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Coronary stents – past history, current controversies and future predictions


2 July, 2009  

Coronary stenting had a spectacular debut and has benefited from much subsequent development, but concerns about restenosis still arise …

Mark Nicholls

Coronary stenting has journeyed a long way since German cardiologist Andreas Grüntzig performed the first percutaneous
transluminal coronary angioplasty (PTCA) on September 16, 1977, in Zurich.

In terms of medical breakthroughs this was truly world-beating, but tragically Gruntzig never lived to see the long-term impact it had on millions of heart patients the world over, having died in a plane crash in October 1985.

Today, when asked about the most satisfying aspect of their work, many cardiologists so often speak of seeing a patient’s relief after they have opened an occluded coronary artery. A critical part of the development of PTCA procedures has been the evolution of coronary stenting.

But that progression has been the subject of much research, discussion, a degree of controversy and important breakthroughs. More  recently the debate has centred on bare-metal stents (BMS) versus drug-eluting stents (DES)
and has surrounded issues of efficacy, cost, mortality and clinical outcome.

History of stenting
The concept of a stent emerged from cardiologists’ early experience with angioplasty after it became clear that the wall of the coronary artery became weakened after balloon dilation.
As techniques developed, the stent, a metal scaffold that could be inserted into the coronary artery after angioplasty, evolved as the primary solution. Then came a second problem – that of
restenosis.

In the USA, Julio Palmaz and Richard Schatz pioneered the development of coronary stents, but it was Jacques Puel and Ulrich Sigwart in France in 1986 who first inserted a stent into the human coronary artery. The flexibility and reliability of these bare-metal stents improved, but the issue of restenosis – the body responding to the procedure Grüntzig called the “controlled injury” of angioplasty – occurred in about onequarter of cases, leading to a repeat procedure.

Research later shifted from a mechanical to a pharmacological option, with scientists looking at drugs that could halt restenosis and stents that were coated in such drugs.

DES v BMS
All approved DES devices have shown a significant reduction in restenosis, though there have been concerns over thrombosis – more recently late stent thrombosis – making the post-stent
antiplatelet therapy particularly important.

Studies on the thrombosis issue and data on a worse long-term prognosis following DES compared with BMS were presented at the September 2006 European Society of Cardiology meeting in Barcelona.1–3 This alarm call was significant and even saw a reduced use of DES, with cardiologists beginning to question whether DES had any clear advantage over BMS, particularly in patients with low-risk blockages.

Following Barcelona, the European Society of Cardiology, together with the European Association for Percutaneous Cardiovascular Interventions, organised a forum on DES in September 2007 to review the data and provide general recommendations to the medical community for the use, clinical development and future assessment of DES.

Among a number of rulings, it found that, overall, the “relative safety and efficacy of DES compared to BMS appears to be consistent across different groups of patients, albeit at
various levels of absolute benefit and risk.” This has been supported by a number of recent studies. A large meta-analysis of DES versus BMS published in the Lancet in 2007 compared 38 randomised trials (18,023 patients) with
a follow-up of up to four years and confirmed that DES and BMS were associated with similar rates of overall and cardiac mortality.4 The study also confirmed the efficacy of DES in markedly reducing TLR.

Research published in the Journal of the American College of Cardiology from the University of Pennsylvania School of Medicine in May 2008 showed a clear lifesaving benefit of
DES compared with BMS.5 Patients with DES were less apt to die, have heart attacks or require extra stents or bypass surgery, in the two years following placement of the stent.

Peter W Groeneveld, assistant professor in Penn’s Division of General Internal Medicine, said: “There is a distinct possibility that drugeluting stents not only reduce the need for future
cardiac procedures, but also save lives.”

