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Transcatheter repair for tricuspid regurgitation holds up at 1 year
SAN DIEGO – Findings were reported in a session and press conference at the Transcatheter Cardiovascular Therapeutics annual meeting.
Research on the tricuspid valve, “the so-called forgotten valve,” is limited, commented lead investigator Jörg Hausleiter, MD, of the Medizinische Klinik und Poliklinik I at the Klinikum der Universität München and the Munich Heart Alliance. But there is unmet need for transcatheter treatment of high-risk patients having symptomatic tricuspid regurgitation (TR).
“The MitraClip has been used in several sites in off-label and compassionate-use programs to treat these patients,” he noted. “But the data which are available so far are really just looking at the early outcome, like 30 days.”
Dr. Hausleiter and his colleagues undertook a retrospective cohort study of a subgroup of 249 patients undergoing edge-to-edge valve repair for symptomatic TR from the international, multidevice TriValve Registry. All received conventional MitraClips (Abbott Vascular) through off-label or compassionate-use programs.
The procedure was successful, reducing regurgitation to mild or moderate levels in nearly four-fifths of patients by discharge. And procedural success was associated with lower risk of rehospitalization and death.
At 1 year, more than two-thirds of all patients had achieved a New York Heart Association (NYHA) functional class of I or II. In addition, prevalence of peripheral edema had fallen dramatically.
“We were able to demonstrate that the TR reduction is durable and that this also improves the clinical outcome at 1 year,” Dr. Hausleiter concluded.
Uptake and applicability
This procedure will likely be increasingly used in Europe and will find its way into U.S. practice in the not-so-distant future, Dr. Hausleiter predicted. “The MitraClip actually is being used now in a modified version in trials, so that this edge-to-edge therapy is applied for TR. And the TRILUMINATE trial has just finished its enrollment in Europe. I guess that we are going to see EU Mark approval for this therapy also next year. At the same time, a U.S. study is currently being planned and will start very soon with this device, so you are going to see this type of therapy at least being investigated within the next few months.”
The procedure is applicable to a large proportion of patients with TR, including the sizable share having comorbid mitral regurgitation (MR), according to Dr. Hausleiter. In fact, more than half of the study patients had treatment of MR during the same procedure for their tricuspid valve.
“How were outcomes compared, mitral clip plus tricuspid clip, versus tricuspid clip alone? Could some of this benefit be attributed to the mitral clip procedure?” asked press conference panelist Mayra Guerrero, MD, a senior associate consultant in interventional cardiology in the department of cardiovascular medicine at the Mayo Clinic Hospital, Rochester, Minn.
The two groups had essentially the same mortality rates and improvements in NYHA class, Dr. Hausleiter said. “So we did not observe any difference between those patients who were just treated on the tricuspid side and those patients who had combined treatment. Of course the patients differed a bit in their baseline characteristics, but the outcome was very much the same.”
“With the new data we have, operators and teams may be encouraged to start treating functional MR. I personally think that, if we do that, we should probably evaluate the response and reevaluate the severity of TR after all therapies to the mitral valve have been provided, before we intervene on the tricuspid valve, until we have more data,” Dr. Guerrero further commented. “Do you agree?”
“The tricuspid regurgitation can also improve after treatment of the mitral side. However, when we look at least at the published data, in at least 50% of patients who have severe TR, this TR is not improving,” Dr. Hausleiter replied. In addition, registry data suggest that these patients with severe TR have higher in-hospital, 30-day, and 1-year mortality, compared with patients whose TR is not severe. “Since these are frail patients and you don’t want to bring them too often back to the hospital, if the procedure can be performed very easily, I think there might be a good rationale to combine this.”
Study details
The patients Dr. Hausleiter and his coinvestigators studied had symptomatic TR, predominantly of grade 3+ or 4+, despite receiving adequate medical therapy, as well as a high operative risk, with an average EuroSCORE II of 11.2%. On average, two MitraClips were placed in their tricuspid valve during the procedure.
