Sapien XT valve shows improvements over original

SAN FRANCISCO – A new, smaller version of the only transcatheter aortic valve available for U.S. use showed noninferior clinical outcomes and safer periprocedural results in a multicenter U.S. comparison of the new and existing devices in a total of 560 patients, raising expectations that the new valve system – the Sapien XT – will soon be on the U.S. market.

Although treatment using the Sapien XT roughly matched treatment with the existing Sapien transcatheter aortic valve in the incidence of the important adverse effect of residual moderate or severe paravalvular leak, several U.S. operators who perform transcatheter aortic valve repair (TAVR) stressed that the leak problem has begun to resolve recently as interventionalists and surgeons have found ways to minimize the issue. They also noted that availability of the new XT device will move the field a step further toward fewer leak issues, because it will allow the option of a larger, 29-mm-diameter valve, a possibility that has not been available with the original Sapien valve.

Mitchel L. Zoler/IMNG Medical Media

"Sapien XT represents a worthwhile advance with incremental clinical value, and it is the preferred balloon-expandable transcatheter aortic valve system," said Dr. Martin B. Leon when he presented the trial data on March 10 at the annual meeting of the American College of Cardiology.

"This second-generation device has demonstrated sufficient clinical benefit for us to say it’s the preferred therapy," said Dr. Leon, professor of medicine and director of the Center for Interventional Vascular Therapy at Columbia University in New York.

"This is an evolutionary technology that is easier to use. The results are superb," commented Dr. Gary S. Mintz, an interventional cardiologist based in Washington and medical director of the Cardiovascular Research Foundation in New York.

The PARTNER II (Placement of Aortic Transcatheter Valves) cohort B trial enrolled 560 patients with aortic stenosis deemed inoperable for surgical valve replacement at 28 U.S. centers during April 2011 through February 2012. The study randomized patients to receive the Sapien XT valve or the approved Sapien valve in a prespecified noninferiority design, with a primary outcome of all-cause death, disabling stroke, or need for repeat hospitalization at 1 year after treatment. Patients averaged 84 years old, they had an average Society of Thoracic Surgeons score of about 10%, 96% had New York Heart Association class III or IV heart failure, and about 60% met the study’s criteria for frailty.

At 1-year follow-up, the combined primary endpoint occurred in 35% of patients treated with the approved valve and in 34% of patients treated with the new XT valve, a result that was not statistically significant and that met the study’s standard for noninferiority. At 1 year, as well as at 30 days after treatment, the two patient groups showed no significant difference for any of the individual components of the clinical endpoints.

However, patients treated with the XT valve had significantly fewer procedural complications, with significantly fewer major vascular events (10% with the XT device, compared with 16% with the approved valve) and significantly fewer disabling bleeding events (8% with the XT device, compared with 13% with the first-generation system), Dr. Leon reported. The category of major vascular events included perforations, dissections, and hematomas. Patients treated with the XT device also required significantly fewer episodes when the initially placed valve had to be replaced (3 replaced valve implants, compared with 10 using the approved valve), and numerically fewer aborted procedures – 2 compared with 8 using the approved valve, although this difference just missed statistical significance (P = .06). Placement of the new valve also required an average of 14 minutes less anesthesia time, a significant difference.

"It’s a smaller device. What you would expect from a smaller device is fewer vascular complications and improved procedural events," Dr. Leon said in an interview. He also highlighted the numerical difference in 30-day mortality – 5.1% with the older valve system, compared with 3.5% using the XT device. While the difference did not reach statistical significance, "to me this difference is not trivial," he said.

The difference in disabling bleeding complications is also important, commented Dr. Mintz, who was not involved in the study. "Bleeding complications are hugely disabling, especially in this older, frail population," he said.

"The big concerns from the first PARTNER trial were vascular complications, strokes, and paravalvular leaks," said Dr. Leon. "The XT device seems to address some of these issues. The vascular complications were reduced, and the stroke rate went down" compared with the first PARTNER trial (N. Engl. J. Med. 2010;363:1597-607). "What is left is the paravalvular leak issue, which is real."

In the new trial, moderate or severe paravalvular leaks, a complication that has previously been linked with worse outcomes and increased mortality, occurred in 17% of the patients who received the approved valve and in 24% of patients who received the XT valve at 30-day follow-up, a difference that did not reach significance.

