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Cardiovascular Research Foundation: Transcatheter Cardiovascular Therapeutics (TCT)
Embolic protection cut lesions, did not aid neurocognition
The largest randomized clinical trial to assess the safety and efficacy of cerebral embolic protection systems during transcatheter aortic valve replacement yielded puzzling and somewhat contradictory results, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology.
Virtually every device in this industry-sponsored study involving 363 elderly patients (mean age, 83.4 years) with severe aortic stenosis trapped particulate debris as intended, the mean volume of new lesions in the protected areas of the brain was reduced by 42%, and the number and volume of new lesions correlated with neurocognitive outcomes at 30 days.
However, the reduction in lesion volume did not achieve statistical significance, and the improvement in neurocognitive function also did not reach statistical significance.
In addition, “the sample size was clearly too low to assess clinical outcomes, and in retrospect, was also too low to evaluate follow-up MRI findings or neurocognitive outcomes.” Nevertheless, the trial “provides reassuring evidence of device safety,” said Samir R. Kapadia, MD, of the Cleveland Clinic (J Am Coll Cardiol. 2016 Nov 1. doi: 10.1016/j.jacc.2016.10.023).
In this prospective study, the investigators assessed patients at 17 medical centers in the United States and 2 in Germany. In addition to being elderly, the study patients were at high risk because of frequent comorbidities, including atrial fibrillation (31.7%) and prior stroke (5.8%).
The remaining 123 patients underwent TAVR but not MRI in a safety arm of the trial.
The protection devices were placed “without safety concerns” in most patients. The rate of major adverse events with the device was 7.3%, markedly less than the 18.3% prespecified performance goal for this outcome. Total procedure time was lengthened by only 13 minutes when the device was used, and total fluoroscopy time was increased by only 3 minutes. These findings demonstrate the overall safety of using the device, Dr. Kapadia said.
Debris including thrombus with tissue elements, artery wall particles, calcifications, valve tissue, and foreign materials was retrieved from the filters in 99% of patients.
The mean volume of new cerebral lesions in areas of the brain protected by the device was reduced by 42%, compared with that in patients who underwent TAVR without the protection device. However, this reduction was not statistically significant, so the primary efficacy endpoint of the study was not met.
Similarly, neurocognitive testing at 30 days showed that the volume of new lesions correlated with poorer outcomes. However, the difference in neurocognitive function between the intervention group and the control group did not reach statistical significance.
The 5-day “window” for MRI assessment having been too long was among the study’s limitations, Dr. Kapadia said.
Claret Medical funded the study and Dr. Kapadia’s associates reported numerous ties to industry sources. The meeting was sponsored by the Cardiovascular Research Foundation.
The authors have demonstrated the safety of cerebral protection systems, but not their clinical benefit in terms of preventing adverse neurological outcomes. As they note, a larger study group might produce a statistical difference. Commentary on the added cost of the device would be helpful to weigh their cost effectiveness.
The authors have demonstrated the safety of cerebral protection systems, but not their clinical benefit in terms of preventing adverse neurological outcomes. As they note, a larger study group might produce a statistical difference. Commentary on the added cost of the device would be helpful to weigh their cost effectiveness.
The authors have demonstrated the safety of cerebral protection systems, but not their clinical benefit in terms of preventing adverse neurological outcomes. As they note, a larger study group might produce a statistical difference. Commentary on the added cost of the device would be helpful to weigh their cost effectiveness.
The largest randomized clinical trial to assess the safety and efficacy of cerebral embolic protection systems during transcatheter aortic valve replacement yielded puzzling and somewhat contradictory results, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology.
Virtually every device in this industry-sponsored study involving 363 elderly patients (mean age, 83.4 years) with severe aortic stenosis trapped particulate debris as intended, the mean volume of new lesions in the protected areas of the brain was reduced by 42%, and the number and volume of new lesions correlated with neurocognitive outcomes at 30 days.
However, the reduction in lesion volume did not achieve statistical significance, and the improvement in neurocognitive function also did not reach statistical significance.
In addition, “the sample size was clearly too low to assess clinical outcomes, and in retrospect, was also too low to evaluate follow-up MRI findings or neurocognitive outcomes.” Nevertheless, the trial “provides reassuring evidence of device safety,” said Samir R. Kapadia, MD, of the Cleveland Clinic (J Am Coll Cardiol. 2016 Nov 1. doi: 10.1016/j.jacc.2016.10.023).
In this prospective study, the investigators assessed patients at 17 medical centers in the United States and 2 in Germany. In addition to being elderly, the study patients were at high risk because of frequent comorbidities, including atrial fibrillation (31.7%) and prior stroke (5.8%).
The remaining 123 patients underwent TAVR but not MRI in a safety arm of the trial.
The protection devices were placed “without safety concerns” in most patients. The rate of major adverse events with the device was 7.3%, markedly less than the 18.3% prespecified performance goal for this outcome. Total procedure time was lengthened by only 13 minutes when the device was used, and total fluoroscopy time was increased by only 3 minutes. These findings demonstrate the overall safety of using the device, Dr. Kapadia said.
Debris including thrombus with tissue elements, artery wall particles, calcifications, valve tissue, and foreign materials was retrieved from the filters in 99% of patients.
The mean volume of new cerebral lesions in areas of the brain protected by the device was reduced by 42%, compared with that in patients who underwent TAVR without the protection device. However, this reduction was not statistically significant, so the primary efficacy endpoint of the study was not met.
Similarly, neurocognitive testing at 30 days showed that the volume of new lesions correlated with poorer outcomes. However, the difference in neurocognitive function between the intervention group and the control group did not reach statistical significance.
The 5-day “window” for MRI assessment having been too long was among the study’s limitations, Dr. Kapadia said.
Claret Medical funded the study and Dr. Kapadia’s associates reported numerous ties to industry sources. The meeting was sponsored by the Cardiovascular Research Foundation.
The largest randomized clinical trial to assess the safety and efficacy of cerebral embolic protection systems during transcatheter aortic valve replacement yielded puzzling and somewhat contradictory results, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology.
Virtually every device in this industry-sponsored study involving 363 elderly patients (mean age, 83.4 years) with severe aortic stenosis trapped particulate debris as intended, the mean volume of new lesions in the protected areas of the brain was reduced by 42%, and the number and volume of new lesions correlated with neurocognitive outcomes at 30 days.
However, the reduction in lesion volume did not achieve statistical significance, and the improvement in neurocognitive function also did not reach statistical significance.
In addition, “the sample size was clearly too low to assess clinical outcomes, and in retrospect, was also too low to evaluate follow-up MRI findings or neurocognitive outcomes.” Nevertheless, the trial “provides reassuring evidence of device safety,” said Samir R. Kapadia, MD, of the Cleveland Clinic (J Am Coll Cardiol. 2016 Nov 1. doi: 10.1016/j.jacc.2016.10.023).
In this prospective study, the investigators assessed patients at 17 medical centers in the United States and 2 in Germany. In addition to being elderly, the study patients were at high risk because of frequent comorbidities, including atrial fibrillation (31.7%) and prior stroke (5.8%).
The remaining 123 patients underwent TAVR but not MRI in a safety arm of the trial.
The protection devices were placed “without safety concerns” in most patients. The rate of major adverse events with the device was 7.3%, markedly less than the 18.3% prespecified performance goal for this outcome. Total procedure time was lengthened by only 13 minutes when the device was used, and total fluoroscopy time was increased by only 3 minutes. These findings demonstrate the overall safety of using the device, Dr. Kapadia said.
Debris including thrombus with tissue elements, artery wall particles, calcifications, valve tissue, and foreign materials was retrieved from the filters in 99% of patients.
The mean volume of new cerebral lesions in areas of the brain protected by the device was reduced by 42%, compared with that in patients who underwent TAVR without the protection device. However, this reduction was not statistically significant, so the primary efficacy endpoint of the study was not met.
Similarly, neurocognitive testing at 30 days showed that the volume of new lesions correlated with poorer outcomes. However, the difference in neurocognitive function between the intervention group and the control group did not reach statistical significance.
The 5-day “window” for MRI assessment having been too long was among the study’s limitations, Dr. Kapadia said.
Claret Medical funded the study and Dr. Kapadia’s associates reported numerous ties to industry sources. The meeting was sponsored by the Cardiovascular Research Foundation.
U.S. okay looms for third drug-coated PAD balloon
WASHINGTON – Good pivotal-trial performance of a drug-coated balloon for treating superficial femoral and popliteal artery stenoses raised the prospect that it might soon be the third drug-coated balloon on the U.S. market, creating an opportunity for lower prices and competitive improvements for an increasingly used device.
“Having another drug-coated balloon would be useful for several reasons,” commented William A. Gray, MD, during the Transcatheter Cardiovascular Therapeutics annual meeting. The competition should mean lower cost, and accumulating reports on performance might identify a specific drug-coated balloon as most effective. Drug-coated balloons for peripheral artery stenoses “have been introduced over the past 2 years, with a significant increase in use during that time. It’s still not a majority of patients, but it’s increasing,” said Dr. Gray, chief of the division of cardiovascular disease at Main Line Health and president of Main Line Health’s Lankenau Heart Institute in Wynnewood, Pa.
The ILLUMENATE pivotal trial enrolled 300 patients at 43 centers in the United States and Europe. Patients had Rutherford 2, 3 or 4 disease, and averaged about 69 years old. More than 60% had class 3 disease and another 30% had class 2 disease.
The study’s primary safety endpoint was freedom from device- or procedure-related death to 30 days, and freedom from clinically drived target lesion revascularization at 12 months, a 92% rate in the 200 patients who had PTA with the Stellarex drug-coated balloon and 83% in the 100 controls who had PTA with an uncoated balloon. This statistically significant eight percentage point difference met the prespecified criteria for safety superiority.
The two drug-coated balloons already approved for U.S. use are the Lutonix and the IN.PACT Admiral.
“All the drug-coated balloons have worked well. It’s pretty exciting to see them work. It will be interesting to compare them against each other. We need side-by-side comparisons,” commented Craig M. Walker, MD, an interventional cardiologist in Houma, La. and a discussant for Dr. Lyden’s report.
The ILLUMENATE Pivotal trial was funded by Spectranetics, the company that is developing the Stellarex drug-coated balloon. Dr. Lyden has been a consultant to Spectranetics and to Biomet, Endologix, and TVA Medical. He received research support from Spectranetics and several other companies. Dr. Gray has been a consultant to Abbott Vascular, Boston Scientific, Cook, Medtronic, and Shockwave. He has received research support from Gore and Intact Vascular. Dr. Walker has been a consultant to Spectranetics as well as to Abbott Vascular, Bard, Boston Scientific, Cook, Gore, and Medtronic.
[email protected]
On Twitter @mitchelzoler
It’s good to have competition among various models of drug-eluting balloons because it will help drive costs down and help drive additional improvements in device design. We win by having a third good drug-coated balloon option available.
Drug-coated balloons are increasingly used in routine U.S. practice. A recent report showed that one of the drug-coated balloons already on the U.S. market outperformed balloon angioplasty out to 3 years of follow-up. Drug-coated balloons hold an advantage over stents by leaving nothing behind. Another attraction of drug-coated balloons is that they can potentially be used as an adjunct to additional interventions for complex lesions, such as atherectomy.
So far, we have not seen a clear winner for safety and efficacy among the two drug-coated balloons already on the U.S. market and this new drug-coated balloon, which may soon be the third option for U.S. practice. But there is no single class effect from these drug-coated balloons; they must be evaluated individually.
D. Christopher Metzger, MD, is an interventional cardiologist and director of cardiac and peripheral vascular catheterization labs at the Wellmont CVA Heart Institute in Kingsport, Tenn. He has been a consultant to and received honoraria from Abbott Vascular, Bard, and Medtronic. He made these comments in an interview.
It’s good to have competition among various models of drug-eluting balloons because it will help drive costs down and help drive additional improvements in device design. We win by having a third good drug-coated balloon option available.
Drug-coated balloons are increasingly used in routine U.S. practice. A recent report showed that one of the drug-coated balloons already on the U.S. market outperformed balloon angioplasty out to 3 years of follow-up. Drug-coated balloons hold an advantage over stents by leaving nothing behind. Another attraction of drug-coated balloons is that they can potentially be used as an adjunct to additional interventions for complex lesions, such as atherectomy.
So far, we have not seen a clear winner for safety and efficacy among the two drug-coated balloons already on the U.S. market and this new drug-coated balloon, which may soon be the third option for U.S. practice. But there is no single class effect from these drug-coated balloons; they must be evaluated individually.
D. Christopher Metzger, MD, is an interventional cardiologist and director of cardiac and peripheral vascular catheterization labs at the Wellmont CVA Heart Institute in Kingsport, Tenn. He has been a consultant to and received honoraria from Abbott Vascular, Bard, and Medtronic. He made these comments in an interview.
It’s good to have competition among various models of drug-eluting balloons because it will help drive costs down and help drive additional improvements in device design. We win by having a third good drug-coated balloon option available.
Drug-coated balloons are increasingly used in routine U.S. practice. A recent report showed that one of the drug-coated balloons already on the U.S. market outperformed balloon angioplasty out to 3 years of follow-up. Drug-coated balloons hold an advantage over stents by leaving nothing behind. Another attraction of drug-coated balloons is that they can potentially be used as an adjunct to additional interventions for complex lesions, such as atherectomy.
So far, we have not seen a clear winner for safety and efficacy among the two drug-coated balloons already on the U.S. market and this new drug-coated balloon, which may soon be the third option for U.S. practice. But there is no single class effect from these drug-coated balloons; they must be evaluated individually.
D. Christopher Metzger, MD, is an interventional cardiologist and director of cardiac and peripheral vascular catheterization labs at the Wellmont CVA Heart Institute in Kingsport, Tenn. He has been a consultant to and received honoraria from Abbott Vascular, Bard, and Medtronic. He made these comments in an interview.
WASHINGTON – Good pivotal-trial performance of a drug-coated balloon for treating superficial femoral and popliteal artery stenoses raised the prospect that it might soon be the third drug-coated balloon on the U.S. market, creating an opportunity for lower prices and competitive improvements for an increasingly used device.
“Having another drug-coated balloon would be useful for several reasons,” commented William A. Gray, MD, during the Transcatheter Cardiovascular Therapeutics annual meeting. The competition should mean lower cost, and accumulating reports on performance might identify a specific drug-coated balloon as most effective. Drug-coated balloons for peripheral artery stenoses “have been introduced over the past 2 years, with a significant increase in use during that time. It’s still not a majority of patients, but it’s increasing,” said Dr. Gray, chief of the division of cardiovascular disease at Main Line Health and president of Main Line Health’s Lankenau Heart Institute in Wynnewood, Pa.
The ILLUMENATE pivotal trial enrolled 300 patients at 43 centers in the United States and Europe. Patients had Rutherford 2, 3 or 4 disease, and averaged about 69 years old. More than 60% had class 3 disease and another 30% had class 2 disease.
The study’s primary safety endpoint was freedom from device- or procedure-related death to 30 days, and freedom from clinically drived target lesion revascularization at 12 months, a 92% rate in the 200 patients who had PTA with the Stellarex drug-coated balloon and 83% in the 100 controls who had PTA with an uncoated balloon. This statistically significant eight percentage point difference met the prespecified criteria for safety superiority.
