TCT 2011

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.

SAN FRANCISCO – Treating in-stent restenosis in patients with drug-eluting stents by using drug-eluting balloon angioplasty limited late lumen loss at 6 months to 0.43 mm instead of 1.03 mm with plain angioplasty in a randomized trial of 110 patients.

PEPCAD (Treatment of DES-In-Stent Restenosis With SeQuent Please Paclitaxel Eluting PTCA Catheter) – a multicenter, single-blind study – randomized 72 patients at seven centers to paclitaxel-coated balloon angioplasty (PCBA) using the SeQuent Please system and 38 patients to plain old balloon angioplasty (POBA), followed by 3 months of dual-antiplatelet therapy. The length of the balloon overlapped the stenotic segment by at least 2 mm at the proximal and distal margins in both groups.

With follow-up on 100% of patients in the first 6 months of the 3-year study, the minimum lumen diameters in the PCBA group were 1.75 mm in the target lesion and 1.65 in the total segment, compared with 1.10 mm and 1 mm, respectively, in the POBA group, Dr. Harald Rittger reported at Transcatheter Cardiovascular Therapeutics 2011, which was sponsored by the Cardiovascular Research Foundation.

The percentage of angiographic restenosis at 6 months was 17% in both the target lesion and the total segment in the PCBA group, compared with 58% in-lesion restenosis and 61% total segment restenosis in the POBA group, said Dr. Rittger of the University of Erlangen, Germany.

These differences between the groups were statistically significant.

The PCBA group also had a significantly lower rate of major adverse cardiovascular events, comprising a combination of target lesion revascularization, MI attributable to the target vessel, and cardiac death. Rates of major adverse cardiovascular events were 17% with PCBA and 50% with POBA. This difference seemed to be driven primarily by a lower rate of target lesion revascularization in the PCBA group (15%), compared with the POBA group (37%), he said.

The study included patients with lesions in native coronary arteries; restenosis in stents eluting sirolimus, everolimus or paclitaxel; and indications for percutaneous coronary intervention. They had reference vessel diameters of 2.5-3.5 mm at enrollment and lesion lengths up to 22 mm.

Dr. Ron Waksman, director of experimental angioplasty at the Washington Hospital Center commented, "With the increased dissemination of drug-eluting stents [DES] and less use of bare-metal stents [BMS], the in-stent restenosis we’re going to see in the future is going to be DES in-stent restenosis. I think that’s why this study is important – to see if this is a good therapy for DES restenosis. I would say these are modest results, and there is room for improvement."

Paclitaxel-coated balloon angioplasty previously has been shown to be superior to POBA and noninferior to implanting a paclitaxel-eluting stent to treat in-stent restenosis in BMS.

The results of the current study showed poorer results in treating DES in-stent restenosis, compared with studies treating BMS in-stent restenosis using paclitaxel-coated balloon angioplasty, Dr. Waksman noted. "So, either this is more difficult to treat, or this is not sufficient treatment for this."

Dr. Rittger said that the difference in results might be due to different populations being treated. Patients with DES in-stent restenosis are more complex patients and are more likely to have multiple stent layers. Half of the current cohort had more than one stent layer. The patient with the most had four stent layers.

Treating in-stent restenosis by implanting an additional stent adds another layer of metal within the coronary arteries, reducing the physiologic vasoreactivity of the vessel.

A subgroup analysis is underway to see if the drug-eluting balloon angioplasty worked better to treat in-stent restenosis in patients with one drug-eluting stent, compared with others.

Dr. Roxana Mehran, professor of medicine and director of interventional cardiovascular research at Mount Sinai School of Medicine, New York, commented, "It’s nice to have a choice of using drug-coated balloons for in-stent restenosis, especially when you’re dealing with multiple layers. I’d like to hear about patterns of restenosis. If these are all focal restenoses, I’m not too thrilled about the binary restenosis rates and the clinical outcomes."

Dr. Rittger said the restenoses were focal in about 80% of cases.

The study excluded patients with acute MI, chronic total occlusions, lesions in bypass grafts or bifurcations, multiple lesions in the target vessel, left main lesions, in-stent restenosis in bare-metal stents, or contraindications to aspirin or clopidogrel therapy.

Even though drug-eluting stents decrease the risk of restenosis, the incidence of in-stent restenosis has remained high because more people are getting drug-eluting stents, Dr. Rittger said.

The study was funded by B. Braun Melsungen Vascular Systems, which makes the SeQuent Please paclitaxel-coated balloon system. Dr. Waksman said he has no relevant conflicts of interest. Dr. Rittger has received fees for consulting, speaking or honoraria from B. Braun and from Siemens Medical Solutions. Dr. Mehran has received honoraria or funds for consulting, speaking, or research from Bristol-Myers Squibb, the Medicines Co., AstraZeneca, and Ortho-McNeil.

SAN FRANCISCO – Treating in-stent restenosis in patients with drug-eluting stents by using drug-eluting balloon angioplasty limited late lumen loss at 6 months to 0.43 mm instead of 1.03 mm with plain angioplasty in a randomized trial of 110 patients.

PEPCAD (Treatment of DES-In-Stent Restenosis With SeQuent Please Paclitaxel Eluting PTCA Catheter) – a multicenter, single-blind study – randomized 72 patients at seven centers to paclitaxel-coated balloon angioplasty (PCBA) using the SeQuent Please system and 38 patients to plain old balloon angioplasty (POBA), followed by 3 months of dual-antiplatelet therapy. The length of the balloon overlapped the stenotic segment by at least 2 mm at the proximal and distal margins in both groups.

With follow-up on 100% of patients in the first 6 months of the 3-year study, the minimum lumen diameters in the PCBA group were 1.75 mm in the target lesion and 1.65 in the total segment, compared with 1.10 mm and 1 mm, respectively, in the POBA group, Dr. Harald Rittger reported at Transcatheter Cardiovascular Therapeutics 2011, which was sponsored by the Cardiovascular Research Foundation.

The percentage of angiographic restenosis at 6 months was 17% in both the target lesion and the total segment in the PCBA group, compared with 58% in-lesion restenosis and 61% total segment restenosis in the POBA group, said Dr. Rittger of the University of Erlangen, Germany.

These differences between the groups were statistically significant.

The PCBA group also had a significantly lower rate of major adverse cardiovascular events, comprising a combination of target lesion revascularization, MI attributable to the target vessel, and cardiac death. Rates of major adverse cardiovascular events were 17% with PCBA and 50% with POBA. This difference seemed to be driven primarily by a lower rate of target lesion revascularization in the PCBA group (15%), compared with the POBA group (37%), he said.

The study included patients with lesions in native coronary arteries; restenosis in stents eluting sirolimus, everolimus or paclitaxel; and indications for percutaneous coronary intervention. They had reference vessel diameters of 2.5-3.5 mm at enrollment and lesion lengths up to 22 mm.

Dr. Ron Waksman, director of experimental angioplasty at the Washington Hospital Center commented, "With the increased dissemination of drug-eluting stents [DES] and less use of bare-metal stents [BMS], the in-stent restenosis we’re going to see in the future is going to be DES in-stent restenosis. I think that’s why this study is important – to see if this is a good therapy for DES restenosis. I would say these are modest results, and there is room for improvement."

Paclitaxel-coated balloon angioplasty previously has been shown to be superior to POBA and noninferior to implanting a paclitaxel-eluting stent to treat in-stent restenosis in BMS.

The results of the current study showed poorer results in treating DES in-stent restenosis, compared with studies treating BMS in-stent restenosis using paclitaxel-coated balloon angioplasty, Dr. Waksman noted. "So, either this is more difficult to treat, or this is not sufficient treatment for this."

Dr. Rittger said that the difference in results might be due to different populations being treated. Patients with DES in-stent restenosis are more complex patients and are more likely to have multiple stent layers. Half of the current cohort had more than one stent layer. The patient with the most had four stent layers.

Treating in-stent restenosis by implanting an additional stent adds another layer of metal within the coronary arteries, reducing the physiologic vasoreactivity of the vessel.

A subgroup analysis is underway to see if the drug-eluting balloon angioplasty worked better to treat in-stent restenosis in patients with one drug-eluting stent, compared with others.

Dr. Roxana Mehran, professor of medicine and director of interventional cardiovascular research at Mount Sinai School of Medicine, New York, commented, "It’s nice to have a choice of using drug-coated balloons for in-stent restenosis, especially when you’re dealing with multiple layers. I’d like to hear about patterns of restenosis. If these are all focal restenoses, I’m not too thrilled about the binary restenosis rates and the clinical outcomes."

Dr. Rittger said the restenoses were focal in about 80% of cases.

The study excluded patients with acute MI, chronic total occlusions, lesions in bypass grafts or bifurcations, multiple lesions in the target vessel, left main lesions, in-stent restenosis in bare-metal stents, or contraindications to aspirin or clopidogrel therapy.

Even though drug-eluting stents decrease the risk of restenosis, the incidence of in-stent restenosis has remained high because more people are getting drug-eluting stents, Dr. Rittger said.

The study was funded by B. Braun Melsungen Vascular Systems, which makes the SeQuent Please paclitaxel-coated balloon system. Dr. Waksman said he has no relevant conflicts of interest. Dr. Rittger has received fees for consulting, speaking or honoraria from B. Braun and from Siemens Medical Solutions. Dr. Mehran has received honoraria or funds for consulting, speaking, or research from Bristol-Myers Squibb, the Medicines Co., AstraZeneca, and Ortho-McNeil.

SAN FRANCISCO – Treating in-stent restenosis in patients with drug-eluting stents by using drug-eluting balloon angioplasty limited late lumen loss at 6 months to 0.43 mm instead of 1.03 mm with plain angioplasty in a randomized trial of 110 patients.

PEPCAD (Treatment of DES-In-Stent Restenosis With SeQuent Please Paclitaxel Eluting PTCA Catheter) – a multicenter, single-blind study – randomized 72 patients at seven centers to paclitaxel-coated balloon angioplasty (PCBA) using the SeQuent Please system and 38 patients to plain old balloon angioplasty (POBA), followed by 3 months of dual-antiplatelet therapy. The length of the balloon overlapped the stenotic segment by at least 2 mm at the proximal and distal margins in both groups.

With follow-up on 100% of patients in the first 6 months of the 3-year study, the minimum lumen diameters in the PCBA group were 1.75 mm in the target lesion and 1.65 in the total segment, compared with 1.10 mm and 1 mm, respectively, in the POBA group, Dr. Harald Rittger reported at Transcatheter Cardiovascular Therapeutics 2011, which was sponsored by the Cardiovascular Research Foundation.

The percentage of angiographic restenosis at 6 months was 17% in both the target lesion and the total segment in the PCBA group, compared with 58% in-lesion restenosis and 61% total segment restenosis in the POBA group, said Dr. Rittger of the University of Erlangen, Germany.

These differences between the groups were statistically significant.

The PCBA group also had a significantly lower rate of major adverse cardiovascular events, comprising a combination of target lesion revascularization, MI attributable to the target vessel, and cardiac death. Rates of major adverse cardiovascular events were 17% with PCBA and 50% with POBA. This difference seemed to be driven primarily by a lower rate of target lesion revascularization in the PCBA group (15%), compared with the POBA group (37%), he said.

The study included patients with lesions in native coronary arteries; restenosis in stents eluting sirolimus, everolimus or paclitaxel; and indications for percutaneous coronary intervention. They had reference vessel diameters of 2.5-3.5 mm at enrollment and lesion lengths up to 22 mm.

Dr. Ron Waksman, director of experimental angioplasty at the Washington Hospital Center commented, "With the increased dissemination of drug-eluting stents [DES] and less use of bare-metal stents [BMS], the in-stent restenosis we’re going to see in the future is going to be DES in-stent restenosis. I think that’s why this study is important – to see if this is a good therapy for DES restenosis. I would say these are modest results, and there is room for improvement."

Paclitaxel-coated balloon angioplasty previously has been shown to be superior to POBA and noninferior to implanting a paclitaxel-eluting stent to treat in-stent restenosis in BMS.

The results of the current study showed poorer results in treating DES in-stent restenosis, compared with studies treating BMS in-stent restenosis using paclitaxel-coated balloon angioplasty, Dr. Waksman noted. "So, either this is more difficult to treat, or this is not sufficient treatment for this."

Dr. Rittger said that the difference in results might be due to different populations being treated. Patients with DES in-stent restenosis are more complex patients and are more likely to have multiple stent layers. Half of the current cohort had more than one stent layer. The patient with the most had four stent layers.

Treating in-stent restenosis by implanting an additional stent adds another layer of metal within the coronary arteries, reducing the physiologic vasoreactivity of the vessel.

A subgroup analysis is underway to see if the drug-eluting balloon angioplasty worked better to treat in-stent restenosis in patients with one drug-eluting stent, compared with others.

Dr. Roxana Mehran, professor of medicine and director of interventional cardiovascular research at Mount Sinai School of Medicine, New York, commented, "It’s nice to have a choice of using drug-coated balloons for in-stent restenosis, especially when you’re dealing with multiple layers. I’d like to hear about patterns of restenosis. If these are all focal restenoses, I’m not too thrilled about the binary restenosis rates and the clinical outcomes."

Dr. Rittger said the restenoses were focal in about 80% of cases.

The study excluded patients with acute MI, chronic total occlusions, lesions in bypass grafts or bifurcations, multiple lesions in the target vessel, left main lesions, in-stent restenosis in bare-metal stents, or contraindications to aspirin or clopidogrel therapy.

Even though drug-eluting stents decrease the risk of restenosis, the incidence of in-stent restenosis has remained high because more people are getting drug-eluting stents, Dr. Rittger said.

The study was funded by B. Braun Melsungen Vascular Systems, which makes the SeQuent Please paclitaxel-coated balloon system. Dr. Waksman said he has no relevant conflicts of interest. Dr. Rittger has received fees for consulting, speaking or honoraria from B. Braun and from Siemens Medical Solutions. Dr. Mehran has received honoraria or funds for consulting, speaking, or research from Bristol-Myers Squibb, the Medicines Co., AstraZeneca, and Ortho-McNeil.

SAN FRANCISCO – Although there are compelling reasons to treat complex calcified coronary lesions with rotablation instead of standard balloon dilatation before implanting drug-eluting stents, this strategy does not improve vascular or clinical outcomes in the long run, according to the results of the randomized ROTAXUS trial.

The results showed that rotablation was more effective at improving lumen dimensions early on, but this was offset by a subsequent proliferative response. Late lumen loss at 9 months was 0.44 mm with rotablation (also known as rotational atherectomy) and stenting vs. 0.31 mm with balloon dilatation and stenting, a significant difference. Rates of target lesion revascularization and other cardiovascular events did not differ significantly between groups.

"Superior acute gain ... after rotablation was counterbalanced by increased late loss, resulting in a neutral effect on restenosis," lead investigator Dr. Gert Richardt said at Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation.

"So balloon dilatation with provisional rotablation – that is my suggestion – prior to stenting remains the default strategy for complex calcified lesions even in the drug-eluting stent era," he said.

Dr. Roxana Mehran, professor of medicine at Mount Sinai Medical Center in New York, noted that rotablation remains helpful, at least from a logistic point of view, in bad lesions. "It’s important to note that rotational atherectomy still does have a place in our armamentarium, but it would be in the severely calcified lesions and in complex morphologies where I think it would make our procedure easier," she explained. "But if it is to reduce late loss," this study, "in a randomized fashion, did not show that."

Discussant Dr. Ron Waksman, director of experimental angioplasty and emerging technologies at the Washington Hospital Center in Hyattsville, Md., agreed, and also expressed concern that the trial’s findings might be interpreted as cause to abandon rotablation.

