TCT 2012

Survival rates remained high 1 year after implantation with the transcatheter aortic CoreValve in the postmarket ADVANCE study, initial results show.

At 1 year, overall survival was 82.1% and cardiovascular survival 88.2%. This compares with survival rates of 87.4% and 91.7% at 6 months and 95.5% and 96.6% at 30 days, principal investigator Dr. Axel Linke reported at Transcatheter Cardiovascular Therapeutics 2012.

"I think they’re outstanding," he said in an interview. "If you put it into the perspective of the PARTNER A and B cohorts [in the pivotal trial in the Sapien transcatheter valve system], our mortality rate is, in absolute values, 8 to 13% lower."

One explanation is that the 1,015-patient, postmarket ADVANCE study sought out centers experienced with transcatheter aortic valve implantation (TAVI). The 44 centers in Western Europe, Asia, and South America were required to have performed at least 40 TAVI procedures, with some German centers having done as many as 500, to be certified by a TAVI proctor and to have a heart team in place.

"Clearly, our centers were out of the learning curve," remarked Dr. Linke of the University of Leipzig (Germany) Heart Center.

By comparison, some centers in the PARTNER trial of the Edwards Lifesciences Sapien valve contributed just six or seven patients and were selected based on their experience with general cardiologic intervention, he observed.

The 1-year survival rates in ADVANCE also surpass those from early registries, notably the French Aortic National CoreValve and Edwards Registry, where the initial experience with TAVI was associated with interventional mistakes, which were linked to early mortality, Dr. Linke said.

The CoreValve System has been implanted in more than 30,000 patients since its approval in the European Union in 2007, but is limited to investigational use in the United States and Japan.

No details were presented regarding mortality in various subgroups or complications such as stroke, paravalvular leaks or left bundle branch block (LBBB). A recent analysis raised concerns about LBBB, showing that one-third of 202 consecutive patients with no prior conduction disturbances developed new-onset LBBB after TAVI with a balloon-expandable valve (Sapien or Sapien XT). Although it resolved in 37.7% by hospital discharge and 57.3% at 6- to 12-month follow-up, patients with persistent LBBB had a significantly higher incidence of syncope and complete atrioventricular block requiring a permanent pacemaker (J. Am. Coll. Cardiol. 2012;60:1743-52 [doi:10.1016/j.jacc.2012.035]).

Dr. Linke said they will look at LBBB in more detailed analyses expected from ADVANCE in the coming weeks, but that there’s been no evidence of a problem with LBBB in earlier follow-up in ADVANCE or from other CoreValve users.

"Survival curves are absolutely identical up to the 6-month follow-up, so there’s no reason to believe they should be worse afterwards, although I can’t be exactly sure right now," he said, adding that in the publication, survival curves from patients with and without new-onset LBBB "started to diverge very early."

Quality of life data from ADVANCE, reported in a separate poster session at the meeting, showed significant benefits with the CoreValve, even among higher-risk patients.

Scores on the European Quality of Life–5 Dimensions (EQ-5D), which ranges from 0 (death) to 1 (perfect health), improved from 0.62 at baseline to 0.72 at 1 month, where it remained at 6 months, both highly significant differences from baseline.

On the Short Form Health Survey–12 (SF-12), scores at baseline, 1 month, and 6 months were 32.8, 39, and 39.7 for the physical component and 46.2, 48.5, and 50 for the mental component.

"Basically, whatever is gained, is gained very early from the baseline to the 1-month follow-up in the majority of the cases," said Dr. Linke.

The 322 higher-risk patients entering the study with a logistic EuroSCORE of more than 20 had significantly worse baseline health-related quality of life than did those with a EuroSCORE of 10 or less, but experienced significant improvements after TAVI on the EQ-5D at 1 month and on both components of the SF-12 at 6 months, all significant changes.

The access route used during TAVI had no impact on quality of life improvement at 6 months.

Dr. Linke reported serving as an adviser or consultant for Medtronic, which sponsored the study.

Survival rates remained high 1 year after implantation with the transcatheter aortic CoreValve in the postmarket ADVANCE study, initial results show.

At 1 year, overall survival was 82.1% and cardiovascular survival 88.2%. This compares with survival rates of 87.4% and 91.7% at 6 months and 95.5% and 96.6% at 30 days, principal investigator Dr. Axel Linke reported at Transcatheter Cardiovascular Therapeutics 2012.

"I think they’re outstanding," he said in an interview. "If you put it into the perspective of the PARTNER A and B cohorts [in the pivotal trial in the Sapien transcatheter valve system], our mortality rate is, in absolute values, 8 to 13% lower."