"Is there a difference in paravalvular leaks between Sapien XT and Sapien? We’re not entirely sure. There was a nonsignificant trend" that will be the subject of further analysis, Dr. Leon said. He stressed that the leak rate is confounded because significantly more patients who received the approved valve underwent a second valve placement, which often occurs because a leak occurred with the first valve. "Putting in a second valve is a big thing and is not good," he said. "No matter how you look at it, there still was a significant leak rate that is not as good as it needs to be." Dr. Leon said that he hopes the issue of paravalvular leaks will be addressed by a third-generation valve system that will enter clinical trials later this year.

But some surgeons and interventionalists involved in the PARTNER II trial noted that the incidence of paravalvular leaks has already begun to come down in the past year or so.

"We are [now] much better at sizing the valve with CT scans, and that is reducing the number of paravalvular leaks, at least anecdotally at our center," said Dr. Michael J. Mack, a cardiothoracic surgeon at the Heart Hospital in Plano, Texas, and a PARTNER II investigator. "We also underfill or overfill our [valve expansion] balloons based on the CT scans, and we’re getting better results with that. We’re fitting the valve better into the space," he said in an interview.

"We do everything we can to minimize patients leaving with a moderate or severe leak by balloon dilatation or putting in a second valve," said Dr. Jeffrey J. Popma, an interventional cardiologist and professor of medicine at Harvard University in Boston and a PARTNER II investigator. He also noted that use of the XT device reduces the number of patients who need transapical valve placement, because the smaller catheter can be more easily manipulated through a patient’s ileofemoral anatomy.

A further advantage of the XT valve for minimizing paravalvular leaks is that it is available in a 29-mm diameter, although the 29-mm valve was not included in the PARTNER II trial. The widest valve available in the original Sapien design was 26 mm.

"The 29-mm valve is a huge advance because we know that [until now] TAVR success is greater in women, probably because about 20% of American men need a larger valve, and their leak rate was higher," said Dr. Joseph E. Bavaria, a professor of surgery at the University of Pennsylvania in Philadelphia and a PARTNER II investigator. "Having the 29-mm valve available will be a big difference," he said in an interview.

The PARTNER II trial has a second cohort, cohort A, that is comparing the Sapien XT valve system against open surgical valve replacement in patients who are deemed eligible by cardiac surgeons for surgical aortic valve replacement and are at "intermediate" risk for undergoing surgery. Enrollment of the roughly 2,000 patients who will enter this study should be complete by this summer, and with a 2-year primary endpoint the results should be available sometime in 2015, Dr. Leon said.

The PARTNER II trial is sponsored by Edwards Lifesciences, which markets the XT transcatheter aortic valve system. The company has not filed an application for approval of the Sapien XT device. Dr. Leon, Dr. Mack, Dr. Popma, and Dr. Bavaria all participated in the trial. Dr. Mintz said that he has been a consultant to Boston Scientific.

SAN FRANCISCO – A new, smaller version of the only transcatheter aortic valve available for U.S. use showed noninferior clinical outcomes and safer periprocedural results in a multicenter U.S. comparison of the new and existing devices in a total of 560 patients, raising expectations that the new valve system – the Sapien XT – will soon be on the U.S. market.

Although treatment using the Sapien XT roughly matched treatment with the existing Sapien transcatheter aortic valve in the incidence of the important adverse effect of residual moderate or severe paravalvular leak, several U.S. operators who perform transcatheter aortic valve repair (TAVR) stressed that the leak problem has begun to resolve recently as interventionalists and surgeons have found ways to minimize the issue. They also noted that availability of the new XT device will move the field a step further toward fewer leak issues, because it will allow the option of a larger, 29-mm-diameter valve, a possibility that has not been available with the original Sapien valve.

Mitchel L. Zoler/IMNG Medical Media

"Sapien XT represents a worthwhile advance with incremental clinical value, and it is the preferred balloon-expandable transcatheter aortic valve system," said Dr. Martin B. Leon when he presented the trial data on March 10 at the annual meeting of the American College of Cardiology.

"This second-generation device has demonstrated sufficient clinical benefit for us to say it’s the preferred therapy," said Dr. Leon, professor of medicine and director of the Center for Interventional Vascular Therapy at Columbia University in New York.