"You don’t do rotablation to [address] the late loss issue, the restenosis. It’s to facilitate stent deployment," he asserted. "In my view, we are underusing rotablation today, and we should use more of this. I’m just afraid that people will interpret this [trial as indicating] that you can do without a rotablator, and that’s not the message. ... We should actually reconsider more usage of rotablation to facilitate stent deployment and [reduce] thromboembolic complications of the procedure."

"Rotablation does not increase the efficacy of drug-eluting stents in calcified lesions."

"We nowadays treat more and more elderly patients with complex and severely calcified lesions," noted Dr. Richardt, who is a professor at the Heart Center, Segeberger Kliniken, in Bad Segeberg, Germany. And there is good rationale for using rotablation before implantation of drug-eluting stents for these lesions, he said.

Calcified lesions not only damage the stent, stripping off its drug-containing polymer coat, but may also impair outward diffusion of the drug. Ablating these lesions facilitates stent deployment and expansion, and possibly also effectiveness.

To be eligible for the trial, patients had to have angina (stable or unstable) and coronary artery disease, plus both of two angiographic criteria (a de novo lesion in a native coronary artery and moderate to severe calcification) and at least one of several others (an ostial location, a bifurcation lesion, or a long lesion).

The 240 patients enrolled in the study were assigned in equal numbers to either rotablation or balloon dilatation, followed by implantation of paclitaxel-eluting stents (Taxus, manufactured by Boston Scientific).

Trial results showed that from the procedural perspective, the rotablation group was more likely to be treated with a 7-French guiding catheter (84% vs. 28%) and had a lower maximal predilatation balloon pressure (13.6 vs. 15.8 atm), Dr. Richardt reported.

In the rotablation group, the maximum burr size was 1.5 mm. "It was mainly the plaque modification concept that we followed, with small burrs, and we usually used just one burr on the study," he commented. The groups were similar with respect to numbers of stents used and the lengths of stented vessels, as well as the use of balloon dilatation after stenting.

Fluoroscopy time was somewhat longer with rotablation, but patients in the two groups received the same amount of contrast dye, according to Dr. Richardt.

The rotablation and balloon dilatation groups had similarly high rates of angiographic success (97% each) and low rates of stent loss (0% and 3%), but the former had a lower rate of crossover (4% vs. 12%).

Despite a greater early gain in lumen dimensions, the rate of in-stent late lumen loss at 9 months – the trial’s primary end point – was higher with rotablation than with balloon dilatation (0.44 vs. 0.31 mm).

The two groups had statistically indistinguishable rates of clinical outcomes such as myocardial infarction, major adverse cardiovascular events, and death. The target lesion revascularization rate – a clinical indicator of restenosis – was about 12% in each group. There was only a single case of definite stent thrombosis, seen in the rotablation group.

"Rotablation and paclitaxel-eluting stent implantation was not superior to balloon dilatation and paclitaxel-eluting stent implantation in reducing the primary end point of late lumen loss at 9 months, indicating that rotablation does not increase the efficacy of drug-eluting stents in calcified lesions," he concluded.

The trial was sponsored by Herz-Kreislauf-Zentrum Segeberger Kliniken GmbH. Dr. Richardt reported that he is a consultant to, is a speaker for, or receives honoraria from Abbott Vascular and Boston Scientific. Dr. Mehran reported that she receives research or grant support from Bristol-Myers Squibb and The Medicines Company; is a consultant to, is a speaker for, or receives honoraria from AstraZeneca and Ortho-McNeil; and receives other, noncategorized financial support from Abbott Vascular. Dr. Waksman reported that he has no relevant conflicts of interest.

SAN FRANCISCO – Although there are compelling reasons to treat complex calcified coronary lesions with rotablation instead of standard balloon dilatation before implanting drug-eluting stents, this strategy does not improve vascular or clinical outcomes in the long run, according to the results of the randomized ROTAXUS trial.

The results showed that rotablation was more effective at improving lumen dimensions early on, but this was offset by a subsequent proliferative response. Late lumen loss at 9 months was 0.44 mm with rotablation (also known as rotational atherectomy) and stenting vs. 0.31 mm with balloon dilatation and stenting, a significant difference. Rates of target lesion revascularization and other cardiovascular events did not differ significantly between groups.

"Superior acute gain ... after rotablation was counterbalanced by increased late loss, resulting in a neutral effect on restenosis," lead investigator Dr. Gert Richardt said at Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation.

"So balloon dilatation with provisional rotablation – that is my suggestion – prior to stenting remains the default strategy for complex calcified lesions even in the drug-eluting stent era," he said.

Dr. Roxana Mehran, professor of medicine at Mount Sinai Medical Center in New York, noted that rotablation remains helpful, at least from a logistic point of view, in bad lesions. "It’s important to note that rotational atherectomy still does have a place in our armamentarium, but it would be in the severely calcified lesions and in complex morphologies where I think it would make our procedure easier," she explained. "But if it is to reduce late loss," this study, "in a randomized fashion, did not show that."

Discussant Dr. Ron Waksman, director of experimental angioplasty and emerging technologies at the Washington Hospital Center in Hyattsville, Md., agreed, and also expressed concern that the trial’s findings might be interpreted as cause to abandon rotablation.

"You don’t do rotablation to [address] the late loss issue, the restenosis. It’s to facilitate stent deployment," he asserted. "In my view, we are underusing rotablation today, and we should use more of this. I’m just afraid that people will interpret this [trial as indicating] that you can do without a rotablator, and that’s not the message. ... We should actually reconsider more usage of rotablation to facilitate stent deployment and [reduce] thromboembolic complications of the procedure."

"Rotablation does not increase the efficacy of drug-eluting stents in calcified lesions."

"We nowadays treat more and more elderly patients with complex and severely calcified lesions," noted Dr. Richardt, who is a professor at the Heart Center, Segeberger Kliniken, in Bad Segeberg, Germany. And there is good rationale for using rotablation before implantation of drug-eluting stents for these lesions, he said.

Calcified lesions not only damage the stent, stripping off its drug-containing polymer coat, but may also impair outward diffusion of the drug. Ablating these lesions facilitates stent deployment and expansion, and possibly also effectiveness.

To be eligible for the trial, patients had to have angina (stable or unstable) and coronary artery disease, plus both of two angiographic criteria (a de novo lesion in a native coronary artery and moderate to severe calcification) and at least one of several others (an ostial location, a bifurcation lesion, or a long lesion).

The 240 patients enrolled in the study were assigned in equal numbers to either rotablation or balloon dilatation, followed by implantation of paclitaxel-eluting stents (Taxus, manufactured by Boston Scientific).

Trial results showed that from the procedural perspective, the rotablation group was more likely to be treated with a 7-French guiding catheter (84% vs. 28%) and had a lower maximal predilatation balloon pressure (13.6 vs. 15.8 atm), Dr. Richardt reported.

In the rotablation group, the maximum burr size was 1.5 mm. "It was mainly the plaque modification concept that we followed, with small burrs, and we usually used just one burr on the study," he commented. The groups were similar with respect to numbers of stents used and the lengths of stented vessels, as well as the use of balloon dilatation after stenting.

Fluoroscopy time was somewhat longer with rotablation, but patients in the two groups received the same amount of contrast dye, according to Dr. Richardt.

The rotablation and balloon dilatation groups had similarly high rates of angiographic success (97% each) and low rates of stent loss (0% and 3%), but the former had a lower rate of crossover (4% vs. 12%).

Despite a greater early gain in lumen dimensions, the rate of in-stent late lumen loss at 9 months – the trial’s primary end point – was higher with rotablation than with balloon dilatation (0.44 vs. 0.31 mm).

The two groups had statistically indistinguishable rates of clinical outcomes such as myocardial infarction, major adverse cardiovascular events, and death. The target lesion revascularization rate – a clinical indicator of restenosis – was about 12% in each group. There was only a single case of definite stent thrombosis, seen in the rotablation group.

"Rotablation and paclitaxel-eluting stent implantation was not superior to balloon dilatation and paclitaxel-eluting stent implantation in reducing the primary end point of late lumen loss at 9 months, indicating that rotablation does not increase the efficacy of drug-eluting stents in calcified lesions," he concluded.

The trial was sponsored by Herz-Kreislauf-Zentrum Segeberger Kliniken GmbH. Dr. Richardt reported that he is a consultant to, is a speaker for, or receives honoraria from Abbott Vascular and Boston Scientific. Dr. Mehran reported that she receives research or grant support from Bristol-Myers Squibb and The Medicines Company; is a consultant to, is a speaker for, or receives honoraria from AstraZeneca and Ortho-McNeil; and receives other, noncategorized financial support from Abbott Vascular. Dr. Waksman reported that he has no relevant conflicts of interest.

SAN FRANCISCO – Although there are compelling reasons to treat complex calcified coronary lesions with rotablation instead of standard balloon dilatation before implanting drug-eluting stents, this strategy does not improve vascular or clinical outcomes in the long run, according to the results of the randomized ROTAXUS trial.

The results showed that rotablation was more effective at improving lumen dimensions early on, but this was offset by a subsequent proliferative response. Late lumen loss at 9 months was 0.44 mm with rotablation (also known as rotational atherectomy) and stenting vs. 0.31 mm with balloon dilatation and stenting, a significant difference. Rates of target lesion revascularization and other cardiovascular events did not differ significantly between groups.

"Superior acute gain ... after rotablation was counterbalanced by increased late loss, resulting in a neutral effect on restenosis," lead investigator Dr. Gert Richardt said at Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation.

"So balloon dilatation with provisional rotablation – that is my suggestion – prior to stenting remains the default strategy for complex calcified lesions even in the drug-eluting stent era," he said.

Dr. Roxana Mehran, professor of medicine at Mount Sinai Medical Center in New York, noted that rotablation remains helpful, at least from a logistic point of view, in bad lesions. "It’s important to note that rotational atherectomy still does have a place in our armamentarium, but it would be in the severely calcified lesions and in complex morphologies where I think it would make our procedure easier," she explained. "But if it is to reduce late loss," this study, "in a randomized fashion, did not show that."

Discussant Dr. Ron Waksman, director of experimental angioplasty and emerging technologies at the Washington Hospital Center in Hyattsville, Md., agreed, and also expressed concern that the trial’s findings might be interpreted as cause to abandon rotablation.

"You don’t do rotablation to [address] the late loss issue, the restenosis. It’s to facilitate stent deployment," he asserted. "In my view, we are underusing rotablation today, and we should use more of this. I’m just afraid that people will interpret this [trial as indicating] that you can do without a rotablator, and that’s not the message. ... We should actually reconsider more usage of rotablation to facilitate stent deployment and [reduce] thromboembolic complications of the procedure."

"Rotablation does not increase the efficacy of drug-eluting stents in calcified lesions."

"We nowadays treat more and more elderly patients with complex and severely calcified lesions," noted Dr. Richardt, who is a professor at the Heart Center, Segeberger Kliniken, in Bad Segeberg, Germany. And there is good rationale for using rotablation before implantation of drug-eluting stents for these lesions, he said.

Calcified lesions not only damage the stent, stripping off its drug-containing polymer coat, but may also impair outward diffusion of the drug. Ablating these lesions facilitates stent deployment and expansion, and possibly also effectiveness.

To be eligible for the trial, patients had to have angina (stable or unstable) and coronary artery disease, plus both of two angiographic criteria (a de novo lesion in a native coronary artery and moderate to severe calcification) and at least one of several others (an ostial location, a bifurcation lesion, or a long lesion).

The 240 patients enrolled in the study were assigned in equal numbers to either rotablation or balloon dilatation, followed by implantation of paclitaxel-eluting stents (Taxus, manufactured by Boston Scientific).

Trial results showed that from the procedural perspective, the rotablation group was more likely to be treated with a 7-French guiding catheter (84% vs. 28%) and had a lower maximal predilatation balloon pressure (13.6 vs. 15.8 atm), Dr. Richardt reported.

In the rotablation group, the maximum burr size was 1.5 mm. "It was mainly the plaque modification concept that we followed, with small burrs, and we usually used just one burr on the study," he commented. The groups were similar with respect to numbers of stents used and the lengths of stented vessels, as well as the use of balloon dilatation after stenting.

Fluoroscopy time was somewhat longer with rotablation, but patients in the two groups received the same amount of contrast dye, according to Dr. Richardt.

The rotablation and balloon dilatation groups had similarly high rates of angiographic success (97% each) and low rates of stent loss (0% and 3%), but the former had a lower rate of crossover (4% vs. 12%).

Despite a greater early gain in lumen dimensions, the rate of in-stent late lumen loss at 9 months – the trial’s primary end point – was higher with rotablation than with balloon dilatation (0.44 vs. 0.31 mm).

The two groups had statistically indistinguishable rates of clinical outcomes such as myocardial infarction, major adverse cardiovascular events, and death. The target lesion revascularization rate – a clinical indicator of restenosis – was about 12% in each group. There was only a single case of definite stent thrombosis, seen in the rotablation group.

"Rotablation and paclitaxel-eluting stent implantation was not superior to balloon dilatation and paclitaxel-eluting stent implantation in reducing the primary end point of late lumen loss at 9 months, indicating that rotablation does not increase the efficacy of drug-eluting stents in calcified lesions," he concluded.

The trial was sponsored by Herz-Kreislauf-Zentrum Segeberger Kliniken GmbH. Dr. Richardt reported that he is a consultant to, is a speaker for, or receives honoraria from Abbott Vascular and Boston Scientific. Dr. Mehran reported that she receives research or grant support from Bristol-Myers Squibb and The Medicines Company; is a consultant to, is a speaker for, or receives honoraria from AstraZeneca and Ortho-McNeil; and receives other, noncategorized financial support from Abbott Vascular. Dr. Waksman reported that he has no relevant conflicts of interest.

SAN FRANCISCO – The first trial in humans of a bioabsorbable polymer-coated everolimus-eluting coronary stent found it was noninferior to a durable-polymer everolimus-eluting stent in a multicenter randomized, single-blind study.

The study randomized 291 patients at 29 sites to receive the permanent-polymer everolimus-eluting Promus Element stent or one of two versions of the bioabsorbable everolimus-eluting Synergy stent. One group received a Synergy stent with an everolimus dose and release profile similar to that of the Promus Element stent; the other received a Synergy stent with half the dose of everolimus.

Patients were treated for new coronary lesions measuring no more than 28 mm in length with a coronary artery reference vessel diameter of 2.25-3.5 mm.

At 6 months of follow-up, average in-stent late loss (the amount of lesion tissue regrowth) was 0.15 mm in the Promus Element group, 0.10 in the full-dose Synergy group, and 0.13 in the half-dose Synergy group. The differences between the Promus Element group and either of the biodegradable stent groups were not significant, proving noninferiority of the Synergy stents, Ian T. Meredith, Ph.D., and his associates reported Nov. 11 at Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation.

At 30 days and 6 months of follow-up, rates of target lesion failure did not differ significantly in the 98 patients in the Promus Element group, compared with either the 94 patients in the full-dose Synergy group or the 99 patients in the half-dose Synergy group. These findings suggest that the bioabsorbable Synergy stents are as safe as durable-polymer stents, said Dr. Meredith, director of Monash Heart Medical Centre and professor of medicine at Monash University, Melbourne.

Target lesion failure was defined as cardiac death or MI related to the target vessel or target lesion revascularization.

At 3 months, target lesion failure occurred in none of the patients who received the Promus Element stent, 1% of the full-dose Synergy group, and 3% of the half-dose Synergy group. At 6 months, the rates were 3%, 2%, and 4%, respectively. The differences in rates between the Promus Element group and either of the Synergy groups were not statistically significant at either time point.

"What we’ve tested in this trial is whether you can go from delivering the same dose of drug on a conformable durable polymer of a certain load, reduce that polymer load to a tiny fraction of what you have with a durable polymer, release the same drug with the same kinetic profile and the same load, and achieve the same results. The answer is that you can," he said at a press briefing. "In fact, you can go to even half the drug dose on that polymer again and still achieve the same results at 6 months."

