Rates of stent thrombosis were 50% lower with the bioerodable polymer stents, said Dr Stephan Windecker (University Hospital, Bern, Switzerland) presented the study results during a late-breaking science session here Friday at EuroPCR 2011.

Study coauthor Dr Robert Byrne (Deutsches Herzzentrum, Munich, Germany), who previewed the results with the press, pointed out that the whole rationale behind using a biodegradable polymer is that it can help control drug release but won't be left behind on the stent, which may aggravate the healing process.

" The issue to date has been that because late adverse events are very rare, we need large numbers of patients so we can detect any differences," he said. " I think this is probably the first time that we've detected a clear signal toward reduced clinical events. It may be that these differences only start to emerge or we can only tease them out after three years, and earlier time points aren't really showing the benefit of these platforms."

Windecker, Byrne, and colleagues combined data from three randomized trials of stents with bioerodable polymers: ISAR-TEST-3 and ISAR-TEST-4, both of which studied the Yukon Choice PC stent (Translumina Therapeutics), and the LEADERS study of biolimus-eluting Biomatrix Flex stent (Biosensors International). All three studies used the Cypher sirolimus-eluting stent for comparison. In all, 2358 patients received a biodegradable-polymer stent and 1704 received a Cypher stent.

At three years, rates of definite stent thrombosis were significantly lower in the biodegradable-stent group, at 1.2%, than in the permanent-polymer group, at 2.1% (hazard ratio 0.50, p=0.013). Despite the fact that the trials used different polymers and different drugs, tests showed little heterogeneity between study results, Byrne said.

Clinical outcomes at three years also tilted in favor of the biodegradable polymer stents, with the composite primary end point, made up of cardiac death, MI, and target lesion revascularization, reaching 18.2% for the patients treated with the biodegradable-polymer stents and 20.1% in the permanent-polymer group (hazard ratio 0.85, p=0.04).

" With a biodegradable polymer DES, when we analyze large numbers of patients, we can see a clear signal toward reduced late adverse events, and we see overall improved cardiovascular outcomes," Byrne said. " We have two different biodegradable polymers in this study, [yet] the results seem consistent."

Newer-generation DES produced by the " big three" stent manufacturers have not moved to biodegradable polymers, although polymer technology is an arena of fast-paced change. Asked if he thought improvements in permanent polymers could ultimately match the promise of a polymer that disappears altogether, Byrne was skeptical.

" I think you can try many different modifications to improve biocompatibility, but with durable polymers, you will still have polyfragments persisting long term in the vessel wall, and these can induce inflammatory reactions," he told heartwire. " I'm not sure that simply enhancing the biocompatibility of durable polymers will necessarily result in improved longer-term outcomes."

Whether bioerodable stents retain this edge when compared against newer stent designs remains to be seen. A similar analysis, comparing pooled results against the Xience stent, is to be presented at this year's upcoming European Society of Cardiology meeting.

Byrne acknowledged that the absolute difference in the rate of the primary end point between the two groups was small, in the range of 2%. " But what was interesting was really some of the differences in stent-thrombosis rates—it's the first time we've seen a signal that's been statistically significant."

 

Axxess™ Self-Expanding Bifurcation Drug-Eluting Stent

Paris, France, 19 May 2011 –

DIVERGE, a prospective, single-arm, multi-center study of 302 patients with de novo bifurcation lesions across 16 sites in Europe, Australia and New Zealand, is the largest study conducted to date with a DES specifically designed for treating coronary bifurcation lesions. Following implantation of Axxess, the sidebranch treatments were left at the operators’ discretion. Additional conventional sirolimus-eluting stents (SES) were placed in 21.7% of the distal parent and/or side branch vessels. In 64.7% of the cases both branches were treated with an additional SES.

At three years post-procedure, the cumulative rate of MACE (a composite of cardiac death, MI and ischemia-driven TLR) was 16.3%. The occurrences of the individual components were 2.0% for cardiac death, 7.5% for myocardial infarction and 10.2% for ischemia-driven TLR.