One explanation is that the 1,015-patient, postmarket ADVANCE study sought out centers experienced with transcatheter aortic valve implantation (TAVI). The 44 centers in Western Europe, Asia, and South America were required to have performed at least 40 TAVI procedures, with some German centers having done as many as 500, to be certified by a TAVI proctor and to have a heart team in place.

"Clearly, our centers were out of the learning curve," remarked Dr. Linke of the University of Leipzig (Germany) Heart Center.

By comparison, some centers in the PARTNER trial of the Edwards Lifesciences Sapien valve contributed just six or seven patients and were selected based on their experience with general cardiologic intervention, he observed.

The 1-year survival rates in ADVANCE also surpass those from early registries, notably the French Aortic National CoreValve and Edwards Registry, where the initial experience with TAVI was associated with interventional mistakes, which were linked to early mortality, Dr. Linke said.

The CoreValve System has been implanted in more than 30,000 patients since its approval in the European Union in 2007, but is limited to investigational use in the United States and Japan.

No details were presented regarding mortality in various subgroups or complications such as stroke, paravalvular leaks or left bundle branch block (LBBB). A recent analysis raised concerns about LBBB, showing that one-third of 202 consecutive patients with no prior conduction disturbances developed new-onset LBBB after TAVI with a balloon-expandable valve (Sapien or Sapien XT). Although it resolved in 37.7% by hospital discharge and 57.3% at 6- to 12-month follow-up, patients with persistent LBBB had a significantly higher incidence of syncope and complete atrioventricular block requiring a permanent pacemaker (J. Am. Coll. Cardiol. 2012;60:1743-52 [doi:10.1016/j.jacc.2012.035]).

Dr. Linke said they will look at LBBB in more detailed analyses expected from ADVANCE in the coming weeks, but that there’s been no evidence of a problem with LBBB in earlier follow-up in ADVANCE or from other CoreValve users.

"Survival curves are absolutely identical up to the 6-month follow-up, so there’s no reason to believe they should be worse afterwards, although I can’t be exactly sure right now," he said, adding that in the publication, survival curves from patients with and without new-onset LBBB "started to diverge very early."

Quality of life data from ADVANCE, reported in a separate poster session at the meeting, showed significant benefits with the CoreValve, even among higher-risk patients.

Scores on the European Quality of Life–5 Dimensions (EQ-5D), which ranges from 0 (death) to 1 (perfect health), improved from 0.62 at baseline to 0.72 at 1 month, where it remained at 6 months, both highly significant differences from baseline.

On the Short Form Health Survey–12 (SF-12), scores at baseline, 1 month, and 6 months were 32.8, 39, and 39.7 for the physical component and 46.2, 48.5, and 50 for the mental component.

"Basically, whatever is gained, is gained very early from the baseline to the 1-month follow-up in the majority of the cases," said Dr. Linke.

The 322 higher-risk patients entering the study with a logistic EuroSCORE of more than 20 had significantly worse baseline health-related quality of life than did those with a EuroSCORE of 10 or less, but experienced significant improvements after TAVI on the EQ-5D at 1 month and on both components of the SF-12 at 6 months, all significant changes.

The access route used during TAVI had no impact on quality of life improvement at 6 months.

Dr. Linke reported serving as an adviser or consultant for Medtronic, which sponsored the study.

Survival rates remained high 1 year after implantation with the transcatheter aortic CoreValve in the postmarket ADVANCE study, initial results show.

At 1 year, overall survival was 82.1% and cardiovascular survival 88.2%. This compares with survival rates of 87.4% and 91.7% at 6 months and 95.5% and 96.6% at 30 days, principal investigator Dr. Axel Linke reported at Transcatheter Cardiovascular Therapeutics 2012.

"I think they’re outstanding," he said in an interview. "If you put it into the perspective of the PARTNER A and B cohorts [in the pivotal trial in the Sapien transcatheter valve system], our mortality rate is, in absolute values, 8 to 13% lower."

One explanation is that the 1,015-patient, postmarket ADVANCE study sought out centers experienced with transcatheter aortic valve implantation (TAVI). The 44 centers in Western Europe, Asia, and South America were required to have performed at least 40 TAVI procedures, with some German centers having done as many as 500, to be certified by a TAVI proctor and to have a heart team in place.

"Clearly, our centers were out of the learning curve," remarked Dr. Linke of the University of Leipzig (Germany) Heart Center.

