis risk by effectively inhibiting neointimal hyperplasia and minimising late loss, and hence delivering low rates of TLR and MACE. Late loss is a reliable discriminator of restenosis propensity between DES platforms19,20 and, despite there being a class effect, not all DES systems are equal. Late loss appears greatest with the Endeavor Sprint ZES (circa 0.62mm),21 intermediate with the TAXUS PES (circa 0.39mm)22 and lowest with the CYPHER SES (circa 0.17mm),23 the Xience V/Promus EES (circa 0.14mm)24 and the Biomatrix BES (circa 0.13mm).25

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Keywords:
Percutaneous coronary intervention,percutaneous coronary intervention stent, angioplasty, angioplasty stents, drug-eluting stents, long lesions, neointimal hyperplasia, restenosis, stent deliverability

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