“We were able to demonstrate that this procedure can be performed very safely. There was a mortality of only 2% in the first 30 days, and one conversion to surgery,” Dr. Hausleiter reported at the meeting, which is sponsored by the Cardiovascular Research Foundation. “We were able to reduce the TR by at least one grade in 89% of patients, and concomitant treatment for mitral regurgitation was also performed in the same procedure in 52%.”
The rate of procedural success, defined as achievement of TR grade of 1+ or 2+ at discharge, was 77%. Independent predictors of procedural failure were noncentral/nonanteroseptal TR jet location and larger TR effective regurgitant orifice area, tenting area, and leaflet gap.
With a mean follow-up of about 10 months, compared with peers in whom the procedure failed, patients in whom it was successful had a higher 1-year rate of freedom from unplanned rehospitalization or death (70.1% vs. 49.7%; P less than .0001).
The 77% rate of procedural success at discharge was largely maintained at 1 year, when it was 72%. There was also a significant improvement in NYHA class distribution in the entire cohort (P less than .001), with 69% of patients attaining class I or II at this time point, compared with virtually none at baseline. Prevalence of peripheral edema fell from 84% to 26% (P less than .001).
Dr. Hausleiter reported that he receives research support and speaker honoraria from Abbott Vascular and Edwards Lifesciences. The registry is sponsored by the University of Zürich.
SAN DIEGO – Findings were reported in a session and press conference at the Transcatheter Cardiovascular Therapeutics annual meeting.
Research on the tricuspid valve, “the so-called forgotten valve,” is limited, commented lead investigator Jörg Hausleiter, MD, of the Medizinische Klinik und Poliklinik I at the Klinikum der Universität München and the Munich Heart Alliance. But there is unmet need for transcatheter treatment of high-risk patients having symptomatic tricuspid regurgitation (TR).
“The MitraClip has been used in several sites in off-label and compassionate-use programs to treat these patients,” he noted. “But the data which are available so far are really just looking at the early outcome, like 30 days.”
Dr. Hausleiter and his colleagues undertook a retrospective cohort study of a subgroup of 249 patients undergoing edge-to-edge valve repair for symptomatic TR from the international, multidevice TriValve Registry. All received conventional MitraClips (Abbott Vascular) through off-label or compassionate-use programs.
The procedure was successful, reducing regurgitation to mild or moderate levels in nearly four-fifths of patients by discharge. And procedural success was associated with lower risk of rehospitalization and death.
At 1 year, more than two-thirds of all patients had achieved a New York Heart Association (NYHA) functional class of I or II. In addition, prevalence of peripheral edema had fallen dramatically.
“We were able to demonstrate that the TR reduction is durable and that this also improves the clinical outcome at 1 year,” Dr. Hausleiter concluded.
Uptake and applicability
This procedure will likely be increasingly used in Europe and will find its way into U.S. practice in the not-so-distant future, Dr. Hausleiter predicted. “The MitraClip actually is being used now in a modified version in trials, so that this edge-to-edge therapy is applied for TR. And the TRILUMINATE trial has just finished its enrollment in Europe. I guess that we are going to see EU Mark approval for this therapy also next year. At the same time, a U.S. study is currently being planned and will start very soon with this device, so you are going to see this type of therapy at least being investigated within the next few months.”
The procedure is applicable to a large proportion of patients with TR, including the sizable share having comorbid mitral regurgitation (MR), according to Dr. Hausleiter. In fact, more than half of the study patients had treatment of MR during the same procedure for their tricuspid valve.
“How were outcomes compared, mitral clip plus tricuspid clip, versus tricuspid clip alone? Could some of this benefit be attributed to the mitral clip procedure?” asked press conference panelist Mayra Guerrero, MD, a senior associate consultant in interventional cardiology in the department of cardiovascular medicine at the Mayo Clinic Hospital, Rochester, Minn.
The two groups had essentially the same mortality rates and improvements in NYHA class, Dr. Hausleiter said. “So we did not observe any difference between those patients who were just treated on the tricuspid side and those patients who had combined treatment. Of course the patients differed a bit in their baseline characteristics, but the outcome was very much the same.”