The two drug-coated balloons already approved for U.S. use are the Lutonix and the IN.PACT Admiral.
“All the drug-coated balloons have worked well. It’s pretty exciting to see them work. It will be interesting to compare them against each other. We need side-by-side comparisons,” commented Craig M. Walker, MD, an interventional cardiologist in Houma, La. and a discussant for Dr. Lyden’s report.
The ILLUMENATE Pivotal trial was funded by Spectranetics, the company that is developing the Stellarex drug-coated balloon. Dr. Lyden has been a consultant to Spectranetics and to Biomet, Endologix, and TVA Medical. He received research support from Spectranetics and several other companies. Dr. Gray has been a consultant to Abbott Vascular, Boston Scientific, Cook, Medtronic, and Shockwave. He has received research support from Gore and Intact Vascular. Dr. Walker has been a consultant to Spectranetics as well as to Abbott Vascular, Bard, Boston Scientific, Cook, Gore, and Medtronic.
[email protected]
On Twitter @mitchelzoler
WASHINGTON – Good pivotal-trial performance of a drug-coated balloon for treating superficial femoral and popliteal artery stenoses raised the prospect that it might soon be the third drug-coated balloon on the U.S. market, creating an opportunity for lower prices and competitive improvements for an increasingly used device.
“Having another drug-coated balloon would be useful for several reasons,” commented William A. Gray, MD, during the Transcatheter Cardiovascular Therapeutics annual meeting. The competition should mean lower cost, and accumulating reports on performance might identify a specific drug-coated balloon as most effective. Drug-coated balloons for peripheral artery stenoses “have been introduced over the past 2 years, with a significant increase in use during that time. It’s still not a majority of patients, but it’s increasing,” said Dr. Gray, chief of the division of cardiovascular disease at Main Line Health and president of Main Line Health’s Lankenau Heart Institute in Wynnewood, Pa.
The ILLUMENATE pivotal trial enrolled 300 patients at 43 centers in the United States and Europe. Patients had Rutherford 2, 3 or 4 disease, and averaged about 69 years old. More than 60% had class 3 disease and another 30% had class 2 disease.
The study’s primary safety endpoint was freedom from device- or procedure-related death to 30 days, and freedom from clinically drived target lesion revascularization at 12 months, a 92% rate in the 200 patients who had PTA with the Stellarex drug-coated balloon and 83% in the 100 controls who had PTA with an uncoated balloon. This statistically significant eight percentage point difference met the prespecified criteria for safety superiority.
The two drug-coated balloons already approved for U.S. use are the Lutonix and the IN.PACT Admiral.
“All the drug-coated balloons have worked well. It’s pretty exciting to see them work. It will be interesting to compare them against each other. We need side-by-side comparisons,” commented Craig M. Walker, MD, an interventional cardiologist in Houma, La. and a discussant for Dr. Lyden’s report.
The ILLUMENATE Pivotal trial was funded by Spectranetics, the company that is developing the Stellarex drug-coated balloon. Dr. Lyden has been a consultant to Spectranetics and to Biomet, Endologix, and TVA Medical. He received research support from Spectranetics and several other companies. Dr. Gray has been a consultant to Abbott Vascular, Boston Scientific, Cook, Medtronic, and Shockwave. He has received research support from Gore and Intact Vascular. Dr. Walker has been a consultant to Spectranetics as well as to Abbott Vascular, Bard, Boston Scientific, Cook, Gore, and Medtronic.
[email protected]
On Twitter @mitchelzoler
Key clinical point:
Major finding: The primary efficacy endpoint occurred in 76% of patients in the drug-coated balloon arm and 58% of controls.
Data source: The ILLUMENATE pivotal trial, which enrolled 300 patients at 63 U.S. and European centers.
Disclosures: The ILLUMENATE pivotal trial was funded by Spectranetics, the company that is developing the Stellarex drug-coated balloon. Dr. Lyden has been a consultant to Spectranetics and to Biomet, Endologix, and TVA Medical. He received research support from Spectranetics and several other companies. Dr. Gray has been a consultant to Abbott Vascular, Boston Scientific, Cook, Medtronic, and Shockwave. He has received research support from Gore and Intact Vascular. Dr. Walker has been a consultant to Spectranetics as well as to Abbott Vascular, Bard, Boston Scientific, Cook, Gore, and Medtronic.
TAVR valve durability supported in large follow-up
WASHINGTON – First-generation, balloon-expandable transcatheter aortic valves had a less than 1% rate of valve failure in planned echocardiography examinations during follow-up that extended as long as 5 years after valve placement in more than 2,400 patients, a demonstration of durability that experts uniformly called “reassuring.”
This finding from patients who underwent transcatheter aortic valve replacement (TAVR) in the first U.S. pivotal trial for these devices, PARTNER 1 parts A and B, and during the subsequent continued-access program at PARTNER 1 study sites, represents the largest and longest systematic ultrasound follow-up of TAVR patients, Pamela S. Douglas, MD, said at the Transcatheter Cardiovascular Therapeutics annual meeting.
This evaluation of 2,404 TAVR patients in the PARTNER 1 trial examined by echocardiography and encompassing 6,493 patient-years of follow-up is the “largest core-lab based study of transcatheter heart valves to date. These data demonstrate excellent durability of transcatheter heart valves, suggesting that the low 5-year survival observed in this cohort is not related to adverse hemodynamics or transcatheter heart valve deterioration,” said Dr. Douglas, professor of medicine at Duke University, Durham, N.C.
Her findings showed that out of the 2,482 patients treated with TAVR (and including those without echo follow-up) either in the trial or during the continued access program and followed for a median of 2.9 years and an average of 2.6 years, 20 patients (0.8%) required a reintervention. Four of these 20 patients (0.2% of the total cohort) showed a “classic pattern” of aortic valve deterioration marked by an increased valve pressure gradient and a reduced valve area, she reported.
“Reintervention was rare, became less frequent over time, and was usually not due to structural deterioration of the transcatheter heart valve,” she said. But Dr. Douglas also cautioned that among the patients who received the first-generation, balloon expandable Sapien valve in this cohort, just 39% survived to 5 years, and a mere 282 patients (11%) actually underwent echocardiographic examination at 5 years.
“This is one of several steps we need to take to figure out the durability of transcatheter valves,” said Jeffrey J. Popma, MD, professor of medicine and an interventional cardiologist at Beth Israel Deaconess Medical Center, Boston. He noted that data are needed from follow-up periods of 8 or 10 years, but these data will not be available until intermediate- or low-risk patients undergo TAVR in controlled circumstances and have long-term follow-up. 
“Ten-year follow-up data will essentially be impossible” for the high-risk or inoperable patients treated with TAVR in the PARTNER 1 trial, which focused on the sickest patients with aortic stenosis, said Dr. Popma, lead investigator for several studies of TAVR using self-expanding aortic valves and marketed as CoreValve devices.
“We obviously need to follow patients longer. The 5-year results look terrific, and so very reassuring, but we need to keep an eye on this as we move TAVR into less sick and younger patients,” said Dr. Robert O. Bonow, professor of cardiology at Northwestern University, Chicago. “Durability is the remaining frontier in terms of moving TAVR into younger patients,” Dr. Bonow said at the meeting, which was sponsored by the Cardiovascular Research Foundation.
These data continue to show that “transcatheter valves have looked hemodynamically superior to surgically-placed valves with respect to the VARC (Valve Academic Research Consortium)–2 criteria” for prosthetic valve function, Dr. Popma noted. “I think the benefits of surgical valves have been overstated and the benefits of transcatheter valves understated,” he said.
“Surgical valves have not been held to the same [very demanding] standard as transcatheter valves,” Dr. Douglas agreed.
The data Dr. Douglas reported contrast with longer-term follow-up reported in May 2016 for 378 patients who underwent TAVR at either of two pioneering centers in a retrospective review. Those data suggested a valve degeneration rate of about 50% after 8 years, Danny Dvir, MD, reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions. Speaking recently in an interview, Dr. Dvir acknowledged some of the challenges in trying to derive valve durability information from a relatively small number of very-high-risk patients who underwent TAVR very early during development of the procedure.
Some TAVR experts have also questioned the criteria that Dr. Dvir used to identify valve structural valve degeneration for this analysis. “The criteria he used were much more stringent that the criteria we have used to assess surgically-placed valves,” said Michael J. Reardon, MD, professor of cardiovascular surgery at Houston Methodist Hospital. “If surgically-placed aortic valves were subjected to the same criteria Dr. Dvir applied then they would perform even worse,” Dr. Reardon said in an interview.
PARTNER 1 was sponsored by Edwards Lifesciences, the company that had marketed the Sapien first-generation, balloon expandable TAVR system. Dr. Douglas has received research support from Edwards. Dr. Bonow had no disclosures. Dr. Popma has been the lead investigator for several studies of a self-expanding TAVR system sponsored by Medtronic, and he has also received research funding from several other companies, has been a consultant to Boston Scientific and Direct Flow, and owns equity in Direct Flow. Dr. Dvir has been a consultant to and received research support from Edwards, Medtronic, and St. Jude. Dr. Reardon has been a consultant to Medtronic.
[email protected]
On Twitter @mitchelzoler
The data reported by Dr. Douglas are very important and very reassuring. It isn’t easy to evaluate long-term results in patients who underwent TAVR in the early days because that population of patients was old and at very high risk. Even when patients had successful procedures their longevity wasn’t long. Only about 10% of the starting population of 2,482 patients in Dr. Douglas’ study actually had echocardiography done after 5 years. To assess durability you need longer-term echo follow-up, but it will be very challenging to have enough patients to have statistical power to do that.
I am not nervous about long-term durability of TAVR in octogenarian patients, the most typical age for TAVR patients today and since we began using it. Durability is more of an issue for patients who are 75 or younger, and we will need data from 7- to 10-year follow-up of younger patients to have a reasonable answer. Younger patients who undergo TAVR may face more of a threat from valve deterioration simply because of their longer life expectancy. In addition, with surgical valves we know that younger age is one of the strongest predictors of valve degeneration.
Danny Dvir, MD , is an interventional cardiologist at the University of Washington in Seattle. He has been a consultant to and received research support from Edwards, Medtronic, and St. Jude. He made these comments in an interview.
The data reported by Dr. Douglas are very important and very reassuring. It isn’t easy to evaluate long-term results in patients who underwent TAVR in the early days because that population of patients was old and at very high risk. Even when patients had successful procedures their longevity wasn’t long. Only about 10% of the starting population of 2,482 patients in Dr. Douglas’ study actually had echocardiography done after 5 years. To assess durability you need longer-term echo follow-up, but it will be very challenging to have enough patients to have statistical power to do that.
I am not nervous about long-term durability of TAVR in octogenarian patients, the most typical age for TAVR patients today and since we began using it. Durability is more of an issue for patients who are 75 or younger, and we will need data from 7- to 10-year follow-up of younger patients to have a reasonable answer. Younger patients who undergo TAVR may face more of a threat from valve deterioration simply because of their longer life expectancy. In addition, with surgical valves we know that younger age is one of the strongest predictors of valve degeneration.
Danny Dvir, MD , is an interventional cardiologist at the University of Washington in Seattle. He has been a consultant to and received research support from Edwards, Medtronic, and St. Jude. He made these comments in an interview.
The data reported by Dr. Douglas are very important and very reassuring. It isn’t easy to evaluate long-term results in patients who underwent TAVR in the early days because that population of patients was old and at very high risk. Even when patients had successful procedures their longevity wasn’t long. Only about 10% of the starting population of 2,482 patients in Dr. Douglas’ study actually had echocardiography done after 5 years. To assess durability you need longer-term echo follow-up, but it will be very challenging to have enough patients to have statistical power to do that.
I am not nervous about long-term durability of TAVR in octogenarian patients, the most typical age for TAVR patients today and since we began using it. Durability is more of an issue for patients who are 75 or younger, and we will need data from 7- to 10-year follow-up of younger patients to have a reasonable answer. Younger patients who undergo TAVR may face more of a threat from valve deterioration simply because of their longer life expectancy. In addition, with surgical valves we know that younger age is one of the strongest predictors of valve degeneration.
Danny Dvir, MD , is an interventional cardiologist at the University of Washington in Seattle. He has been a consultant to and received research support from Edwards, Medtronic, and St. Jude. He made these comments in an interview.
WASHINGTON – First-generation, balloon-expandable transcatheter aortic valves had a less than 1% rate of valve failure in planned echocardiography examinations during follow-up that extended as long as 5 years after valve placement in more than 2,400 patients, a demonstration of durability that experts uniformly called “reassuring.”
This finding from patients who underwent transcatheter aortic valve replacement (TAVR) in the first U.S. pivotal trial for these devices, PARTNER 1 parts A and B, and during the subsequent continued-access program at PARTNER 1 study sites, represents the largest and longest systematic ultrasound follow-up of TAVR patients, Pamela S. Douglas, MD, said at the Transcatheter Cardiovascular Therapeutics annual meeting.
This evaluation of 2,404 TAVR patients in the PARTNER 1 trial examined by echocardiography and encompassing 6,493 patient-years of follow-up is the “largest core-lab based study of transcatheter heart valves to date. These data demonstrate excellent durability of transcatheter heart valves, suggesting that the low 5-year survival observed in this cohort is not related to adverse hemodynamics or transcatheter heart valve deterioration,” said Dr. Douglas, professor of medicine at Duke University, Durham, N.C.
Her findings showed that out of the 2,482 patients treated with TAVR (and including those without echo follow-up) either in the trial or during the continued access program and followed for a median of 2.9 years and an average of 2.6 years, 20 patients (0.8%) required a reintervention. Four of these 20 patients (0.2% of the total cohort) showed a “classic pattern” of aortic valve deterioration marked by an increased valve pressure gradient and a reduced valve area, she reported.
“Reintervention was rare, became less frequent over time, and was usually not due to structural deterioration of the transcatheter heart valve,” she said. But Dr. Douglas also cautioned that among the patients who received the first-generation, balloon expandable Sapien valve in this cohort, just 39% survived to 5 years, and a mere 282 patients (11%) actually underwent echocardiographic examination at 5 years.
“This is one of several steps we need to take to figure out the durability of transcatheter valves,” said Jeffrey J. Popma, MD, professor of medicine and an interventional cardiologist at Beth Israel Deaconess Medical Center, Boston. He noted that data are needed from follow-up periods of 8 or 10 years, but these data will not be available until intermediate- or low-risk patients undergo TAVR in controlled circumstances and have long-term follow-up.
“Ten-year follow-up data will essentially be impossible” for the high-risk or inoperable patients treated with TAVR in the PARTNER 1 trial, which focused on the sickest patients with aortic stenosis, said Dr. Popma, lead investigator for several studies of TAVR using self-expanding aortic valves and marketed as CoreValve devices.
“We obviously need to follow patients longer. The 5-year results look terrific, and so very reassuring, but we need to keep an eye on this as we move TAVR into less sick and younger patients,” said Dr. Robert O. Bonow, professor of cardiology at Northwestern University, Chicago. “Durability is the remaining frontier in terms of moving TAVR into younger patients,” Dr. Bonow said at the meeting, which was sponsored by the Cardiovascular Research Foundation.
