Bioengineered, Sirolimus-Eluting Stent Found ‘Safe,’ and ‘Effective’

SAN FRANCISCO – A new stent that combines antibody bioengineering with drug elution technology works at least as well as a paclitaxel-eluting stent for treating coronary artery lesions, the randomized REMEDEE trial showed.

Investigators led by Dr. Michael Haude found that the 9-month in-stent late lumen loss was statistically noninferior with the combination stent, which elutes sirolimus to inhibit cellular proliferation and has surface antibodies to promote endothelial coverage. The absolute difference between stents was only 0.05 mm, according to data reported at Transcatheter Cardiovascular Therapeutics 2011, which was sponsored by the Cardiovascular Research Foundation.

There were no stent thromboses or cardiac deaths with either stent. The two stents also yielded similar 9-month rates of clinically driven target lesion revascularization, myocardial infarction, and major adverse cardiovascular events.

"In this first-in-man study, the [combination stent] effectively controlled neointimal proliferation," Dr. Haude commented in a press conference. "I think we can conclude that [it] is shown to be effective and safe in this trial."

Given that both stents eluted an antiproliferative agent, patients in the trial received the usual antiplatelet therapy for a year to be on the safe side, said Dr. Haude, professor and director at Lukas Hospital Neuss (Germany).

The long-term goal "is to document that, by having this more secure, more firm, more homogeneous coverage of the stent struts [by endothelium], at the end of the day, you will be able to shorten dual antiplatelet therapy," he said. Indeed, intravascular ultrasound images and optical coherence tomography (OCT) images in a subset of patients showed that the combination stent achieved better coverage than the paclitaxel-eluting stent at 9 months.

"There was a little bit more late [lumen] loss than you would have expected with a Cypher or a Xience or one of the other stents."

Additionally, an ongoing, related trial, REMEDEE-OCT, is comparing the combination stent with the newer everolimus-eluting stents, with special attention to strut coverage at 60 days.

In an interview, Dr. John M. Hodgson, chairman of the department of cardiology at Geisinger Health System in Wilkes-Barre, Pa., commented "We’re clearly in a phase of stent development where we are trying to tailor specific aspects of it, with the feeling that less polymer is better, the feeling that something that may help reendothelialize the stent is better. And I think this trial shows that this stent has some promise for that."

He pointed out that the trial was not powered to evaluate end points other than basic vascular indicators of stent function. On that level, Dr. Hodgson said, "it showed that it’s effective compared to a stent that I think all of us would agree now is pretty obsolete."

Another potential issue was the magnitude of late lumen loss with the combination stent. "There was a little bit more late loss than you would have expected with a Cypher or a Xience or one of the other stents," he said. "So whether that little bit more late loss ends up being a problem in the future, we’ll just have to wait for the big studies."

The combination stent has two features designed to address specific known issues with stenting and current stent technologies, Dr. Haude explained. The first is an abluminal, biodegradable, sirolimus-eluting matrix to reduce cellular proliferation and hence restenosis; the second is an anti-CD34 antibody coating to capture circulating endothelial progenitor cells, promoting endothelial coverage and reducing the risk of late thrombosis.

The combination stent’s drug content is approximately half that of the Cypher stent, but the release profile is similar, he noted.

A total of 183 patients in the trial had single de novo native coronary artery lesions no greater than 20 mm in length. They were randomized 2:1 to receive the combination stent (Combo Dual Therapy Stent, manufactured by OrbusNeich) or a paclitaxel-eluting stent (Taxus Liberté, manufactured by Boston Scientific).

Results of the trial showed that the combination and paclitaxel-eluting stent groups had similar, very high, and statistically indistinguishable rates of device, lesion, and procedure success.

The angiographic 9-month in-stent late lumen loss was 0.39 mm with the combination stent and 0.44 mm with the paclitaxel-eluting stent. Both the absolute difference of 0.05 mm and the upper bound of the 95% confidence interval were well within the predefined margin of 0.20 mm for noninferiority (P for noninferiority = .001; P for superiority = .55).

The combination and paclitaxel-eluting stent groups had statistically indistinguishable rates of angiographic in-stent restenosis (5.5% vs. 9.6%, respectively) and in-segment restenosis (8.3% vs. 13.5%).

No patient in either group experienced stent thrombosis or died from cardiac causes. The two groups had similar rates of clinically driven target lesion revascularization (5.2% vs. 9.5%), myocardial infarction (2.4% vs. 1.7%), and major adverse cardiovascular events (8.7% vs. 11.0%).

Dr. Haude reported that he receives research or grant support from OrbusNeich and Biotronik and consultant fees and honoraria from Medtronic, Abbott Vascular, and Volcano Corp. Dr. Hodgson reported that he receives research or grant support from Boston Scientific, Volcano Corp., and St. Jude Medical, and that he is a consultant to, is a speaker for, or receives honoraria from Volcano Corp. The trial was sponsored by OrbusNeich.