“With the new data we have, operators and teams may be encouraged to start treating functional MR. I personally think that, if we do that, we should probably evaluate the response and reevaluate the severity of TR after all therapies to the mitral valve have been provided, before we intervene on the tricuspid valve, until we have more data,” Dr. Guerrero further commented. “Do you agree?”
“The tricuspid regurgitation can also improve after treatment of the mitral side. However, when we look at least at the published data, in at least 50% of patients who have severe TR, this TR is not improving,” Dr. Hausleiter replied. In addition, registry data suggest that these patients with severe TR have higher in-hospital, 30-day, and 1-year mortality, compared with patients whose TR is not severe. “Since these are frail patients and you don’t want to bring them too often back to the hospital, if the procedure can be performed very easily, I think there might be a good rationale to combine this.”
Study details
The patients Dr. Hausleiter and his coinvestigators studied had symptomatic TR, predominantly of grade 3+ or 4+, despite receiving adequate medical therapy, as well as a high operative risk, with an average EuroSCORE II of 11.2%. On average, two MitraClips were placed in their tricuspid valve during the procedure.
“We were able to demonstrate that this procedure can be performed very safely. There was a mortality of only 2% in the first 30 days, and one conversion to surgery,” Dr. Hausleiter reported at the meeting, which is sponsored by the Cardiovascular Research Foundation. “We were able to reduce the TR by at least one grade in 89% of patients, and concomitant treatment for mitral regurgitation was also performed in the same procedure in 52%.”
The rate of procedural success, defined as achievement of TR grade of 1+ or 2+ at discharge, was 77%. Independent predictors of procedural failure were noncentral/nonanteroseptal TR jet location and larger TR effective regurgitant orifice area, tenting area, and leaflet gap.
With a mean follow-up of about 10 months, compared with peers in whom the procedure failed, patients in whom it was successful had a higher 1-year rate of freedom from unplanned rehospitalization or death (70.1% vs. 49.7%; P less than .0001).
The 77% rate of procedural success at discharge was largely maintained at 1 year, when it was 72%. There was also a significant improvement in NYHA class distribution in the entire cohort (P less than .001), with 69% of patients attaining class I or II at this time point, compared with virtually none at baseline. Prevalence of peripheral edema fell from 84% to 26% (P less than .001).
Dr. Hausleiter reported that he receives research support and speaker honoraria from Abbott Vascular and Edwards Lifesciences. The registry is sponsored by the University of Zürich.
SAN DIEGO – Findings were reported in a session and press conference at the Transcatheter Cardiovascular Therapeutics annual meeting.
Research on the tricuspid valve, “the so-called forgotten valve,” is limited, commented lead investigator Jörg Hausleiter, MD, of the Medizinische Klinik und Poliklinik I at the Klinikum der Universität München and the Munich Heart Alliance. But there is unmet need for transcatheter treatment of high-risk patients having symptomatic tricuspid regurgitation (TR).
“The MitraClip has been used in several sites in off-label and compassionate-use programs to treat these patients,” he noted. “But the data which are available so far are really just looking at the early outcome, like 30 days.”
Dr. Hausleiter and his colleagues undertook a retrospective cohort study of a subgroup of 249 patients undergoing edge-to-edge valve repair for symptomatic TR from the international, multidevice TriValve Registry. All received conventional MitraClips (Abbott Vascular) through off-label or compassionate-use programs.
The procedure was successful, reducing regurgitation to mild or moderate levels in nearly four-fifths of patients by discharge. And procedural success was associated with lower risk of rehospitalization and death.
At 1 year, more than two-thirds of all patients had achieved a New York Heart Association (NYHA) functional class of I or II. In addition, prevalence of peripheral edema had fallen dramatically.
“We were able to demonstrate that the TR reduction is durable and that this also improves the clinical outcome at 1 year,” Dr. Hausleiter concluded.
Uptake and applicability
This procedure will likely be increasingly used in Europe and will find its way into U.S. practice in the not-so-distant future, Dr. Hausleiter predicted. “The MitraClip actually is being used now in a modified version in trials, so that this edge-to-edge therapy is applied for TR. And the TRILUMINATE trial has just finished its enrollment in Europe. I guess that we are going to see EU Mark approval for this therapy also next year. At the same time, a U.S. study is currently being planned and will start very soon with this device, so you are going to see this type of therapy at least being investigated within the next few months.”