These data continue to show that “transcatheter valves have looked hemodynamically superior to surgically-placed valves with respect to the VARC (Valve Academic Research Consortium)–2 criteria” for prosthetic valve function, Dr. Popma noted. “I think the benefits of surgical valves have been overstated and the benefits of transcatheter valves understated,” he said.
“Surgical valves have not been held to the same [very demanding] standard as transcatheter valves,” Dr. Douglas agreed.
The data Dr. Douglas reported contrast with longer-term follow-up reported in May 2016 for 378 patients who underwent TAVR at either of two pioneering centers in a retrospective review. Those data suggested a valve degeneration rate of about 50% after 8 years, Danny Dvir, MD, reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions. Speaking recently in an interview, Dr. Dvir acknowledged some of the challenges in trying to derive valve durability information from a relatively small number of very-high-risk patients who underwent TAVR very early during development of the procedure.
Some TAVR experts have also questioned the criteria that Dr. Dvir used to identify valve structural valve degeneration for this analysis. “The criteria he used were much more stringent that the criteria we have used to assess surgically-placed valves,” said Michael J. Reardon, MD, professor of cardiovascular surgery at Houston Methodist Hospital. “If surgically-placed aortic valves were subjected to the same criteria Dr. Dvir applied then they would perform even worse,” Dr. Reardon said in an interview.
PARTNER 1 was sponsored by Edwards Lifesciences, the company that had marketed the Sapien first-generation, balloon expandable TAVR system. Dr. Douglas has received research support from Edwards. Dr. Bonow had no disclosures. Dr. Popma has been the lead investigator for several studies of a self-expanding TAVR system sponsored by Medtronic, and he has also received research funding from several other companies, has been a consultant to Boston Scientific and Direct Flow, and owns equity in Direct Flow. Dr. Dvir has been a consultant to and received research support from Edwards, Medtronic, and St. Jude. Dr. Reardon has been a consultant to Medtronic.
[email protected]
On Twitter @mitchelzoler
WASHINGTON – First-generation, balloon-expandable transcatheter aortic valves had a less than 1% rate of valve failure in planned echocardiography examinations during follow-up that extended as long as 5 years after valve placement in more than 2,400 patients, a demonstration of durability that experts uniformly called “reassuring.”
This finding from patients who underwent transcatheter aortic valve replacement (TAVR) in the first U.S. pivotal trial for these devices, PARTNER 1 parts A and B, and during the subsequent continued-access program at PARTNER 1 study sites, represents the largest and longest systematic ultrasound follow-up of TAVR patients, Pamela S. Douglas, MD, said at the Transcatheter Cardiovascular Therapeutics annual meeting.
This evaluation of 2,404 TAVR patients in the PARTNER 1 trial examined by echocardiography and encompassing 6,493 patient-years of follow-up is the “largest core-lab based study of transcatheter heart valves to date. These data demonstrate excellent durability of transcatheter heart valves, suggesting that the low 5-year survival observed in this cohort is not related to adverse hemodynamics or transcatheter heart valve deterioration,” said Dr. Douglas, professor of medicine at Duke University, Durham, N.C.
Her findings showed that out of the 2,482 patients treated with TAVR (and including those without echo follow-up) either in the trial or during the continued access program and followed for a median of 2.9 years and an average of 2.6 years, 20 patients (0.8%) required a reintervention. Four of these 20 patients (0.2% of the total cohort) showed a “classic pattern” of aortic valve deterioration marked by an increased valve pressure gradient and a reduced valve area, she reported.
“Reintervention was rare, became less frequent over time, and was usually not due to structural deterioration of the transcatheter heart valve,” she said. But Dr. Douglas also cautioned that among the patients who received the first-generation, balloon expandable Sapien valve in this cohort, just 39% survived to 5 years, and a mere 282 patients (11%) actually underwent echocardiographic examination at 5 years.
“This is one of several steps we need to take to figure out the durability of transcatheter valves,” said Jeffrey J. Popma, MD, professor of medicine and an interventional cardiologist at Beth Israel Deaconess Medical Center, Boston. He noted that data are needed from follow-up periods of 8 or 10 years, but these data will not be available until intermediate- or low-risk patients undergo TAVR in controlled circumstances and have long-term follow-up.
“Ten-year follow-up data will essentially be impossible” for the high-risk or inoperable patients treated with TAVR in the PARTNER 1 trial, which focused on the sickest patients with aortic stenosis, said Dr. Popma, lead investigator for several studies of TAVR using self-expanding aortic valves and marketed as CoreValve devices.
“We obviously need to follow patients longer. The 5-year results look terrific, and so very reassuring, but we need to keep an eye on this as we move TAVR into less sick and younger patients,” said Dr. Robert O. Bonow, professor of cardiology at Northwestern University, Chicago. “Durability is the remaining frontier in terms of moving TAVR into younger patients,” Dr. Bonow said at the meeting, which was sponsored by the Cardiovascular Research Foundation.
These data continue to show that “transcatheter valves have looked hemodynamically superior to surgically-placed valves with respect to the VARC (Valve Academic Research Consortium)–2 criteria” for prosthetic valve function, Dr. Popma noted. “I think the benefits of surgical valves have been overstated and the benefits of transcatheter valves understated,” he said.
“Surgical valves have not been held to the same [very demanding] standard as transcatheter valves,” Dr. Douglas agreed.
The data Dr. Douglas reported contrast with longer-term follow-up reported in May 2016 for 378 patients who underwent TAVR at either of two pioneering centers in a retrospective review. Those data suggested a valve degeneration rate of about 50% after 8 years, Danny Dvir, MD, reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions. Speaking recently in an interview, Dr. Dvir acknowledged some of the challenges in trying to derive valve durability information from a relatively small number of very-high-risk patients who underwent TAVR very early during development of the procedure.
Some TAVR experts have also questioned the criteria that Dr. Dvir used to identify valve structural valve degeneration for this analysis. “The criteria he used were much more stringent that the criteria we have used to assess surgically-placed valves,” said Michael J. Reardon, MD, professor of cardiovascular surgery at Houston Methodist Hospital. “If surgically-placed aortic valves were subjected to the same criteria Dr. Dvir applied then they would perform even worse,” Dr. Reardon said in an interview.
PARTNER 1 was sponsored by Edwards Lifesciences, the company that had marketed the Sapien first-generation, balloon expandable TAVR system. Dr. Douglas has received research support from Edwards. Dr. Bonow had no disclosures. Dr. Popma has been the lead investigator for several studies of a self-expanding TAVR system sponsored by Medtronic, and he has also received research funding from several other companies, has been a consultant to Boston Scientific and Direct Flow, and owns equity in Direct Flow. Dr. Dvir has been a consultant to and received research support from Edwards, Medtronic, and St. Jude. Dr. Reardon has been a consultant to Medtronic.
[email protected]
On Twitter @mitchelzoler
AT TCT 2016
Key clinical point:
Major finding: During median follow-up of 2.9 years, 0.2% of patients had valves with classic hemodynamic signs of valve deterioration.
Data source: A total of 2,482 TAVR patients either enrolled in the PARTNER 1 trial or who underwent TAVR during a continued access program.
Disclosures: PARTNER 1 was sponsored by Edwards Lifesciences, the company that had marketed the Sapien first-generation, balloon expandable TAVR system. Dr. Douglas has received research support from Edwards. Dr. Bonow had no disclosures. Dr. Popma has been the lead investigator for several studies of a self-expanding TAVR system sponsored by Medtronic, and he has also received research funding from several other companies, has been a consultant to Boston Scientific and Direct Flow, and owns equity in Direct Flow. Dr. Dvir has been a consultant to and received research support from Edwards, Medtronic, and St. Jude. Dr. Reardon has been a consultant to Medtronic.
Absorb’s problems will revise coronary scaffold standards
One-year outcome results of the first bioresorbable coronary scaffold on the U.S. and world markets, Absorb, failed to show longer-term problems with the device that only became apparent with 3-year follow-up.
The failure of Absorb to show benefits after 3 years in the ABSORB II trial will probably not dampen enthusiasm for the concept of a bioresorbable coronary scaffold (BRS). The idea of treating coronary stenoses with a stent that disappears after a few years once it has done its job is a powerfully attractive idea, and reports from several early-stage clinical tests of new BRSs during TCT 2016 showed that many next-generation versions of these devices are in very active development.
The surprising ABSORB II results showed more than just a failure of the Absorb BRS to produce 3 years after placement the improved coronary artery vasomotion and reduced late lumen loss that were the two primary efficacy endpoints of the trial.
The results also showed troubling signs of harm from the BRS, including significantly worse late lumen loss, compared with a contemporary drug-eluting metallic stent. In addition, there was a shocking 1%/year rate of late stent thrombosis during both the second and third years following Absorb placement in coronary arteries, the period when the Absorb BRS was in the process of disappearing, and which did not occur in the study’s control patients who received a conventional, metallic drug-eluting stent.
Patrick W. Serruys, MD, lead investigator of ABSORB II, attributed these adverse outcomes to the “highly thrombogenic” proteoglycan material that formed as the Absorb BRS resorbed, and a “structural discontinuity” of the BRS as it resorbed in some patients, resulting in parts of the scaffold remnant sticking out from the coronary artery wall toward the center of the vessel.
These late flaws in the bioresorption process will now need closer scrutiny during future studies of next-generation BRSs, and will surely mean longer follow-up of pivotal trials and a shift from the 1-year follow-up data used by the Food and Drug Administration when it approved the Absorb BRS last July.
“The challenge for the field [of BRS development] is the late results, as we saw in ABSORB II,” commented David J. Cohen, MD, an interventional cardiologist at Saint Luke’s Health System in Kansas City, Mo. The ABSORB II results “will lead to reexamination of the trial design and endpoints for the next generation of BRSs,” Dr. Cohen predicted at the meeting, sponsored by the Cardiovascular Research Foundation.
“It’s not clear that BRS reduces the duration for DAPT,” Dr. Cohen noted, at least for the Absorb device, which is not full resorbed until it’s been in patients for about 3 years.
A striking property of the next-generation BRSs reported at the meeting was their use of thinner struts and faster resorption times. “These iterations hold immense promise for improving late outcomes,” commented Dean J. Kereiakes, MD, an interventional cardiologist at the Christ Hospital in Cincinnati who helped lead the large U.S. clinical trial of the Absorb BRS, ABSORB III.
[email protected]
On Twitter @mitchelzoler
One-year outcome results of the first bioresorbable coronary scaffold on the U.S. and world markets, Absorb, failed to show longer-term problems with the device that only became apparent with 3-year follow-up.
The failure of Absorb to show benefits after 3 years in the ABSORB II trial will probably not dampen enthusiasm for the concept of a bioresorbable coronary scaffold (BRS). The idea of treating coronary stenoses with a stent that disappears after a few years once it has done its job is a powerfully attractive idea, and reports from several early-stage clinical tests of new BRSs during TCT 2016 showed that many next-generation versions of these devices are in very active development.
The surprising ABSORB II results showed more than just a failure of the Absorb BRS to produce 3 years after placement the improved coronary artery vasomotion and reduced late lumen loss that were the two primary efficacy endpoints of the trial.
The results also showed troubling signs of harm from the BRS, including significantly worse late lumen loss, compared with a contemporary drug-eluting metallic stent. In addition, there was a shocking 1%/year rate of late stent thrombosis during both the second and third years following Absorb placement in coronary arteries, the period when the Absorb BRS was in the process of disappearing, and which did not occur in the study’s control patients who received a conventional, metallic drug-eluting stent.
Patrick W. Serruys, MD, lead investigator of ABSORB II, attributed these adverse outcomes to the “highly thrombogenic” proteoglycan material that formed as the Absorb BRS resorbed, and a “structural discontinuity” of the BRS as it resorbed in some patients, resulting in parts of the scaffold remnant sticking out from the coronary artery wall toward the center of the vessel.
These late flaws in the bioresorption process will now need closer scrutiny during future studies of next-generation BRSs, and will surely mean longer follow-up of pivotal trials and a shift from the 1-year follow-up data used by the Food and Drug Administration when it approved the Absorb BRS last July.
“The challenge for the field [of BRS development] is the late results, as we saw in ABSORB II,” commented David J. Cohen, MD, an interventional cardiologist at Saint Luke’s Health System in Kansas City, Mo. The ABSORB II results “will lead to reexamination of the trial design and endpoints for the next generation of BRSs,” Dr. Cohen predicted at the meeting, sponsored by the Cardiovascular Research Foundation.
“It’s not clear that BRS reduces the duration for DAPT,” Dr. Cohen noted, at least for the Absorb device, which is not full resorbed until it’s been in patients for about 3 years.
A striking property of the next-generation BRSs reported at the meeting was their use of thinner struts and faster resorption times. “These iterations hold immense promise for improving late outcomes,” commented Dean J. Kereiakes, MD, an interventional cardiologist at the Christ Hospital in Cincinnati who helped lead the large U.S. clinical trial of the Absorb BRS, ABSORB III.
[email protected]
On Twitter @mitchelzoler
One-year outcome results of the first bioresorbable coronary scaffold on the U.S. and world markets, Absorb, failed to show longer-term problems with the device that only became apparent with 3-year follow-up.
The failure of Absorb to show benefits after 3 years in the ABSORB II trial will probably not dampen enthusiasm for the concept of a bioresorbable coronary scaffold (BRS). The idea of treating coronary stenoses with a stent that disappears after a few years once it has done its job is a powerfully attractive idea, and reports from several early-stage clinical tests of new BRSs during TCT 2016 showed that many next-generation versions of these devices are in very active development.
The surprising ABSORB II results showed more than just a failure of the Absorb BRS to produce 3 years after placement the improved coronary artery vasomotion and reduced late lumen loss that were the two primary efficacy endpoints of the trial.
The results also showed troubling signs of harm from the BRS, including significantly worse late lumen loss, compared with a contemporary drug-eluting metallic stent. In addition, there was a shocking 1%/year rate of late stent thrombosis during both the second and third years following Absorb placement in coronary arteries, the period when the Absorb BRS was in the process of disappearing, and which did not occur in the study’s control patients who received a conventional, metallic drug-eluting stent.
Patrick W. Serruys, MD, lead investigator of ABSORB II, attributed these adverse outcomes to the “highly thrombogenic” proteoglycan material that formed as the Absorb BRS resorbed, and a “structural discontinuity” of the BRS as it resorbed in some patients, resulting in parts of the scaffold remnant sticking out from the coronary artery wall toward the center of the vessel.
These late flaws in the bioresorption process will now need closer scrutiny during future studies of next-generation BRSs, and will surely mean longer follow-up of pivotal trials and a shift from the 1-year follow-up data used by the Food and Drug Administration when it approved the Absorb BRS last July.
“The challenge for the field [of BRS development] is the late results, as we saw in ABSORB II,” commented David J. Cohen, MD, an interventional cardiologist at Saint Luke’s Health System in Kansas City, Mo. The ABSORB II results “will lead to reexamination of the trial design and endpoints for the next generation of BRSs,” Dr. Cohen predicted at the meeting, sponsored by the Cardiovascular Research Foundation.
“It’s not clear that BRS reduces the duration for DAPT,” Dr. Cohen noted, at least for the Absorb device, which is not full resorbed until it’s been in patients for about 3 years.