There were only three cases (1.0%) of definite VLST (Very Late Stent Thrombosis), all of which involved at least one SES: however, just one of these cases also involved Axxess.

" These long-term results from DIVERGE are important because of the frequent presentation of bifurcation lesions in our daily clinical practice," commented Principal Investigator Dr. Stefan Verheye, Middelheim Hospital, Antwerp, Belgium. " These types of lesions are associated with higher complication and restenosis rates compared to conventional lesions. The three-year results confirm the earlier results already presented, and strengthen the evidence that the Axxess stent is a safe and effective alternative for patients with certain bifurcation lesions."

The Axxess bifurcation DES consists of a self-expanding, conically-shaped Nitinol (nickel/titanium) stent platform, specifically designed to conform to the shape of the bifurcation anatomy. It supports the carina while preserving the side branch. The Axxess stent is abluminally coated with a biodegradable poly-lactic acid (PLA) polymer that releases Biolimus A9™ (BA9™), an anti-restenotic drug developed and patented by Biosensors specifically for use with drug-eluting stents. BA9 is a vital component of

the BioMatrix Flex™ DES system, which has been proven safe and effective in the landmark " all-comers" LEADERS study.

Biosensors received CE Mark approval for the Axxess bifurcation DES in April 2011, supported by the positive nine-month results from the DIVERGE trial, which were published in the Journal of the American College of Cardiology (JACC) in March 2009. These demonstrated low overall rates of MACE (7.6%), restenosis (0.7%) and late stent thrombosis (0.3%) in patients treated with Axxess.

Biosensors expects to make the Axxess bifurcation DES available later this year. The device will be manufactured in diameters of 3.0 mm and 3.5 mm, and lengths of 11 mm and 14 mm. New long-term data from the DIVERGE study, presented yesterday at EuroPCR 2011, showed that the use of the Axxess™ DES for the treatment of complex coronary bifurcation lesions resulted in low levels of both MACE and VLST over a three-year period. Axxess™ is a self-expanding bifurcation stent which releases Biolimus A9™ from an abluminal biodegradable polymer coating.

Shown To Be Safe And Effective Up To Three Years

 

Axxess™ Self-Expanding Bifurcation Drug-Eluting Stent

Paris, France, 19 May 2011 –

DIVERGE, a prospective, single-arm, multi-center study of 302 patients with de novo bifurcation lesions across 16 sites in Europe, Australia and New Zealand, is the largest study conducted to date with a DES specifically designed for treating coronary bifurcation lesions. Following implantation of Axxess, the sidebranch treatments were left at the operators’ discretion. Additional conventional sirolimus-eluting stents (SES) were placed in 21.7% of the distal parent and/or side branch vessels. In 64.7% of the cases both branches were treated with an additional SES.

At three years post-procedure, the cumulative rate of MACE (a composite of cardiac death, MI and ischemia-driven TLR) was 16.3%. The occurrences of the individual components were 2.0% for cardiac death, 7.5% for myocardial infarction and 10.2% for ischemia-driven TLR.

There were only three cases (1.0%) of definite VLST (Very Late Stent Thrombosis), all of which involved at least one SES: however, just one of these cases also involved Axxess.

" These long-term results from DIVERGE are important because of the frequent presentation of bifurcation lesions in our daily clinical practice," commented Principal Investigator Dr. Stefan Verheye, Middelheim Hospital, Antwerp, Belgium. " These types of lesions are associated with higher complication and restenosis rates compared to conventional lesions. The three-year results confirm the earlier results already presented, and strengthen the evidence that the Axxess stent is a safe and effective alternative for patients with certain bifurcation lesions."

