Stents at 25 years: A revolution in revascularization

Throughout the history of cardiology, several milestones have marked modern medicine’s fascination with and research into the heart: the first description of the heart’s chambers and vessels by French professor Raymond de Vieussens in 1706; the first measuring of BP by English scientist Stephen Hales in 1733; the development of the electrocardiograph by Dutch physiologist Willem Einthoven in 1903; and the first heart surgery performed in 1938 by American surgeon Robert E. Gross.

These achievements, although only representing a sampling of those milestones, have each forever changed the way CV health is understood and how to diagnose and treat conditions that are often life-threatening.

Cardiology Today chief medical editor Carl J. Pepine, MD, and several intervention leaders look back on the stenting era. Source: Cardiology Today

In the field of revascularization, one such platform-changing milestone was the first insertion of a stent into a human coronary artery. This feat, performed by Jacques Puel in France in March 1986 and shortly afterward by Ulrich Sigwart in Switzerland, set the stage for what would end up changing the way physicians care for patients with problematic vessels.

Yet, years before these fateful procedures were performed, stenting was the direction many cardiologists, including Carl J. Pepine, MD, professor, division of cardiovascular medicine, University of Florida, Gainesville, and chief medical editor of Cardiology Today, were looking for the field of intervention to head, based on research that had been done in animal models.

“There had been substantial experience in animal models in the early 1980s with a variety of stents,” Pepine said in an interview. “I’d say that by the time the two groups, Puel in France and Sigwart in Switzerland, performed coronary stenting in patients in 1986, we were aware of the problems and were all looking to prevent restenosis.”

However, it would still take close to a decade — with the FDA’s approval of the Palmaz-Schatz stent (Johnson & Johnson) in 1994 — for stenting to begin to transform clinical practice in the United States.

Revascularization before stenting

In the years preceding approval, many patients who would by today’s standards be treated percutaneously — particularly in single-vessel disease, but even now in multivessel disease — instead underwent bypass surgery. Balloon angioplasty, the interventional precursor to stenting first performed on a coronary artery in 1977 by Andreas Gruentzig, MD, was also beginning to gain momentum as an interventional option for those needing to undergo revascularization.

Renu Virmani

“I remember Gruentzig coming to the NHLBI and giving us a lecture about [balloon angioplasty] being the greatest way to treat coronary disease,” said Renu Virmani, MD, president and medical director, CVPath Institute, Gaithersburg, Md., and Cardiology Today Editorial Board member. “Some of us said at that time it didn’t sound like a smart idea.”

This apprehension would later be validated by the oftentimes serious complications that surrounded the procedure. “We had a high procedural success rate [with balloon angioplasty], but we had the bane of restenosis that might occur in 20% or more of the cases,” Pepine said. “We also had the issue of acute dissection and occlusion. If we couldn’t tack up that dissection with the balloon, it resulted in a need for emergency bypass surgery. Consequently, all of the procedures then were backed up with a surgical team on an emergency basis.”

Stenting obstacles

In 1985, just before the first stent was inserted in a human, Virmani and Martin Leon, MD, had performed work with the Palmaz-Schatz stent.

“My first impressions with stents were that they were weird looking and didn’t deploy properly,” Virmani said. “The problems had to do with the quality of the balloons and the deployment, as well as how much may have slipped off the stent. Those understandings weren’t there in those days.”

The initial shortcomings with the first bare metal stents led to a number of critical problems during its early usage, said Spencer King III, MD, Cardiology Today Editorial Board member and president of the Saint Joseph’s Heart and Vascular Institute in Atlanta.

“Acute closure of stents was a major problem,” King said. “And at that time, we were treating these patients with heparin in hospital and then Coumadin (warfarin, Bristol-Myers Squibb). If you put a stent in, you were committed to a long and expensive hospitalization for several days, changing over to Coumadin and discharging them on Coumadin. So stenting was a laborious prospect to do at that time.”

“Initially, there was even some controversy over whether stents should be used only for bail-out purposes, that is if the balloon angioplasty results didn’t look good, or as a default strategy,” Deepak L. Bhatt, MD, MPH, chief of cardiology, VA Boston Healthcare System and member of Cardiology Today’s Editorial Board, said in an interview. “There were also some competing strategies that, for the most part, fell by the wayside, like techniques such as atherectomy … which some thought might supplant the need for stenting.”

Spencer King III

Despite these hitches, once the stent became approved in 1994, there was no looking back for revascularization or for the field of cardiology.

“Within a short time, stents became the default interventional strategy,” King said. “Stenting became easier than balloon angioplasty because now you didn’t have to sit around and wait and see if the artery was going to close, or if it was open enough, or if it might leave you with a dissection or irregular surface that might undergo acute closure. Now you could solve all that with a stent.”