By comparison, some centers in the PARTNER trial of the Edwards Lifesciences Sapien valve contributed just six or seven patients and were selected based on their experience with general cardiologic intervention, he observed.

The 1-year survival rates in ADVANCE also surpass those from early registries, notably the French Aortic National CoreValve and Edwards Registry, where the initial experience with TAVI was associated with interventional mistakes, which were linked to early mortality, Dr. Linke said.

The CoreValve System has been implanted in more than 30,000 patients since its approval in the European Union in 2007, but is limited to investigational use in the United States and Japan.

No details were presented regarding mortality in various subgroups or complications such as stroke, paravalvular leaks or left bundle branch block (LBBB). A recent analysis raised concerns about LBBB, showing that one-third of 202 consecutive patients with no prior conduction disturbances developed new-onset LBBB after TAVI with a balloon-expandable valve (Sapien or Sapien XT). Although it resolved in 37.7% by hospital discharge and 57.3% at 6- to 12-month follow-up, patients with persistent LBBB had a significantly higher incidence of syncope and complete atrioventricular block requiring a permanent pacemaker (J. Am. Coll. Cardiol. 2012;60:1743-52 [doi:10.1016/j.jacc.2012.035]).

Dr. Linke said they will look at LBBB in more detailed analyses expected from ADVANCE in the coming weeks, but that there’s been no evidence of a problem with LBBB in earlier follow-up in ADVANCE or from other CoreValve users.

"Survival curves are absolutely identical up to the 6-month follow-up, so there’s no reason to believe they should be worse afterwards, although I can’t be exactly sure right now," he said, adding that in the publication, survival curves from patients with and without new-onset LBBB "started to diverge very early."

Quality of life data from ADVANCE, reported in a separate poster session at the meeting, showed significant benefits with the CoreValve, even among higher-risk patients.

Scores on the European Quality of Life–5 Dimensions (EQ-5D), which ranges from 0 (death) to 1 (perfect health), improved from 0.62 at baseline to 0.72 at 1 month, where it remained at 6 months, both highly significant differences from baseline.

On the Short Form Health Survey–12 (SF-12), scores at baseline, 1 month, and 6 months were 32.8, 39, and 39.7 for the physical component and 46.2, 48.5, and 50 for the mental component.

"Basically, whatever is gained, is gained very early from the baseline to the 1-month follow-up in the majority of the cases," said Dr. Linke.

The 322 higher-risk patients entering the study with a logistic EuroSCORE of more than 20 had significantly worse baseline health-related quality of life than did those with a EuroSCORE of 10 or less, but experienced significant improvements after TAVI on the EQ-5D at 1 month and on both components of the SF-12 at 6 months, all significant changes.

The access route used during TAVI had no impact on quality of life improvement at 6 months.

Dr. Linke reported serving as an adviser or consultant for Medtronic, which sponsored the study.

When patients who received a Resolute stent prematurely stopped their dual antiplatelet therapy, all the stent-thrombosis events that followed clustered in the patients who stopped their drugs during the first month after stent placement, in a review of nearly 5,000 patients.

The 1,076 Resolute recipients who interrupted their mandated treatment with aspirin and a thienopyridine included 169 patients who stopped during the first month after getting their stent. Five of these patients (3%) had stent thrombosis, compared with a 0.7% rate of stent thrombosis during the first month after placement among 3,858 patients who received a Resolute zotarolimus-eluting coronary stent and remained on their dual antiplatelet therapy (DAPT) for the prescribed 12 months, Dr. Sigmund Silber reported at Transcatheter Cardiovascular Therapeutics 2012.

Courtesy Dr. Sigmund Silber

Among the remaining 907 patients who interrupted their DAPT sometime during months 2-12 after getting their stent, no additional episodes of stent thrombosis occurred. The 3,858 patients who remained on DAPT throughout the full 12 months of mandated treatment had eight additional stent thromboses, a 0.2% rate, said Dr. Silber, a cardiologist and professor at Ludwig-Maximilians University in Munich.

"If patients took DAPT for only 1 month, they had no increased risk for stent thrombosis" compared with patients who stayed on DAPT for 1 year. "This is a very surprising finding," Dr. Silber said in an interview.

"This was a post hoc analysis, and it does not mean that you can take patients who get a Resolute stent off of DAPT after 4 weeks. But if, for some reason, the patient has to come off of DAPT after 4 weeks, the risk of stent thrombosis is not as big as we had feared," he said.