However, a study published in the Canadian Medical Association Journal early this year sought to establish the long-term safety of DES compared with BMS in a usual care setting. It found that DES were safe and effective in the
first year following insertion but, thereafter, the possibility of longer-term adverse events could not be ruled out.6

Cost-effectiveness of DES
Consultant cardiologist Anthony Gershlick, professor of interventional cardiology at University Hospitals Leicester, stresses the importance of looking at the wider implications when considering the cost-effectiveness of DES.

In a paper titled “Health economics: drugeluting stents – are they worth the money?” Professor Gershlick acknowledges that technologies such as DES with their “undoubted benefits” and
role in reducing restenosis cost more than BMS but believes that additional acquisition cost can be partly offset by avoiding costs of repeat revascularisation that would have been incurred had the patient been treated with BMS.

While bodies such as the National Institute for Health and Clinical Excellence (NICE) in the UK use the quality-adjusted life year (QALY) as the measure of effectiveness, he warns this can become complex when factoring in the advantages of DES vs BMS along with the risk of restenosis, bearing in mind that not all BMS patients restenose.

In what some clinicians perceived as a turnaround, NICE last year recommended DES for use in patients with lesions longer than 15 mm or vessels less than 3 mm in diameter, despite
draft guidance of August 2007 that DES were not recommended in the treatment of coronary heart disease.

A factor in the change was clinical input from the British Cardiovascular Intervention Society (BCIS), which presented evidence on QALY and the incremental cost-effectiveness ratio to show that DES are cost-effective in these indications at a price premium of approximately £300–400.

BCIS has estimated that, had NICE’s draft guidance prevailed, cardiologists would have had to refer large numbers of patients at high risk of restenosis back to bypass surgery because they
could not be effectively treated with BMS. The net effect of this was estimated to be about a 40% increase in bypass surgery and a net cost increase to the health service of £55–60 million.

“It is important therefore that heath technology assessment groups take account of the wider implications of their recommendations and do not rely solely on an economic model,” said Professor Gershlick, who was the BCIS medical expert to the NICE review of DES (2003–2008).

A study published in the June 2008 issue of the American Heart Journal found that drugeluting stents offer cost savings in the USA during the first year after placement.7 Although the
initial cost of the device (averaging $16,000) was higher than BMS at $14,000, researchers at Penn University found that, among patients with the DES, 12% of those studied needed additional stents placed in the first year, compared with 15%
of patients who received BMS.

The future for DES
DES now comprise at least 85% of stents used in the USA and more than 40% of stents elsewhere. Yet the evolution of the stent continues, with the advent of bioabsorbable DES.

Patrick Serruys, professor of interventional cardiology at Erasmus University Thoraxcentrum, Rotterdam, is one of the leading experts on DES and believes they have had tremendous benefit for patients.

“With DES [patients] know that there is a 92–95% chance that they will not be back on my table, and that is important physically and psychologically for a patient. With BMS there was a 20–25% chance that they may be back,” he said.

But restenosis, while not a “catastrophic” issue, has been a consistent problem, said Professor Serruys, who believes the future of coronary stents lies in bioabsorbable DES. He has spent the last two years studying 30 patients using bioabsorbable DES, with findings due to be reported soon.

“We have seen so much potential with them,” he said, “and there will be much more investigation in the coming years with bioabsorbable stents.

“You do not need a stent in the artery for a period of longer than 6–9 months. I used to feel almost guilty when I first put BMS in a patient because the coronary artery does not want to be caged with a piece of metal. Bioabsorbable is the next generation of DES, and it will take us one step further on.”

Such stents being developed include a stent that, rather than using drugs to suppress excess tissue growth, utilises a bioengineered coating to attract a thin endothelial layer, while other companies are working on drug/polymer/stent
combinations.

Conclusion
The debate continues over which type of coronary stent is best for which patient. BMS still have a relevant role to play, yet the emergence of DES – particularly in the fight against restenosis
– has been crucial. Research and analysis will continue, along with the further evolution of bioabsorbable stents. Meanwhile, as cardiologists and researchers work on their efficacy and
safety, the patient continues to benefit … and live longer.