A striking property of the next-generation BRSs reported at the meeting was their use of thinner struts and faster resorption times. “These iterations hold immense promise for improving late outcomes,” commented Dean J. Kereiakes, MD, an interventional cardiologist at the Christ Hospital in Cincinnati who helped lead the large U.S. clinical trial of the Absorb BRS, ABSORB III.
[email protected]
On Twitter @mitchelzoler
VIDEO: PCI outcomes lag in women, minorities
WASHINGTON – The relatively low number of women and minority-group patients enrolled into cardiovascular disease clinical trials may skew the results, based on a comparison of outcomes following coronary stenting in an analysis of more than 4,000 patients.
During 12 months following coronary-disease treatment with percutaneous coronary intervention (PCI), women of diverse racial and ethnic backgrounds had a statistically significant 60% relative increase in death and myocardial infarctions, compared with white men, after adjustment for known baseline variables, Wayne B. Batchelor, MD, reported at the Transcatheter Cardiovascular Therapeutics annual meeting.
Minority patients, a mix of women and men, had a 90% relative rise in death and MIs, and a 60% higher rate of MIs after adjustment, both statistically significant differences.
Dr. Batchelor and his associates have not yet analyzed what factors are behind these worse outcomes in women and minority patients. But he suspects social and economic factors may provide at least some explanation, including income, education, language fluency, exercise habits, and access to health care.
“I think the trends we saw are real; the question is what accounts for the differences,” said Dr. Batchelor, an interventional cardiologist in Tallahassee, Fla. Regardless of the causes, he believes that the outcome differences have important immediate messages.
“We need to ensure better representation of women and minorities in clinical trials,” he said in an interview. “We don’t collect enough data from women and minorities. Historically, they have been underrepresented in trials.”
Another lesson is the importance of putting women and minority patients with cardiovascular disease on guideline-directed treatment, including dual antiplatelet therapy, lipid-lowering drugs, and antihypertensive drugs. The results show potential opportunity to further improve outcomes in women and minority patients, Dr. Batchelor said at the meeting, sponsored by the Cardiovascular Research Foundation.
The PLATINUM Diversity trial enrolled 1,501 women and men from minority groups with coronary disease who required PCI at one of 52 U.S. sites. For his analysis, Dr. Batchelor combined the 12-month outcomes of these patients with 12-month data from 2,687 unselected patients enrolled in the PROMUS Element Plus post-marketing approval study, a group of mostly white men.
The PLATINUM Diversity trial was sponsored by Boston Scientific. Dr. Batchelor has received research support from and has been a speaker for and consultant to Boston Scientific. He also has been a speaker for and consultant to Abbott Vascular and Medtronic.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected] On Twitter @mitchelzoler
WASHINGTON – The relatively low number of women and minority-group patients enrolled into cardiovascular disease clinical trials may skew the results, based on a comparison of outcomes following coronary stenting in an analysis of more than 4,000 patients.
During 12 months following coronary-disease treatment with percutaneous coronary intervention (PCI), women of diverse racial and ethnic backgrounds had a statistically significant 60% relative increase in death and myocardial infarctions, compared with white men, after adjustment for known baseline variables, Wayne B. Batchelor, MD, reported at the Transcatheter Cardiovascular Therapeutics annual meeting.
Minority patients, a mix of women and men, had a 90% relative rise in death and MIs, and a 60% higher rate of MIs after adjustment, both statistically significant differences.
Dr. Batchelor and his associates have not yet analyzed what factors are behind these worse outcomes in women and minority patients. But he suspects social and economic factors may provide at least some explanation, including income, education, language fluency, exercise habits, and access to health care.
“I think the trends we saw are real; the question is what accounts for the differences,” said Dr. Batchelor, an interventional cardiologist in Tallahassee, Fla. Regardless of the causes, he believes that the outcome differences have important immediate messages.
“We need to ensure better representation of women and minorities in clinical trials,” he said in an interview. “We don’t collect enough data from women and minorities. Historically, they have been underrepresented in trials.”
Another lesson is the importance of putting women and minority patients with cardiovascular disease on guideline-directed treatment, including dual antiplatelet therapy, lipid-lowering drugs, and antihypertensive drugs. The results show potential opportunity to further improve outcomes in women and minority patients, Dr. Batchelor said at the meeting, sponsored by the Cardiovascular Research Foundation.
The PLATINUM Diversity trial enrolled 1,501 women and men from minority groups with coronary disease who required PCI at one of 52 U.S. sites. For his analysis, Dr. Batchelor combined the 12-month outcomes of these patients with 12-month data from 2,687 unselected patients enrolled in the PROMUS Element Plus post-marketing approval study, a group of mostly white men.
The PLATINUM Diversity trial was sponsored by Boston Scientific. Dr. Batchelor has received research support from and has been a speaker for and consultant to Boston Scientific. He also has been a speaker for and consultant to Abbott Vascular and Medtronic.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected] On Twitter @mitchelzoler
WASHINGTON – The relatively low number of women and minority-group patients enrolled into cardiovascular disease clinical trials may skew the results, based on a comparison of outcomes following coronary stenting in an analysis of more than 4,000 patients.
During 12 months following coronary-disease treatment with percutaneous coronary intervention (PCI), women of diverse racial and ethnic backgrounds had a statistically significant 60% relative increase in death and myocardial infarctions, compared with white men, after adjustment for known baseline variables, Wayne B. Batchelor, MD, reported at the Transcatheter Cardiovascular Therapeutics annual meeting.
Minority patients, a mix of women and men, had a 90% relative rise in death and MIs, and a 60% higher rate of MIs after adjustment, both statistically significant differences.
Dr. Batchelor and his associates have not yet analyzed what factors are behind these worse outcomes in women and minority patients. But he suspects social and economic factors may provide at least some explanation, including income, education, language fluency, exercise habits, and access to health care.
“I think the trends we saw are real; the question is what accounts for the differences,” said Dr. Batchelor, an interventional cardiologist in Tallahassee, Fla. Regardless of the causes, he believes that the outcome differences have important immediate messages.
“We need to ensure better representation of women and minorities in clinical trials,” he said in an interview. “We don’t collect enough data from women and minorities. Historically, they have been underrepresented in trials.”
Another lesson is the importance of putting women and minority patients with cardiovascular disease on guideline-directed treatment, including dual antiplatelet therapy, lipid-lowering drugs, and antihypertensive drugs. The results show potential opportunity to further improve outcomes in women and minority patients, Dr. Batchelor said at the meeting, sponsored by the Cardiovascular Research Foundation.
The PLATINUM Diversity trial enrolled 1,501 women and men from minority groups with coronary disease who required PCI at one of 52 U.S. sites. For his analysis, Dr. Batchelor combined the 12-month outcomes of these patients with 12-month data from 2,687 unselected patients enrolled in the PROMUS Element Plus post-marketing approval study, a group of mostly white men.
The PLATINUM Diversity trial was sponsored by Boston Scientific. Dr. Batchelor has received research support from and has been a speaker for and consultant to Boston Scientific. He also has been a speaker for and consultant to Abbott Vascular and Medtronic.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected] On Twitter @mitchelzoler
Key clinical point:
Major finding: One year after percutaneous coronary intervention, death or myocardial infarction was 60% higher in women and 90% higher in minorities, compared with white men.
Data source: PLATINUM Diversity, a multicenter, single-arm study with 1,501 patients, and the PROMUS Element Plus U.S. postmarketing approval study with 2,683 patients.
Disclosures: The PLATINUM Diversity trial was sponsored by Boston Scientific. Dr. Batchelor has received research support from and has been a speaker for and consultant to Boston Scientific. He also has been a speaker for and consultant to Abbott Vascular and Medtronic.
‘Excellent’ real-world experience with LAA closure device
A device that closes the left atrial appendage to prevent stroke in patients with nonvalvular atrial fibrillation showed a 95.6% procedural success rate in a study of real-world experience since it was approved by the FDA in 2015, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology.
The study was based on data collected by Boston Scientific, the manufacturer of the Watchman device, regarding 3,822 consecutive patients who underwent the implantation during a 14-month period. The “excellent” procedural success rate, together with low short-term complication rates, are especially “remarkable” because 71% of the interventional cardiologists and electrophysiologists who performed these procedures had no experience with the device prior to FDA approval, said Vivek Y. Reddy, MD, of Mount Sinai Medical Center, New York.
For this study, the implantations were done by 382 physicians at 169 U.S. medical centers. A total of 3,653 procedures were successful. The median duration of the implantation was “an acceptable” 50 minutes (range, 10-210 minutes), and an average of 1.38 devices (range, 1-6) were required per patient. In 23% of cases, a “partial recapture” of a device was necessary to reposition it (J Am Coll Cardiol. 2016 Nov. doi: 10.1016/j.jacc.2016.10.010).
The rates of major complications within 1 week – pericardial tamponade (<1%), procedure-related stroke (0.08%), and mortality (0.08%) – were characterized as “favorable.”
The most common complication was pericardial effusion requiring intervention, which developed in 39 patients (1.02%). The effusions were drained percutaneously in most (24) of these patients. Another 11 patients (0.29%) developed mild pericardial effusions requiring only conservative management.
Three strokes, two ischemic and one hemorrhagic, were deemed related to the procedure, though the hemorrhagic bleed may have resulted chiefly from anticoagulation medications. Three deaths were judged to be related to the procedure: All were secondary to pericardial tamponade associated with perforation by the device.
“It is worth comparing [this] cardiac tamponade rate with [that of] another left atrial cardiovascular procedure, catheter ablation of atrial fibrillation,” Dr. Reddy noted.
A worldwide survey of more than 20,000 catheter ablations reported a pericardial tamponade rate of 1.31%, and another study of more than 93,000 ablation procedures performed during a 1-year period reported a rate of 1.52%, he said at the meeting, which was sponsored by the Cardiovascular Research Foundation.
Other short-term complications in this study included nine cases of device embolization (0.24%). Six of these required surgical removal of the device, while three were retrieved percutaneously.
No sponsor was cited for this study. Boston Scientific, maker of the Watchman left atrial appendage closure device, collected the data on all implantations of the device in the United States following FDA approval. Dr. Reddy and his associates reported ties to Boston Scientific, Coherex, SentreHeart, Abbott Vascular, and St. Jude Medical.
The results reported by Dr. Reddy and his colleagues are remarkably favorable for the earliest phase of widespread dissemination of this technology, especially in the context of the much higher rates of medication-related adverse events that occur with long-term oral anticoagulation. These findings should reassure us that left atrial appendage device closure has been safely introduced into clinical practice in the United States.
The study design, however, raises some concerns, and clinicians should be aware that complications may have been underreported. The manufacturer’s employees collected the data regarding complications in a somewhat informal manner, so this was not an objective study meeting the rigorous standards of clinical trials or postmarketing registries. These “clinical specialists” only included complications that developed within 1 week of the procedure, which fails to address possible delayed complications such as device-related thrombus. And they also didn’t track some important complications such as vascular events and bleeding events.
Jacqueline Saw, MD, of Vancouver General Hospital, and Matthew J. Price, MD, of Scripps Clinic in La Jolla, Calif., made these remarks in an editorial (J Am Coll Cardiol. 2016 Nov. doi: 10.1016/j.jacc.2016.10.019) accompanying Dr. Reddy’s report. Dr. Saw reported ties to Boston Scientific, AstraZeneca, Abbott Vascular, St. Jude Medical, Servier, Bayer, and Sunovion. Dr. Price reported ties to Boston Scientific, St. Jude Medical, W.L. Gore, Medtronic, AstraZeneca, Abbott Vascular, and Terumo.
The results reported by Dr. Reddy and his colleagues are remarkably favorable for the earliest phase of widespread dissemination of this technology, especially in the context of the much higher rates of medication-related adverse events that occur with long-term oral anticoagulation. These findings should reassure us that left atrial appendage device closure has been safely introduced into clinical practice in the United States.
The study design, however, raises some concerns, and clinicians should be aware that complications may have been underreported. The manufacturer’s employees collected the data regarding complications in a somewhat informal manner, so this was not an objective study meeting the rigorous standards of clinical trials or postmarketing registries. These “clinical specialists” only included complications that developed within 1 week of the procedure, which fails to address possible delayed complications such as device-related thrombus. And they also didn’t track some important complications such as vascular events and bleeding events.
Jacqueline Saw, MD, of Vancouver General Hospital, and Matthew J. Price, MD, of Scripps Clinic in La Jolla, Calif., made these remarks in an editorial (J Am Coll Cardiol. 2016 Nov. doi: 10.1016/j.jacc.2016.10.019) accompanying Dr. Reddy’s report. Dr. Saw reported ties to Boston Scientific, AstraZeneca, Abbott Vascular, St. Jude Medical, Servier, Bayer, and Sunovion. Dr. Price reported ties to Boston Scientific, St. Jude Medical, W.L. Gore, Medtronic, AstraZeneca, Abbott Vascular, and Terumo.
The results reported by Dr. Reddy and his colleagues are remarkably favorable for the earliest phase of widespread dissemination of this technology, especially in the context of the much higher rates of medication-related adverse events that occur with long-term oral anticoagulation. These findings should reassure us that left atrial appendage device closure has been safely introduced into clinical practice in the United States.
The study design, however, raises some concerns, and clinicians should be aware that complications may have been underreported. The manufacturer’s employees collected the data regarding complications in a somewhat informal manner, so this was not an objective study meeting the rigorous standards of clinical trials or postmarketing registries. These “clinical specialists” only included complications that developed within 1 week of the procedure, which fails to address possible delayed complications such as device-related thrombus. And they also didn’t track some important complications such as vascular events and bleeding events.
Jacqueline Saw, MD, of Vancouver General Hospital, and Matthew J. Price, MD, of Scripps Clinic in La Jolla, Calif., made these remarks in an editorial (J Am Coll Cardiol. 2016 Nov. doi: 10.1016/j.jacc.2016.10.019) accompanying Dr. Reddy’s report. Dr. Saw reported ties to Boston Scientific, AstraZeneca, Abbott Vascular, St. Jude Medical, Servier, Bayer, and Sunovion. Dr. Price reported ties to Boston Scientific, St. Jude Medical, W.L. Gore, Medtronic, AstraZeneca, Abbott Vascular, and Terumo.
A device that closes the left atrial appendage to prevent stroke in patients with nonvalvular atrial fibrillation showed a 95.6% procedural success rate in a study of real-world experience since it was approved by the FDA in 2015, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology.
The study was based on data collected by Boston Scientific, the manufacturer of the Watchman device, regarding 3,822 consecutive patients who underwent the implantation during a 14-month period. The “excellent” procedural success rate, together with low short-term complication rates, are especially “remarkable” because 71% of the interventional cardiologists and electrophysiologists who performed these procedures had no experience with the device prior to FDA approval, said Vivek Y. Reddy, MD, of Mount Sinai Medical Center, New York.
For this study, the implantations were done by 382 physicians at 169 U.S. medical centers. A total of 3,653 procedures were successful. The median duration of the implantation was “an acceptable” 50 minutes (range, 10-210 minutes), and an average of 1.38 devices (range, 1-6) were required per patient. In 23% of cases, a “partial recapture” of a device was necessary to reposition it (J Am Coll Cardiol. 2016 Nov. doi: 10.1016/j.jacc.2016.10.010).