This performance of the Resolute zotarolimus-eluting stent contrasts with the performance of first-generation drug-eluting coronary stents, which consistently showed elevated rates of stent thrombosis when DAPT was not maintained for at least 6 months after placement, he noted. In addition, review of experience with the Xience everolimus-eluting stent, another second-generation coronary stent, showed a similar pattern when DAPT was maintained for at least 3 months. But "as far as I know, no data were reported on Xience after 4 weeks," said Dr. Silber, who is also director of the Isar Heart Center in Munich.

Although this was a post hoc analysis, one message is clear, he said: "Physicians should do everything possible to continue DAPT during the first month." So far, it remains unclear whether interruption of DAPT followed by a restart led to any difference in the stent thrombosis rate compared with full discontinuation. An analysis that compares these two types of stoppages is in process.

In addition, the findings suggest running a prospective trial to test the efficacy and safety of using DAPT for 1 month in patients who receive a Resolute stent compared with patients who receive DAPT for 6 or 12 months, Dr. Silber said. But he acknowledged that this would be a challenging trial to run – randomizing patients to DAPT for just 1 month after placing a drug-eluting stent, plus enrolling several thousand patients. "Does anyone have the guts to do that?" he asked.

Medtronic may consider funding a trial to test the hypothesis that 1 month of DAPT is adequate in patients who receive Resolute stents, but no such study is yet in process, said Jason Fontana, Ph.D., vice president for coronary strategy and development at Medtronic. "We’re beginning to think about what we may do with these data," Dr. Fontana said in an interview.

Dr. Silber’s analysis used data collected from nearly 5,000 patients enrolled in four pivotal trials of Resolute that ran in the United States, Europe, Japan, and elsewhere, and formed part of the new device application that Medtronic filed with the Food and Drug Administration.

The Resolute studies were funded by Medtronic, the company that markets the stent. Dr. Silber said that he has received research support from Medtronic, as well as from Abbott and Boston Scientific. Dr. Fontana is a Medtronic employee.

When patients who received a Resolute stent prematurely stopped their dual antiplatelet therapy, all the stent-thrombosis events that followed clustered in the patients who stopped their drugs during the first month after stent placement, in a review of nearly 5,000 patients.

The 1,076 Resolute recipients who interrupted their mandated treatment with aspirin and a thienopyridine included 169 patients who stopped during the first month after getting their stent. Five of these patients (3%) had stent thrombosis, compared with a 0.7% rate of stent thrombosis during the first month after placement among 3,858 patients who received a Resolute zotarolimus-eluting coronary stent and remained on their dual antiplatelet therapy (DAPT) for the prescribed 12 months, Dr. Sigmund Silber reported at Transcatheter Cardiovascular Therapeutics 2012.

Courtesy Dr. Sigmund Silber

Among the remaining 907 patients who interrupted their DAPT sometime during months 2-12 after getting their stent, no additional episodes of stent thrombosis occurred. The 3,858 patients who remained on DAPT throughout the full 12 months of mandated treatment had eight additional stent thromboses, a 0.2% rate, said Dr. Silber, a cardiologist and professor at Ludwig-Maximilians University in Munich.

"If patients took DAPT for only 1 month, they had no increased risk for stent thrombosis" compared with patients who stayed on DAPT for 1 year. "This is a very surprising finding," Dr. Silber said in an interview.

"This was a post hoc analysis, and it does not mean that you can take patients who get a Resolute stent off of DAPT after 4 weeks. But if, for some reason, the patient has to come off of DAPT after 4 weeks, the risk of stent thrombosis is not as big as we had feared," he said.

This performance of the Resolute zotarolimus-eluting stent contrasts with the performance of first-generation drug-eluting coronary stents, which consistently showed elevated rates of stent thrombosis when DAPT was not maintained for at least 6 months after placement, he noted. In addition, review of experience with the Xience everolimus-eluting stent, another second-generation coronary stent, showed a similar pattern when DAPT was maintained for at least 3 months. But "as far as I know, no data were reported on Xience after 4 weeks," said Dr. Silber, who is also director of the Isar Heart Center in Munich.

Although this was a post hoc analysis, one message is clear, he said: "Physicians should do everything possible to continue DAPT during the first month." So far, it remains unclear whether interruption of DAPT followed by a restart led to any difference in the stent thrombosis rate compared with full discontinuation. An analysis that compares these two types of stoppages is in process.

In addition, the findings suggest running a prospective trial to test the efficacy and safety of using DAPT for 1 month in patients who receive a Resolute stent compared with patients who receive DAPT for 6 or 12 months, Dr. Silber said. But he acknowledged that this would be a challenging trial to run – randomizing patients to DAPT for just 1 month after placing a drug-eluting stent, plus enrolling several thousand patients. "Does anyone have the guts to do that?" he asked.