The caveats are that these were relatively straightforward lesions in noncomplex patients with only 6 months follow-up so far. "But it certainly proves the concept," he added.

The study was not powered to detect differences in clinical events.

Commenting on the study at a press briefing, Dr. Ron Waksman, director of experimental angioplasty at the Washington Hospital Center, expressed some concern about fairly large standard deviations around the mean estimates of late loss, but said he is "always excited" by any bioavailable polymer technology that shows noninferiority to durable stents.

Dr. Roxana Mehran, professor of medicine and director of interventional cardiovascular research at Mount Sinai School of Medicine, N.Y., said it will be challenging for the investigators to design a clinical trial that might show "something that’s exciting and different. That will be a challenge, because event rates are low," she said.

Dr. Meredith noted that the Prodigy stent uses a thinner bioabsorbable polymer coating – 3-5 mcm thick – compared with the BioMatrix Flex biodegradable polymer biolimus-eluting stent. Earlier at this meeting, other investigators reported 4-year results with the BioMatrix stent, showing noninferiority to durable drug-eluting stents and possibly improved clinical outcomes.

Patients in the current study had a mean age of 63 years, 73% were male, and 19% were being treated for diabetes.

More research on the Synergy stents are needed to evaluate clinical event rates and to explore the possibility of reducing the need for dual-antiplatelet therapy in patients receiving bioabsorbable stents, he said.

The Synergy stent is a thin-strut, platinum chromium stent platform loaded with everolimus delivered by an ultrathin bioabsorbable polymer applied to the abluminal surface of the stent. Durable polymers on drug-eluting stents have been associated with chronic inflammation and impaired healing. The polymer on the Synergy stent is reabsorbed by 4 months after implantation.

Baseline demographics and procedural characteristics were similar between treatment groups.

An "element of chance" was introduced in baseline lesion characteristics, with the half-dose Synergy group showing statistically significantly larger reference vessel diameters, averaging 2.65 mm, compared with 2.53 mm in the Promus Element group, Dr. Meredith said. Postprocedure angiography showed significantly greater in-stent and in-segment minimal lumen diameter, acute in-stent and in-segment gain, and in-segment stenosis diameter in the half-dose Synergy group, compared with the Promus Element group. "Again, most likely a play of chance," Dr. Meredith said.

The study was funded by Boston Scientific Corp., which makes all the stents used in the study. Dr. Meredith has been a consultant to Boston Scientific and Medtronic CardioVascular. One of his coinvestigators has received research funding from Boston Scientific and two other companies. Dr. Waksman said he has no relevant conflicts of interest. Dr. Mehran has received honoraria or funds for consulting, speaking, or research from Bristol-Myers Squibb, The Medicines Company, AstraZeneca, and Ortho-McNeil.*

*This story was updated November 12, 2011.

SAN FRANCISCO – The first trial in humans of a bioabsorbable polymer-coated everolimus-eluting coronary stent found it was noninferior to a durable-polymer everolimus-eluting stent in a multicenter randomized, single-blind study.

The study randomized 291 patients at 29 sites to receive the permanent-polymer everolimus-eluting Promus Element stent or one of two versions of the bioabsorbable everolimus-eluting Synergy stent. One group received a Synergy stent with an everolimus dose and release profile similar to that of the Promus Element stent; the other received a Synergy stent with half the dose of everolimus.

Patients were treated for new coronary lesions measuring no more than 28 mm in length with a coronary artery reference vessel diameter of 2.25-3.5 mm.

At 6 months of follow-up, average in-stent late loss (the amount of lesion tissue regrowth) was 0.15 mm in the Promus Element group, 0.10 in the full-dose Synergy group, and 0.13 in the half-dose Synergy group. The differences between the Promus Element group and either of the biodegradable stent groups were not significant, proving noninferiority of the Synergy stents, Ian T. Meredith, Ph.D., and his associates reported Nov. 11 at Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation.

At 30 days and 6 months of follow-up, rates of target lesion failure did not differ significantly in the 98 patients in the Promus Element group, compared with either the 94 patients in the full-dose Synergy group or the 99 patients in the half-dose Synergy group. These findings suggest that the bioabsorbable Synergy stents are as safe as durable-polymer stents, said Dr. Meredith, director of Monash Heart Medical Centre and professor of medicine at Monash University, Melbourne.

Target lesion failure was defined as cardiac death or MI related to the target vessel or target lesion revascularization.

At 3 months, target lesion failure occurred in none of the patients who received the Promus Element stent, 1% of the full-dose Synergy group, and 3% of the half-dose Synergy group. At 6 months, the rates were 3%, 2%, and 4%, respectively. The differences in rates between the Promus Element group and either of the Synergy groups were not statistically significant at either time point.

"What we’ve tested in this trial is whether you can go from delivering the same dose of drug on a conformable durable polymer of a certain load, reduce that polymer load to a tiny fraction of what you have with a durable polymer, release the same drug with the same kinetic profile and the same load, and achieve the same results. The answer is that you can," he said at a press briefing. "In fact, you can go to even half the drug dose on that polymer again and still achieve the same results at 6 months."

The caveats are that these were relatively straightforward lesions in noncomplex patients with only 6 months follow-up so far. "But it certainly proves the concept," he added.

The study was not powered to detect differences in clinical events.

Commenting on the study at a press briefing, Dr. Ron Waksman, director of experimental angioplasty at the Washington Hospital Center, expressed some concern about fairly large standard deviations around the mean estimates of late loss, but said he is "always excited" by any bioavailable polymer technology that shows noninferiority to durable stents.

Dr. Roxana Mehran, professor of medicine and director of interventional cardiovascular research at Mount Sinai School of Medicine, N.Y., said it will be challenging for the investigators to design a clinical trial that might show "something that’s exciting and different. That will be a challenge, because event rates are low," she said.

Dr. Meredith noted that the Prodigy stent uses a thinner bioabsorbable polymer coating – 3-5 mcm thick – compared with the BioMatrix Flex biodegradable polymer biolimus-eluting stent. Earlier at this meeting, other investigators reported 4-year results with the BioMatrix stent, showing noninferiority to durable drug-eluting stents and possibly improved clinical outcomes.

Patients in the current study had a mean age of 63 years, 73% were male, and 19% were being treated for diabetes.

More research on the Synergy stents are needed to evaluate clinical event rates and to explore the possibility of reducing the need for dual-antiplatelet therapy in patients receiving bioabsorbable stents, he said.

The Synergy stent is a thin-strut, platinum chromium stent platform loaded with everolimus delivered by an ultrathin bioabsorbable polymer applied to the abluminal surface of the stent. Durable polymers on drug-eluting stents have been associated with chronic inflammation and impaired healing. The polymer on the Synergy stent is reabsorbed by 4 months after implantation.

Baseline demographics and procedural characteristics were similar between treatment groups.

An "element of chance" was introduced in baseline lesion characteristics, with the half-dose Synergy group showing statistically significantly larger reference vessel diameters, averaging 2.65 mm, compared with 2.53 mm in the Promus Element group, Dr. Meredith said. Postprocedure angiography showed significantly greater in-stent and in-segment minimal lumen diameter, acute in-stent and in-segment gain, and in-segment stenosis diameter in the half-dose Synergy group, compared with the Promus Element group. "Again, most likely a play of chance," Dr. Meredith said.

The study was funded by Boston Scientific Corp., which makes all the stents used in the study. Dr. Meredith has been a consultant to Boston Scientific and Medtronic CardioVascular. One of his coinvestigators has received research funding from Boston Scientific and two other companies. Dr. Waksman said he has no relevant conflicts of interest. Dr. Mehran has received honoraria or funds for consulting, speaking, or research from Bristol-Myers Squibb, The Medicines Company, AstraZeneca, and Ortho-McNeil.*

*This story was updated November 12, 2011.

SAN FRANCISCO – The first trial in humans of a bioabsorbable polymer-coated everolimus-eluting coronary stent found it was noninferior to a durable-polymer everolimus-eluting stent in a multicenter randomized, single-blind study.

The study randomized 291 patients at 29 sites to receive the permanent-polymer everolimus-eluting Promus Element stent or one of two versions of the bioabsorbable everolimus-eluting Synergy stent. One group received a Synergy stent with an everolimus dose and release profile similar to that of the Promus Element stent; the other received a Synergy stent with half the dose of everolimus.

Patients were treated for new coronary lesions measuring no more than 28 mm in length with a coronary artery reference vessel diameter of 2.25-3.5 mm.

At 6 months of follow-up, average in-stent late loss (the amount of lesion tissue regrowth) was 0.15 mm in the Promus Element group, 0.10 in the full-dose Synergy group, and 0.13 in the half-dose Synergy group. The differences between the Promus Element group and either of the biodegradable stent groups were not significant, proving noninferiority of the Synergy stents, Ian T. Meredith, Ph.D., and his associates reported Nov. 11 at Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation.

At 30 days and 6 months of follow-up, rates of target lesion failure did not differ significantly in the 98 patients in the Promus Element group, compared with either the 94 patients in the full-dose Synergy group or the 99 patients in the half-dose Synergy group. These findings suggest that the bioabsorbable Synergy stents are as safe as durable-polymer stents, said Dr. Meredith, director of Monash Heart Medical Centre and professor of medicine at Monash University, Melbourne.

Target lesion failure was defined as cardiac death or MI related to the target vessel or target lesion revascularization.

At 3 months, target lesion failure occurred in none of the patients who received the Promus Element stent, 1% of the full-dose Synergy group, and 3% of the half-dose Synergy group. At 6 months, the rates were 3%, 2%, and 4%, respectively. The differences in rates between the Promus Element group and either of the Synergy groups were not statistically significant at either time point.

"What we’ve tested in this trial is whether you can go from delivering the same dose of drug on a conformable durable polymer of a certain load, reduce that polymer load to a tiny fraction of what you have with a durable polymer, release the same drug with the same kinetic profile and the same load, and achieve the same results. The answer is that you can," he said at a press briefing. "In fact, you can go to even half the drug dose on that polymer again and still achieve the same results at 6 months."

The caveats are that these were relatively straightforward lesions in noncomplex patients with only 6 months follow-up so far. "But it certainly proves the concept," he added.

The study was not powered to detect differences in clinical events.

Commenting on the study at a press briefing, Dr. Ron Waksman, director of experimental angioplasty at the Washington Hospital Center, expressed some concern about fairly large standard deviations around the mean estimates of late loss, but said he is "always excited" by any bioavailable polymer technology that shows noninferiority to durable stents.

Dr. Roxana Mehran, professor of medicine and director of interventional cardiovascular research at Mount Sinai School of Medicine, N.Y., said it will be challenging for the investigators to design a clinical trial that might show "something that’s exciting and different. That will be a challenge, because event rates are low," she said.

Dr. Meredith noted that the Prodigy stent uses a thinner bioabsorbable polymer coating – 3-5 mcm thick – compared with the BioMatrix Flex biodegradable polymer biolimus-eluting stent. Earlier at this meeting, other investigators reported 4-year results with the BioMatrix stent, showing noninferiority to durable drug-eluting stents and possibly improved clinical outcomes.

Patients in the current study had a mean age of 63 years, 73% were male, and 19% were being treated for diabetes.

More research on the Synergy stents are needed to evaluate clinical event rates and to explore the possibility of reducing the need for dual-antiplatelet therapy in patients receiving bioabsorbable stents, he said.

The Synergy stent is a thin-strut, platinum chromium stent platform loaded with everolimus delivered by an ultrathin bioabsorbable polymer applied to the abluminal surface of the stent. Durable polymers on drug-eluting stents have been associated with chronic inflammation and impaired healing. The polymer on the Synergy stent is reabsorbed by 4 months after implantation.

Baseline demographics and procedural characteristics were similar between treatment groups.

An "element of chance" was introduced in baseline lesion characteristics, with the half-dose Synergy group showing statistically significantly larger reference vessel diameters, averaging 2.65 mm, compared with 2.53 mm in the Promus Element group, Dr. Meredith said. Postprocedure angiography showed significantly greater in-stent and in-segment minimal lumen diameter, acute in-stent and in-segment gain, and in-segment stenosis diameter in the half-dose Synergy group, compared with the Promus Element group. "Again, most likely a play of chance," Dr. Meredith said.

The study was funded by Boston Scientific Corp., which makes all the stents used in the study. Dr. Meredith has been a consultant to Boston Scientific and Medtronic CardioVascular. One of his coinvestigators has received research funding from Boston Scientific and two other companies. Dr. Waksman said he has no relevant conflicts of interest. Dr. Mehran has received honoraria or funds for consulting, speaking, or research from Bristol-Myers Squibb, The Medicines Company, AstraZeneca, and Ortho-McNeil.*

*This story was updated November 12, 2011.

SAN FRANCISCO – Zotarolimus-eluting stents are generally as safe and effective as everolimus-eluting stents for coronary stenting in the real-world setting, according to results from a randomized, noninferiority phase IV trial comparing them head to head.

Among the 1,391 patients studied, all of whom were treated at the tertiary-care Thoraxcentrum Twente in the Netherlands, about 8% experienced events signaling a failure of the target vessel within a year, no matter which of these second-generation drug-eluting stents they received.

The difference between groups was well within the predefined boundary for noninferiority, lead investigator Dr. Clemens von Birgelen reported at Transcatheter Cardiovascular Therapeutics 2011, which is sponsored by the Cardiovascular Research Foundation. Additionally, both groups had very low and statistically indistinguishable rates of definite or probable stent thrombosis.

The bottom line is that the choice between the two stents will come down to a matter of physicians’ personal preference, he said in an interview. "There are emotional arguments" favoring one stent or the other, Dr. von Birgelen noted. He declined to say whether other factors might give one stent the edge.

The trial’s findings confirm those of the similar Resolute All Comers trial (N. Engl. J. Med. 2010;363:136-46), although that trial was larger and multicenter in nature. Collectively, these data show that "both stents are safe and efficacious, and you can use either one or the other," Dr. von Birgelen maintained. "So the physician has to decide at the end of the day which one to use."

The practice of dilatation after stenting – used in most of the procedures in the new trial – may be important to getting the same results, according to Dr. von Birgelen. "Postdilatation of stents is something to consider in the proximal and mid part [of the lesion] to get good stent apposition, and could be part of the reason why we found such nice results in this study," he explained.

Discussant Dr. Ron Waksman, director of Experimental Angioplasty & Emerging Technologies, Cardiovascular Research Institute in Washington, said, "It’s very hard to differentiate between the stents right now. The data is almost identical ... I think it’s really going to be a question of availability of sizes and lengths, pricing, et cetera, but not in terms of performance of the stent."

Dr. John McB. Hodgson, chairman of the department of cardiology at Geisinger Health System in Wilkes-Barre, Pa., agreed and noted that these second-generation drug-eluting stents are a major technological advance. "Both of these platforms are fantastic compared to what we had 5 years ago. We are splitting hairs – these are both great platforms," he commented.

Patients were eligible for the trial, known as the TWENTE trial and jointly supported by Abbott Vascular and Medtronic, if they had stable angina or a non–ST-elevation acute coronary syndrome plus an indication for implantation of a drug-eluting stent.

The enrolled patients, 82% of all those who were eligible, were randomized in balanced fashion to receive either zotarolimus-eluting stents (Resolute, manufactured by Medtronic and currently investigational in the United States) or everolimus-eluting stents (Xience V, manufactured by Abbott). Patients and data analysts, but not treating clinicians, were blinded to group assignment.

There was no limit on the number of lesions or vessels treated, the lesion length, or the vessel size, noted Dr. von Birgelen, who is a professor at the Thoraxcentrum Twente. All types of lesions, including those in bypass grafts and at bifurcations, were permitted.