The rates of major complications within 1 week – pericardial tamponade (<1%), procedure-related stroke (0.08%), and mortality (0.08%) – were characterized as “favorable.”
The most common complication was pericardial effusion requiring intervention, which developed in 39 patients (1.02%). The effusions were drained percutaneously in most (24) of these patients. Another 11 patients (0.29%) developed mild pericardial effusions requiring only conservative management.
Three strokes, two ischemic and one hemorrhagic, were deemed related to the procedure, though the hemorrhagic bleed may have resulted chiefly from anticoagulation medications. Three deaths were judged to be related to the procedure: All were secondary to pericardial tamponade associated with perforation by the device.
“It is worth comparing [this] cardiac tamponade rate with [that of] another left atrial cardiovascular procedure, catheter ablation of atrial fibrillation,” Dr. Reddy noted.
A worldwide survey of more than 20,000 catheter ablations reported a pericardial tamponade rate of 1.31%, and another study of more than 93,000 ablation procedures performed during a 1-year period reported a rate of 1.52%, he said at the meeting, which was sponsored by the Cardiovascular Research Foundation.
Other short-term complications in this study included nine cases of device embolization (0.24%). Six of these required surgical removal of the device, while three were retrieved percutaneously.
No sponsor was cited for this study. Boston Scientific, maker of the Watchman left atrial appendage closure device, collected the data on all implantations of the device in the United States following FDA approval. Dr. Reddy and his associates reported ties to Boston Scientific, Coherex, SentreHeart, Abbott Vascular, and St. Jude Medical.
A device that closes the left atrial appendage to prevent stroke in patients with nonvalvular atrial fibrillation showed a 95.6% procedural success rate in a study of real-world experience since it was approved by the FDA in 2015, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology.
The study was based on data collected by Boston Scientific, the manufacturer of the Watchman device, regarding 3,822 consecutive patients who underwent the implantation during a 14-month period. The “excellent” procedural success rate, together with low short-term complication rates, are especially “remarkable” because 71% of the interventional cardiologists and electrophysiologists who performed these procedures had no experience with the device prior to FDA approval, said Vivek Y. Reddy, MD, of Mount Sinai Medical Center, New York.
For this study, the implantations were done by 382 physicians at 169 U.S. medical centers. A total of 3,653 procedures were successful. The median duration of the implantation was “an acceptable” 50 minutes (range, 10-210 minutes), and an average of 1.38 devices (range, 1-6) were required per patient. In 23% of cases, a “partial recapture” of a device was necessary to reposition it (J Am Coll Cardiol. 2016 Nov. doi: 10.1016/j.jacc.2016.10.010).
The rates of major complications within 1 week – pericardial tamponade (<1%), procedure-related stroke (0.08%), and mortality (0.08%) – were characterized as “favorable.”
The most common complication was pericardial effusion requiring intervention, which developed in 39 patients (1.02%). The effusions were drained percutaneously in most (24) of these patients. Another 11 patients (0.29%) developed mild pericardial effusions requiring only conservative management.
Three strokes, two ischemic and one hemorrhagic, were deemed related to the procedure, though the hemorrhagic bleed may have resulted chiefly from anticoagulation medications. Three deaths were judged to be related to the procedure: All were secondary to pericardial tamponade associated with perforation by the device.
“It is worth comparing [this] cardiac tamponade rate with [that of] another left atrial cardiovascular procedure, catheter ablation of atrial fibrillation,” Dr. Reddy noted.
A worldwide survey of more than 20,000 catheter ablations reported a pericardial tamponade rate of 1.31%, and another study of more than 93,000 ablation procedures performed during a 1-year period reported a rate of 1.52%, he said at the meeting, which was sponsored by the Cardiovascular Research Foundation.
Other short-term complications in this study included nine cases of device embolization (0.24%). Six of these required surgical removal of the device, while three were retrieved percutaneously.
No sponsor was cited for this study. Boston Scientific, maker of the Watchman left atrial appendage closure device, collected the data on all implantations of the device in the United States following FDA approval. Dr. Reddy and his associates reported ties to Boston Scientific, Coherex, SentreHeart, Abbott Vascular, and St. Jude Medical.
FROM TCT 2016
Key clinical point: A left atrial appendage closure device to prevent stroke in patients with nonvalvular atrial fibrillation showed a 95.6% procedural success rate.
Major finding: Of 3,822 implantations, 3,653 (95.6%) were successful, and 1-week complication rates were low, with <1% pericardial tamponade, 0.08% procedure-related stroke, and 0.08% mortality.
Data source: An analysis of manufacturer-collected data on all 3,822 consecutive device implantations at 169 medical centers from March 2015 to May 2016.
Disclosures: No sponsor was cited for this study. Boston Scientific, maker of the Watchman left atrial appendage closure device, collected the data on all implantations of the device in the United States following FDA approval. Dr. Reddy and his associates reported ties to Boston Scientific, Coherex, SentreHeart, Abbott Vascular, and St. Jude Medical.
VIDEO: Two PCI vs. CABG trials produce conflicting results
WASHINGTON – Results from two large, multicenter comparisons of coronary stenting and coronary bypass surgery for treating patients with unprotected left main coronary disease may have superficially shown sharp differences, but the bottom line will likely be greater empowerment of percutaneous coronary intervention as an option for selected patients with less complex coronary disease.
Prior to the results from the EXCEL and NOBLE trials, reported at the Transcatheter Cardiovascular Therapeutics annual meeting, “guidelines put PCI [percutaneous coronary intervention] into a class 1, 2 or 3 status for treating left main coronary disease depending on disease complexity, but in the United States, PCI for patients eligible for CABG [coronary artery bypass grafting] has not been frequently done. I think these results, in a very circumscribed subset of patients and using a state-of-the-art stent, will affect the guidelines,” predicted Gregg W. Stone, MD, lead investigator for EXCEL and professor of medicine at Columbia University in New York.
“What the guidelines have not addressed are the patients with low- or intermediate-complexity disease who have an acceptable risk for undergoing either PCI or CABG. I think the trial results answer this question,” said David Kandzari, MD, director of interventional cardiology and chief scientific officer at the Piedmont Heart Institute in Atlanta and an EXCEL investigator.
While the EXCEL and NOBLE results don’t provide a simple answer on the relative merits of PCI and CABG, many of their outcome differences seem explicable, several experts said at the meeting.
The Nordic-Baltic-British Left Main Revascularisation (NOBLE) trial randomized 1,201 patients who had unprotected left main coronary disease and were judged by a heart team to be reasonable candidates for both PCI or CABG at 36 centers in nine European countries during 2008-2015. The primary endpoint was death from any cause, nonprocedural MIs, stroke, or repeat revascularization.
The researchers followed patients for a median of just over 3 years, but they calculated the primary endpoint based on a Kaplan-Meier estimate for 5-year outcomes, which showed the primary endpoint in 29% of the PCI patients and in 19% of the CABG patients, a statistically significant benefit in favor of CABG, Evald H. Christiansen, MD, reported at the meeting, which was sponsored by the Cardiovascular Research Foundation. Concurrently with his report, the results were published online (Lancet. 2016 Oct. 31. doi: 10.1016/S0140-6736[16]32052-9).
This difference between PCI and CABG was largely driven by an excess of postprocedural MIs and repeat revascularizations among the PCI patients, said Dr. Christiansen, an interventional cardiologist at Aarhus University Hospital in Denmark. Another notable finding was that the superior outcomes with CABG primarily occurred among patients with a SYNTAX score – a measure of coronary disease complexity – of 22 or less, which identifies patients with low complexity disease. The outcomes of patients with SYNTAX scores of 23-32, which identifies intermediate complexity disease, and of patients with scores of 33 or higher, with very complex disease, were similar in the PCI and CABG arms, he reported. This finding was “very surprising,” Dr. Christiansen said, because it reversed the finding originally made in the SYNTAX trial that PCI performed best compared with CABG in patients with the lowest scores and least-complex coronary disease.
The superiority of CABG over PCI seen in the NOBLE results, especially in patients with lower SYNTAX scores, seemed at odds with the EXCEL results, reported at the meeting by Dr. Stone and simultaneously online (N Engl J Med. 2016 Oct. 31. doi: 10.1056/NEJMoa1610227). In EXCEL, which enrolled only patients with a SYNTAX score of 32 or less (low- or intermediate-complexity coronary disease), patients had a 3-year incidence of death, stroke or MI of 15% in both the PCI and CABG arms.
But the EXCEL and NOBLE trials had several important differences, and it seemed like cumulatively these differences account for their differing results.
“One of the biggest differences” was the exclusion of procedural MIs in the NOBLE tally of adverse events, noted Dr. Stone. These were diagnosed in EXCEL using the MI definition published in 2013 by a panel of the Society for Cardiovascular Angiography and Interventions (SCAI). NOBLE disregarded procedural MIs because many of its participating hospitals did not have the laboratory resources to make these diagnoses and because the trial’s design predated the SCAI definition by several years, Dr. Christiansen explained.
Other important differences included the shorter follow-up in EXCEL, the inclusion of revascularization as an endpoint component in NOBLE but not in EXCEL, and differences in the stents used. In EXCEL, all patients undergoing PCI received Xience everolimus-eluting stents. In NOBLE, the first 11% of the enrolled patients received first-generation, sirolimus-eluting Cypher stents; the next 89% of enrollees received a biolimus-eluting Biomatrix Flex stent. Dr. Christiansen acknowledged the confounding caused by having many patients in the NOBLE PCI arm who received outmoded Cypher stents, especially because their relatively longer follow-up made them overrepresented in the primary outcome results. Plus, the Biomatrix Flex stent was disparaged by Martin B. Leon, MD, an EXCEL investigator and professor of medicine at Columbia University, who called the device “not currently widely used for PCI and more of historic interest.”
Dr. Leon added that the EXCEL and NOBLE patients also had substantially different prevalence rates of diabetes and acute coronary syndrome.
“The huge difference [between EXCEL and NOBLE] is the endpoint,” declared Marc Ruel, MD, another EXCEL investigator and head of cardiac surgery at the Ottawa Heart Institute. “The EXCEL endpoint was driven by the high rate of periprocedural MIs in the CABG arm. Once you get past 30 days, the noninferiority is not met by PCI.”
Another big endpoint difference was leaving revascularizations out of the EXCEL composite. “Once you take revascularization out of the primary endpoint, the outcome [of EXCEL] was more or less preordained,” noted Craig R. Smith, MD, chairman of surgery at Columbia University and an EXCEL investigator. “It’s the slope of events [in the PCI arm] after 3 months that’s the story. I think the CABG and PCI slopes in EXCEL will continue to diverge with time” beyond the current 3-year follow-up, Dr. Smith said.
“I agree that after 30 days surgery was the more durable procedure,” said Dr. Stone. “There is a big upfront hit for patients to take with surgery compared with PCI. If patients get through that, then they have a more durable procedure. That’s the trade-off.”
Dr. Stone hinted that future reports of EXCEL data will highlight other hits that patients must endure upfront if they choose CABG over PCI. “The early difference was quite profound not only for the primary endpoint but also for renal failure, infections, arrhythmias, and blood transfusions,” he said. Choosing between PCI and CABG for patients with left main disease and a lower SYNTAX score “is a decision that should be made by the heart team and patients. Some patients will prefer surgery, and some will prefer PCI.”
The NOBLE trial received partial funding from Biosensors, the company that markets the Biomatrix Flex stent used in the trial. The EXCEL trial was sponsored by Abbott Vascular, the company that markets the Xience stent used in the trial. Dr. Stone, Dr. Kandzari, Dr. Christiansen, Dr. Ruel, and Dr. Smith had no disclosures. Dr. Leon has been a consultant to and received research support from Abbott Vascular and Boston Scientific and has also received research support from Edwards, Medtronic and St. Jude.
[email protected]
On Twitter @mitchelzoler
The results from EXCEL and NOBLE were not that different, but what was different was how the two trials were designed and how their endpoints were defined. The biggest difference between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) seemed to be in the rate of late MIs, with a little higher rate following PCI, and more repeat revascularizations with PCI, but with similar mortality rates with both treatments. There was a lot of similarity in the results despite the differences in the trials.
The evidence in both studies gives more support to the concept that, for patients with simpler left main lesions, PCI is a competitive alternative to CABG. Until now, in U.S. practice patients with left main coronary disease have been preferentially referred for CABG. These results will open us up to giving selected patients a more balanced view of the two options. After we explain differences in recovery and late events patients can decide which treatment to receive.
Despite these new findings, PCI is still not for every patient. A substantial fraction of patients with left main coronary disease were excluded from these studies because they had more complex coronary anatomy, and for patients like that, CABG remains the clear standard of care.
David J. Cohen, MD, is director of cardiovascular research and an interventional cardiologist at Saint Luke’s Health System in Kansas City, Mo. He made these comments in a video interview. He had received research support from Abbott Vascular, and is an investigator in the EXCEL trial.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The results from EXCEL and NOBLE were not that different, but what was different was how the two trials were designed and how their endpoints were defined. The biggest difference between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) seemed to be in the rate of late MIs, with a little higher rate following PCI, and more repeat revascularizations with PCI, but with similar mortality rates with both treatments. There was a lot of similarity in the results despite the differences in the trials.
The evidence in both studies gives more support to the concept that, for patients with simpler left main lesions, PCI is a competitive alternative to CABG. Until now, in U.S. practice patients with left main coronary disease have been preferentially referred for CABG. These results will open us up to giving selected patients a more balanced view of the two options. After we explain differences in recovery and late events patients can decide which treatment to receive.
Despite these new findings, PCI is still not for every patient. A substantial fraction of patients with left main coronary disease were excluded from these studies because they had more complex coronary anatomy, and for patients like that, CABG remains the clear standard of care.
David J. Cohen, MD, is director of cardiovascular research and an interventional cardiologist at Saint Luke’s Health System in Kansas City, Mo. He made these comments in a video interview. He had received research support from Abbott Vascular, and is an investigator in the EXCEL trial.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The results from EXCEL and NOBLE were not that different, but what was different was how the two trials were designed and how their endpoints were defined. The biggest difference between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) seemed to be in the rate of late MIs, with a little higher rate following PCI, and more repeat revascularizations with PCI, but with similar mortality rates with both treatments. There was a lot of similarity in the results despite the differences in the trials.
The evidence in both studies gives more support to the concept that, for patients with simpler left main lesions, PCI is a competitive alternative to CABG. Until now, in U.S. practice patients with left main coronary disease have been preferentially referred for CABG. These results will open us up to giving selected patients a more balanced view of the two options. After we explain differences in recovery and late events patients can decide which treatment to receive.
Despite these new findings, PCI is still not for every patient. A substantial fraction of patients with left main coronary disease were excluded from these studies because they had more complex coronary anatomy, and for patients like that, CABG remains the clear standard of care.
David J. Cohen, MD, is director of cardiovascular research and an interventional cardiologist at Saint Luke’s Health System in Kansas City, Mo. He made these comments in a video interview. He had received research support from Abbott Vascular, and is an investigator in the EXCEL trial.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WASHINGTON – Results from two large, multicenter comparisons of coronary stenting and coronary bypass surgery for treating patients with unprotected left main coronary disease may have superficially shown sharp differences, but the bottom line will likely be greater empowerment of percutaneous coronary intervention as an option for selected patients with less complex coronary disease.
