Medical Device Daily

PARIS – The clinical case for revascularization using drug-eluting stents advanced modestly at this year's congress for the European Society of Cardiology.

The third-generation of drug-eluting stents (DES) won a green light for effectiveness, and a national strategy for rushing acute cases directly to the cath lab for immediate revascularization was shown to result in lower mortality.

Yet another study showed that for complex cases where patients have triple vessel disease, percutaneous coronary intervention (PCI) was associated with a significantly higher risk for serious adverse events.

What was especially significant is that not one of these studies was sponsored by industry, and all had large-scale patient populations reflecting real-world practice, precisely the long-awaited evidence ESC has called for.

The absence of industry's heavy footprint in stents was remarkable at ESC 2011, a stunning silence after the blaring grandstanding for DES at past congresses.

With the exception of the French manufacturer Hexacath (Rueil-Malmaison) that set up a counter and modest backdrop, there was no promotion of stents on the exhibition floor, nor in the distributed publications and literature.

This retreat from the floor is all the more surprising considering the worldwide market for stents is estimated to be well north of $4 billion.

Despite the overwhelming commercial success that stents have brought to medical device companies and the rapid clinical adoption, the evidence that the metal sleeves are better than optimal medical therapy or traditional bypass surgery has remained dubious.

Findings about DES were criticized as coming from underpowered studies with selective data or masked p-values, which show the significance of results (Medical Device Daily, September 1, 2009).

More recently, the European Association of Percutaneous Cardiovascular Interventions (EAPCI; Sophia Antipolis, France) went so far as to ask manufacturers to retrospectively report their data by recasting the results using criteria for patient-oriented outcomes rather than device-oriented outcomes (MDD, May 20, 2011).

New generation DES win SCAAR approval

Five years ago stent utilization was soaring and sales were cresting $5 billion.

Then came the firestorm in Barcelona when the efficacy of DES was criticized during a packed plenary session at the ESC congress.

If this was the spark, it was the report at that same congress from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) that threw gasoline on the fire by questioning the long term safety of DES due to blood clotting.

European usage of DES dipped slightly after the ESC meeting, but sales in the U.S. crashed from over 90% usage in PCI procedures in early 2006 to around 55% before the end of that year (MDD, Sept. 3, 2008).

At ESC 2011, SCAAR was back, this time to report that third generation DES are associated with a 38% lower risk of clinically meaningful restenosis and a 50% lower risk of stent thrombosis compared to old generation DES.

The study included 94,384 stent implantations in Sweden from November 2006 to October 2010 using a national registry where all consecutive patients undergoing coronary angiography or PCI are included.

The performance up to two years of 10,551 different types of DES considered “new“ was evaluated in an un-selected large real-world population – including patients with myocardial infarction, three-vessel and/or left main disease, bifurcation lesions, graft disease, restenotic lesions and chronic total occlusions.

The new stents needed to be represented by more than 500 cases to be include, according to Giovanna Sarno, MD, with the Department of Cardiology at Uppsala University (Sweden).

Sarno told MDD the three dominant stents in the new generation analysis of the SCAAR registry were Xience V and Xience Prime from Abbott Laboratories (Abbott Park, Illinois), PROMUS Element from Boston Scientific and Endeavor Resolute from Medtronic (Minneapolis).

Also included were 64,631 bare metal stents, as well as 19,202 DES considered to be “old,“ and including the Taxus line from Boston Scientific (Natick, Massachusetts), Cypher from the Cordis division of Johnson & Johnson (New Brunswick, New Jersey) and Endeavor from Medtronic.

Sarno attributed the improved performance for the new generation to stent designs with thinner struts, and especially greater biocompatibility of polymers that bind the therapeutic to the strut, which “may have an important impact on drug elution profiles, endothelial coverage, and functional recovery.“

She concluded that patients treated with PCI with “new generation“ DES have a considerably lower risk of restenosis and stent thrombosis at two years compared to older generation DES in a large real world population.

The most remarkable finding in the SCAAR study was the lack of any cardiac events after 15 months for patients receiving the new DES, where such adverse events continued, and even increased beyond that point for patients with older generation stents and even more so with bare metal stents.