The study population was 64 years old on average. About one-fifth of patients had diabetes. The slight majority had acute coronary syndromes. Nearly 25% had multiple vessels treated, and 77% had at least one off-label indication for drug-eluting stent implantation, such as stenting of the left main stem, long lesions, or very small vessels.

Roughly two-thirds of treated lesions were complex, and one-quarter were at bifurcations. The stent was implanted directly, without predilatation of the lesion, in 39% of lesions, a rate similar to that seen in other studies. "Postdilatation, however, was performed particularly often in our center, in 82% of the stented lesions," Dr. von Birgelen noted. "It’s a kind of standard strategy in our center for several years with drug-eluting stents, because we think that the postdilatation leads to better apposition of the stent to the vessel wall, with a better drug transition into the vessel wall, and this could avoid stent thrombosis and other events."

Additionally, use of postdilatation increased as the center began stenting longer lesions, given that coronary vessels naturally taper over their length. "We have to choose a stent of a certain size, and then by postdilatation, try to mimic the biological situation by being more aggressive with postdilatation in the proximal part, somewhat less in the mid part, and then distal," he explained.

Study results showed that both treatment groups had nearly 100% rates of lesion success and 96% rates of procedure success.

In intent-to-treat analyses, the 1-year rate of target vessel failure – a composite of cardiac death, target vessel–related myocardial infarction, and clinically driven target vessel revascularization – was 8.2% with zotarolimus-eluting stents and 8.1% with everolimus-eluting stents. The absolute difference of 0.1% and upper limit of the one-sided 95% confidence interval of 2.53% were well within the predefined noninferiority margin of 4.48% (P for noninferiority = .001; P for superiority = .94).

The findings were similar across patient subgroups stratified by disease and lesion characteristics, and similar for each of the three components of the composite end point individually.

There was an interaction between treatment group and diabetes status (P = .045), but more-detailed analysis failed to show a significant benefit of one stent over the other. "This is a trend which is hypothesis generating and interesting," Dr. von Birgelen commented. "It may raise some more pooling of data and analysis."

The trial’s main results were much the same when the investigators used a broader, patient-oriented composite end point of all deaths, any myocardial infarction, and any revascularization (11.2% vs. 10.5%; P for superiority = .69).

The zotarolimus- and everolimus-eluting stent groups also had very low and statistically indistinguishable rates of definite or probable stent thrombosis (0.86% vs. 1.16%). These rates are "relatively low, certainly when you consider the complexity of patients and lesions that were studied in this trial," he noted.

"Zotarolimus-eluting Resolute stents were noninferior to everolimus-eluting Xience V stents in terms of safety and efficacy for treating real-world patients with a vast majority of complex lesions and off-label indications for drug-eluting stents, which were implanted with liberal use of postdilatation," Dr. von Birgelen concluded.

Follow-up continues, he added. "It makes sense, and we must learn from the first-generation drug-eluting stents that we should follow up these patients longer than just 1 year. There is a 2-year follow-up already running at this moment, and we will follow these patients even further," he said.

Dr. von Birgelen reported that he is a consultant to and has received speaker honoraria and/or traveling expenses from Abbott Vascular, Medtronic, and Boston Scientific. Dr. Waksman reported that he had no relevant conflicts of interest. Dr. Hodgson reported that he receives research or grant support from Boston Scientific, Volcano, and St. Jude Medical, and that he is a consultant to, is a speaker for, or receives honoraria from Volcano.

SAN FRANCISCO – Zotarolimus-eluting stents are generally as safe and effective as everolimus-eluting stents for coronary stenting in the real-world setting, according to results from a randomized, noninferiority phase IV trial comparing them head to head.

Among the 1,391 patients studied, all of whom were treated at the tertiary-care Thoraxcentrum Twente in the Netherlands, about 8% experienced events signaling a failure of the target vessel within a year, no matter which of these second-generation drug-eluting stents they received.

The difference between groups was well within the predefined boundary for noninferiority, lead investigator Dr. Clemens von Birgelen reported at Transcatheter Cardiovascular Therapeutics 2011, which is sponsored by the Cardiovascular Research Foundation. Additionally, both groups had very low and statistically indistinguishable rates of definite or probable stent thrombosis.

The bottom line is that the choice between the two stents will come down to a matter of physicians’ personal preference, he said in an interview. "There are emotional arguments" favoring one stent or the other, Dr. von Birgelen noted. He declined to say whether other factors might give one stent the edge.

The trial’s findings confirm those of the similar Resolute All Comers trial (N. Engl. J. Med. 2010;363:136-46), although that trial was larger and multicenter in nature. Collectively, these data show that "both stents are safe and efficacious, and you can use either one or the other," Dr. von Birgelen maintained. "So the physician has to decide at the end of the day which one to use."

The practice of dilatation after stenting – used in most of the procedures in the new trial – may be important to getting the same results, according to Dr. von Birgelen. "Postdilatation of stents is something to consider in the proximal and mid part [of the lesion] to get good stent apposition, and could be part of the reason why we found such nice results in this study," he explained.

Discussant Dr. Ron Waksman, director of Experimental Angioplasty & Emerging Technologies, Cardiovascular Research Institute in Washington, said, "It’s very hard to differentiate between the stents right now. The data is almost identical ... I think it’s really going to be a question of availability of sizes and lengths, pricing, et cetera, but not in terms of performance of the stent."

Dr. John McB. Hodgson, chairman of the department of cardiology at Geisinger Health System in Wilkes-Barre, Pa., agreed and noted that these second-generation drug-eluting stents are a major technological advance. "Both of these platforms are fantastic compared to what we had 5 years ago. We are splitting hairs – these are both great platforms," he commented.

Patients were eligible for the trial, known as the TWENTE trial and jointly supported by Abbott Vascular and Medtronic, if they had stable angina or a non–ST-elevation acute coronary syndrome plus an indication for implantation of a drug-eluting stent.

The enrolled patients, 82% of all those who were eligible, were randomized in balanced fashion to receive either zotarolimus-eluting stents (Resolute, manufactured by Medtronic and currently investigational in the United States) or everolimus-eluting stents (Xience V, manufactured by Abbott). Patients and data analysts, but not treating clinicians, were blinded to group assignment.

There was no limit on the number of lesions or vessels treated, the lesion length, or the vessel size, noted Dr. von Birgelen, who is a professor at the Thoraxcentrum Twente. All types of lesions, including those in bypass grafts and at bifurcations, were permitted.

The study population was 64 years old on average. About one-fifth of patients had diabetes. The slight majority had acute coronary syndromes. Nearly 25% had multiple vessels treated, and 77% had at least one off-label indication for drug-eluting stent implantation, such as stenting of the left main stem, long lesions, or very small vessels.

Roughly two-thirds of treated lesions were complex, and one-quarter were at bifurcations. The stent was implanted directly, without predilatation of the lesion, in 39% of lesions, a rate similar to that seen in other studies. "Postdilatation, however, was performed particularly often in our center, in 82% of the stented lesions," Dr. von Birgelen noted. "It’s a kind of standard strategy in our center for several years with drug-eluting stents, because we think that the postdilatation leads to better apposition of the stent to the vessel wall, with a better drug transition into the vessel wall, and this could avoid stent thrombosis and other events."

Additionally, use of postdilatation increased as the center began stenting longer lesions, given that coronary vessels naturally taper over their length. "We have to choose a stent of a certain size, and then by postdilatation, try to mimic the biological situation by being more aggressive with postdilatation in the proximal part, somewhat less in the mid part, and then distal," he explained.

Study results showed that both treatment groups had nearly 100% rates of lesion success and 96% rates of procedure success.

In intent-to-treat analyses, the 1-year rate of target vessel failure – a composite of cardiac death, target vessel–related myocardial infarction, and clinically driven target vessel revascularization – was 8.2% with zotarolimus-eluting stents and 8.1% with everolimus-eluting stents. The absolute difference of 0.1% and upper limit of the one-sided 95% confidence interval of 2.53% were well within the predefined noninferiority margin of 4.48% (P for noninferiority = .001; P for superiority = .94).

The findings were similar across patient subgroups stratified by disease and lesion characteristics, and similar for each of the three components of the composite end point individually.

There was an interaction between treatment group and diabetes status (P = .045), but more-detailed analysis failed to show a significant benefit of one stent over the other. "This is a trend which is hypothesis generating and interesting," Dr. von Birgelen commented. "It may raise some more pooling of data and analysis."

The trial’s main results were much the same when the investigators used a broader, patient-oriented composite end point of all deaths, any myocardial infarction, and any revascularization (11.2% vs. 10.5%; P for superiority = .69).

The zotarolimus- and everolimus-eluting stent groups also had very low and statistically indistinguishable rates of definite or probable stent thrombosis (0.86% vs. 1.16%). These rates are "relatively low, certainly when you consider the complexity of patients and lesions that were studied in this trial," he noted.

"Zotarolimus-eluting Resolute stents were noninferior to everolimus-eluting Xience V stents in terms of safety and efficacy for treating real-world patients with a vast majority of complex lesions and off-label indications for drug-eluting stents, which were implanted with liberal use of postdilatation," Dr. von Birgelen concluded.

Follow-up continues, he added. "It makes sense, and we must learn from the first-generation drug-eluting stents that we should follow up these patients longer than just 1 year. There is a 2-year follow-up already running at this moment, and we will follow these patients even further," he said.

Dr. von Birgelen reported that he is a consultant to and has received speaker honoraria and/or traveling expenses from Abbott Vascular, Medtronic, and Boston Scientific. Dr. Waksman reported that he had no relevant conflicts of interest. Dr. Hodgson reported that he receives research or grant support from Boston Scientific, Volcano, and St. Jude Medical, and that he is a consultant to, is a speaker for, or receives honoraria from Volcano.

SAN FRANCISCO – Zotarolimus-eluting stents are generally as safe and effective as everolimus-eluting stents for coronary stenting in the real-world setting, according to results from a randomized, noninferiority phase IV trial comparing them head to head.

Among the 1,391 patients studied, all of whom were treated at the tertiary-care Thoraxcentrum Twente in the Netherlands, about 8% experienced events signaling a failure of the target vessel within a year, no matter which of these second-generation drug-eluting stents they received.

The difference between groups was well within the predefined boundary for noninferiority, lead investigator Dr. Clemens von Birgelen reported at Transcatheter Cardiovascular Therapeutics 2011, which is sponsored by the Cardiovascular Research Foundation. Additionally, both groups had very low and statistically indistinguishable rates of definite or probable stent thrombosis.

The bottom line is that the choice between the two stents will come down to a matter of physicians’ personal preference, he said in an interview. "There are emotional arguments" favoring one stent or the other, Dr. von Birgelen noted. He declined to say whether other factors might give one stent the edge.

The trial’s findings confirm those of the similar Resolute All Comers trial (N. Engl. J. Med. 2010;363:136-46), although that trial was larger and multicenter in nature. Collectively, these data show that "both stents are safe and efficacious, and you can use either one or the other," Dr. von Birgelen maintained. "So the physician has to decide at the end of the day which one to use."

The practice of dilatation after stenting – used in most of the procedures in the new trial – may be important to getting the same results, according to Dr. von Birgelen. "Postdilatation of stents is something to consider in the proximal and mid part [of the lesion] to get good stent apposition, and could be part of the reason why we found such nice results in this study," he explained.

Discussant Dr. Ron Waksman, director of Experimental Angioplasty & Emerging Technologies, Cardiovascular Research Institute in Washington, said, "It’s very hard to differentiate between the stents right now. The data is almost identical ... I think it’s really going to be a question of availability of sizes and lengths, pricing, et cetera, but not in terms of performance of the stent."

Dr. John McB. Hodgson, chairman of the department of cardiology at Geisinger Health System in Wilkes-Barre, Pa., agreed and noted that these second-generation drug-eluting stents are a major technological advance. "Both of these platforms are fantastic compared to what we had 5 years ago. We are splitting hairs – these are both great platforms," he commented.

Patients were eligible for the trial, known as the TWENTE trial and jointly supported by Abbott Vascular and Medtronic, if they had stable angina or a non–ST-elevation acute coronary syndrome plus an indication for implantation of a drug-eluting stent.

The enrolled patients, 82% of all those who were eligible, were randomized in balanced fashion to receive either zotarolimus-eluting stents (Resolute, manufactured by Medtronic and currently investigational in the United States) or everolimus-eluting stents (Xience V, manufactured by Abbott). Patients and data analysts, but not treating clinicians, were blinded to group assignment.

There was no limit on the number of lesions or vessels treated, the lesion length, or the vessel size, noted Dr. von Birgelen, who is a professor at the Thoraxcentrum Twente. All types of lesions, including those in bypass grafts and at bifurcations, were permitted.

The study population was 64 years old on average. About one-fifth of patients had diabetes. The slight majority had acute coronary syndromes. Nearly 25% had multiple vessels treated, and 77% had at least one off-label indication for drug-eluting stent implantation, such as stenting of the left main stem, long lesions, or very small vessels.

Roughly two-thirds of treated lesions were complex, and one-quarter were at bifurcations. The stent was implanted directly, without predilatation of the lesion, in 39% of lesions, a rate similar to that seen in other studies. "Postdilatation, however, was performed particularly often in our center, in 82% of the stented lesions," Dr. von Birgelen noted. "It’s a kind of standard strategy in our center for several years with drug-eluting stents, because we think that the postdilatation leads to better apposition of the stent to the vessel wall, with a better drug transition into the vessel wall, and this could avoid stent thrombosis and other events."

Additionally, use of postdilatation increased as the center began stenting longer lesions, given that coronary vessels naturally taper over their length. "We have to choose a stent of a certain size, and then by postdilatation, try to mimic the biological situation by being more aggressive with postdilatation in the proximal part, somewhat less in the mid part, and then distal," he explained.

Study results showed that both treatment groups had nearly 100% rates of lesion success and 96% rates of procedure success.

In intent-to-treat analyses, the 1-year rate of target vessel failure – a composite of cardiac death, target vessel–related myocardial infarction, and clinically driven target vessel revascularization – was 8.2% with zotarolimus-eluting stents and 8.1% with everolimus-eluting stents. The absolute difference of 0.1% and upper limit of the one-sided 95% confidence interval of 2.53% were well within the predefined noninferiority margin of 4.48% (P for noninferiority = .001; P for superiority = .94).

The findings were similar across patient subgroups stratified by disease and lesion characteristics, and similar for each of the three components of the composite end point individually.

There was an interaction between treatment group and diabetes status (P = .045), but more-detailed analysis failed to show a significant benefit of one stent over the other. "This is a trend which is hypothesis generating and interesting," Dr. von Birgelen commented. "It may raise some more pooling of data and analysis."

The trial’s main results were much the same when the investigators used a broader, patient-oriented composite end point of all deaths, any myocardial infarction, and any revascularization (11.2% vs. 10.5%; P for superiority = .69).

The zotarolimus- and everolimus-eluting stent groups also had very low and statistically indistinguishable rates of definite or probable stent thrombosis (0.86% vs. 1.16%). These rates are "relatively low, certainly when you consider the complexity of patients and lesions that were studied in this trial," he noted.

"Zotarolimus-eluting Resolute stents were noninferior to everolimus-eluting Xience V stents in terms of safety and efficacy for treating real-world patients with a vast majority of complex lesions and off-label indications for drug-eluting stents, which were implanted with liberal use of postdilatation," Dr. von Birgelen concluded.

Follow-up continues, he added. "It makes sense, and we must learn from the first-generation drug-eluting stents that we should follow up these patients longer than just 1 year. There is a 2-year follow-up already running at this moment, and we will follow these patients even further," he said.