"This is an evolutionary technology that is easier to use. The results are superb," commented Dr. Gary S. Mintz, an interventional cardiologist based in Washington and medical director of the Cardiovascular Research Foundation in New York.

The PARTNER II (Placement of Aortic Transcatheter Valves) cohort B trial enrolled 560 patients with aortic stenosis deemed inoperable for surgical valve replacement at 28 U.S. centers during April 2011 through February 2012. The study randomized patients to receive the Sapien XT valve or the approved Sapien valve in a prespecified noninferiority design, with a primary outcome of all-cause death, disabling stroke, or need for repeat hospitalization at 1 year after treatment. Patients averaged 84 years old, they had an average Society of Thoracic Surgeons score of about 10%, 96% had New York Heart Association class III or IV heart failure, and about 60% met the study’s criteria for frailty.

At 1-year follow-up, the combined primary endpoint occurred in 35% of patients treated with the approved valve and in 34% of patients treated with the new XT valve, a result that was not statistically significant and that met the study’s standard for noninferiority. At 1 year, as well as at 30 days after treatment, the two patient groups showed no significant difference for any of the individual components of the clinical endpoints.

However, patients treated with the XT valve had significantly fewer procedural complications, with significantly fewer major vascular events (10% with the XT device, compared with 16% with the approved valve) and significantly fewer disabling bleeding events (8% with the XT device, compared with 13% with the first-generation system), Dr. Leon reported. The category of major vascular events included perforations, dissections, and hematomas. Patients treated with the XT device also required significantly fewer episodes when the initially placed valve had to be replaced (3 replaced valve implants, compared with 10 using the approved valve), and numerically fewer aborted procedures – 2 compared with 8 using the approved valve, although this difference just missed statistical significance (P = .06). Placement of the new valve also required an average of 14 minutes less anesthesia time, a significant difference.

"It’s a smaller device. What you would expect from a smaller device is fewer vascular complications and improved procedural events," Dr. Leon said in an interview. He also highlighted the numerical difference in 30-day mortality – 5.1% with the older valve system, compared with 3.5% using the XT device. While the difference did not reach statistical significance, "to me this difference is not trivial," he said.

The difference in disabling bleeding complications is also important, commented Dr. Mintz, who was not involved in the study. "Bleeding complications are hugely disabling, especially in this older, frail population," he said.

"The big concerns from the first PARTNER trial were vascular complications, strokes, and paravalvular leaks," said Dr. Leon. "The XT device seems to address some of these issues. The vascular complications were reduced, and the stroke rate went down" compared with the first PARTNER trial (N. Engl. J. Med. 2010;363:1597-607). "What is left is the paravalvular leak issue, which is real."

In the new trial, moderate or severe paravalvular leaks, a complication that has previously been linked with worse outcomes and increased mortality, occurred in 17% of the patients who received the approved valve and in 24% of patients who received the XT valve at 30-day follow-up, a difference that did not reach significance.

"Is there a difference in paravalvular leaks between Sapien XT and Sapien? We’re not entirely sure. There was a nonsignificant trend" that will be the subject of further analysis, Dr. Leon said. He stressed that the leak rate is confounded because significantly more patients who received the approved valve underwent a second valve placement, which often occurs because a leak occurred with the first valve. "Putting in a second valve is a big thing and is not good," he said. "No matter how you look at it, there still was a significant leak rate that is not as good as it needs to be." Dr. Leon said that he hopes the issue of paravalvular leaks will be addressed by a third-generation valve system that will enter clinical trials later this year.

But some surgeons and interventionalists involved in the PARTNER II trial noted that the incidence of paravalvular leaks has already begun to come down in the past year or so.

"We are [now] much better at sizing the valve with CT scans, and that is reducing the number of paravalvular leaks, at least anecdotally at our center," said Dr. Michael J. Mack, a cardiothoracic surgeon at the Heart Hospital in Plano, Texas, and a PARTNER II investigator. "We also underfill or overfill our [valve expansion] balloons based on the CT scans, and we’re getting better results with that. We’re fitting the valve better into the space," he said in an interview.

"We do everything we can to minimize patients leaving with a moderate or severe leak by balloon dilatation or putting in a second valve," said Dr. Jeffrey J. Popma, an interventional cardiologist and professor of medicine at Harvard University in Boston and a PARTNER II investigator. He also noted that use of the XT device reduces the number of patients who need transapical valve placement, because the smaller catheter can be more easily manipulated through a patient’s ileofemoral anatomy.