The procedure is applicable to a large proportion of patients with TR, including the sizable share having comorbid mitral regurgitation (MR), according to Dr. Hausleiter. In fact, more than half of the study patients had treatment of MR during the same procedure for their tricuspid valve.
“How were outcomes compared, mitral clip plus tricuspid clip, versus tricuspid clip alone? Could some of this benefit be attributed to the mitral clip procedure?” asked press conference panelist Mayra Guerrero, MD, a senior associate consultant in interventional cardiology in the department of cardiovascular medicine at the Mayo Clinic Hospital, Rochester, Minn.
The two groups had essentially the same mortality rates and improvements in NYHA class, Dr. Hausleiter said. “So we did not observe any difference between those patients who were just treated on the tricuspid side and those patients who had combined treatment. Of course the patients differed a bit in their baseline characteristics, but the outcome was very much the same.”
“With the new data we have, operators and teams may be encouraged to start treating functional MR. I personally think that, if we do that, we should probably evaluate the response and reevaluate the severity of TR after all therapies to the mitral valve have been provided, before we intervene on the tricuspid valve, until we have more data,” Dr. Guerrero further commented. “Do you agree?”
“The tricuspid regurgitation can also improve after treatment of the mitral side. However, when we look at least at the published data, in at least 50% of patients who have severe TR, this TR is not improving,” Dr. Hausleiter replied. In addition, registry data suggest that these patients with severe TR have higher in-hospital, 30-day, and 1-year mortality, compared with patients whose TR is not severe. “Since these are frail patients and you don’t want to bring them too often back to the hospital, if the procedure can be performed very easily, I think there might be a good rationale to combine this.”
Study details
The patients Dr. Hausleiter and his coinvestigators studied had symptomatic TR, predominantly of grade 3+ or 4+, despite receiving adequate medical therapy, as well as a high operative risk, with an average EuroSCORE II of 11.2%. On average, two MitraClips were placed in their tricuspid valve during the procedure.
“We were able to demonstrate that this procedure can be performed very safely. There was a mortality of only 2% in the first 30 days, and one conversion to surgery,” Dr. Hausleiter reported at the meeting, which is sponsored by the Cardiovascular Research Foundation. “We were able to reduce the TR by at least one grade in 89% of patients, and concomitant treatment for mitral regurgitation was also performed in the same procedure in 52%.”
The rate of procedural success, defined as achievement of TR grade of 1+ or 2+ at discharge, was 77%. Independent predictors of procedural failure were noncentral/nonanteroseptal TR jet location and larger TR effective regurgitant orifice area, tenting area, and leaflet gap.
With a mean follow-up of about 10 months, compared with peers in whom the procedure failed, patients in whom it was successful had a higher 1-year rate of freedom from unplanned rehospitalization or death (70.1% vs. 49.7%; P less than .0001).
The 77% rate of procedural success at discharge was largely maintained at 1 year, when it was 72%. There was also a significant improvement in NYHA class distribution in the entire cohort (P less than .001), with 69% of patients attaining class I or II at this time point, compared with virtually none at baseline. Prevalence of peripheral edema fell from 84% to 26% (P less than .001).
Dr. Hausleiter reported that he receives research support and speaker honoraria from Abbott Vascular and Edwards Lifesciences. The registry is sponsored by the University of Zürich.
REPORTING FROM TCT 2018
Key clinical point: Transcatheter edge-to-edge valve repair for tricuspid regurgitation is safe and effective at 1 year.
Major finding: The procedure had a success rate of 77% and netted a 1-year improvement in New York Heart Association class (P less than .001), with 69% of patients achieving class I or II.
Study details: A retrospective cohort study of a subgroup of 249 patients undergoing edge-to-edge valve repair for symptomatic tricuspid regurgitation from the TriValve Registry.