Dr. von Birgelen reported that he is a consultant to and has received speaker honoraria and/or traveling expenses from Abbott Vascular, Medtronic, and Boston Scientific. Dr. Waksman reported that he had no relevant conflicts of interest. Dr. Hodgson reported that he receives research or grant support from Boston Scientific, Volcano, and St. Jude Medical, and that he is a consultant to, is a speaker for, or receives honoraria from Volcano.

SAN FRANCISCO – Treating a coronary artery with both a drug-eluting balloon and a bare metal stent is feasible in patients with acute ST-elevation myocardial infarction but does not significantly reduce late lumen loss, compared with bare metals stents alone or with drug-eluting stents alone.

The Drug-Eluting Balloon in Acute Myocardial Infarction (DEB-AMI) trial failed to meet its primary end point of a 50% reduction in late lumen loss at 6 months with the combination, Dr. Pieter R. Stella reported at Transcatheter Cardiovascular Therapeutics 2011. There was also no advantage for the combination in terms of clinical outcomes.

The drug-eluting balloon and bare metal stent combination "induces some morphological changes that are seen with [optical coherence tomography] and acetylcholine testing, but this is insufficient to result in superior angiographic results," he said in a press conference. "The drug-eluting stent is better in all comparisons."

However, he added, more detailed analyses suggested that results with the combination may have been influenced by procedural factors and differences across centers and operators.

"The use of the drug-eluting balloon probably needs special dedication by the operator," Dr. Stella maintained. "Further investigation is needed to optimize the results; we think that predilatation is extremely important with a drug-eluting balloon."

The trial took a futuristic approach to STEMI treatment, according to Dr. Juan F. Granada, executive director and chief scientific officer at the Jack H. Skirball Center for Cardiovascular Research, New York.

Much is unknown about the use of drug-eluting balloons in this context, he explained. "We really don’t know what is the drug uptake, especially with high doses delivered in the setting of ruptured plaque and thrombotic burden, and the pharmacokinetic profile in their presence, and the potential for toxicity that exists, especially when you combine drug elution with a bare metal stent."

He said it was "very interesting" to see that results for the combination were between those of a bare metal stent alone and the drug-eluting stent alone.

"So even though I applaud the hypothesis and investigators’ initiative, I think this was a bold approach to do the trial, knowing the pharmacokinetic profiles of drug-eluting balloons," Dr. Granada said.

Explaining the trial’s rationale, Dr. Stella noted that bare metal stents are safe but have high restenosis rates. And drug-eluting stents carry the potential risks of malapposition to the vessel wall and uncovered struts, which could increase the risk of late stent thrombosis.

Thus, hypothetically, there might be advantages to combined use of a drug-eluting balloon and bare metal stents: The combination might permit local drug delivery just to the vulnerable plaque; allow brief exposure of the vessel to an antiproliferative drug, leading to better healing of the endothelium; cause less restenosis than bare metal stents alone; cause less late (acquired) malapposition of the stent, compared with a drug-eluting stent; and preserve endothelial function.

To be eligible for the trial, sponsored by UMC Utrecht, patients had to first undergo successful thrombus aspiration. They were then randomized in balanced fashion to treatment with bare metal stents alone (Magic, manufactured by EuroCor), the combination of a drug-eluting balloon (Dior, manufactured by EuroCor) and bare metal stents (Magic), or drug-eluting stents alone (Taxus Liberté, manufactured by Boston Scientific).

For the sake of comparability, the drug-eluting balloon and drug-eluting stents both delivered paclitaxel, Dr. Stella, an interventional cardiologist at the University Medical Centre Utrecht (the Netherlands), said at the meeting sponsored by the Cardiovascular Research Foundation.

The patients were reevaluated clinically and angiographically with quantitative coronary analysis at 6 months. About one-fourth also underwent optical coherence tomography (OCT) with acetylcholine endothelial testing at that time.

Results for 127 patients showed that the angiographic late lumen loss at 6 months, the trial’s primary end point, averaged 0.78 mm in the group treated with bare metal stents alone, 0.64 mm in the group treated with the drug-eluting balloon and bare metal stent combination (a nonsignificant reduction), and 0.21 mm in the group treated with drug-eluting stents.

Dr. Stella pointed out that although predilatation was mandated in all three groups, it was done in only 60% of cases in the combination group and within that group, the rate of late lumen loss was indeed greater when the vessel was predilated (0.49 vs. 0.85 mm, P = .04).

"We found out that experienced [drug-eluting balloon] operators had better results than nonexperienced operators," he also noted, with a smaller late lumen loss seen for the principal investigator than for the operators overall.

The bare metal stent and balloon plus bare metal stent groups had similar rates of clinical outcomes such as major adverse cardiovascular events (24% and 20%) and target lesion revascularization (18% and 20%). By comparison, the drug-eluting stent group had dramatically lower rates of major adverse cardiovascular events (4%) and target lesion revascularization (2%).

In the subset of patients who underwent OCT, the combination was marginally superior to bare metal stents alone in terms of mean neointimal area (4.14 vs. 2.86 mm², P = .05). But there was also a trend toward a higher percentage of stent struts showing malapposition (1.74% vs. 0.56%, P = .06). Drug-eluting stents were significantly superior to the combination in terms of maximum neointimal area, mean neointimal area, and the percentage of covered embedded stents.

Acetylcholine testing did not show any significant differences in coronary vasodilation between the combination and the bare metal stents alone. But vasodilation was significantly better for the combination than for drug-eluting stents.

Dr. Stella reported that he is a consultant to, is a speaker for, or receives honoraria from EuroCor, and Sahajanand Medical Technologies (SMT). Dr. Granada reported that he had no relevant conflicts of interest.

SAN FRANCISCO – Treating a coronary artery with both a drug-eluting balloon and a bare metal stent is feasible in patients with acute ST-elevation myocardial infarction but does not significantly reduce late lumen loss, compared with bare metals stents alone or with drug-eluting stents alone.

The Drug-Eluting Balloon in Acute Myocardial Infarction (DEB-AMI) trial failed to meet its primary end point of a 50% reduction in late lumen loss at 6 months with the combination, Dr. Pieter R. Stella reported at Transcatheter Cardiovascular Therapeutics 2011. There was also no advantage for the combination in terms of clinical outcomes.

The drug-eluting balloon and bare metal stent combination "induces some morphological changes that are seen with [optical coherence tomography] and acetylcholine testing, but this is insufficient to result in superior angiographic results," he said in a press conference. "The drug-eluting stent is better in all comparisons."

However, he added, more detailed analyses suggested that results with the combination may have been influenced by procedural factors and differences across centers and operators.

"The use of the drug-eluting balloon probably needs special dedication by the operator," Dr. Stella maintained. "Further investigation is needed to optimize the results; we think that predilatation is extremely important with a drug-eluting balloon."

The trial took a futuristic approach to STEMI treatment, according to Dr. Juan F. Granada, executive director and chief scientific officer at the Jack H. Skirball Center for Cardiovascular Research, New York.

Much is unknown about the use of drug-eluting balloons in this context, he explained. "We really don’t know what is the drug uptake, especially with high doses delivered in the setting of ruptured plaque and thrombotic burden, and the pharmacokinetic profile in their presence, and the potential for toxicity that exists, especially when you combine drug elution with a bare metal stent."

He said it was "very interesting" to see that results for the combination were between those of a bare metal stent alone and the drug-eluting stent alone.

"So even though I applaud the hypothesis and investigators’ initiative, I think this was a bold approach to do the trial, knowing the pharmacokinetic profiles of drug-eluting balloons," Dr. Granada said.

Explaining the trial’s rationale, Dr. Stella noted that bare metal stents are safe but have high restenosis rates. And drug-eluting stents carry the potential risks of malapposition to the vessel wall and uncovered struts, which could increase the risk of late stent thrombosis.

Thus, hypothetically, there might be advantages to combined use of a drug-eluting balloon and bare metal stents: The combination might permit local drug delivery just to the vulnerable plaque; allow brief exposure of the vessel to an antiproliferative drug, leading to better healing of the endothelium; cause less restenosis than bare metal stents alone; cause less late (acquired) malapposition of the stent, compared with a drug-eluting stent; and preserve endothelial function.

To be eligible for the trial, sponsored by UMC Utrecht, patients had to first undergo successful thrombus aspiration. They were then randomized in balanced fashion to treatment with bare metal stents alone (Magic, manufactured by EuroCor), the combination of a drug-eluting balloon (Dior, manufactured by EuroCor) and bare metal stents (Magic), or drug-eluting stents alone (Taxus Liberté, manufactured by Boston Scientific).

For the sake of comparability, the drug-eluting balloon and drug-eluting stents both delivered paclitaxel, Dr. Stella, an interventional cardiologist at the University Medical Centre Utrecht (the Netherlands), said at the meeting sponsored by the Cardiovascular Research Foundation.

The patients were reevaluated clinically and angiographically with quantitative coronary analysis at 6 months. About one-fourth also underwent optical coherence tomography (OCT) with acetylcholine endothelial testing at that time.

Results for 127 patients showed that the angiographic late lumen loss at 6 months, the trial’s primary end point, averaged 0.78 mm in the group treated with bare metal stents alone, 0.64 mm in the group treated with the drug-eluting balloon and bare metal stent combination (a nonsignificant reduction), and 0.21 mm in the group treated with drug-eluting stents.

Dr. Stella pointed out that although predilatation was mandated in all three groups, it was done in only 60% of cases in the combination group and within that group, the rate of late lumen loss was indeed greater when the vessel was predilated (0.49 vs. 0.85 mm, P = .04).

"We found out that experienced [drug-eluting balloon] operators had better results than nonexperienced operators," he also noted, with a smaller late lumen loss seen for the principal investigator than for the operators overall.

The bare metal stent and balloon plus bare metal stent groups had similar rates of clinical outcomes such as major adverse cardiovascular events (24% and 20%) and target lesion revascularization (18% and 20%). By comparison, the drug-eluting stent group had dramatically lower rates of major adverse cardiovascular events (4%) and target lesion revascularization (2%).

In the subset of patients who underwent OCT, the combination was marginally superior to bare metal stents alone in terms of mean neointimal area (4.14 vs. 2.86 mm², P = .05). But there was also a trend toward a higher percentage of stent struts showing malapposition (1.74% vs. 0.56%, P = .06). Drug-eluting stents were significantly superior to the combination in terms of maximum neointimal area, mean neointimal area, and the percentage of covered embedded stents.

Acetylcholine testing did not show any significant differences in coronary vasodilation between the combination and the bare metal stents alone. But vasodilation was significantly better for the combination than for drug-eluting stents.

Dr. Stella reported that he is a consultant to, is a speaker for, or receives honoraria from EuroCor, and Sahajanand Medical Technologies (SMT). Dr. Granada reported that he had no relevant conflicts of interest.

SAN FRANCISCO – Treating a coronary artery with both a drug-eluting balloon and a bare metal stent is feasible in patients with acute ST-elevation myocardial infarction but does not significantly reduce late lumen loss, compared with bare metals stents alone or with drug-eluting stents alone.

The Drug-Eluting Balloon in Acute Myocardial Infarction (DEB-AMI) trial failed to meet its primary end point of a 50% reduction in late lumen loss at 6 months with the combination, Dr. Pieter R. Stella reported at Transcatheter Cardiovascular Therapeutics 2011. There was also no advantage for the combination in terms of clinical outcomes.

The drug-eluting balloon and bare metal stent combination "induces some morphological changes that are seen with [optical coherence tomography] and acetylcholine testing, but this is insufficient to result in superior angiographic results," he said in a press conference. "The drug-eluting stent is better in all comparisons."

However, he added, more detailed analyses suggested that results with the combination may have been influenced by procedural factors and differences across centers and operators.

"The use of the drug-eluting balloon probably needs special dedication by the operator," Dr. Stella maintained. "Further investigation is needed to optimize the results; we think that predilatation is extremely important with a drug-eluting balloon."

The trial took a futuristic approach to STEMI treatment, according to Dr. Juan F. Granada, executive director and chief scientific officer at the Jack H. Skirball Center for Cardiovascular Research, New York.

Much is unknown about the use of drug-eluting balloons in this context, he explained. "We really don’t know what is the drug uptake, especially with high doses delivered in the setting of ruptured plaque and thrombotic burden, and the pharmacokinetic profile in their presence, and the potential for toxicity that exists, especially when you combine drug elution with a bare metal stent."

He said it was "very interesting" to see that results for the combination were between those of a bare metal stent alone and the drug-eluting stent alone.

"So even though I applaud the hypothesis and investigators’ initiative, I think this was a bold approach to do the trial, knowing the pharmacokinetic profiles of drug-eluting balloons," Dr. Granada said.

Explaining the trial’s rationale, Dr. Stella noted that bare metal stents are safe but have high restenosis rates. And drug-eluting stents carry the potential risks of malapposition to the vessel wall and uncovered struts, which could increase the risk of late stent thrombosis.

Thus, hypothetically, there might be advantages to combined use of a drug-eluting balloon and bare metal stents: The combination might permit local drug delivery just to the vulnerable plaque; allow brief exposure of the vessel to an antiproliferative drug, leading to better healing of the endothelium; cause less restenosis than bare metal stents alone; cause less late (acquired) malapposition of the stent, compared with a drug-eluting stent; and preserve endothelial function.

To be eligible for the trial, sponsored by UMC Utrecht, patients had to first undergo successful thrombus aspiration. They were then randomized in balanced fashion to treatment with bare metal stents alone (Magic, manufactured by EuroCor), the combination of a drug-eluting balloon (Dior, manufactured by EuroCor) and bare metal stents (Magic), or drug-eluting stents alone (Taxus Liberté, manufactured by Boston Scientific).

For the sake of comparability, the drug-eluting balloon and drug-eluting stents both delivered paclitaxel, Dr. Stella, an interventional cardiologist at the University Medical Centre Utrecht (the Netherlands), said at the meeting sponsored by the Cardiovascular Research Foundation.

The patients were reevaluated clinically and angiographically with quantitative coronary analysis at 6 months. About one-fourth also underwent optical coherence tomography (OCT) with acetylcholine endothelial testing at that time.

Results for 127 patients showed that the angiographic late lumen loss at 6 months, the trial’s primary end point, averaged 0.78 mm in the group treated with bare metal stents alone, 0.64 mm in the group treated with the drug-eluting balloon and bare metal stent combination (a nonsignificant reduction), and 0.21 mm in the group treated with drug-eluting stents.

Dr. Stella pointed out that although predilatation was mandated in all three groups, it was done in only 60% of cases in the combination group and within that group, the rate of late lumen loss was indeed greater when the vessel was predilated (0.49 vs. 0.85 mm, P = .04).

"We found out that experienced [drug-eluting balloon] operators had better results than nonexperienced operators," he also noted, with a smaller late lumen loss seen for the principal investigator than for the operators overall.

The bare metal stent and balloon plus bare metal stent groups had similar rates of clinical outcomes such as major adverse cardiovascular events (24% and 20%) and target lesion revascularization (18% and 20%). By comparison, the drug-eluting stent group had dramatically lower rates of major adverse cardiovascular events (4%) and target lesion revascularization (2%).

In the subset of patients who underwent OCT, the combination was marginally superior to bare metal stents alone in terms of mean neointimal area (4.14 vs. 2.86 mm², P = .05). But there was also a trend toward a higher percentage of stent struts showing malapposition (1.74% vs. 0.56%, P = .06). Drug-eluting stents were significantly superior to the combination in terms of maximum neointimal area, mean neointimal area, and the percentage of covered embedded stents.

Acetylcholine testing did not show any significant differences in coronary vasodilation between the combination and the bare metal stents alone. But vasodilation was significantly better for the combination than for drug-eluting stents.

Dr. Stella reported that he is a consultant to, is a speaker for, or receives honoraria from EuroCor, and Sahajanand Medical Technologies (SMT). Dr. Granada reported that he had no relevant conflicts of interest.

