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Abbott Heart Stent Better at Keeping Coronary Arteries Open and Reducing Adverse Events
XIENCE Stent -- Part of a New Generation of "DES 2.0"

May 13, 2008 -- Two-year outcomes from the SPIRIT III trial, studying the XIENCE™ V Everolimus Eluting Coronary Stent System, were presented today at the EuroPCR 2008 meeting in Barcelona -- and the results showed Abbott's second generation stent to be superior to Boston Scientific's market-leading TAXUS paclitaxel-eluting stent in several important criteria.

  • Major Adverse Cardiac Events (MACE) -- a 45% reduction for XIENCE V compared to TAXUS (7.3% vs. 12.8%, p-value=0.004)*. MACE is an important composite clinical measure of safety and efficacy outcomes for patients, defined as cardiac death, heart attack (MI), or ischemia-driven target lesion revascularization;
  • Target Vessel Failure (TVF) -- a 32% reduction in the risk of cardiac events related to the treated vessel compared to TAXUS (10.7% vs. 15.4%, p-value=0.04)*. TVF is a composite clinical measure of safety and efficacy outcomes defined as cardiac death, heart attack or target vessel revascularization (TVR);
  • Target Lesion Revascularization (TLR) -- a 40% percent reduction in the risk of ischemia-driven target lesion revascularization as compared to TAXUS (4.6% vs. 7.5%, p-value=0.07)*;
  • Very Late Stent Thrombosis -- stent thrombosis, occurring between one and two years, as per the Academic Research Consortium (ARC) definition of definite/probable stent thrombosis was 0.3% XIENCE V and 1.0% for TAXUS; using the the SPIRIT III protocol definition (which pre-dated ARC) the rate was 0.2% vs. 1.0%.

The SPIRIT III two-year results were presented by Gregg W. Stone, M.D., principal investigator of the SPIRIT III trial, during the late-breaking clinical trials session at EuroPCR 2008. Dr. Stone has a unique perspective on the XIENCE vs. TAXUS comparison, since he was also the principal investigator for the first generation TAXUS stent which was approved by the FDA four years ago.

Gregg W. Stone MD
Gregg W. Stone, MD

When the one-year results for the SPIRIT III XIENCE trial were published three weeks ago in JAMA, Dr. Stone commented:

"This large-scale, prospective, randomized, single-blind, controlled study demonstrates that an everolimus-eluting stent, compared with a widely used paclitaxel-eluting stent, results in a significant reduction in angiographic in-segment late loss at 8 months, with non-inferior 9-month rates of ischemia-driven target vessel failure. Thus, the 2 prespecified FDA regulatory requirements required for the trial to be considered successful were met.

"The reduction in late loss was confirmed by the findings from intravascular ultrasound, which demonstrated an approximate 50% reduction in volumetric neointimal hyperplasia."

Today Dr. Stone added: "Not only did XIENCE V clearly differentiate itself from the TAXUS stent in the first year after treatment, it has now demonstrated even more positive effects at two years in the SPIRIT III trial. As measured by clinically significant reductions in target vessel failure and MACE, XIENCE V demonstrated an even greater improvement in patient outcomes compared to TAXUS at two years than at one year, driven by numerically lower rates of heart attacks and lower observed rates of re-intervention of the target lesion. We also saw encouraging trends for lower observed rates of late and very late stent thrombosis in XIENCE V-treated patients, especially in those who discontinued dual antiplatelet therapy."

Utilizing a different drug, a more flexible stent with thinner struts and a thinner polymeric-coating, Abbott's XIENCE stent represents another major potential addition to the interventional cardiologist's armamentarium -- a package of second generation devices, drugs, diagnostics and techniques which Angioplasty.Org has dubbed, "DES 2.0".

The XIENCE™ V everolimus-eluting stent, available since October 2006 in Europe, has not yet been approved for use in the United States, although the FDA's own Circulatory System Devices Advisory Panel recommended approval five months ago. Publication of the SPIRIT III trial findings in JAMA and the longer-term safety results, shown in today's presentation, may move that approval forward, although the FDA is certain to require long-term follow-up of a large patient cohort as part of the approval, much as it did for Medtronic's Endeavor stent, approved in February 2008.