Medtronic may consider funding a trial to test the hypothesis that 1 month of DAPT is adequate in patients who receive Resolute stents, but no such study is yet in process, said Jason Fontana, Ph.D., vice president for coronary strategy and development at Medtronic. "We’re beginning to think about what we may do with these data," Dr. Fontana said in an interview.

Dr. Silber’s analysis used data collected from nearly 5,000 patients enrolled in four pivotal trials of Resolute that ran in the United States, Europe, Japan, and elsewhere, and formed part of the new device application that Medtronic filed with the Food and Drug Administration.

The Resolute studies were funded by Medtronic, the company that markets the stent. Dr. Silber said that he has received research support from Medtronic, as well as from Abbott and Boston Scientific. Dr. Fontana is a Medtronic employee.

When patients who received a Resolute stent prematurely stopped their dual antiplatelet therapy, all the stent-thrombosis events that followed clustered in the patients who stopped their drugs during the first month after stent placement, in a review of nearly 5,000 patients.

The 1,076 Resolute recipients who interrupted their mandated treatment with aspirin and a thienopyridine included 169 patients who stopped during the first month after getting their stent. Five of these patients (3%) had stent thrombosis, compared with a 0.7% rate of stent thrombosis during the first month after placement among 3,858 patients who received a Resolute zotarolimus-eluting coronary stent and remained on their dual antiplatelet therapy (DAPT) for the prescribed 12 months, Dr. Sigmund Silber reported at Transcatheter Cardiovascular Therapeutics 2012.

Courtesy Dr. Sigmund Silber

Among the remaining 907 patients who interrupted their DAPT sometime during months 2-12 after getting their stent, no additional episodes of stent thrombosis occurred. The 3,858 patients who remained on DAPT throughout the full 12 months of mandated treatment had eight additional stent thromboses, a 0.2% rate, said Dr. Silber, a cardiologist and professor at Ludwig-Maximilians University in Munich.

"If patients took DAPT for only 1 month, they had no increased risk for stent thrombosis" compared with patients who stayed on DAPT for 1 year. "This is a very surprising finding," Dr. Silber said in an interview.

"This was a post hoc analysis, and it does not mean that you can take patients who get a Resolute stent off of DAPT after 4 weeks. But if, for some reason, the patient has to come off of DAPT after 4 weeks, the risk of stent thrombosis is not as big as we had feared," he said.

This performance of the Resolute zotarolimus-eluting stent contrasts with the performance of first-generation drug-eluting coronary stents, which consistently showed elevated rates of stent thrombosis when DAPT was not maintained for at least 6 months after placement, he noted. In addition, review of experience with the Xience everolimus-eluting stent, another second-generation coronary stent, showed a similar pattern when DAPT was maintained for at least 3 months. But "as far as I know, no data were reported on Xience after 4 weeks," said Dr. Silber, who is also director of the Isar Heart Center in Munich.

Although this was a post hoc analysis, one message is clear, he said: "Physicians should do everything possible to continue DAPT during the first month." So far, it remains unclear whether interruption of DAPT followed by a restart led to any difference in the stent thrombosis rate compared with full discontinuation. An analysis that compares these two types of stoppages is in process.

In addition, the findings suggest running a prospective trial to test the efficacy and safety of using DAPT for 1 month in patients who receive a Resolute stent compared with patients who receive DAPT for 6 or 12 months, Dr. Silber said. But he acknowledged that this would be a challenging trial to run – randomizing patients to DAPT for just 1 month after placing a drug-eluting stent, plus enrolling several thousand patients. "Does anyone have the guts to do that?" he asked.

Medtronic may consider funding a trial to test the hypothesis that 1 month of DAPT is adequate in patients who receive Resolute stents, but no such study is yet in process, said Jason Fontana, Ph.D., vice president for coronary strategy and development at Medtronic. "We’re beginning to think about what we may do with these data," Dr. Fontana said in an interview.

Dr. Silber’s analysis used data collected from nearly 5,000 patients enrolled in four pivotal trials of Resolute that ran in the United States, Europe, Japan, and elsewhere, and formed part of the new device application that Medtronic filed with the Food and Drug Administration.

The Resolute studies were funded by Medtronic, the company that markets the stent. Dr. Silber said that he has received research support from Medtronic, as well as from Abbott and Boston Scientific. Dr. Fontana is a Medtronic employee.