A further advantage of the XT valve for minimizing paravalvular leaks is that it is available in a 29-mm diameter, although the 29-mm valve was not included in the PARTNER II trial. The widest valve available in the original Sapien design was 26 mm.

"The 29-mm valve is a huge advance because we know that [until now] TAVR success is greater in women, probably because about 20% of American men need a larger valve, and their leak rate was higher," said Dr. Joseph E. Bavaria, a professor of surgery at the University of Pennsylvania in Philadelphia and a PARTNER II investigator. "Having the 29-mm valve available will be a big difference," he said in an interview.

The PARTNER II trial has a second cohort, cohort A, that is comparing the Sapien XT valve system against open surgical valve replacement in patients who are deemed eligible by cardiac surgeons for surgical aortic valve replacement and are at "intermediate" risk for undergoing surgery. Enrollment of the roughly 2,000 patients who will enter this study should be complete by this summer, and with a 2-year primary endpoint the results should be available sometime in 2015, Dr. Leon said.

The PARTNER II trial is sponsored by Edwards Lifesciences, which markets the XT transcatheter aortic valve system. The company has not filed an application for approval of the Sapien XT device. Dr. Leon, Dr. Mack, Dr. Popma, and Dr. Bavaria all participated in the trial. Dr. Mintz said that he has been a consultant to Boston Scientific.

SAN FRANCISCO – A new, smaller version of the only transcatheter aortic valve available for U.S. use showed noninferior clinical outcomes and safer periprocedural results in a multicenter U.S. comparison of the new and existing devices in a total of 560 patients, raising expectations that the new valve system – the Sapien XT – will soon be on the U.S. market.

Although treatment using the Sapien XT roughly matched treatment with the existing Sapien transcatheter aortic valve in the incidence of the important adverse effect of residual moderate or severe paravalvular leak, several U.S. operators who perform transcatheter aortic valve repair (TAVR) stressed that the leak problem has begun to resolve recently as interventionalists and surgeons have found ways to minimize the issue. They also noted that availability of the new XT device will move the field a step further toward fewer leak issues, because it will allow the option of a larger, 29-mm-diameter valve, a possibility that has not been available with the original Sapien valve.

Mitchel L. Zoler/IMNG Medical Media

"Sapien XT represents a worthwhile advance with incremental clinical value, and it is the preferred balloon-expandable transcatheter aortic valve system," said Dr. Martin B. Leon when he presented the trial data on March 10 at the annual meeting of the American College of Cardiology.

"This second-generation device has demonstrated sufficient clinical benefit for us to say it’s the preferred therapy," said Dr. Leon, professor of medicine and director of the Center for Interventional Vascular Therapy at Columbia University in New York.

"This is an evolutionary technology that is easier to use. The results are superb," commented Dr. Gary S. Mintz, an interventional cardiologist based in Washington and medical director of the Cardiovascular Research Foundation in New York.

The PARTNER II (Placement of Aortic Transcatheter Valves) cohort B trial enrolled 560 patients with aortic stenosis deemed inoperable for surgical valve replacement at 28 U.S. centers during April 2011 through February 2012. The study randomized patients to receive the Sapien XT valve or the approved Sapien valve in a prespecified noninferiority design, with a primary outcome of all-cause death, disabling stroke, or need for repeat hospitalization at 1 year after treatment. Patients averaged 84 years old, they had an average Society of Thoracic Surgeons score of about 10%, 96% had New York Heart Association class III or IV heart failure, and about 60% met the study’s criteria for frailty.

At 1-year follow-up, the combined primary endpoint occurred in 35% of patients treated with the approved valve and in 34% of patients treated with the new XT valve, a result that was not statistically significant and that met the study’s standard for noninferiority. At 1 year, as well as at 30 days after treatment, the two patient groups showed no significant difference for any of the individual components of the clinical endpoints.

However, patients treated with the XT valve had significantly fewer procedural complications, with significantly fewer major vascular events (10% with the XT device, compared with 16% with the approved valve) and significantly fewer disabling bleeding events (8% with the XT device, compared with 13% with the first-generation system), Dr. Leon reported. The category of major vascular events included perforations, dissections, and hematomas. Patients treated with the XT device also required significantly fewer episodes when the initially placed valve had to be replaced (3 replaced valve implants, compared with 10 using the approved valve), and numerically fewer aborted procedures – 2 compared with 8 using the approved valve, although this difference just missed statistical significance (P = .06). Placement of the new valve also required an average of 14 minutes less anesthesia time, a significant difference.