The Axxess bifurcation DES consists of a self-expanding, conically-shaped Nitinol (nickel/titanium) stent platform, specifically designed to conform to the shape of the bifurcation anatomy. It supports the carina while preserving the side branch. The Axxess stent is abluminally coated with a biodegradable poly-lactic acid (PLA) polymer that releases Biolimus A9™ (BA9™), an anti-restenotic drug developed and patented by Biosensors specifically for use with drug-eluting stents. BA9 is a vital component of

the BioMatrix Flex™ DES system, which has been proven safe and effective in the landmark " all-comers" LEADERS study.

Biosensors received CE Mark approval for the Axxess bifurcation DES in April 2011, supported by the positive nine-month results from the DIVERGE trial, which were published in the Journal of the American College of Cardiology (JACC) in March 2009. These demonstrated low overall rates of MACE (7.6%), restenosis (0.7%) and late stent thrombosis (0.3%) in patients treated with Axxess.

Biosensors expects to make the Axxess bifurcation DES available later this year. The device will be manufactured in diameters of 3.0 mm and 3.5 mm, and lengths of 11 mm and 14 mm. New long-term data from the DIVERGE study, presented yesterday at EuroPCR 2011, showed that the use of the Axxess™ DES for the treatment of complex coronary bifurcation lesions resulted in low levels of both MACE and VLST over a three-year period. Axxess™ is a self-expanding bifurcation stent which releases Biolimus A9™ from an abluminal biodegradable polymer coating.

Shown To Be Safe And Effective Up To Three Years

 

New Data Confirms Safety of BioMatrix™ at One Year

Paris, France, 19 May 2011 –

The e-BioMatrix PMS Registry, initiated in March 2008, is a prospective, multi-center, observational registry to assess the outcomes of over 1,000 " real-world" patients across nine European study sites over a five-year period. Enrolment was completed in September 2009. All patients are being comprehensively monitored, including for baseline information, index hospitalization and the patient file until last reported cardiac-related event. The primary endpoint of the registry was MACE (a composite of cardiac death, MI and clinically-driven TVR) at 12 months. Of the 1102 patients studied over this period, 74 (6.7%) experienced a clinical adverse event that could be included in the primary endpoint according to the independent Critical Events Committee. The registry will also examine a range of secondary endpoints, including primary and stent thrombosis over several periods MACE at intervals up to five years and death and MI rates for up to five years.

A broad range of inclusion criteria have ensured that e-BioMatrix is a " real-world" registry: patients have had to be at least 18 years old need treatment with a DES and have one or more coronary artery stenoses in a native coronary artery or a saphenous bypass graft from 2.25 to 4.0 mm in diameter that can be covered with one or multiple stents. There have been no limitations on the number of treated lesions, vessels, or lesion length.

" These registry findings provide further reassurance on the safety of a biolimus-eluting stent with biodegradable polymer in a wide range of patient types requiring PCI that we routinely see in our daily practice" , commented Principle Investigator Dr. Philip Urban, La Tour Hospital, Geneva, Switzerland. " The results are especially reputable due to the high levels of follow-up that have been achieved, with 97.6 percent at one year."

A similar registry to e-BioMatrix PMS, the e-BioMatrix Post-Marketing Registry (PMR), was initiated at the same time, involving up to 4,800 patients. The protocols of the two studies are identical, with

e-BioMatrix PMR monitoring for reported cardiac-related events only. Enrollment for this second registry is due to be completed by October 2011.

The PMS registry solely involved patients given the original BioMatrix, whereas the PMR involved patients given both BioMatrix and BioMatrix Flex™. Introduced in May 2010, BioMatrix Flex incorporates an improved mechanical platform for enhanced deliverability, whilst retaining the

Biosensors-developed abluminally-coated biodegradable polymer and Biolimus A9, an anti-restenotic drug developed by Biosensors exclusively for use with drug-eluting stents, as used in the original BioMatrix stent system. e-BioMatrix post-marketing surveillance (PMS) registry information presented for the first time yesterday at EuroPCR 2011 has confirmed that BioMatrix™, Biosensors’ Biolimus A9™-eluting stent system with abluminal biodegradable polymer, is safe over a 12-month period in a " real-world" patient population.