Disclosures: Dr. Hausleiter reported that he receives research support and speaker honoraria from Abbott Vascular and Edwards Lifesciences. The registry is sponsored by the University of Zürich.
BIOFLOW V: Orsiro outperforms Xience stent
SAN DIEGO – Seemingly nuanced differences between drug-eluting stents can translate to substantial differences in clinical outcomes longer term, updated results of the BIOFLOW V randomized trial reported at the Transcatheter Cardiovascular Therapeutics annual meeting suggest.
“As we have celebrated recently the 30th year of stent implantation, coronary drug-eluting stent development has included new metal alloys, changes in stent architecture, and bioresorbable polymers,” commented lead investigator David E. Kandzari, MD, director of interventional cardiology and chief scientific officer at the Piedmont Heart Institute, Atlanta. “Yet whether these advancements improve long-term clinical safety and efficacy has been inconsistent in previous studies.”
BIOFLOW V compared the Orsiro ultrathin-strut, bioresorbable-polymer, sirolimus-eluting stent with the Xience thin-strut, durable-polymer, everolimus-eluting stent among 1,334 patients undergoing percutaneous coronary intervention.
Initial results showed that the primary outcome of 1-year target lesion failure – the composite of cardiac death, ischemia-driven target lesion revascularization, and target vessel–related myocardial infarction – was significantly lower in the Orsiro stent group (6% vs. 10%, P = .0399) (Lancet. 2017;390:1843-52). Superiority at this time point was mainly driven by a lower rate of target vessel–related MI (5% vs. 8%, P = .0155).
With the update, now at 2 years of follow-up, the significant difference in target lesion failure rate persisted, with a rate of 7.1% with Orsiro stents versus 11.9% with Xience stents (P = .015), according to results reported at the meeting and simultaneously published (J Am Coll Cardiol. 2018 Sep 19. doi: 10.1016/j.jacc.2018.09.019).
There was likewise still a significant difference in favor of the Orsiro stent in target vessel–related MI, but the rate of ischemia-driven target lesion revascularization was now significantly lower as well. In addition, this stent yielded a lower rate of definite or probable stent thrombosis occurring late or very late.
“Altogether, these results not only advance a standard of comparison for new drug-eluting stents, but they direct our attention to strut thickness and polymer composition as key features for iterative drug-eluting stent development,” Dr. Kandzari summarized. Additional BIOFLOW V follow-up, out to 5 years, is planned, he noted.
Session comoderator Fernando Alfonso, MD, PhD, an interventional cardiologist at the Cardiovascular Institute at San Carlos University Hospital in Madrid, wondered about the role of dual-antiplatelet therapy. “Was that treatment related in some way to events? Was there any kind of interaction between those who were maintained on dual-antiplatelet therapy and those having late events?” he asked.
“Through 2 years of follow-up, adherence to dual-antiplatelet therapy was numerically identical in both groups. But it was not related in any way to either target vessel MI–related events or stent thrombosis events,” Dr. Kandzari replied.
Trial details
The BIOFLOW V trialists recruited patients from 13 countries and enrolled those who had up to three de novo target lesions in up to two native target vessels. Patients were randomized 2:1 to receive Orsiro stents (Biotronik) or Xience stents (Abbott).
At 2 years, 45.6% of those in the former group and 45.1% of those in the latter group were adherent to dual antiplatelet therapy (P = .88), Dr. Kandzari reported at the meeting, which was sponsored by the Cardiovascular Research Foundation.
The lower 2-year rate of the primary composite outcome of target lesion failure with the Orsiro stent was driven by lower rates of both target vessel–related MI (5.3% vs. 9.5%, P = .01) and ischemia-driven target lesion revascularization (2.6% vs. 4.9%, P = .04). There was still no significant difference for cardiac death (0.6% vs. 0.5%, P = 1.0).
The edge of Orsiro stents over Xience stents for target lesion failure was similar across subgroups, with the possible exception of greater benefit of the latter in patients older than 75 (P for interaction = .039).