"It’s a smaller device. What you would expect from a smaller device is fewer vascular complications and improved procedural events," Dr. Leon said in an interview. He also highlighted the numerical difference in 30-day mortality – 5.1% with the older valve system, compared with 3.5% using the XT device. While the difference did not reach statistical significance, "to me this difference is not trivial," he said.

The difference in disabling bleeding complications is also important, commented Dr. Mintz, who was not involved in the study. "Bleeding complications are hugely disabling, especially in this older, frail population," he said.

"The big concerns from the first PARTNER trial were vascular complications, strokes, and paravalvular leaks," said Dr. Leon. "The XT device seems to address some of these issues. The vascular complications were reduced, and the stroke rate went down" compared with the first PARTNER trial (N. Engl. J. Med. 2010;363:1597-607). "What is left is the paravalvular leak issue, which is real."

In the new trial, moderate or severe paravalvular leaks, a complication that has previously been linked with worse outcomes and increased mortality, occurred in 17% of the patients who received the approved valve and in 24% of patients who received the XT valve at 30-day follow-up, a difference that did not reach significance.

"Is there a difference in paravalvular leaks between Sapien XT and Sapien? We’re not entirely sure. There was a nonsignificant trend" that will be the subject of further analysis, Dr. Leon said. He stressed that the leak rate is confounded because significantly more patients who received the approved valve underwent a second valve placement, which often occurs because a leak occurred with the first valve. "Putting in a second valve is a big thing and is not good," he said. "No matter how you look at it, there still was a significant leak rate that is not as good as it needs to be." Dr. Leon said that he hopes the issue of paravalvular leaks will be addressed by a third-generation valve system that will enter clinical trials later this year.

But some surgeons and interventionalists involved in the PARTNER II trial noted that the incidence of paravalvular leaks has already begun to come down in the past year or so.

"We are [now] much better at sizing the valve with CT scans, and that is reducing the number of paravalvular leaks, at least anecdotally at our center," said Dr. Michael J. Mack, a cardiothoracic surgeon at the Heart Hospital in Plano, Texas, and a PARTNER II investigator. "We also underfill or overfill our [valve expansion] balloons based on the CT scans, and we’re getting better results with that. We’re fitting the valve better into the space," he said in an interview.

"We do everything we can to minimize patients leaving with a moderate or severe leak by balloon dilatation or putting in a second valve," said Dr. Jeffrey J. Popma, an interventional cardiologist and professor of medicine at Harvard University in Boston and a PARTNER II investigator. He also noted that use of the XT device reduces the number of patients who need transapical valve placement, because the smaller catheter can be more easily manipulated through a patient’s ileofemoral anatomy.

A further advantage of the XT valve for minimizing paravalvular leaks is that it is available in a 29-mm diameter, although the 29-mm valve was not included in the PARTNER II trial. The widest valve available in the original Sapien design was 26 mm.

"The 29-mm valve is a huge advance because we know that [until now] TAVR success is greater in women, probably because about 20% of American men need a larger valve, and their leak rate was higher," said Dr. Joseph E. Bavaria, a professor of surgery at the University of Pennsylvania in Philadelphia and a PARTNER II investigator. "Having the 29-mm valve available will be a big difference," he said in an interview.

The PARTNER II trial has a second cohort, cohort A, that is comparing the Sapien XT valve system against open surgical valve replacement in patients who are deemed eligible by cardiac surgeons for surgical aortic valve replacement and are at "intermediate" risk for undergoing surgery. Enrollment of the roughly 2,000 patients who will enter this study should be complete by this summer, and with a 2-year primary endpoint the results should be available sometime in 2015, Dr. Leon said.

The PARTNER II trial is sponsored by Edwards Lifesciences, which markets the XT transcatheter aortic valve system. The company has not filed an application for approval of the Sapien XT device. Dr. Leon, Dr. Mack, Dr. Popma, and Dr. Bavaria all participated in the trial. Dr. Mintz said that he has been a consultant to Boston Scientific.