SAN FRANCISCO – A new stent that combines antibody bioengineering with drug elution technology works at least as well as a paclitaxel-eluting stent for treating coronary artery lesions, the randomized REMEDEE trial showed.

Investigators led by Dr. Michael Haude found that the 9-month in-stent late lumen loss was statistically noninferior with the combination stent, which elutes sirolimus to inhibit cellular proliferation and has surface antibodies to promote endothelial coverage. The absolute difference between stents was only 0.05 mm, according to data reported at Transcatheter Cardiovascular Therapeutics 2011, which was sponsored by the Cardiovascular Research Foundation.

There were no stent thromboses or cardiac deaths with either stent. The two stents also yielded similar 9-month rates of clinically driven target lesion revascularization, myocardial infarction, and major adverse cardiovascular events.

"In this first-in-man study, the [combination stent] effectively controlled neointimal proliferation," Dr. Haude commented in a press conference. "I think we can conclude that [it] is shown to be effective and safe in this trial."

Given that both stents eluted an antiproliferative agent, patients in the trial received the usual antiplatelet therapy for a year to be on the safe side, said Dr. Haude, professor and director at Lukas Hospital Neuss (Germany).

The long-term goal "is to document that, by having this more secure, more firm, more homogeneous coverage of the stent struts [by endothelium], at the end of the day, you will be able to shorten dual antiplatelet therapy," he said. Indeed, intravascular ultrasound images and optical coherence tomography (OCT) images in a subset of patients showed that the combination stent achieved better coverage than the paclitaxel-eluting stent at 9 months.

"There was a little bit more late [lumen] loss than you would have expected with a Cypher or a Xience or one of the other stents."

Additionally, an ongoing, related trial, REMEDEE-OCT, is comparing the combination stent with the newer everolimus-eluting stents, with special attention to strut coverage at 60 days.

In an interview, Dr. John M. Hodgson, chairman of the department of cardiology at Geisinger Health System in Wilkes-Barre, Pa., commented "We’re clearly in a phase of stent development where we are trying to tailor specific aspects of it, with the feeling that less polymer is better, the feeling that something that may help reendothelialize the stent is better. And I think this trial shows that this stent has some promise for that."

He pointed out that the trial was not powered to evaluate end points other than basic vascular indicators of stent function. On that level, Dr. Hodgson said, "it showed that it’s effective compared to a stent that I think all of us would agree now is pretty obsolete."

Another potential issue was the magnitude of late lumen loss with the combination stent. "There was a little bit more late loss than you would have expected with a Cypher or a Xience or one of the other stents," he said. "So whether that little bit more late loss ends up being a problem in the future, we’ll just have to wait for the big studies."

The combination stent has two features designed to address specific known issues with stenting and current stent technologies, Dr. Haude explained. The first is an abluminal, biodegradable, sirolimus-eluting matrix to reduce cellular proliferation and hence restenosis; the second is an anti-CD34 antibody coating to capture circulating endothelial progenitor cells, promoting endothelial coverage and reducing the risk of late thrombosis.

The combination stent’s drug content is approximately half that of the Cypher stent, but the release profile is similar, he noted.

A total of 183 patients in the trial had single de novo native coronary artery lesions no greater than 20 mm in length. They were randomized 2:1 to receive the combination stent (Combo Dual Therapy Stent, manufactured by OrbusNeich) or a paclitaxel-eluting stent (Taxus Liberté, manufactured by Boston Scientific).

Results of the trial showed that the combination and paclitaxel-eluting stent groups had similar, very high, and statistically indistinguishable rates of device, lesion, and procedure success.

The angiographic 9-month in-stent late lumen loss was 0.39 mm with the combination stent and 0.44 mm with the paclitaxel-eluting stent. Both the absolute difference of 0.05 mm and the upper bound of the 95% confidence interval were well within the predefined margin of 0.20 mm for noninferiority (P for noninferiority = .001; P for superiority = .55).

The combination and paclitaxel-eluting stent groups had statistically indistinguishable rates of angiographic in-stent restenosis (5.5% vs. 9.6%, respectively) and in-segment restenosis (8.3% vs. 13.5%).

No patient in either group experienced stent thrombosis or died from cardiac causes. The two groups had similar rates of clinically driven target lesion revascularization (5.2% vs. 9.5%), myocardial infarction (2.4% vs. 1.7%), and major adverse cardiovascular events (8.7% vs. 11.0%).

Dr. Haude reported that he receives research or grant support from OrbusNeich and Biotronik and consultant fees and honoraria from Medtronic, Abbott Vascular, and Volcano Corp. Dr. Hodgson reported that he receives research or grant support from Boston Scientific, Volcano Corp., and St. Jude Medical, and that he is a consultant to, is a speaker for, or receives honoraria from Volcano Corp. The trial was sponsored by OrbusNeich.