In landmark analyses, a significant difference in rates of target vessel–related MI favoring Orsiro stents was evident both in the first 30 days after the procedure (P = .04) and from 30 days to 2 years, presumably reflecting fewer spontaneous MIs (P = .01). Ischemia-driven target lesion revascularization did not difference in the first year of follow-up (P = .72) but it did between the first and second years (P = .01).
Most measures of stent thrombosis were similar for the two groups. However, the rate of definite or probable stent thrombosis occurring late or very late (between 30 days and 2 years) was just 0.1% for Orsiro stents, compared with 1.0% for Xience stents (P = .045).
Dr. Kandzari disclosed that he receives grant/research support from Biotronik, Boston Scientific, Medtronic CardioVascular, Medinol, and Orbus Neich, and that he receives consulting fees and honoraria from Biotronik, Boston Scientific Corporation, Cardinal Health, and Medtronic CardioVascular. The trial was sponsored by Biotronik.
SAN DIEGO – Seemingly nuanced differences between drug-eluting stents can translate to substantial differences in clinical outcomes longer term, updated results of the BIOFLOW V randomized trial reported at the Transcatheter Cardiovascular Therapeutics annual meeting suggest.
“As we have celebrated recently the 30th year of stent implantation, coronary drug-eluting stent development has included new metal alloys, changes in stent architecture, and bioresorbable polymers,” commented lead investigator David E. Kandzari, MD, director of interventional cardiology and chief scientific officer at the Piedmont Heart Institute, Atlanta. “Yet whether these advancements improve long-term clinical safety and efficacy has been inconsistent in previous studies.”
BIOFLOW V compared the Orsiro ultrathin-strut, bioresorbable-polymer, sirolimus-eluting stent with the Xience thin-strut, durable-polymer, everolimus-eluting stent among 1,334 patients undergoing percutaneous coronary intervention.
Initial results showed that the primary outcome of 1-year target lesion failure – the composite of cardiac death, ischemia-driven target lesion revascularization, and target vessel–related myocardial infarction – was significantly lower in the Orsiro stent group (6% vs. 10%, P = .0399) (Lancet. 2017;390:1843-52). Superiority at this time point was mainly driven by a lower rate of target vessel–related MI (5% vs. 8%, P = .0155).
With the update, now at 2 years of follow-up, the significant difference in target lesion failure rate persisted, with a rate of 7.1% with Orsiro stents versus 11.9% with Xience stents (P = .015), according to results reported at the meeting and simultaneously published (J Am Coll Cardiol. 2018 Sep 19. doi: 10.1016/j.jacc.2018.09.019).
There was likewise still a significant difference in favor of the Orsiro stent in target vessel–related MI, but the rate of ischemia-driven target lesion revascularization was now significantly lower as well. In addition, this stent yielded a lower rate of definite or probable stent thrombosis occurring late or very late.
“Altogether, these results not only advance a standard of comparison for new drug-eluting stents, but they direct our attention to strut thickness and polymer composition as key features for iterative drug-eluting stent development,” Dr. Kandzari summarized. Additional BIOFLOW V follow-up, out to 5 years, is planned, he noted.
Session comoderator Fernando Alfonso, MD, PhD, an interventional cardiologist at the Cardiovascular Institute at San Carlos University Hospital in Madrid, wondered about the role of dual-antiplatelet therapy. “Was that treatment related in some way to events? Was there any kind of interaction between those who were maintained on dual-antiplatelet therapy and those having late events?” he asked.
“Through 2 years of follow-up, adherence to dual-antiplatelet therapy was numerically identical in both groups. But it was not related in any way to either target vessel MI–related events or stent thrombosis events,” Dr. Kandzari replied.
Trial details
The BIOFLOW V trialists recruited patients from 13 countries and enrolled those who had up to three de novo target lesions in up to two native target vessels. Patients were randomized 2:1 to receive Orsiro stents (Biotronik) or Xience stents (Abbott).
At 2 years, 45.6% of those in the former group and 45.1% of those in the latter group were adherent to dual antiplatelet therapy (P = .88), Dr. Kandzari reported at the meeting, which was sponsored by the Cardiovascular Research Foundation.