Prior to the results from the EXCEL and NOBLE trials, reported at the Transcatheter Cardiovascular Therapeutics annual meeting, “guidelines put PCI [percutaneous coronary intervention] into a class 1, 2 or 3 status for treating left main coronary disease depending on disease complexity, but in the United States, PCI for patients eligible for CABG [coronary artery bypass grafting] has not been frequently done. I think these results, in a very circumscribed subset of patients and using a state-of-the-art stent, will affect the guidelines,” predicted Gregg W. Stone, MD, lead investigator for EXCEL and professor of medicine at Columbia University in New York.
“What the guidelines have not addressed are the patients with low- or intermediate-complexity disease who have an acceptable risk for undergoing either PCI or CABG. I think the trial results answer this question,” said David Kandzari, MD, director of interventional cardiology and chief scientific officer at the Piedmont Heart Institute in Atlanta and an EXCEL investigator.
While the EXCEL and NOBLE results don’t provide a simple answer on the relative merits of PCI and CABG, many of their outcome differences seem explicable, several experts said at the meeting.
The Nordic-Baltic-British Left Main Revascularisation (NOBLE) trial randomized 1,201 patients who had unprotected left main coronary disease and were judged by a heart team to be reasonable candidates for both PCI or CABG at 36 centers in nine European countries during 2008-2015. The primary endpoint was death from any cause, nonprocedural MIs, stroke, or repeat revascularization.
The researchers followed patients for a median of just over 3 years, but they calculated the primary endpoint based on a Kaplan-Meier estimate for 5-year outcomes, which showed the primary endpoint in 29% of the PCI patients and in 19% of the CABG patients, a statistically significant benefit in favor of CABG, Evald H. Christiansen, MD, reported at the meeting, which was sponsored by the Cardiovascular Research Foundation. Concurrently with his report, the results were published online (Lancet. 2016 Oct. 31. doi: 10.1016/S0140-6736[16]32052-9).
This difference between PCI and CABG was largely driven by an excess of postprocedural MIs and repeat revascularizations among the PCI patients, said Dr. Christiansen, an interventional cardiologist at Aarhus University Hospital in Denmark. Another notable finding was that the superior outcomes with CABG primarily occurred among patients with a SYNTAX score – a measure of coronary disease complexity – of 22 or less, which identifies patients with low complexity disease. The outcomes of patients with SYNTAX scores of 23-32, which identifies intermediate complexity disease, and of patients with scores of 33 or higher, with very complex disease, were similar in the PCI and CABG arms, he reported. This finding was “very surprising,” Dr. Christiansen said, because it reversed the finding originally made in the SYNTAX trial that PCI performed best compared with CABG in patients with the lowest scores and least-complex coronary disease.
The superiority of CABG over PCI seen in the NOBLE results, especially in patients with lower SYNTAX scores, seemed at odds with the EXCEL results, reported at the meeting by Dr. Stone and simultaneously online (N Engl J Med. 2016 Oct. 31. doi: 10.1056/NEJMoa1610227). In EXCEL, which enrolled only patients with a SYNTAX score of 32 or less (low- or intermediate-complexity coronary disease), patients had a 3-year incidence of death, stroke or MI of 15% in both the PCI and CABG arms.
But the EXCEL and NOBLE trials had several important differences, and it seemed like cumulatively these differences account for their differing results.
“One of the biggest differences” was the exclusion of procedural MIs in the NOBLE tally of adverse events, noted Dr. Stone. These were diagnosed in EXCEL using the MI definition published in 2013 by a panel of the Society for Cardiovascular Angiography and Interventions (SCAI). NOBLE disregarded procedural MIs because many of its participating hospitals did not have the laboratory resources to make these diagnoses and because the trial’s design predated the SCAI definition by several years, Dr. Christiansen explained.
Other important differences included the shorter follow-up in EXCEL, the inclusion of revascularization as an endpoint component in NOBLE but not in EXCEL, and differences in the stents used. In EXCEL, all patients undergoing PCI received Xience everolimus-eluting stents. In NOBLE, the first 11% of the enrolled patients received first-generation, sirolimus-eluting Cypher stents; the next 89% of enrollees received a biolimus-eluting Biomatrix Flex stent. Dr. Christiansen acknowledged the confounding caused by having many patients in the NOBLE PCI arm who received outmoded Cypher stents, especially because their relatively longer follow-up made them overrepresented in the primary outcome results. Plus, the Biomatrix Flex stent was disparaged by Martin B. Leon, MD, an EXCEL investigator and professor of medicine at Columbia University, who called the device “not currently widely used for PCI and more of historic interest.”
Dr. Leon added that the EXCEL and NOBLE patients also had substantially different prevalence rates of diabetes and acute coronary syndrome.
“The huge difference [between EXCEL and NOBLE] is the endpoint,” declared Marc Ruel, MD, another EXCEL investigator and head of cardiac surgery at the Ottawa Heart Institute. “The EXCEL endpoint was driven by the high rate of periprocedural MIs in the CABG arm. Once you get past 30 days, the noninferiority is not met by PCI.”
Another big endpoint difference was leaving revascularizations out of the EXCEL composite. “Once you take revascularization out of the primary endpoint, the outcome [of EXCEL] was more or less preordained,” noted Craig R. Smith, MD, chairman of surgery at Columbia University and an EXCEL investigator. “It’s the slope of events [in the PCI arm] after 3 months that’s the story. I think the CABG and PCI slopes in EXCEL will continue to diverge with time” beyond the current 3-year follow-up, Dr. Smith said.
“I agree that after 30 days surgery was the more durable procedure,” said Dr. Stone. “There is a big upfront hit for patients to take with surgery compared with PCI. If patients get through that, then they have a more durable procedure. That’s the trade-off.”
Dr. Stone hinted that future reports of EXCEL data will highlight other hits that patients must endure upfront if they choose CABG over PCI. “The early difference was quite profound not only for the primary endpoint but also for renal failure, infections, arrhythmias, and blood transfusions,” he said. Choosing between PCI and CABG for patients with left main disease and a lower SYNTAX score “is a decision that should be made by the heart team and patients. Some patients will prefer surgery, and some will prefer PCI.”
The NOBLE trial received partial funding from Biosensors, the company that markets the Biomatrix Flex stent used in the trial. The EXCEL trial was sponsored by Abbott Vascular, the company that markets the Xience stent used in the trial. Dr. Stone, Dr. Kandzari, Dr. Christiansen, Dr. Ruel, and Dr. Smith had no disclosures. Dr. Leon has been a consultant to and received research support from Abbott Vascular and Boston Scientific and has also received research support from Edwards, Medtronic and St. Jude.
[email protected]
On Twitter @mitchelzoler
WASHINGTON – Results from two large, multicenter comparisons of coronary stenting and coronary bypass surgery for treating patients with unprotected left main coronary disease may have superficially shown sharp differences, but the bottom line will likely be greater empowerment of percutaneous coronary intervention as an option for selected patients with less complex coronary disease.
Prior to the results from the EXCEL and NOBLE trials, reported at the Transcatheter Cardiovascular Therapeutics annual meeting, “guidelines put PCI [percutaneous coronary intervention] into a class 1, 2 or 3 status for treating left main coronary disease depending on disease complexity, but in the United States, PCI for patients eligible for CABG [coronary artery bypass grafting] has not been frequently done. I think these results, in a very circumscribed subset of patients and using a state-of-the-art stent, will affect the guidelines,” predicted Gregg W. Stone, MD, lead investigator for EXCEL and professor of medicine at Columbia University in New York.
“What the guidelines have not addressed are the patients with low- or intermediate-complexity disease who have an acceptable risk for undergoing either PCI or CABG. I think the trial results answer this question,” said David Kandzari, MD, director of interventional cardiology and chief scientific officer at the Piedmont Heart Institute in Atlanta and an EXCEL investigator.
While the EXCEL and NOBLE results don’t provide a simple answer on the relative merits of PCI and CABG, many of their outcome differences seem explicable, several experts said at the meeting.
The Nordic-Baltic-British Left Main Revascularisation (NOBLE) trial randomized 1,201 patients who had unprotected left main coronary disease and were judged by a heart team to be reasonable candidates for both PCI or CABG at 36 centers in nine European countries during 2008-2015. The primary endpoint was death from any cause, nonprocedural MIs, stroke, or repeat revascularization.
The researchers followed patients for a median of just over 3 years, but they calculated the primary endpoint based on a Kaplan-Meier estimate for 5-year outcomes, which showed the primary endpoint in 29% of the PCI patients and in 19% of the CABG patients, a statistically significant benefit in favor of CABG, Evald H. Christiansen, MD, reported at the meeting, which was sponsored by the Cardiovascular Research Foundation. Concurrently with his report, the results were published online (Lancet. 2016 Oct. 31. doi: 10.1016/S0140-6736[16]32052-9).
This difference between PCI and CABG was largely driven by an excess of postprocedural MIs and repeat revascularizations among the PCI patients, said Dr. Christiansen, an interventional cardiologist at Aarhus University Hospital in Denmark. Another notable finding was that the superior outcomes with CABG primarily occurred among patients with a SYNTAX score – a measure of coronary disease complexity – of 22 or less, which identifies patients with low complexity disease. The outcomes of patients with SYNTAX scores of 23-32, which identifies intermediate complexity disease, and of patients with scores of 33 or higher, with very complex disease, were similar in the PCI and CABG arms, he reported. This finding was “very surprising,” Dr. Christiansen said, because it reversed the finding originally made in the SYNTAX trial that PCI performed best compared with CABG in patients with the lowest scores and least-complex coronary disease.
The superiority of CABG over PCI seen in the NOBLE results, especially in patients with lower SYNTAX scores, seemed at odds with the EXCEL results, reported at the meeting by Dr. Stone and simultaneously online (N Engl J Med. 2016 Oct. 31. doi: 10.1056/NEJMoa1610227). In EXCEL, which enrolled only patients with a SYNTAX score of 32 or less (low- or intermediate-complexity coronary disease), patients had a 3-year incidence of death, stroke or MI of 15% in both the PCI and CABG arms.
But the EXCEL and NOBLE trials had several important differences, and it seemed like cumulatively these differences account for their differing results.
“One of the biggest differences” was the exclusion of procedural MIs in the NOBLE tally of adverse events, noted Dr. Stone. These were diagnosed in EXCEL using the MI definition published in 2013 by a panel of the Society for Cardiovascular Angiography and Interventions (SCAI). NOBLE disregarded procedural MIs because many of its participating hospitals did not have the laboratory resources to make these diagnoses and because the trial’s design predated the SCAI definition by several years, Dr. Christiansen explained.
Other important differences included the shorter follow-up in EXCEL, the inclusion of revascularization as an endpoint component in NOBLE but not in EXCEL, and differences in the stents used. In EXCEL, all patients undergoing PCI received Xience everolimus-eluting stents. In NOBLE, the first 11% of the enrolled patients received first-generation, sirolimus-eluting Cypher stents; the next 89% of enrollees received a biolimus-eluting Biomatrix Flex stent. Dr. Christiansen acknowledged the confounding caused by having many patients in the NOBLE PCI arm who received outmoded Cypher stents, especially because their relatively longer follow-up made them overrepresented in the primary outcome results. Plus, the Biomatrix Flex stent was disparaged by Martin B. Leon, MD, an EXCEL investigator and professor of medicine at Columbia University, who called the device “not currently widely used for PCI and more of historic interest.”
Dr. Leon added that the EXCEL and NOBLE patients also had substantially different prevalence rates of diabetes and acute coronary syndrome.
“The huge difference [between EXCEL and NOBLE] is the endpoint,” declared Marc Ruel, MD, another EXCEL investigator and head of cardiac surgery at the Ottawa Heart Institute. “The EXCEL endpoint was driven by the high rate of periprocedural MIs in the CABG arm. Once you get past 30 days, the noninferiority is not met by PCI.”
Another big endpoint difference was leaving revascularizations out of the EXCEL composite. “Once you take revascularization out of the primary endpoint, the outcome [of EXCEL] was more or less preordained,” noted Craig R. Smith, MD, chairman of surgery at Columbia University and an EXCEL investigator. “It’s the slope of events [in the PCI arm] after 3 months that’s the story. I think the CABG and PCI slopes in EXCEL will continue to diverge with time” beyond the current 3-year follow-up, Dr. Smith said.
“I agree that after 30 days surgery was the more durable procedure,” said Dr. Stone. “There is a big upfront hit for patients to take with surgery compared with PCI. If patients get through that, then they have a more durable procedure. That’s the trade-off.”
Dr. Stone hinted that future reports of EXCEL data will highlight other hits that patients must endure upfront if they choose CABG over PCI. “The early difference was quite profound not only for the primary endpoint but also for renal failure, infections, arrhythmias, and blood transfusions,” he said. Choosing between PCI and CABG for patients with left main disease and a lower SYNTAX score “is a decision that should be made by the heart team and patients. Some patients will prefer surgery, and some will prefer PCI.”
The NOBLE trial received partial funding from Biosensors, the company that markets the Biomatrix Flex stent used in the trial. The EXCEL trial was sponsored by Abbott Vascular, the company that markets the Xience stent used in the trial. Dr. Stone, Dr. Kandzari, Dr. Christiansen, Dr. Ruel, and Dr. Smith had no disclosures. Dr. Leon has been a consultant to and received research support from Abbott Vascular and Boston Scientific and has also received research support from Edwards, Medtronic and St. Jude.
[email protected]
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM TCT 2016
ReACT: No benefit from routine coronary angiography after PCI
Routine follow-up coronary angiography after percutaneous coronary intervention leads to increased rates of coronary revascularization but without any significant benefits for outcomes, according to a study presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously on Nov. 1 in the Journal of the American College of Cardiology: Cardiovascular Interventions.
Hiroki Shiomi, MD, from Kyoto University, and his coauthors reported on ReACT, a prospective, open-label randomized controlled trial of routine follow-up coronary angiography in 700 patients who underwent successful percutaneous coronary intervention (PCI).
Among the 349 patients randomized to follow-up coronary angiography (FUCAG), 12.8% underwent any coronary revascularization within the first year after PCI, compared with 3.8% of the 351 patients randomized to standard clinical follow-up. The routine angiography group also had a higher incidence of target lesion revascularization in the first year after the index PCI (7.0% vs. 1.7%).
In both these cases, the cumulative 5-year incidence of coronary or target lesion revascularization was not significantly different between the routine angiography and control groups. However researchers saw no significant benefit from routine FUCAG in terms of the cumulative 5-year incidence of all-cause death, myocardial infarction, stroke, or emergency hospitalizations for acute coronary syndrome or heart failure, compared with clinical follow-up (22.4% vs. 24.7%; P = 0.70).
Nor were there any significant differences between the two groups in these individual components, or in the cumulative 5-year incidence of major bleeding (JACC Cardiovasc Interv. 2016 Nov 1.)
The authors commented that several previous studies have shown that routine FUCAG does not improve clinical outcomes, although it is still commonly performed in Japan after PCI.