Anatomy of the XIENCE V Stent
As described in Angioplasty.Org's Drug-Eluting Stent Overview, there are three major components to a drug-eluting stent (DES):

  • The type of metal stent that carries the drug coating;
  • The stent coating (polymeric or other) which contains the drug and delivers it to the arterial wall;
  • The drug itself -- how it acts in the body to prevent restenosis.
Improvements in each of these components may be one reason that the XIENCE has outperformed the first generation TAXUS.
    XIENCE V Stent
Artist Rendition of XIENCE V Coronary Stent (an investigational device in the United States)

The bare-metal foundation stent of the XIENCE system is the Multi-Link Vision stent, originally developed by Guidant (before the company was split up and acquired by Abbott and Boston Scientific). The Multi-Link was one of the most popular bare metal stents and was made not of stainless steel, like first generation stents, but of a cobalt-chromium alloy -- allowing greater strength with thinner metal struts -- 40% thinner than the TAXUS struts (89 vs 148 µm). Thinner metal surfaces may translate to a lower tendency for cell growth which can reblock a stent; thinner struts can make the stent more flexible or "deliverable" as well.

Like the TAXUS, the polymer (plastic) coating of the XIENCE is a permanent durable coating (biocompatible, but not biodegradable). However, the coating is much thinner, less than half the thickness of the TAXUS (7.8 µm vs 16.0 µm). What effect this may have is not proven, but some cardiologists feel that a thinner polymer allows the stent to be more easily expanded. Additionally, Angioplasty.Org has been working with cardiologists at the University of Texas, San Antonio, who believe that the polymers of first generation DES may be associated with long-term hypersensitivity reactions. Whether a thinner or different polymer will have any effect is yet to be seen.

Finally, the drug itself -- everolimus is a derivative of rapamycin (sirolimus) which is used in the CYPHER stent. However, in preclinical studies, everolimus-eluting stents are reported to have shown more rapid endothelialization (covering of the stent by the body's endothelial cells) than either paclitaxel or sirolimus-based devices. Delayed endothelialization has been posited as one of the causes of increased late stent thrombosis in DES. Although at one year, there was no measured difference in late stent thrombosis between the XIENCE and TAXUS stents, during the period between one and two years, the TAXUS cohort experienced three times the stent thrombosis.

DES 2.0
Devices -- The interventional cardiology community is clearly looking forward to this new generation of devices. Already the sales of drug-eluting stents are beginning to pick up, having dropped from 90% penetration down to the low 60% ranges, due to the fears about stent thrombosis. But the new devices are only a part of the story.

Drugs -- Many lessons have now been learned about the required and concomitant antiplatelet therapy. Originally prescribed for six months, that regimen has now been extended to a year or more. Cardiologists and related medical personnel are also much more aware of the dangers of premature cessation and protocols are being developed for those patients who are in need of surgery and must stop.

Additionally, a very recent study has identified a possible "rebound" effect with clopidogrel (Plavix) -- a spiking of increased platelet activation right after stopping -- something that carries double the risk of heart attack, something that may turn out to be of much greater concern than the stent thrombosis issue. If a safer method for stopping Plavix, such as a tapering off of the dosage, can be found, the benefits for patients will be extensive.

Diagnostics -- A final component of "DES 2.0", as Angioplasty.Org defines it, is the much more advanced process of diagnosing coronary artery disease, of determining whether or not a blockage needs intervention or can be treated with medical therapy and lifestyle changes, of deciding on the best strategy for revascularization, if the blockage does need an intervention. The new imaging technologies of multislice or multidetector CT angiography, CT perfusion imaging, intravascular ultrasound (IVUS), the futuristic Optical Coherence Tomography (OCT), cardiac Magnetic Resonance, as well as new types of functional measurement such as FFR -- all these recent technologies are creating a new paradigm for the way cardiologists look at the coronary circulation and the patient.

The "dawning" of this new age differs considerably from the rushed enthusiasm of the first generation of drug-eluting stents, where many believed that the two decade-old battle against restenosis had finally been won. The "DES 2.0" world is more cautious, more complex, yet more precise and ultimately will push the treatment of heart disease forward, benefiting tens of thousands of patients.

In the same issue of JAMA as the XIENCE one-year results, angioplasty pioneer Dr. David Holmes of the Mayo Clinic and Dr. Manesh R. Patel of Duke used these words to conclude their editorial, "Next-Generation DES: A Spirited Step Forward or More of the Same?":

"These outcomes measured over time will provide both efficacy and safety measures for currently available and future interventional devices. Patients will not distinguish between target lesion and target vessel failure, even if clinicians do not think the device is plausibly related. Indeed, these are the outcomes that practicing interventional cardiologists must demand prior to widespread use of a new device. Physicians must continue to be judicious stewards of the interventional toolbox so that patients continue to allow them the privilege of performing procedures intended to improve their health."


reported by Burt Cohen, Angioplasty,Org, May 13, 2008