SAN FRANCISCO – Transradial access for angioplasty to treat ST elevation acute coronary syndrome significantly reduced the risk of morbidity and mortality by 40%, compared with a transfemoral approach in a multicenter randomized controlled trial in 1,001 patients.

In the first 30 days after treatment, 14% in the radial access group and 21% in the femoral access group met the primary composite endpoint of cardiac death, MI, stroke, target lesion revascularization, or bleeding not related to coronary artery bypass graft (CABG), Dr. Enrico Romagnoli reported at Transcatheter Cardiovascular Therapeutics 2011, which was sponsored by the Cardiovascular Research Foundation.

He and his associates conducted the prospective RIFLE STEACS trial (Radial Versus Femoral Investigation in ST Elevation Acute Coronary Syndrome) at four high-volume clinical sites in Italy between January 2009 and July 2011.

Results for both the primary composite endpoint and the individual components of that endpoint showed significantly lower morbidity and mortality using the radial approach instead of the femoral approach in these patients.

"The radial approach should thus no more be considered a valid alternative to the femoral one, but become the recommended access site" when treating ST elevation acute coronary syndrome (STEACS), said Dr. Romagnoli, an interventional cardiologist at Policlinico Casilino, Rome.

It’s time for U.S. interventional radiologists to catch up with the rest of the world in offering the radial approach to patients undergoing angioplasty for ST elevation acute coronary syndrome, several commentators said at a press briefing held at the meeting.

"In most parts of the world outside the United States, radial is the dominant access," noted Dr. John A. Ormiston, an interventional cardiologist at the University of Auckland (New Zealand), and medical director of Mercy Angiography, Auckland. "In our records, probably 90% of all procedures are now radial. We’re not surprised about this data. The more we hear about this, the more the U.S. has to do it."

"The radial approach should thus no more be considered a valid alternative to the femoral one, but become the recommended access site."

Patients prefer the radial approach and seek treatment from physicians who offer it instead of the femoral approach, he said. "That’s one thing that will drive the U.S. change."

Dr. Pieter R. Stella of University Medical Center in Utrecht, the Netherlands, cautioned that physicians who choose the transradial approach for angioplasty should use it in all cases, not just in a select group, for the safest practices and best outcomes.

Among components of the composite endpoint in the study, rates of major adverse cardiac and cerebrovascular events were 7% in the radial group and 11% in the femoral group. Bleeding occurred in 8% of the radial group and 12% of the femoral group (Bleeding Academic Research Consortium types 2-5).

Cardiac death rates were 5% in the radial group and 9% in the femoral group. "This is the strongest message of this study," Dr. Romagnoli said.

All of these differences between groups were statistically significant.

The groups did not differ significantly in 30-day rates of MI (1.2% in the radial group vs. 1.4% in the femoral group), target lesion revascularization (1.2% vs. 1.8%, respectively), or cerebrovascular accident (0.8% vs. 0.5%, respectively).

The differences in bleeding were driven by a significantly lower rate of access site–related bleeding in the radial group (3% of patients), compared with the femoral group (7%). Rates of bleeding not related to the access site were 5% in each group.

"We all know that bleeding and hemorrhagic events are an important predictor of mortality in acute coronary syndrome. A radial approach virtually eliminates vascular access-site bleeding. Thus, the systematic use of a radial approach in patients with acute ST elevation MI – who are patients at high risk of bleeding from the aggressive antiplatelets and antithrombotics they receive – could improve the clinical outcome, in particular by reducing mortality," Dr. Romagnoli said in an interview.

In an analysis of predictors of the primary composite outcome, radial access was the only factor that significantly reduced risk, by 40%, he said. Four other factors each doubled the risk for the composite outcome: female gender; chronic kidney disease; Killip class; presence of culprit lesions in the left anterior descending coronary artery, and left ventricular ejection fraction less than 50%.

The study was sponsored by the independent investigators. Dr. Romagnoli said he had no relevant conflicts of interest. Dr. Ormiston has received honoraria or fees for consulting or speaking from Abbott Vascular and Boston Scientific Corp. Dr. Stella has received honoraria or fees for consulting or speaking from Eurocor and SMT Medical. Dr. Rao has received honoraria or fees for consulting, speaking or research from the Cordis Corp., Ikaria, the Medicines Co., Boehringer Ingelheim, Abbott Vascular, Terumo Medical Corp., and AstraZeneca.

SAN FRANCISCO – Transradial access for angioplasty to treat ST elevation acute coronary syndrome significantly reduced the risk of morbidity and mortality by 40%, compared with a transfemoral approach in a multicenter randomized controlled trial in 1,001 patients.

In the first 30 days after treatment, 14% in the radial access group and 21% in the femoral access group met the primary composite endpoint of cardiac death, MI, stroke, target lesion revascularization, or bleeding not related to coronary artery bypass graft (CABG), Dr. Enrico Romagnoli reported at Transcatheter Cardiovascular Therapeutics 2011, which was sponsored by the Cardiovascular Research Foundation.

He and his associates conducted the prospective RIFLE STEACS trial (Radial Versus Femoral Investigation in ST Elevation Acute Coronary Syndrome) at four high-volume clinical sites in Italy between January 2009 and July 2011.

Results for both the primary composite endpoint and the individual components of that endpoint showed significantly lower morbidity and mortality using the radial approach instead of the femoral approach in these patients.

"The radial approach should thus no more be considered a valid alternative to the femoral one, but become the recommended access site" when treating ST elevation acute coronary syndrome (STEACS), said Dr. Romagnoli, an interventional cardiologist at Policlinico Casilino, Rome.

It’s time for U.S. interventional radiologists to catch up with the rest of the world in offering the radial approach to patients undergoing angioplasty for ST elevation acute coronary syndrome, several commentators said at a press briefing held at the meeting.

"In most parts of the world outside the United States, radial is the dominant access," noted Dr. John A. Ormiston, an interventional cardiologist at the University of Auckland (New Zealand), and medical director of Mercy Angiography, Auckland. "In our records, probably 90% of all procedures are now radial. We’re not surprised about this data. The more we hear about this, the more the U.S. has to do it."

"The radial approach should thus no more be considered a valid alternative to the femoral one, but become the recommended access site."

Patients prefer the radial approach and seek treatment from physicians who offer it instead of the femoral approach, he said. "That’s one thing that will drive the U.S. change."

Dr. Pieter R. Stella of University Medical Center in Utrecht, the Netherlands, cautioned that physicians who choose the transradial approach for angioplasty should use it in all cases, not just in a select group, for the safest practices and best outcomes.

Among components of the composite endpoint in the study, rates of major adverse cardiac and cerebrovascular events were 7% in the radial group and 11% in the femoral group. Bleeding occurred in 8% of the radial group and 12% of the femoral group (Bleeding Academic Research Consortium types 2-5).

Cardiac death rates were 5% in the radial group and 9% in the femoral group. "This is the strongest message of this study," Dr. Romagnoli said.

All of these differences between groups were statistically significant.

The groups did not differ significantly in 30-day rates of MI (1.2% in the radial group vs. 1.4% in the femoral group), target lesion revascularization (1.2% vs. 1.8%, respectively), or cerebrovascular accident (0.8% vs. 0.5%, respectively).

The differences in bleeding were driven by a significantly lower rate of access site–related bleeding in the radial group (3% of patients), compared with the femoral group (7%). Rates of bleeding not related to the access site were 5% in each group.

"We all know that bleeding and hemorrhagic events are an important predictor of mortality in acute coronary syndrome. A radial approach virtually eliminates vascular access-site bleeding. Thus, the systematic use of a radial approach in patients with acute ST elevation MI – who are patients at high risk of bleeding from the aggressive antiplatelets and antithrombotics they receive – could improve the clinical outcome, in particular by reducing mortality," Dr. Romagnoli said in an interview.

In an analysis of predictors of the primary composite outcome, radial access was the only factor that significantly reduced risk, by 40%, he said. Four other factors each doubled the risk for the composite outcome: female gender; chronic kidney disease; Killip class; presence of culprit lesions in the left anterior descending coronary artery, and left ventricular ejection fraction less than 50%.

The study was sponsored by the independent investigators. Dr. Romagnoli said he had no relevant conflicts of interest. Dr. Ormiston has received honoraria or fees for consulting or speaking from Abbott Vascular and Boston Scientific Corp. Dr. Stella has received honoraria or fees for consulting or speaking from Eurocor and SMT Medical. Dr. Rao has received honoraria or fees for consulting, speaking or research from the Cordis Corp., Ikaria, the Medicines Co., Boehringer Ingelheim, Abbott Vascular, Terumo Medical Corp., and AstraZeneca.

SAN FRANCISCO – Transradial access for angioplasty to treat ST elevation acute coronary syndrome significantly reduced the risk of morbidity and mortality by 40%, compared with a transfemoral approach in a multicenter randomized controlled trial in 1,001 patients.

In the first 30 days after treatment, 14% in the radial access group and 21% in the femoral access group met the primary composite endpoint of cardiac death, MI, stroke, target lesion revascularization, or bleeding not related to coronary artery bypass graft (CABG), Dr. Enrico Romagnoli reported at Transcatheter Cardiovascular Therapeutics 2011, which was sponsored by the Cardiovascular Research Foundation.

He and his associates conducted the prospective RIFLE STEACS trial (Radial Versus Femoral Investigation in ST Elevation Acute Coronary Syndrome) at four high-volume clinical sites in Italy between January 2009 and July 2011.

Results for both the primary composite endpoint and the individual components of that endpoint showed significantly lower morbidity and mortality using the radial approach instead of the femoral approach in these patients.

"The radial approach should thus no more be considered a valid alternative to the femoral one, but become the recommended access site" when treating ST elevation acute coronary syndrome (STEACS), said Dr. Romagnoli, an interventional cardiologist at Policlinico Casilino, Rome.

It’s time for U.S. interventional radiologists to catch up with the rest of the world in offering the radial approach to patients undergoing angioplasty for ST elevation acute coronary syndrome, several commentators said at a press briefing held at the meeting.

"In most parts of the world outside the United States, radial is the dominant access," noted Dr. John A. Ormiston, an interventional cardiologist at the University of Auckland (New Zealand), and medical director of Mercy Angiography, Auckland. "In our records, probably 90% of all procedures are now radial. We’re not surprised about this data. The more we hear about this, the more the U.S. has to do it."

"The radial approach should thus no more be considered a valid alternative to the femoral one, but become the recommended access site."

Patients prefer the radial approach and seek treatment from physicians who offer it instead of the femoral approach, he said. "That’s one thing that will drive the U.S. change."

Dr. Pieter R. Stella of University Medical Center in Utrecht, the Netherlands, cautioned that physicians who choose the transradial approach for angioplasty should use it in all cases, not just in a select group, for the safest practices and best outcomes.

Among components of the composite endpoint in the study, rates of major adverse cardiac and cerebrovascular events were 7% in the radial group and 11% in the femoral group. Bleeding occurred in 8% of the radial group and 12% of the femoral group (Bleeding Academic Research Consortium types 2-5).

Cardiac death rates were 5% in the radial group and 9% in the femoral group. "This is the strongest message of this study," Dr. Romagnoli said.

All of these differences between groups were statistically significant.

The groups did not differ significantly in 30-day rates of MI (1.2% in the radial group vs. 1.4% in the femoral group), target lesion revascularization (1.2% vs. 1.8%, respectively), or cerebrovascular accident (0.8% vs. 0.5%, respectively).

The differences in bleeding were driven by a significantly lower rate of access site–related bleeding in the radial group (3% of patients), compared with the femoral group (7%). Rates of bleeding not related to the access site were 5% in each group.

"We all know that bleeding and hemorrhagic events are an important predictor of mortality in acute coronary syndrome. A radial approach virtually eliminates vascular access-site bleeding. Thus, the systematic use of a radial approach in patients with acute ST elevation MI – who are patients at high risk of bleeding from the aggressive antiplatelets and antithrombotics they receive – could improve the clinical outcome, in particular by reducing mortality," Dr. Romagnoli said in an interview.

In an analysis of predictors of the primary composite outcome, radial access was the only factor that significantly reduced risk, by 40%, he said. Four other factors each doubled the risk for the composite outcome: female gender; chronic kidney disease; Killip class; presence of culprit lesions in the left anterior descending coronary artery, and left ventricular ejection fraction less than 50%.

The study was sponsored by the independent investigators. Dr. Romagnoli said he had no relevant conflicts of interest. Dr. Ormiston has received honoraria or fees for consulting or speaking from Abbott Vascular and Boston Scientific Corp. Dr. Stella has received honoraria or fees for consulting or speaking from Eurocor and SMT Medical. Dr. Rao has received honoraria or fees for consulting, speaking or research from the Cordis Corp., Ikaria, the Medicines Co., Boehringer Ingelheim, Abbott Vascular, Terumo Medical Corp., and AstraZeneca.

SAN FRANCISCO – Transcatheter aortic-valve implantation in high-risk patients with aortic stenosis who were not eligible for surgery reduced all-cause mortality at 2 years from 68% to 43%, compared with standard therapy, extending the positive 1-year results of a multicenter, randomized trial in 358 patients.

The 24% absolute reduction in risk of death means that four patients would need to be treated with transcatheter aortic-valve implantation (TAVI) to save one life at 2 years, compared with standard therapy, Dr. Raj Makkar and his associates reported on Nov. 10 at the Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation.

The number needed to treat improved upon 1-year data presented at this meeting last year and subsequently published, which showed five patients would need to be treated to save one life at 1-year follow-up. All-cause mortality rates at 1 year were 51% on standard therapy and 31% with TAVI in the PARTNER (Placement of Aortic Transcatheter Valves) trial (N. Engl. J. Med. 2010;363:1597-1607).

Among patients who survived beyond 1 year of follow-up, all-cause mortality was halved, from 35% in the standard therapy group to 18% in the TAVI group by year 2. Overall deaths from cardiovascular causes in an intent-to-treat analysis decreased from 62% with standard therapy to 31% in the TAVI group, said Dr. Makkar, director of interventional cardiology and the cardiac catheterization laboratory at Cedars-Sinai Medical Center, Los Angeles.

"These are absolutely dramatic results. It validated and bolstered the 1-year results, an extremely positive trial," Dr. Michael Mack said at a press briefing on the study. "In this end-of-life, expensive therapy, there is a sustained benefit now out to 2 years and, hopefully, longer than that," said Dr. Mack of the Cardiopulmonary Research Science and Technology Institute, Dallas. Dr. Mack is also president of the Society of Thoracic Surgeons.

When deaths were stratified by Society of Thoracic Surgeons (STS) scores, it appeared that TAVI provided the most benefit to patients with lower STS scores who were less sick, but STS score did not affect mortality risk in the standard therapy group.

"The ultimate value will depend on careful selection of patients who are not surgical candidates and yet do not have extreme comorbidities that overwhelm the benefits of TAVI and render the intervention futile," Dr. Makkar said.

The 358-patient PARTNER trial compared TAVI with standard therapy in high-risk patients with severe aortic stenosis at 21 centers. Patients were randomized to transfemoral implantation of a balloon-expandable bovine pericardial valve (the Edwards Sapien valve) or standard therapy (including balloon aortic valvuloplasty in 84%) between May 2007 and March 2009.

The reported results applied to a prespecified cohort of patients whom surgeons considered not to be suitable candidates for surgery (cohort B). An ongoing portion of the trial is following a separate cohort of patients with high surgical risk who nevertheless were considered to be candidates for surgery (cohort A).

Based on the results from cohort B, the Food and Drug Administration approved the Edwards Sapien valve in November for the treatment of patients with aortic stenosis who are not considered candidates for surgery.

The 2-year results also showed that rates of repeat hospitalization were lower in the TAVI group at year 2 (35%), compared with the standard therapy group (72%), Dr. Makkar reported. Patients in the TAVI group gained nearly a year of days alive outside of the hospital, compared with patients given standard therapy – 699 days vs. 355.