“However, previous studies in the drug-eluting stents (DES) era were conducted in the context of pivotal randomized trials of DES and there have been no randomized clinical trials evaluating long-term clinical impact of routine FUCAG after PCI in the real world clinical practice including high-risk patients for cardiovascular events risk such as complex coronary artery disease and acute myocardial infarction (AMI) presentation,” the authors wrote.
Overall, 85.4% of patients in the routine angiography group and 12% of those in the clinical care group underwent coronary angiography in the first year, including for clinical reasons.
In the clinical follow-up group, coronary angiography was performed because of acute coronary syndrome (14%), recurrence of angina (60%), other clinical reasons (14%), or no clinical reason (12%). The control group also had more noninvasive physiological stress testing such as treadmill exercise test and stress nuclear study.
“Considering the invasive nature of coronary angiography and increased medical expenses, routine FUCAG after PCI would not be allowed as the usual clinical practice, unless patients have recurrent symptoms or objective evidence of ischemia,” the authors wrote.
“On the other hand, there was no excess of adverse clinical events with routine angiographic follow-up strategy except for the increased rate of 1-year repeat coronary revascularization.”
Given this, they suggested that scheduled angiographic follow-up might still be considered acceptable for early in vivo or significant coronary device trials.
While the authors said the trial ended up being underpowered because of a reduced final sample size and lower-than-anticipated event rate, it did warrant further larger-scale studies. In particular, they highlighted the question of what impact routine follow-up angiography might have in higher-risk patients, such as those with left main or multivessel coronary artery disease.
“Finally, because patient demographics, practice patterns including the indication of coronary revascularization, and clinical outcomes in Japan may be different from those outside Japan, generalizing the present study results to populations outside Japan should be done with caution.”
This study was supported by an educational grant from the Research Institute for Production Development (Kyoto). One author declared honoraria for education consulting from Boston Scientific Corporation.
Routine follow-up coronary angiography after percutaneous coronary intervention leads to increased rates of coronary revascularization but without any significant benefits for outcomes, according to a study presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously on Nov. 1 in the Journal of the American College of Cardiology: Cardiovascular Interventions.
Hiroki Shiomi, MD, from Kyoto University, and his coauthors reported on ReACT, a prospective, open-label randomized controlled trial of routine follow-up coronary angiography in 700 patients who underwent successful percutaneous coronary intervention (PCI).
Among the 349 patients randomized to follow-up coronary angiography (FUCAG), 12.8% underwent any coronary revascularization within the first year after PCI, compared with 3.8% of the 351 patients randomized to standard clinical follow-up. The routine angiography group also had a higher incidence of target lesion revascularization in the first year after the index PCI (7.0% vs. 1.7%).
In both these cases, the cumulative 5-year incidence of coronary or target lesion revascularization was not significantly different between the routine angiography and control groups. However researchers saw no significant benefit from routine FUCAG in terms of the cumulative 5-year incidence of all-cause death, myocardial infarction, stroke, or emergency hospitalizations for acute coronary syndrome or heart failure, compared with clinical follow-up (22.4% vs. 24.7%; P = 0.70).
Nor were there any significant differences between the two groups in these individual components, or in the cumulative 5-year incidence of major bleeding (JACC Cardiovasc Interv. 2016 Nov 1.)
The authors commented that several previous studies have shown that routine FUCAG does not improve clinical outcomes, although it is still commonly performed in Japan after PCI.
“However, previous studies in the drug-eluting stents (DES) era were conducted in the context of pivotal randomized trials of DES and there have been no randomized clinical trials evaluating long-term clinical impact of routine FUCAG after PCI in the real world clinical practice including high-risk patients for cardiovascular events risk such as complex coronary artery disease and acute myocardial infarction (AMI) presentation,” the authors wrote.
Overall, 85.4% of patients in the routine angiography group and 12% of those in the clinical care group underwent coronary angiography in the first year, including for clinical reasons.
In the clinical follow-up group, coronary angiography was performed because of acute coronary syndrome (14%), recurrence of angina (60%), other clinical reasons (14%), or no clinical reason (12%). The control group also had more noninvasive physiological stress testing such as treadmill exercise test and stress nuclear study.
“Considering the invasive nature of coronary angiography and increased medical expenses, routine FUCAG after PCI would not be allowed as the usual clinical practice, unless patients have recurrent symptoms or objective evidence of ischemia,” the authors wrote.
“On the other hand, there was no excess of adverse clinical events with routine angiographic follow-up strategy except for the increased rate of 1-year repeat coronary revascularization.”
Given this, they suggested that scheduled angiographic follow-up might still be considered acceptable for early in vivo or significant coronary device trials.
While the authors said the trial ended up being underpowered because of a reduced final sample size and lower-than-anticipated event rate, it did warrant further larger-scale studies. In particular, they highlighted the question of what impact routine follow-up angiography might have in higher-risk patients, such as those with left main or multivessel coronary artery disease.
“Finally, because patient demographics, practice patterns including the indication of coronary revascularization, and clinical outcomes in Japan may be different from those outside Japan, generalizing the present study results to populations outside Japan should be done with caution.”
This study was supported by an educational grant from the Research Institute for Production Development (Kyoto). One author declared honoraria for education consulting from Boston Scientific Corporation.
Routine follow-up coronary angiography after percutaneous coronary intervention leads to increased rates of coronary revascularization but without any significant benefits for outcomes, according to a study presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously on Nov. 1 in the Journal of the American College of Cardiology: Cardiovascular Interventions.
Hiroki Shiomi, MD, from Kyoto University, and his coauthors reported on ReACT, a prospective, open-label randomized controlled trial of routine follow-up coronary angiography in 700 patients who underwent successful percutaneous coronary intervention (PCI).
Among the 349 patients randomized to follow-up coronary angiography (FUCAG), 12.8% underwent any coronary revascularization within the first year after PCI, compared with 3.8% of the 351 patients randomized to standard clinical follow-up. The routine angiography group also had a higher incidence of target lesion revascularization in the first year after the index PCI (7.0% vs. 1.7%).
In both these cases, the cumulative 5-year incidence of coronary or target lesion revascularization was not significantly different between the routine angiography and control groups. However researchers saw no significant benefit from routine FUCAG in terms of the cumulative 5-year incidence of all-cause death, myocardial infarction, stroke, or emergency hospitalizations for acute coronary syndrome or heart failure, compared with clinical follow-up (22.4% vs. 24.7%; P = 0.70).
Nor were there any significant differences between the two groups in these individual components, or in the cumulative 5-year incidence of major bleeding (JACC Cardiovasc Interv. 2016 Nov 1.)
The authors commented that several previous studies have shown that routine FUCAG does not improve clinical outcomes, although it is still commonly performed in Japan after PCI.
“However, previous studies in the drug-eluting stents (DES) era were conducted in the context of pivotal randomized trials of DES and there have been no randomized clinical trials evaluating long-term clinical impact of routine FUCAG after PCI in the real world clinical practice including high-risk patients for cardiovascular events risk such as complex coronary artery disease and acute myocardial infarction (AMI) presentation,” the authors wrote.
Overall, 85.4% of patients in the routine angiography group and 12% of those in the clinical care group underwent coronary angiography in the first year, including for clinical reasons.
In the clinical follow-up group, coronary angiography was performed because of acute coronary syndrome (14%), recurrence of angina (60%), other clinical reasons (14%), or no clinical reason (12%). The control group also had more noninvasive physiological stress testing such as treadmill exercise test and stress nuclear study.
“Considering the invasive nature of coronary angiography and increased medical expenses, routine FUCAG after PCI would not be allowed as the usual clinical practice, unless patients have recurrent symptoms or objective evidence of ischemia,” the authors wrote.
“On the other hand, there was no excess of adverse clinical events with routine angiographic follow-up strategy except for the increased rate of 1-year repeat coronary revascularization.”
Given this, they suggested that scheduled angiographic follow-up might still be considered acceptable for early in vivo or significant coronary device trials.
While the authors said the trial ended up being underpowered because of a reduced final sample size and lower-than-anticipated event rate, it did warrant further larger-scale studies. In particular, they highlighted the question of what impact routine follow-up angiography might have in higher-risk patients, such as those with left main or multivessel coronary artery disease.
“Finally, because patient demographics, practice patterns including the indication of coronary revascularization, and clinical outcomes in Japan may be different from those outside Japan, generalizing the present study results to populations outside Japan should be done with caution.”
This study was supported by an educational grant from the Research Institute for Production Development (Kyoto). One author declared honoraria for education consulting from Boston Scientific Corporation.
Key clinical point: Routine follow-up coronary angiography after percutaneous coronary intervention increases rates of coronary revascularization but does not improve outcomes.
Major finding: Patients who underwent routine angiographic follow-up had a similar cumulative 5-year incidence of all-cause death, myocardial infarction, stroke, or emergency hospitalizations for acute coronary syndrome or heart failure as those who had standard clinical follow-up.
Data source: ReACT: a prospective, open-label randomized controlled trial in 700 patients after percutaneous coronary intervention.
Disclosures: This study was supported by an educational grant from the Research Institute for Production Development (Kyoto). One author declared honoraria for education consulting from Boston Scientific Corporation.
Results puzzling for embolic protection during TAVR
The largest randomized clinical trial to assess the safety and efficacy of cerebral embolic protection systems during transcatheter aortic valve replacement yielded puzzling and somewhat contradictory results, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology.
Virtually every device in this industry-sponsored study involving 363 elderly patients (mean age, 83.4 years) with severe aortic stenosis trapped particulate debris as intended, the mean volume of new lesions in the protected areas of the brain was reduced by 42%, and the number and volume of new lesions correlated with neurocognitive outcomes at 30 days.
However, the reduction in lesion volume did not achieve statistical significance, and the improvement in neurocognitive function also did not reach statistical significance.
In addition, “the sample size was clearly too low to assess clinical outcomes, and in retrospect, was also too low to evaluate follow-up MRI findings or neurocognitive outcomes.” Nevertheless, the trial “provides reassuring evidence of device safety,” said Samir R. Kapadia, MD, of the Cleveland Clinic (J Am Coll Cardiol. 2016 Nov 1. doi: 10.1016/j.jacc.2016.10.023).
In this prospective study, the investigators assessed patients at 17 medical centers in the United States and 2 in Germany. In addition to being elderly, the study patients were at high risk because of frequent comorbidities, including atrial fibrillation (31.7%) and prior stroke (5.8%).
The remaining 123 patients underwent TAVR but not MRI in a safety arm of the trial.
The protection devices were placed “without safety concerns” in most patients. The rate of major adverse events with the device was 7.3%, markedly less than the 18.3% prespecified performance goal for this outcome. Total procedure time was lengthened by only 13 minutes when the device was used, and total fluoroscopy time was increased by only 3 minutes. These findings demonstrate the overall safety of using the device, Dr. Kapadia said.
Debris including thrombus with tissue elements, artery wall particles, calcifications, valve tissue, and foreign materials was retrieved from the filters in 99% of patients.
The mean volume of new cerebral lesions in areas of the brain protected by the device was reduced by 42%, compared with that in patients who underwent TAVR without the protection device. However, this reduction was not statistically significant, so the primary efficacy endpoint of the study was not met.
Similarly, neurocognitive testing at 30 days showed that the volume of new lesions correlated with poorer outcomes. However, the difference in neurocognitive function between the intervention group and the control group did not reach statistical significance.
Several limitations likely contributed to this lack of statistical significance, Dr. Kapadia said.
First, the 5-day “window” for MRI assessment was too long. Both the number and the volume of new lesions rapidly changed over time, which led to marked variance in MRI findings depending on when the images were taken.
In addition, only one TAVR device was available at the time the trial was designed, so the study wasn’t stratified by type of valve device. But several new devices became available during the study, and the study investigators were permitted to use any of them. Both pre- and postimplantation techniques differ among these TAVR devices, but these differences could not be accounted for, given the study design.
Also, certain risk factors for stroke, especially certain findings on baseline MRI, were not understood when the trial was designed, and those factors also were not accounted for, Dr. Kapadia said.
Claret Medical funded the study. Dr. Kapadia reported having no relevant financial disclosures; his associates reported numerous ties to industry sources. The meeting was sponsored by the Cardiovascular Research Foundation.
From a logical standpoint, a device that collects cerebral embolic material in 99% of cases should prevent ischemic brain injury, yet the findings from this randomized trial don’t appear to support the routine use of such devices. But it would be inappropriate and unfair to close the book on cerebral protection after this chapter.
The authors acknowledge that an MRI “window” of 5 days creates too much heterogeneity in the data, that multiple TAVR devices requiring different implantation techniques further muddy the picture, and that in retrospect the sample size was inadequate and the study was underpowered. In addition, rigorous neurocognitive assessment can be challenging in elderly, recovering patients, and results can depend on the time of day and the patient’s alertness.
Despite the negative findings regarding both primary and secondary endpoints, the data do show the overall safety of embolic protection devices. We are dealing with a potential benefit that cannot be ignored as TAVR shifts to younger and lower-risk patients.
Azeem Latib, MD, is in the interventional cardiology unit at San Raffaele Scientific Institute in Milan. Matteo Pagnesi, MD, is in the interventional cardiology unit at EMO-GVM Centro Cuore Columbus in Milan. San Raffaele Scientific Institute has been involved in clinical studies of embolic protection devices made by Claret Medical, Innovative Cardiovascular Solutions, and Keystone Heart. Dr. Latib and Dr. Pagnesi reported having no other relevant financial disclosures. They made these remarks in an editorial accompanying Dr. Kapadia’s report (J Am Coll Cardiol. 2016 Nov 1. doi: 10.1016/j.jacc.2016.10.036).
From a logical standpoint, a device that collects cerebral embolic material in 99% of cases should prevent ischemic brain injury, yet the findings from this randomized trial don’t appear to support the routine use of such devices. But it would be inappropriate and unfair to close the book on cerebral protection after this chapter.
The authors acknowledge that an MRI “window” of 5 days creates too much heterogeneity in the data, that multiple TAVR devices requiring different implantation techniques further muddy the picture, and that in retrospect the sample size was inadequate and the study was underpowered. In addition, rigorous neurocognitive assessment can be challenging in elderly, recovering patients, and results can depend on the time of day and the patient’s alertness.
Despite the negative findings regarding both primary and secondary endpoints, the data do show the overall safety of embolic protection devices. We are dealing with a potential benefit that cannot be ignored as TAVR shifts to younger and lower-risk patients.
Azeem Latib, MD, is in the interventional cardiology unit at San Raffaele Scientific Institute in Milan. Matteo Pagnesi, MD, is in the interventional cardiology unit at EMO-GVM Centro Cuore Columbus in Milan. San Raffaele Scientific Institute has been involved in clinical studies of embolic protection devices made by Claret Medical, Innovative Cardiovascular Solutions, and Keystone Heart. Dr. Latib and Dr. Pagnesi reported having no other relevant financial disclosures. They made these remarks in an editorial accompanying Dr. Kapadia’s report (J Am Coll Cardiol. 2016 Nov 1. doi: 10.1016/j.jacc.2016.10.036).
From a logical standpoint, a device that collects cerebral embolic material in 99% of cases should prevent ischemic brain injury, yet the findings from this randomized trial don’t appear to support the routine use of such devices. But it would be inappropriate and unfair to close the book on cerebral protection after this chapter.