The lower 2-year rate of the primary composite outcome of target lesion failure with the Orsiro stent was driven by lower rates of both target vessel–related MI (5.3% vs. 9.5%, P = .01) and ischemia-driven target lesion revascularization (2.6% vs. 4.9%, P = .04). There was still no significant difference for cardiac death (0.6% vs. 0.5%, P = 1.0).
The edge of Orsiro stents over Xience stents for target lesion failure was similar across subgroups, with the possible exception of greater benefit of the latter in patients older than 75 (P for interaction = .039).
In landmark analyses, a significant difference in rates of target vessel–related MI favoring Orsiro stents was evident both in the first 30 days after the procedure (P = .04) and from 30 days to 2 years, presumably reflecting fewer spontaneous MIs (P = .01). Ischemia-driven target lesion revascularization did not difference in the first year of follow-up (P = .72) but it did between the first and second years (P = .01).
Most measures of stent thrombosis were similar for the two groups. However, the rate of definite or probable stent thrombosis occurring late or very late (between 30 days and 2 years) was just 0.1% for Orsiro stents, compared with 1.0% for Xience stents (P = .045).
Dr. Kandzari disclosed that he receives grant/research support from Biotronik, Boston Scientific, Medtronic CardioVascular, Medinol, and Orbus Neich, and that he receives consulting fees and honoraria from Biotronik, Boston Scientific Corporation, Cardinal Health, and Medtronic CardioVascular. The trial was sponsored by Biotronik.
SAN DIEGO – Seemingly nuanced differences between drug-eluting stents can translate to substantial differences in clinical outcomes longer term, updated results of the BIOFLOW V randomized trial reported at the Transcatheter Cardiovascular Therapeutics annual meeting suggest.
“As we have celebrated recently the 30th year of stent implantation, coronary drug-eluting stent development has included new metal alloys, changes in stent architecture, and bioresorbable polymers,” commented lead investigator David E. Kandzari, MD, director of interventional cardiology and chief scientific officer at the Piedmont Heart Institute, Atlanta. “Yet whether these advancements improve long-term clinical safety and efficacy has been inconsistent in previous studies.”
BIOFLOW V compared the Orsiro ultrathin-strut, bioresorbable-polymer, sirolimus-eluting stent with the Xience thin-strut, durable-polymer, everolimus-eluting stent among 1,334 patients undergoing percutaneous coronary intervention.
Initial results showed that the primary outcome of 1-year target lesion failure – the composite of cardiac death, ischemia-driven target lesion revascularization, and target vessel–related myocardial infarction – was significantly lower in the Orsiro stent group (6% vs. 10%, P = .0399) (Lancet. 2017;390:1843-52). Superiority at this time point was mainly driven by a lower rate of target vessel–related MI (5% vs. 8%, P = .0155).
With the update, now at 2 years of follow-up, the significant difference in target lesion failure rate persisted, with a rate of 7.1% with Orsiro stents versus 11.9% with Xience stents (P = .015), according to results reported at the meeting and simultaneously published (J Am Coll Cardiol. 2018 Sep 19. doi: 10.1016/j.jacc.2018.09.019).
There was likewise still a significant difference in favor of the Orsiro stent in target vessel–related MI, but the rate of ischemia-driven target lesion revascularization was now significantly lower as well. In addition, this stent yielded a lower rate of definite or probable stent thrombosis occurring late or very late.
“Altogether, these results not only advance a standard of comparison for new drug-eluting stents, but they direct our attention to strut thickness and polymer composition as key features for iterative drug-eluting stent development,” Dr. Kandzari summarized. Additional BIOFLOW V follow-up, out to 5 years, is planned, he noted.
Session comoderator Fernando Alfonso, MD, PhD, an interventional cardiologist at the Cardiovascular Institute at San Carlos University Hospital in Madrid, wondered about the role of dual-antiplatelet therapy. “Was that treatment related in some way to events? Was there any kind of interaction between those who were maintained on dual-antiplatelet therapy and those having late events?” he asked.
“Through 2 years of follow-up, adherence to dual-antiplatelet therapy was numerically identical in both groups. But it was not related in any way to either target vessel MI–related events or stent thrombosis events,” Dr. Kandzari replied.