By year 2, only 17% of patients in the TAVI group had New York Heart Association Class III or IV symptoms, compared with 58% in the standard therapy group.

Strokes were more common in the TAVI group (14%), compared with the standard therapy group (6%) at year 2. The TAVI group had higher rates of strokes than did the standard therapy group in the first 30 days after treatment and between years 1 and 2, but not between 30 days and 1 year after treatment, he said. Excess strokes in the TAVI group in the first 30 days were driven by ischemic causes, but excess strokes between years 1 and 2 were mainly due to hemorrhagic strokes, Dr. Makkar said.

The reasons for the hemorrhagic strokes appear to be multifactorial, including severe falls in three patients in the TAVI group, potential effects of medications, and other factors.

For strokes and all-cause mortality combined, 46% in the TAVI group and 68% in the standard therapy met this end point. Five patients would need to be treated with TAVI to avoid stroke or death, compared with usual care.

In explaining the risks to patients, Dr. Makkar said he would tell them that for every four patients treated with TAVI instead of standard therapy, one patient will survive. For every 12-13 patients treated with TAVI instead of standard therapy, 1 will develop a stroke.

Or, as Dr. Samir Kapadia of the Cleveland Clinic phrased it at a press briefing, patients in this population have a 50-50 chance of being alive at 2 years if they’re treated with TAVI and a 1 in 20 chance of having a stroke.

Patients in both treatment groups had a mean age of 83 years.

The hemodynamic effects of the implanted valves appeared to be stable between years 1 and 2, with sustained mean gradients and valve areas. Among patients with paravalvular leaks, 41% in each group died.

Edwards Lifesciences, which markets the Edwards Sapien valve, funded the study and was involved in its design, data collection, and monitoring. Dr. Makkar holds stock in Entourage Technologies, has received fees for consulting, speaking, or honoraria from Abbott Vascular, Medtronic and Abiomed, and has received research funds from Edwards Lifesciences. Dr. Mack and Dr. Kapadia said they have no conflicts of interest.

SAN FRANCISCO – Transcatheter aortic-valve implantation in high-risk patients with aortic stenosis who were not eligible for surgery reduced all-cause mortality at 2 years from 68% to 43%, compared with standard therapy, extending the positive 1-year results of a multicenter, randomized trial in 358 patients.

The 24% absolute reduction in risk of death means that four patients would need to be treated with transcatheter aortic-valve implantation (TAVI) to save one life at 2 years, compared with standard therapy, Dr. Raj Makkar and his associates reported on Nov. 10 at the Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation.

The number needed to treat improved upon 1-year data presented at this meeting last year and subsequently published, which showed five patients would need to be treated to save one life at 1-year follow-up. All-cause mortality rates at 1 year were 51% on standard therapy and 31% with TAVI in the PARTNER (Placement of Aortic Transcatheter Valves) trial (N. Engl. J. Med. 2010;363:1597-1607).

Among patients who survived beyond 1 year of follow-up, all-cause mortality was halved, from 35% in the standard therapy group to 18% in the TAVI group by year 2. Overall deaths from cardiovascular causes in an intent-to-treat analysis decreased from 62% with standard therapy to 31% in the TAVI group, said Dr. Makkar, director of interventional cardiology and the cardiac catheterization laboratory at Cedars-Sinai Medical Center, Los Angeles.

"These are absolutely dramatic results. It validated and bolstered the 1-year results, an extremely positive trial," Dr. Michael Mack said at a press briefing on the study. "In this end-of-life, expensive therapy, there is a sustained benefit now out to 2 years and, hopefully, longer than that," said Dr. Mack of the Cardiopulmonary Research Science and Technology Institute, Dallas. Dr. Mack is also president of the Society of Thoracic Surgeons.

When deaths were stratified by Society of Thoracic Surgeons (STS) scores, it appeared that TAVI provided the most benefit to patients with lower STS scores who were less sick, but STS score did not affect mortality risk in the standard therapy group.

"The ultimate value will depend on careful selection of patients who are not surgical candidates and yet do not have extreme comorbidities that overwhelm the benefits of TAVI and render the intervention futile," Dr. Makkar said.

The 358-patient PARTNER trial compared TAVI with standard therapy in high-risk patients with severe aortic stenosis at 21 centers. Patients were randomized to transfemoral implantation of a balloon-expandable bovine pericardial valve (the Edwards Sapien valve) or standard therapy (including balloon aortic valvuloplasty in 84%) between May 2007 and March 2009.

The reported results applied to a prespecified cohort of patients whom surgeons considered not to be suitable candidates for surgery (cohort B). An ongoing portion of the trial is following a separate cohort of patients with high surgical risk who nevertheless were considered to be candidates for surgery (cohort A).

Based on the results from cohort B, the Food and Drug Administration approved the Edwards Sapien valve in November for the treatment of patients with aortic stenosis who are not considered candidates for surgery.

The 2-year results also showed that rates of repeat hospitalization were lower in the TAVI group at year 2 (35%), compared with the standard therapy group (72%), Dr. Makkar reported. Patients in the TAVI group gained nearly a year of days alive outside of the hospital, compared with patients given standard therapy – 699 days vs. 355.

By year 2, only 17% of patients in the TAVI group had New York Heart Association Class III or IV symptoms, compared with 58% in the standard therapy group.

Strokes were more common in the TAVI group (14%), compared with the standard therapy group (6%) at year 2. The TAVI group had higher rates of strokes than did the standard therapy group in the first 30 days after treatment and between years 1 and 2, but not between 30 days and 1 year after treatment, he said. Excess strokes in the TAVI group in the first 30 days were driven by ischemic causes, but excess strokes between years 1 and 2 were mainly due to hemorrhagic strokes, Dr. Makkar said.

The reasons for the hemorrhagic strokes appear to be multifactorial, including severe falls in three patients in the TAVI group, potential effects of medications, and other factors.

For strokes and all-cause mortality combined, 46% in the TAVI group and 68% in the standard therapy met this end point. Five patients would need to be treated with TAVI to avoid stroke or death, compared with usual care.

In explaining the risks to patients, Dr. Makkar said he would tell them that for every four patients treated with TAVI instead of standard therapy, one patient will survive. For every 12-13 patients treated with TAVI instead of standard therapy, 1 will develop a stroke.

Or, as Dr. Samir Kapadia of the Cleveland Clinic phrased it at a press briefing, patients in this population have a 50-50 chance of being alive at 2 years if they’re treated with TAVI and a 1 in 20 chance of having a stroke.

Patients in both treatment groups had a mean age of 83 years.

The hemodynamic effects of the implanted valves appeared to be stable between years 1 and 2, with sustained mean gradients and valve areas. Among patients with paravalvular leaks, 41% in each group died.

Edwards Lifesciences, which markets the Edwards Sapien valve, funded the study and was involved in its design, data collection, and monitoring. Dr. Makkar holds stock in Entourage Technologies, has received fees for consulting, speaking, or honoraria from Abbott Vascular, Medtronic and Abiomed, and has received research funds from Edwards Lifesciences. Dr. Mack and Dr. Kapadia said they have no conflicts of interest.

SAN FRANCISCO – Transcatheter aortic-valve implantation in high-risk patients with aortic stenosis who were not eligible for surgery reduced all-cause mortality at 2 years from 68% to 43%, compared with standard therapy, extending the positive 1-year results of a multicenter, randomized trial in 358 patients.

The 24% absolute reduction in risk of death means that four patients would need to be treated with transcatheter aortic-valve implantation (TAVI) to save one life at 2 years, compared with standard therapy, Dr. Raj Makkar and his associates reported on Nov. 10 at the Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation.

The number needed to treat improved upon 1-year data presented at this meeting last year and subsequently published, which showed five patients would need to be treated to save one life at 1-year follow-up. All-cause mortality rates at 1 year were 51% on standard therapy and 31% with TAVI in the PARTNER (Placement of Aortic Transcatheter Valves) trial (N. Engl. J. Med. 2010;363:1597-1607).

Among patients who survived beyond 1 year of follow-up, all-cause mortality was halved, from 35% in the standard therapy group to 18% in the TAVI group by year 2. Overall deaths from cardiovascular causes in an intent-to-treat analysis decreased from 62% with standard therapy to 31% in the TAVI group, said Dr. Makkar, director of interventional cardiology and the cardiac catheterization laboratory at Cedars-Sinai Medical Center, Los Angeles.

"These are absolutely dramatic results. It validated and bolstered the 1-year results, an extremely positive trial," Dr. Michael Mack said at a press briefing on the study. "In this end-of-life, expensive therapy, there is a sustained benefit now out to 2 years and, hopefully, longer than that," said Dr. Mack of the Cardiopulmonary Research Science and Technology Institute, Dallas. Dr. Mack is also president of the Society of Thoracic Surgeons.

When deaths were stratified by Society of Thoracic Surgeons (STS) scores, it appeared that TAVI provided the most benefit to patients with lower STS scores who were less sick, but STS score did not affect mortality risk in the standard therapy group.

"The ultimate value will depend on careful selection of patients who are not surgical candidates and yet do not have extreme comorbidities that overwhelm the benefits of TAVI and render the intervention futile," Dr. Makkar said.

The 358-patient PARTNER trial compared TAVI with standard therapy in high-risk patients with severe aortic stenosis at 21 centers. Patients were randomized to transfemoral implantation of a balloon-expandable bovine pericardial valve (the Edwards Sapien valve) or standard therapy (including balloon aortic valvuloplasty in 84%) between May 2007 and March 2009.

The reported results applied to a prespecified cohort of patients whom surgeons considered not to be suitable candidates for surgery (cohort B). An ongoing portion of the trial is following a separate cohort of patients with high surgical risk who nevertheless were considered to be candidates for surgery (cohort A).

Based on the results from cohort B, the Food and Drug Administration approved the Edwards Sapien valve in November for the treatment of patients with aortic stenosis who are not considered candidates for surgery.

The 2-year results also showed that rates of repeat hospitalization were lower in the TAVI group at year 2 (35%), compared with the standard therapy group (72%), Dr. Makkar reported. Patients in the TAVI group gained nearly a year of days alive outside of the hospital, compared with patients given standard therapy – 699 days vs. 355.

By year 2, only 17% of patients in the TAVI group had New York Heart Association Class III or IV symptoms, compared with 58% in the standard therapy group.

Strokes were more common in the TAVI group (14%), compared with the standard therapy group (6%) at year 2. The TAVI group had higher rates of strokes than did the standard therapy group in the first 30 days after treatment and between years 1 and 2, but not between 30 days and 1 year after treatment, he said. Excess strokes in the TAVI group in the first 30 days were driven by ischemic causes, but excess strokes between years 1 and 2 were mainly due to hemorrhagic strokes, Dr. Makkar said.

The reasons for the hemorrhagic strokes appear to be multifactorial, including severe falls in three patients in the TAVI group, potential effects of medications, and other factors.

For strokes and all-cause mortality combined, 46% in the TAVI group and 68% in the standard therapy met this end point. Five patients would need to be treated with TAVI to avoid stroke or death, compared with usual care.

In explaining the risks to patients, Dr. Makkar said he would tell them that for every four patients treated with TAVI instead of standard therapy, one patient will survive. For every 12-13 patients treated with TAVI instead of standard therapy, 1 will develop a stroke.

Or, as Dr. Samir Kapadia of the Cleveland Clinic phrased it at a press briefing, patients in this population have a 50-50 chance of being alive at 2 years if they’re treated with TAVI and a 1 in 20 chance of having a stroke.

Patients in both treatment groups had a mean age of 83 years.

The hemodynamic effects of the implanted valves appeared to be stable between years 1 and 2, with sustained mean gradients and valve areas. Among patients with paravalvular leaks, 41% in each group died.

Edwards Lifesciences, which markets the Edwards Sapien valve, funded the study and was involved in its design, data collection, and monitoring. Dr. Makkar holds stock in Entourage Technologies, has received fees for consulting, speaking, or honoraria from Abbott Vascular, Medtronic and Abiomed, and has received research funds from Edwards Lifesciences. Dr. Mack and Dr. Kapadia said they have no conflicts of interest.

SAN FRANCISCO – The relative impact of transcatheter aortic valve replacement on patients’ quality of life depends on which access site is used for the procedure, suggest new data from Cohort A of the randomized PARTNER trial.

The trial compared transcatheter aortic valve replacement (TAVR) with surgical valve replacement among nearly 700 patients at high surgical risk. Lead investigator Dr. David J. Cohen presented its key quality of life findings – notably as perceived by patients themselves – at Transcatheter Cardiovascular Therapeutics 2011.

These findings showed that patients having TAVR by transfemoral access had better summary scores on the Kansas City Cardiomyopathy Questionnaire at 1 month than their surgical counterparts, with a difference between groups of about 10 points on the 100-point scale. The difference disappeared thereafter.

In contrast, patients having TAVR by transapical access had worse scores than their surgical counterparts at 6 months, with a difference between groups of about 8 points, although this difference likewise abated with longer follow-up.

"Taken together with previous data that have been reported, these findings demonstrate that for patients suitable for a transfemoral approach, TAVR provides important benefits compared with surgical aortic valve replacement from the patients’ perspective," Dr. Cohen said in a press conference. "The lack of benefit and suggestion of worse quality of life among patients who were ineligible for the transfemoral approach suggest the transapical approach may not be preferable to surgical aortic valve replacement in such patients."

"Whether further experience and refinements in the transapical approach can overcome these limitations should be the subject of future investigation," he added.

The findings provide reassurance about the transfemoral approach, according to Dr. Michael J. Mack, medical director of cardiovascular surgery at the Baylor Health Care System, Heart Hospital Baylor Plano, in Plano, Tex.

The trial "does validate that transfemoral does improve quality of life over surgery, especially early on. It’s a less invasive procedure, and patients recover quicker. That’s kind of what we always hoped and thought [that] clinically" that would be the case, he commented.

But the findings regarding transapical TAVR are not as worrisome as the data might suggest in light of certain aspects of the trial; in fact, "it’s very dangerous to go down that route to say it" is worse than surgery, he asserted.

Dr. Mack noted that transfemoral TAVR "got a head start," and many centers in the trial were just beginning to use transapical TAVR by the end of the trial. "It is clear there is a learning curve to it, and you had to think of this as a feasibility trial in the United States," he commented. Moreover, transfemoral access was attempted first in patients; thus, "the worst of the worst got left for transapical." A final factor to consider was the better-than-expected performance of surgery in the trial.

"So not to ignore the message and not to say there aren’t some concerns here, but I think that the data everywhere else in the world on transapical, with ... [rare exceptions] all is positive for transapical," he concluded at the meeting, which was sponsored by the Cardiovascular Research Foundation. "So I think, yes, concern. And yes, it should be noted. But I am not as concerned about it as the data may speak."

The trial data that Dr. Cohen reported came out of a prospective, preplanned quality of life substudy within Cohort A of the PARTNER trial, which enrolled 699 patients with severe, symptomatic aortic stenosis who had a high risk for surgical complications.

The patients were randomized 1:1 to undergo TAVR (with an Edwards Sapien valve, Edwards Lifesciences, either transfemoral or transapical) vs. surgical aortic valve replacement (with any other valve).

Previously reported safety and efficacy results for Cohort A indicated that TAVR and surgical aortic valve replacement yielded similar rates of 1-year survival (N. Engl. J. Med. 2011;364:2187-98). The former was associated with a higher rate of major vascular complications, whereas the latter was associated with higher rates of major bleeding and new-onset atrial fibrillation.

Patients’ health-related quality of life was assessed with the Kansas City Cardiomyopathy Questionnaire. Dr. Cohen stressed that this questionnaire captures quality of life data from the patient’s perspective, differentiating it from the New York Heart Association class, which instead reflects the physician’s perspective.