The authors acknowledge that an MRI “window” of 5 days creates too much heterogeneity in the data, that multiple TAVR devices requiring different implantation techniques further muddy the picture, and that in retrospect the sample size was inadequate and the study was underpowered. In addition, rigorous neurocognitive assessment can be challenging in elderly, recovering patients, and results can depend on the time of day and the patient’s alertness.
Despite the negative findings regarding both primary and secondary endpoints, the data do show the overall safety of embolic protection devices. We are dealing with a potential benefit that cannot be ignored as TAVR shifts to younger and lower-risk patients.
Azeem Latib, MD, is in the interventional cardiology unit at San Raffaele Scientific Institute in Milan. Matteo Pagnesi, MD, is in the interventional cardiology unit at EMO-GVM Centro Cuore Columbus in Milan. San Raffaele Scientific Institute has been involved in clinical studies of embolic protection devices made by Claret Medical, Innovative Cardiovascular Solutions, and Keystone Heart. Dr. Latib and Dr. Pagnesi reported having no other relevant financial disclosures. They made these remarks in an editorial accompanying Dr. Kapadia’s report (J Am Coll Cardiol. 2016 Nov 1. doi: 10.1016/j.jacc.2016.10.036).
The largest randomized clinical trial to assess the safety and efficacy of cerebral embolic protection systems during transcatheter aortic valve replacement yielded puzzling and somewhat contradictory results, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology.
Virtually every device in this industry-sponsored study involving 363 elderly patients (mean age, 83.4 years) with severe aortic stenosis trapped particulate debris as intended, the mean volume of new lesions in the protected areas of the brain was reduced by 42%, and the number and volume of new lesions correlated with neurocognitive outcomes at 30 days.
However, the reduction in lesion volume did not achieve statistical significance, and the improvement in neurocognitive function also did not reach statistical significance.
In addition, “the sample size was clearly too low to assess clinical outcomes, and in retrospect, was also too low to evaluate follow-up MRI findings or neurocognitive outcomes.” Nevertheless, the trial “provides reassuring evidence of device safety,” said Samir R. Kapadia, MD, of the Cleveland Clinic (J Am Coll Cardiol. 2016 Nov 1. doi: 10.1016/j.jacc.2016.10.023).
In this prospective study, the investigators assessed patients at 17 medical centers in the United States and 2 in Germany. In addition to being elderly, the study patients were at high risk because of frequent comorbidities, including atrial fibrillation (31.7%) and prior stroke (5.8%).
The remaining 123 patients underwent TAVR but not MRI in a safety arm of the trial.
The protection devices were placed “without safety concerns” in most patients. The rate of major adverse events with the device was 7.3%, markedly less than the 18.3% prespecified performance goal for this outcome. Total procedure time was lengthened by only 13 minutes when the device was used, and total fluoroscopy time was increased by only 3 minutes. These findings demonstrate the overall safety of using the device, Dr. Kapadia said.
Debris including thrombus with tissue elements, artery wall particles, calcifications, valve tissue, and foreign materials was retrieved from the filters in 99% of patients.
The mean volume of new cerebral lesions in areas of the brain protected by the device was reduced by 42%, compared with that in patients who underwent TAVR without the protection device. However, this reduction was not statistically significant, so the primary efficacy endpoint of the study was not met.
Similarly, neurocognitive testing at 30 days showed that the volume of new lesions correlated with poorer outcomes. However, the difference in neurocognitive function between the intervention group and the control group did not reach statistical significance.
Several limitations likely contributed to this lack of statistical significance, Dr. Kapadia said.
First, the 5-day “window” for MRI assessment was too long. Both the number and the volume of new lesions rapidly changed over time, which led to marked variance in MRI findings depending on when the images were taken.
In addition, only one TAVR device was available at the time the trial was designed, so the study wasn’t stratified by type of valve device. But several new devices became available during the study, and the study investigators were permitted to use any of them. Both pre- and postimplantation techniques differ among these TAVR devices, but these differences could not be accounted for, given the study design.
Also, certain risk factors for stroke, especially certain findings on baseline MRI, were not understood when the trial was designed, and those factors also were not accounted for, Dr. Kapadia said.
Claret Medical funded the study. Dr. Kapadia reported having no relevant financial disclosures; his associates reported numerous ties to industry sources. The meeting was sponsored by the Cardiovascular Research Foundation.
The largest randomized clinical trial to assess the safety and efficacy of cerebral embolic protection systems during transcatheter aortic valve replacement yielded puzzling and somewhat contradictory results, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology.
Virtually every device in this industry-sponsored study involving 363 elderly patients (mean age, 83.4 years) with severe aortic stenosis trapped particulate debris as intended, the mean volume of new lesions in the protected areas of the brain was reduced by 42%, and the number and volume of new lesions correlated with neurocognitive outcomes at 30 days.
However, the reduction in lesion volume did not achieve statistical significance, and the improvement in neurocognitive function also did not reach statistical significance.
In addition, “the sample size was clearly too low to assess clinical outcomes, and in retrospect, was also too low to evaluate follow-up MRI findings or neurocognitive outcomes.” Nevertheless, the trial “provides reassuring evidence of device safety,” said Samir R. Kapadia, MD, of the Cleveland Clinic (J Am Coll Cardiol. 2016 Nov 1. doi: 10.1016/j.jacc.2016.10.023).
In this prospective study, the investigators assessed patients at 17 medical centers in the United States and 2 in Germany. In addition to being elderly, the study patients were at high risk because of frequent comorbidities, including atrial fibrillation (31.7%) and prior stroke (5.8%).
The remaining 123 patients underwent TAVR but not MRI in a safety arm of the trial.
The protection devices were placed “without safety concerns” in most patients. The rate of major adverse events with the device was 7.3%, markedly less than the 18.3% prespecified performance goal for this outcome. Total procedure time was lengthened by only 13 minutes when the device was used, and total fluoroscopy time was increased by only 3 minutes. These findings demonstrate the overall safety of using the device, Dr. Kapadia said.
Debris including thrombus with tissue elements, artery wall particles, calcifications, valve tissue, and foreign materials was retrieved from the filters in 99% of patients.
The mean volume of new cerebral lesions in areas of the brain protected by the device was reduced by 42%, compared with that in patients who underwent TAVR without the protection device. However, this reduction was not statistically significant, so the primary efficacy endpoint of the study was not met.
Similarly, neurocognitive testing at 30 days showed that the volume of new lesions correlated with poorer outcomes. However, the difference in neurocognitive function between the intervention group and the control group did not reach statistical significance.
Several limitations likely contributed to this lack of statistical significance, Dr. Kapadia said.
First, the 5-day “window” for MRI assessment was too long. Both the number and the volume of new lesions rapidly changed over time, which led to marked variance in MRI findings depending on when the images were taken.
In addition, only one TAVR device was available at the time the trial was designed, so the study wasn’t stratified by type of valve device. But several new devices became available during the study, and the study investigators were permitted to use any of them. Both pre- and postimplantation techniques differ among these TAVR devices, but these differences could not be accounted for, given the study design.
Also, certain risk factors for stroke, especially certain findings on baseline MRI, were not understood when the trial was designed, and those factors also were not accounted for, Dr. Kapadia said.
Claret Medical funded the study. Dr. Kapadia reported having no relevant financial disclosures; his associates reported numerous ties to industry sources. The meeting was sponsored by the Cardiovascular Research Foundation.
Key clinical point: The largest randomized clinical trial to assess the safety and efficacy of cerebral embolic protection systems during TAVR yielded puzzling and contradictory results.
Major finding: Debris including thrombus with tissue elements, artery wall particles, calcifications, valve tissue, and foreign materials was retrieved from the cerebral protection filters in 99% of patients.
Data source: A prospective, international, randomized trial involving 363 elderly patients undergoing TAVR for severe aortic stenosis.
Disclosures: Claret Medical funded the study. Dr. Kapadia reported having no relevant financial disclosures; his associates reported numerous ties to industry sources.
Resorbable scaffold appears safe, effective in diabetes patients
An everolimus-eluting resorbable scaffold appeared to be safe and effective for percutaneous coronary intervention (PCI) in patients with diabetes and noncomplex coronary lesions, according to a study presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology: Cardiovascular Interventions.
Patients with diabetes constitute an important and increasingly prevalent subgroup of PCI patients, who are at high risk of adverse clinical and angiographic outcomes such as MI, stent thrombosis, restenosis, and death. This is thought to be due to diabetic patients’ greater level of vascular inflammation and tendency toward a prothrombotic state and more complex angiographic features, said Dean J. Kereiakes, MD, of the Christ Hospital Heart and Vascular Center, Lindner Research Center, Cincinnati.
The substudy participants all received at least one resorbable scaffold in at least one target lesion. A total of 27.3% were insulin dependent and nearly 60% had HbA1c levels exceeding 7.0%. Notably, 18% of all the treated lesions in this analysis were less than 2.25 mm in diameter as assessed by quantitative coronary angiography, and approximately 60% had moderately to severely complex morphology.
The primary endpoint – the rate of target-lesion failure at 1-year follow-up – was 8.3%, which was well below the prespecified performance goal of 12.7%. This rate ranged from 4.4% to 10.9% across the different trials. A sensitivity analysis confirmed that the 1-year rate of target-lesion failure was significantly lower than the prespecified performance goal.
The rates of target-lesion failure, target-vessel MI, ischemia-driven target-lesion revascularization, and scaffold thrombosis were significantly higher in diabetic patients who required insulin than in those who did not. Older patient age, insulin dependency, and small target-vessel diameter all were independent predictors of target-lesion failure at 1 year.
The overall 1-year rate of scaffold thrombosis in this study was 2.3%, which is not surprising given the study population’s risk factors. For diabetic patients with appropriately sized vessels of greater than 2.25 mm diameter, the scaffold thrombosis rate was lower (1.3%).
In addition to being underpowered to assess rare adverse events, this study was limited in that it reported outcomes at 1 year, before resorption of the device was complete. It also reflects the first-time clinical experience with a resorbable scaffold for most of the participating investigators, “and one would expect that as with all new medical procedures, results will improve over time with increased operator experience,” the coauthors wrote.
Dr. Kereiakes reported being a consultant to Abbott Vascular, and his associates also reported ties to the company and to other industry sources.
An everolimus-eluting resorbable scaffold appeared to be safe and effective for percutaneous coronary intervention (PCI) in patients with diabetes and noncomplex coronary lesions, according to a study presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology: Cardiovascular Interventions.
Patients with diabetes constitute an important and increasingly prevalent subgroup of PCI patients, who are at high risk of adverse clinical and angiographic outcomes such as MI, stent thrombosis, restenosis, and death. This is thought to be due to diabetic patients’ greater level of vascular inflammation and tendency toward a prothrombotic state and more complex angiographic features, said Dean J. Kereiakes, MD, of the Christ Hospital Heart and Vascular Center, Lindner Research Center, Cincinnati.
The substudy participants all received at least one resorbable scaffold in at least one target lesion. A total of 27.3% were insulin dependent and nearly 60% had HbA1c levels exceeding 7.0%. Notably, 18% of all the treated lesions in this analysis were less than 2.25 mm in diameter as assessed by quantitative coronary angiography, and approximately 60% had moderately to severely complex morphology.
The primary endpoint – the rate of target-lesion failure at 1-year follow-up – was 8.3%, which was well below the prespecified performance goal of 12.7%. This rate ranged from 4.4% to 10.9% across the different trials. A sensitivity analysis confirmed that the 1-year rate of target-lesion failure was significantly lower than the prespecified performance goal.
The rates of target-lesion failure, target-vessel MI, ischemia-driven target-lesion revascularization, and scaffold thrombosis were significantly higher in diabetic patients who required insulin than in those who did not. Older patient age, insulin dependency, and small target-vessel diameter all were independent predictors of target-lesion failure at 1 year.
The overall 1-year rate of scaffold thrombosis in this study was 2.3%, which is not surprising given the study population’s risk factors. For diabetic patients with appropriately sized vessels of greater than 2.25 mm diameter, the scaffold thrombosis rate was lower (1.3%).
In addition to being underpowered to assess rare adverse events, this study was limited in that it reported outcomes at 1 year, before resorption of the device was complete. It also reflects the first-time clinical experience with a resorbable scaffold for most of the participating investigators, “and one would expect that as with all new medical procedures, results will improve over time with increased operator experience,” the coauthors wrote.
Dr. Kereiakes reported being a consultant to Abbott Vascular, and his associates also reported ties to the company and to other industry sources.
An everolimus-eluting resorbable scaffold appeared to be safe and effective for percutaneous coronary intervention (PCI) in patients with diabetes and noncomplex coronary lesions, according to a study presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology: Cardiovascular Interventions.
Patients with diabetes constitute an important and increasingly prevalent subgroup of PCI patients, who are at high risk of adverse clinical and angiographic outcomes such as MI, stent thrombosis, restenosis, and death. This is thought to be due to diabetic patients’ greater level of vascular inflammation and tendency toward a prothrombotic state and more complex angiographic features, said Dean J. Kereiakes, MD, of the Christ Hospital Heart and Vascular Center, Lindner Research Center, Cincinnati.
The substudy participants all received at least one resorbable scaffold in at least one target lesion. A total of 27.3% were insulin dependent and nearly 60% had HbA1c levels exceeding 7.0%. Notably, 18% of all the treated lesions in this analysis were less than 2.25 mm in diameter as assessed by quantitative coronary angiography, and approximately 60% had moderately to severely complex morphology.
The primary endpoint – the rate of target-lesion failure at 1-year follow-up – was 8.3%, which was well below the prespecified performance goal of 12.7%. This rate ranged from 4.4% to 10.9% across the different trials. A sensitivity analysis confirmed that the 1-year rate of target-lesion failure was significantly lower than the prespecified performance goal.
The rates of target-lesion failure, target-vessel MI, ischemia-driven target-lesion revascularization, and scaffold thrombosis were significantly higher in diabetic patients who required insulin than in those who did not. Older patient age, insulin dependency, and small target-vessel diameter all were independent predictors of target-lesion failure at 1 year.
The overall 1-year rate of scaffold thrombosis in this study was 2.3%, which is not surprising given the study population’s risk factors. For diabetic patients with appropriately sized vessels of greater than 2.25 mm diameter, the scaffold thrombosis rate was lower (1.3%).
In addition to being underpowered to assess rare adverse events, this study was limited in that it reported outcomes at 1 year, before resorption of the device was complete. It also reflects the first-time clinical experience with a resorbable scaffold for most of the participating investigators, “and one would expect that as with all new medical procedures, results will improve over time with increased operator experience,” the coauthors wrote.
Dr. Kereiakes reported being a consultant to Abbott Vascular, and his associates also reported ties to the company and to other industry sources.
Key clinical point:
Major finding: The primary endpoint – the rate of target-lesion failure at 1 year follow-up – was 8.3%, which was well below the prespecified performance goal of 12.7%.
Data source: A prespecified formal substudy of 754 patients with diabetes who participated in three clinical trials and one device registry, assessing 1-year outcomes after PCI.
Disclosures: This pooled analysis, plus all the contributing trials and the device registry, were funded by Abbott Vascular, maker of the resorbable scaffold. Dr. Kereiakes reported being a consultant to Abbott Vascular, and his associates also reported ties to the company and to other industry sources.