SAN FRANCISCO – A new stent that combines antibody bioengineering with drug elution technology works at least as well as a paclitaxel-eluting stent for treating coronary artery lesions, the randomized REMEDEE trial showed.

Investigators led by Dr. Michael Haude found that the 9-month in-stent late lumen loss was statistically noninferior with the combination stent, which elutes sirolimus to inhibit cellular proliferation and has surface antibodies to promote endothelial coverage. The absolute difference between stents was only 0.05 mm, according to data reported at Transcatheter Cardiovascular Therapeutics 2011, which was sponsored by the Cardiovascular Research Foundation.

There were no stent thromboses or cardiac deaths with either stent. The two stents also yielded similar 9-month rates of clinically driven target lesion revascularization, myocardial infarction, and major adverse cardiovascular events.

"In this first-in-man study, the [combination stent] effectively controlled neointimal proliferation," Dr. Haude commented in a press conference. "I think we can conclude that [it] is shown to be effective and safe in this trial."

Given that both stents eluted an antiproliferative agent, patients in the trial received the usual antiplatelet therapy for a year to be on the safe side, said Dr. Haude, professor and director at Lukas Hospital Neuss (Germany).

The long-term goal "is to document that, by having this more secure, more firm, more homogeneous coverage of the stent struts [by endothelium], at the end of the day, you will be able to shorten dual antiplatelet therapy," he said. Indeed, intravascular ultrasound images and optical coherence tomography (OCT) images in a subset of patients showed that the combination stent achieved better coverage than the paclitaxel-eluting stent at 9 months.

"There was a little bit more late [lumen] loss than you would have expected with a Cypher or a Xience or one of the other stents."

Additionally, an ongoing, related trial, REMEDEE-OCT, is comparing the combination stent with the newer everolimus-eluting stents, with special attention to strut coverage at 60 days.

In an interview, Dr. John M. Hodgson, chairman of the department of cardiology at Geisinger Health System in Wilkes-Barre, Pa., commented "We’re clearly in a phase of stent development where we are trying to tailor specific aspects of it, with the feeling that less polymer is better, the feeling that something that may help reendothelialize the stent is better. And I think this trial shows that this stent has some promise for that."

He pointed out that the trial was not powered to evaluate end points other than basic vascular indicators of stent function. On that level, Dr. Hodgson said, "it showed that it’s effective compared to a stent that I think all of us would agree now is pretty obsolete."

Another potential issue was the magnitude of late lumen loss with the combination stent. "There was a little bit more late loss than you would have expected with a Cypher or a Xience or one of the other stents," he said. "So whether that little bit more late loss ends up being a problem in the future, we’ll just have to wait for the big studies."

The combination stent has two features designed to address specific known issues with stenting and current stent technologies, Dr. Haude explained. The first is an abluminal, biodegradable, sirolimus-eluting matrix to reduce cellular proliferation and hence restenosis; the second is an anti-CD34 antibody coating to capture circulating endothelial progenitor cells, promoting endothelial coverage and reducing the risk of late thrombosis.

The combination stent’s drug content is approximately half that of the Cypher stent, but the release profile is similar, he noted.

A total of 183 patients in the trial had single de novo native coronary artery lesions no greater than 20 mm in length. They were randomized 2:1 to receive the combination stent (Combo Dual Therapy Stent, manufactured by OrbusNeich) or a paclitaxel-eluting stent (Taxus Liberté, manufactured by Boston Scientific).

Results of the trial showed that the combination and paclitaxel-eluting stent groups had similar, very high, and statistically indistinguishable rates of device, lesion, and procedure success.

The angiographic 9-month in-stent late lumen loss was 0.39 mm with the combination stent and 0.44 mm with the paclitaxel-eluting stent. Both the absolute difference of 0.05 mm and the upper bound of the 95% confidence interval were well within the predefined margin of 0.20 mm for noninferiority (P for noninferiority = .001; P for superiority = .55).

The combination and paclitaxel-eluting stent groups had statistically indistinguishable rates of angiographic in-stent restenosis (5.5% vs. 9.6%, respectively) and in-segment restenosis (8.3% vs. 13.5%).

No patient in either group experienced stent thrombosis or died from cardiac causes. The two groups had similar rates of clinically driven target lesion revascularization (5.2% vs. 9.5%), myocardial infarction (2.4% vs. 1.7%), and major adverse cardiovascular events (8.7% vs. 11.0%).

Dr. Haude reported that he receives research or grant support from OrbusNeich and Biotronik and consultant fees and honoraria from Medtronic, Abbott Vascular, and Volcano Corp. Dr. Hodgson reported that he receives research or grant support from Boston Scientific, Volcano Corp., and St. Jude Medical, and that he is a consultant to, is a speaker for, or receives honoraria from Volcano Corp. The trial was sponsored by OrbusNeich.