The risk of mortality was reduced 23% with the newer stents compared to other versions.

A 'protective effect' of by-pass surgery

The SYNTAX study will not go away.

Commissioned by ESC after the Barcelona disaster, and funded by Boston Scientific, the Synergy between PCI with Taxus and cardiac surgery was a head-to-head comparison between clinical outcomes for bypass surgery and DES.

But instead of closing the door on criticisms of DES, it turned out PCI is not always as good as surgery for patients, and that among patients with severe coronary artery disease (CAD), CABG was found to have a benefit (MDD, Sept. 3, 2008).

The legacy of SYNTAX is an objective scoring system for assessing the complexity of a patient's CAD.

Now the trial has inspired a Japanese study to retrospectively assess a 26-center registry enrolling consecutive patients having a first coronary revascularization between January 2005 and December 2007.

CREDO-Kyoto (Coronary Revascularization Demonstrating Outcome Study in Kyoto) PCI/CABG registry cohort-2 is a physician-initiated non-company sponsored study that looked at 2,981 patients with triple vessel disease where 1,825 patients underwent PCI and 1, 156 patients had coronary bypass surgery.

The primary endpoint of the study was a composite of all-cause death, myocardial infarction (MI) and stroke.

Presenting the findings, investigator Hiroki Shiomi, MD, from Kyoto University Hospital (Japan), reported PCI was associated with significantly higher risk for serious adverse events in these patients.

PCI as compared with CABG was associated with a higher 3-year risk for this primary endpoint, though the risk for cardiac death was not found to be significantly different.

Yet the risk for all-cause death was found to be significantly higher after PCI.

“Especially remarkable was a protective effect of CABG for myocardial infarction,“ according to Shiomi.

Frans Van de Werf, MD, with the University Hospitals (Leuven, Belgium) was the discussant for the presentation of the CREDO-Kyoto during a ESC signature Hotline plenary session.

“This study confirms the overall findings of the SYNTAX trial in a large, real-world population,“ he said, adding it also confirms the usefulness of the SYNTAX score in clinical practice.

“A big surprise was to see there is a benefit with CABG, even among patients with a low syntax score,“ he said.

'Get thee to a cath lab'

Forget the door-to-balloon time, the critical measure for success in revascularization is call-to-balloon time.

“Americans are obsessed with reducing the time from door-to-balloon,“ said Christian Juhl Terkelsen, MD, with the University Hospital of Aarhus (Denmark).

“Yet when they do not see improved outcomes they wonder what they are doing wrong,“ he said.

Door-to-balloon time improvements have failed to produce changes to survival and long-term risk of subsequent cardiac events for patients who do survive, he said.

The answer turns out to be what he called the system delay, of the call-to-balloon time.

By reducing the critical moments between the onset of symptoms and the inflation of the angioplasty balloon to reopen the culprit artery, the informed patient and a well-trained emergency medical technician with the ambulance.

If you are having a cardiac crisis, he said, do not take a taxi.

“It's unbelievable, but that is how some of our patients arrive,“ he said.

Results of a registry analysis for 9,514 patients treated by a regional cath lab from 1999 to 2009 included 1,656 of the self-presenters, 4,805 patients transferred from a hospital and 3,053 who were delivered direct to the center after calling the emergency hotline.

These patients did the best, leading Terkelsen to suggest that in the event of a heart attack, patients should not go to the nearest hospital.

“Field triage by the EMT cuts out an hour of hospital processing,“ he said.

The exception is where the hospital is also a qualified cath lab, which Terkelsen defines as one performing PCI 24/7.

More than 50% of PCI patients in the region are today brought direct to the cath lab and the program's goal is 85%, he said.

In 2003 the western Denmark region decided on a strategy for reperfusion by PCI rather than with medical treatment.

The healthcare system covering 3 million people was realigned to assure fast response among three regional centers in coordination with EMT services. Public education was also a critical factor for success, Kristensen said.

Steen Dalby Kristensen, MD, with the Skejby Hospital (Aarhus, Denmark) today leads a Europe-wide program called Stent for Life that is backed by ESC and the European Association for PCI.

The goal is to expand the Denmark experience to participating countries.