Advancements further stent usage

After the adoption of stents into clinical practice, changes and advancements to their design became regular facets in cardiology news, with many now vying for the honor as having the greatest effect on clinical practice. Although it is still a topic for debate, one of the advancements that is regularly placed at the top of the list is the drug-eluting stent. As the first drug-eluting stent approved by the FDA in 2003, the Cypher (Johnson & Johnson/Cordis) was a significant step forward in the fight to reduce restenosis, which was followed by numerous other manufacturers’ models that continued to try to improve upon the design and, ultimately, the treatment of patients.

“Obviously, the drug-eluting stent has been an advancement and has certainly improved the likelihood of [revascularization] success in patients,” Virmani said. “But at the same time, it’s made [revascularization] harder because we do not have control over when patients are going to have late stent thrombosis. We clinically can’t recognize when that event is going to occur and in whom it’s going to occur. So therein lies the problem of the drug-eluting stent. They will get better, as the second generation of stents is definitely better than the first generation.”

Deepak L. Bhatt

Other advancements that are perhaps overshadowed by the creation of the drug-eluting stent have, in their own ways, transformed the field of percutaneous coronary intervention, according to Bhatt, including improvements to stent design that have made them smaller and more deliverable.

“This is actually a big deal,” he said. “It means we can use smaller equipment, whether we’re going through the femoral or radial artery, and treat more complex lesions.”

Although relatively new to industry, one of the variations to the bare metal stent design that has piqued the interest of many interventionalists is the bioabsorbable stent. In fact, in January, Abbott Laboratories announced that its bioresorbable vascular scaffold received CE mark approval in Europe.

“Mechanically, it’s a compliant stent. It allows the artery to retain its normal contour and dissolves over a period of time, but it takes a long time to do that completely,” King said. “The hope is that this kind of stent will offer some kind of advantage. We don’t know that yet because it’s going to be necessary to have those stents in humans for an extended period of time to see what the late outcome is and whether it is an advantage over metal stents or not. But it is certainly an area of interesting development.”

Pepine said the bioabsorbable stent holds promise in the field of intervention.

“The stent is only necessary to maintain its scaffolding function for a period of time. If you get adequate healing of the vessel, then presumably, in a few months, the stent could degrade, and you would be relatively free of some of the issues we have now, like stent thrombosis and the need for prolonged dual or more antiplatelet therapy,” he said.

Future of stenting

For Bhatt, one expectation he has for stenting in the next couple of decades is to see it move beyond the sphere of cardiology and into other realms of medicine. “For the future, there is still much potential for breakthroughs because the stent is a platform for drug delivery or delivery of gene products. Those areas are still largely untapped,” he said.

“Perhaps the most important thing to watch in the long term will be the effect of other therapies, such as medical therapies, that might stabilize the arterial system to make some stenting unnecessary,” King said. “This could certainly impact the utilization of stents in the future and the appropriateness for them if additional medical developments make cardiac events rarer.”

Still, as Virmani said, there will still be room for some of the present day staples, such as the drug-eluting stent, in the future landscape of revascularization.

“The drug-eluting stent is here to stay and will improve,” she said. “Someday, we will understand more about how to put them in bifurcation lesions and how to make them even better than the designs we have today.”

Despite these varying opinions, one thing most cardiologists can agree on is that in the years ahead, the effect of stents will continue to broaden. This belief was validated in January with the FDA advisory panel’s vote to expand indication of carotid stenting for patients with carotid artery stenosis and then shortly afterward with the 2011 Guideline on the Management of Patients with Extracranial Carotid and Vertebral Artery Disease that upgraded carotid stenting use.

“Carotid artery stenting, much like coronary stenting, will continue to be refined and eventually be the dominant mode of carotid revascularization,” Bhatt said. “But we still have a few iterations of carotid stenting technology before it becomes completely dominant, like its precursor.”– by Brian Ellis

For more information:

• The Franklin Institute. History of the Heart: www.fi.edu/learn/heart/history/firsts.html.
• History of Angioplasty: www.ptca.org/history_timeline.html.

Disclosures: Dr. Bhatt reports having received research grants from Astra Zeneca, Bristol-Meyers Squibb, Eisai, Sanofi-Aventis and The Medicines Company; Dr. King reports no relevant financial disclosures; Dr. Pepine reports no relevant financial disclosures; Dr. Virmani reports having consulted for many stent companies, including Medtronic, Abbott, Terumo and Atrium, and speaks on behalf of the companies at seminars.