The primary quality of life end point was the summary score on this questionnaire. "This has been shown to predict mortality and cost among patients with heart failure," he noted. "And just to give you some reference, a minimum clinically important difference on this specific scale is 5 points."

Preliminary results showed a significant interaction between treatment effect and access site used for TAVR – transfemoral vs. transapical – and trial outcomes, according to Dr. Cohen, who is director of cardiovascular research at Saint Luke’s Mid-America Heart and Vascular Institute, University of Missouri–Kansas City. Therefore, analyses considered these subgroups separately.

Patients undergoing transfemoral TAVR had better scores on the Kansas City Cardiomyopathy Questionnaire at 1 month than their surgical counterparts (difference, 9.9 points; P less than .001). But there was no longer a significant difference at 6 or 12 months.

Patients undergoing transapical TAVR had worse scores than their surgical counterparts at 6 months (difference, 7.9 points; P = .04). But there was no significant difference at 1 or 12 months.

The findings were much the same for the individual subscales of the Kansas City Cardiomyopathy Questionnaire, and for additional, generic measures of health and quality of life assessed in the trial (the Short Form-12 Health Survey and the EQ-5D questionnaire), according to Dr. Cohen.

Furthermore, the findings held up in sensitivity analyses that were restricted to only patients who actually had attempted valve replacement, that used worst-case values for patients with missing data, and that instead categorized outcomes dichotomously.

The trial was sponsored by Edwards Lifesciences. Dr. Cohen reported that he receives research or grant support from Abbott Vascular, Boston Scientific, Medtronic, AstraZeneca, and Edwards Lifesciences; and is a consultant to, is a speaker for, or receives honoraria from Daiichi-Sankyo/Eli Lilly and Medtronic. Dr. Mack reported that he had no relevant conflicts of interest.

SAN FRANCISCO – The relative impact of transcatheter aortic valve replacement on patients’ quality of life depends on which access site is used for the procedure, suggest new data from Cohort A of the randomized PARTNER trial.

The trial compared transcatheter aortic valve replacement (TAVR) with surgical valve replacement among nearly 700 patients at high surgical risk. Lead investigator Dr. David J. Cohen presented its key quality of life findings – notably as perceived by patients themselves – at Transcatheter Cardiovascular Therapeutics 2011.

These findings showed that patients having TAVR by transfemoral access had better summary scores on the Kansas City Cardiomyopathy Questionnaire at 1 month than their surgical counterparts, with a difference between groups of about 10 points on the 100-point scale. The difference disappeared thereafter.

In contrast, patients having TAVR by transapical access had worse scores than their surgical counterparts at 6 months, with a difference between groups of about 8 points, although this difference likewise abated with longer follow-up.

"Taken together with previous data that have been reported, these findings demonstrate that for patients suitable for a transfemoral approach, TAVR provides important benefits compared with surgical aortic valve replacement from the patients’ perspective," Dr. Cohen said in a press conference. "The lack of benefit and suggestion of worse quality of life among patients who were ineligible for the transfemoral approach suggest the transapical approach may not be preferable to surgical aortic valve replacement in such patients."

"Whether further experience and refinements in the transapical approach can overcome these limitations should be the subject of future investigation," he added.

The findings provide reassurance about the transfemoral approach, according to Dr. Michael J. Mack, medical director of cardiovascular surgery at the Baylor Health Care System, Heart Hospital Baylor Plano, in Plano, Tex.

The trial "does validate that transfemoral does improve quality of life over surgery, especially early on. It’s a less invasive procedure, and patients recover quicker. That’s kind of what we always hoped and thought [that] clinically" that would be the case, he commented.

But the findings regarding transapical TAVR are not as worrisome as the data might suggest in light of certain aspects of the trial; in fact, "it’s very dangerous to go down that route to say it" is worse than surgery, he asserted.

Dr. Mack noted that transfemoral TAVR "got a head start," and many centers in the trial were just beginning to use transapical TAVR by the end of the trial. "It is clear there is a learning curve to it, and you had to think of this as a feasibility trial in the United States," he commented. Moreover, transfemoral access was attempted first in patients; thus, "the worst of the worst got left for transapical." A final factor to consider was the better-than-expected performance of surgery in the trial.

"So not to ignore the message and not to say there aren’t some concerns here, but I think that the data everywhere else in the world on transapical, with ... [rare exceptions] all is positive for transapical," he concluded at the meeting, which was sponsored by the Cardiovascular Research Foundation. "So I think, yes, concern. And yes, it should be noted. But I am not as concerned about it as the data may speak."

The trial data that Dr. Cohen reported came out of a prospective, preplanned quality of life substudy within Cohort A of the PARTNER trial, which enrolled 699 patients with severe, symptomatic aortic stenosis who had a high risk for surgical complications.

The patients were randomized 1:1 to undergo TAVR (with an Edwards Sapien valve, Edwards Lifesciences, either transfemoral or transapical) vs. surgical aortic valve replacement (with any other valve).

Previously reported safety and efficacy results for Cohort A indicated that TAVR and surgical aortic valve replacement yielded similar rates of 1-year survival (N. Engl. J. Med. 2011;364:2187-98). The former was associated with a higher rate of major vascular complications, whereas the latter was associated with higher rates of major bleeding and new-onset atrial fibrillation.

Patients’ health-related quality of life was assessed with the Kansas City Cardiomyopathy Questionnaire. Dr. Cohen stressed that this questionnaire captures quality of life data from the patient’s perspective, differentiating it from the New York Heart Association class, which instead reflects the physician’s perspective.

The primary quality of life end point was the summary score on this questionnaire. "This has been shown to predict mortality and cost among patients with heart failure," he noted. "And just to give you some reference, a minimum clinically important difference on this specific scale is 5 points."

Preliminary results showed a significant interaction between treatment effect and access site used for TAVR – transfemoral vs. transapical – and trial outcomes, according to Dr. Cohen, who is director of cardiovascular research at Saint Luke’s Mid-America Heart and Vascular Institute, University of Missouri–Kansas City. Therefore, analyses considered these subgroups separately.

Patients undergoing transfemoral TAVR had better scores on the Kansas City Cardiomyopathy Questionnaire at 1 month than their surgical counterparts (difference, 9.9 points; P less than .001). But there was no longer a significant difference at 6 or 12 months.

Patients undergoing transapical TAVR had worse scores than their surgical counterparts at 6 months (difference, 7.9 points; P = .04). But there was no significant difference at 1 or 12 months.

The findings were much the same for the individual subscales of the Kansas City Cardiomyopathy Questionnaire, and for additional, generic measures of health and quality of life assessed in the trial (the Short Form-12 Health Survey and the EQ-5D questionnaire), according to Dr. Cohen.

Furthermore, the findings held up in sensitivity analyses that were restricted to only patients who actually had attempted valve replacement, that used worst-case values for patients with missing data, and that instead categorized outcomes dichotomously.

The trial was sponsored by Edwards Lifesciences. Dr. Cohen reported that he receives research or grant support from Abbott Vascular, Boston Scientific, Medtronic, AstraZeneca, and Edwards Lifesciences; and is a consultant to, is a speaker for, or receives honoraria from Daiichi-Sankyo/Eli Lilly and Medtronic. Dr. Mack reported that he had no relevant conflicts of interest.

SAN FRANCISCO – The relative impact of transcatheter aortic valve replacement on patients’ quality of life depends on which access site is used for the procedure, suggest new data from Cohort A of the randomized PARTNER trial.

The trial compared transcatheter aortic valve replacement (TAVR) with surgical valve replacement among nearly 700 patients at high surgical risk. Lead investigator Dr. David J. Cohen presented its key quality of life findings – notably as perceived by patients themselves – at Transcatheter Cardiovascular Therapeutics 2011.

These findings showed that patients having TAVR by transfemoral access had better summary scores on the Kansas City Cardiomyopathy Questionnaire at 1 month than their surgical counterparts, with a difference between groups of about 10 points on the 100-point scale. The difference disappeared thereafter.

In contrast, patients having TAVR by transapical access had worse scores than their surgical counterparts at 6 months, with a difference between groups of about 8 points, although this difference likewise abated with longer follow-up.

"Taken together with previous data that have been reported, these findings demonstrate that for patients suitable for a transfemoral approach, TAVR provides important benefits compared with surgical aortic valve replacement from the patients’ perspective," Dr. Cohen said in a press conference. "The lack of benefit and suggestion of worse quality of life among patients who were ineligible for the transfemoral approach suggest the transapical approach may not be preferable to surgical aortic valve replacement in such patients."

"Whether further experience and refinements in the transapical approach can overcome these limitations should be the subject of future investigation," he added.

The findings provide reassurance about the transfemoral approach, according to Dr. Michael J. Mack, medical director of cardiovascular surgery at the Baylor Health Care System, Heart Hospital Baylor Plano, in Plano, Tex.

The trial "does validate that transfemoral does improve quality of life over surgery, especially early on. It’s a less invasive procedure, and patients recover quicker. That’s kind of what we always hoped and thought [that] clinically" that would be the case, he commented.

But the findings regarding transapical TAVR are not as worrisome as the data might suggest in light of certain aspects of the trial; in fact, "it’s very dangerous to go down that route to say it" is worse than surgery, he asserted.

Dr. Mack noted that transfemoral TAVR "got a head start," and many centers in the trial were just beginning to use transapical TAVR by the end of the trial. "It is clear there is a learning curve to it, and you had to think of this as a feasibility trial in the United States," he commented. Moreover, transfemoral access was attempted first in patients; thus, "the worst of the worst got left for transapical." A final factor to consider was the better-than-expected performance of surgery in the trial.

"So not to ignore the message and not to say there aren’t some concerns here, but I think that the data everywhere else in the world on transapical, with ... [rare exceptions] all is positive for transapical," he concluded at the meeting, which was sponsored by the Cardiovascular Research Foundation. "So I think, yes, concern. And yes, it should be noted. But I am not as concerned about it as the data may speak."

The trial data that Dr. Cohen reported came out of a prospective, preplanned quality of life substudy within Cohort A of the PARTNER trial, which enrolled 699 patients with severe, symptomatic aortic stenosis who had a high risk for surgical complications.

The patients were randomized 1:1 to undergo TAVR (with an Edwards Sapien valve, Edwards Lifesciences, either transfemoral or transapical) vs. surgical aortic valve replacement (with any other valve).

Previously reported safety and efficacy results for Cohort A indicated that TAVR and surgical aortic valve replacement yielded similar rates of 1-year survival (N. Engl. J. Med. 2011;364:2187-98). The former was associated with a higher rate of major vascular complications, whereas the latter was associated with higher rates of major bleeding and new-onset atrial fibrillation.

Patients’ health-related quality of life was assessed with the Kansas City Cardiomyopathy Questionnaire. Dr. Cohen stressed that this questionnaire captures quality of life data from the patient’s perspective, differentiating it from the New York Heart Association class, which instead reflects the physician’s perspective.

The primary quality of life end point was the summary score on this questionnaire. "This has been shown to predict mortality and cost among patients with heart failure," he noted. "And just to give you some reference, a minimum clinically important difference on this specific scale is 5 points."

Preliminary results showed a significant interaction between treatment effect and access site used for TAVR – transfemoral vs. transapical – and trial outcomes, according to Dr. Cohen, who is director of cardiovascular research at Saint Luke’s Mid-America Heart and Vascular Institute, University of Missouri–Kansas City. Therefore, analyses considered these subgroups separately.

Patients undergoing transfemoral TAVR had better scores on the Kansas City Cardiomyopathy Questionnaire at 1 month than their surgical counterparts (difference, 9.9 points; P less than .001). But there was no longer a significant difference at 6 or 12 months.

Patients undergoing transapical TAVR had worse scores than their surgical counterparts at 6 months (difference, 7.9 points; P = .04). But there was no significant difference at 1 or 12 months.

The findings were much the same for the individual subscales of the Kansas City Cardiomyopathy Questionnaire, and for additional, generic measures of health and quality of life assessed in the trial (the Short Form-12 Health Survey and the EQ-5D questionnaire), according to Dr. Cohen.

Furthermore, the findings held up in sensitivity analyses that were restricted to only patients who actually had attempted valve replacement, that used worst-case values for patients with missing data, and that instead categorized outcomes dichotomously.

The trial was sponsored by Edwards Lifesciences. Dr. Cohen reported that he receives research or grant support from Abbott Vascular, Boston Scientific, Medtronic, AstraZeneca, and Edwards Lifesciences; and is a consultant to, is a speaker for, or receives honoraria from Daiichi-Sankyo/Eli Lilly and Medtronic. Dr. Mack reported that he had no relevant conflicts of interest.

In patients who had undergone stent implantation, nonadherence to dual-antiplatelet therapy was associated with an increase in ischemic and bleeding events, according to early results from the 5,033-patient PARIS registry.

"There was a sixfold increase in odds for definite or probable stent thrombosis associated with nonadherence compared to adherence to DAPT at 30 days," Dr. Roxana Mehran of Mount Sinai School of Medicine, New York, and coprincipal investigator of the PARIS (Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients: An Observational Single Arm Study) reported at Transcatheter Cardiovascular Therapeutics 2011.

The incidence of nonadherence to dual-antiplatelet therapy at the 30-day follow-up was 2.0%. Among the nonadherent subjects, 69% had disruption of therapy, 19% had interruption, and 12% had discontinuation of therapy, Dr. Mehran said.

The PARIS trial is sponsored by Mount Sinai School of Medicine with grant support from Sanofi-aventis and Bristol-Myers Squibb. Dr. Mehran reported no other financial support from the companies except the research grant.

Note: Based on data for 5,033 patients who received bare-metal or drug-eluting stents.

Source: Dr. Mehran

In patients who had undergone stent implantation, nonadherence to dual-antiplatelet therapy was associated with an increase in ischemic and bleeding events, according to early results from the 5,033-patient PARIS registry.

"There was a sixfold increase in odds for definite or probable stent thrombosis associated with nonadherence compared to adherence to DAPT at 30 days," Dr. Roxana Mehran of Mount Sinai School of Medicine, New York, and coprincipal investigator of the PARIS (Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients: An Observational Single Arm Study) reported at Transcatheter Cardiovascular Therapeutics 2011.

The incidence of nonadherence to dual-antiplatelet therapy at the 30-day follow-up was 2.0%. Among the nonadherent subjects, 69% had disruption of therapy, 19% had interruption, and 12% had discontinuation of therapy, Dr. Mehran said.

The PARIS trial is sponsored by Mount Sinai School of Medicine with grant support from Sanofi-aventis and Bristol-Myers Squibb. Dr. Mehran reported no other financial support from the companies except the research grant.

Note: Based on data for 5,033 patients who received bare-metal or drug-eluting stents.

Source: Dr. Mehran

In patients who had undergone stent implantation, nonadherence to dual-antiplatelet therapy was associated with an increase in ischemic and bleeding events, according to early results from the 5,033-patient PARIS registry.

"There was a sixfold increase in odds for definite or probable stent thrombosis associated with nonadherence compared to adherence to DAPT at 30 days," Dr. Roxana Mehran of Mount Sinai School of Medicine, New York, and coprincipal investigator of the PARIS (Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients: An Observational Single Arm Study) reported at Transcatheter Cardiovascular Therapeutics 2011.

The incidence of nonadherence to dual-antiplatelet therapy at the 30-day follow-up was 2.0%. Among the nonadherent subjects, 69% had disruption of therapy, 19% had interruption, and 12% had discontinuation of therapy, Dr. Mehran said.

The PARIS trial is sponsored by Mount Sinai School of Medicine with grant support from Sanofi-aventis and Bristol-Myers Squibb. Dr. Mehran reported no other financial support from the companies except the research grant.

Note: Based on data for 5,033 patients who received bare-metal or drug-eluting stents.

Source: Dr. Mehran