Trial details
The BIOFLOW V trialists recruited patients from 13 countries and enrolled those who had up to three de novo target lesions in up to two native target vessels. Patients were randomized 2:1 to receive Orsiro stents (Biotronik) or Xience stents (Abbott).
At 2 years, 45.6% of those in the former group and 45.1% of those in the latter group were adherent to dual antiplatelet therapy (P = .88), Dr. Kandzari reported at the meeting, which was sponsored by the Cardiovascular Research Foundation.
The lower 2-year rate of the primary composite outcome of target lesion failure with the Orsiro stent was driven by lower rates of both target vessel–related MI (5.3% vs. 9.5%, P = .01) and ischemia-driven target lesion revascularization (2.6% vs. 4.9%, P = .04). There was still no significant difference for cardiac death (0.6% vs. 0.5%, P = 1.0).
The edge of Orsiro stents over Xience stents for target lesion failure was similar across subgroups, with the possible exception of greater benefit of the latter in patients older than 75 (P for interaction = .039).
In landmark analyses, a significant difference in rates of target vessel–related MI favoring Orsiro stents was evident both in the first 30 days after the procedure (P = .04) and from 30 days to 2 years, presumably reflecting fewer spontaneous MIs (P = .01). Ischemia-driven target lesion revascularization did not difference in the first year of follow-up (P = .72) but it did between the first and second years (P = .01).
Most measures of stent thrombosis were similar for the two groups. However, the rate of definite or probable stent thrombosis occurring late or very late (between 30 days and 2 years) was just 0.1% for Orsiro stents, compared with 1.0% for Xience stents (P = .045).
Dr. Kandzari disclosed that he receives grant/research support from Biotronik, Boston Scientific, Medtronic CardioVascular, Medinol, and Orbus Neich, and that he receives consulting fees and honoraria from Biotronik, Boston Scientific Corporation, Cardinal Health, and Medtronic CardioVascular. The trial was sponsored by Biotronik.
REPORTING FROM TCT 2018
Key clinical point: The Orsiro stent outperformed the Xience stent in patients undergoing PCI.
Major finding: The 2-year rate of target lesion failure was lower with the Orsiro stent than with the Xience stent (7.5% vs. 11.9%, P = .015).
Study details: A randomized controlled trial comparing the Orsiro ultrathin-strut, bioresorbable-polymer, sirolimus-eluting stent and the Xience thin-strut, durable-polymer, everolimus-eluting stent among 1,334 patients undergoing PCI (BIOFLOW V trial).
Disclosures: Dr. Kandzari disclosed that he receives grant/research support from Biotronik, Boston Scientific, Medtronic CardioVascular, Medinol, and Orbus Neich, and that he receives consulting fees and honoraria from Biotronik, Boston Scientific Corporation, Cardinal Health, and Medtronic CardioVascular. The trial was sponsored by Biotronik.
Striking racial/ethnic differences seen in RCC features
In a southwestern U.S. population having renal cell carcinoma (RCC), patient and disease characteristics differ by race/ethnicity in ways that may have implications for prevention, diagnosis, prognosis, and treatment, finds a single-center cohort study.
Investigators led by Ken Batai, PhD, of University of Arizona, Tucson, retrospectively reviewed the medical records of 294 patients with RCC as their first cancer who underwent partial or radical nephrectomy: 151 European Americans, 95 Hispanic Americans, 22 Native Americans, 9 African Americans, and 17 other race/ethnicity. About 12% overall had metastases at presentation.
On average, compared with European Americans, Hispanic Americans were about 5 years younger at diagnosis (55.8 vs. 60.5) and had higher odds of diagnosis before the age of 50 (odds ratio, 2.77), according to results published in Clinical Genitourinary Cancer.
Native Americans were even younger (49.7) and had dramatically elevated odds of diagnosis before that age (odds ratio, 6.23).
Relative to their European American counterparts, Hispanic Americans less commonly smoked (30.5% vs 48.6%) and African Americans more commonly had chronic kidney disease (37.5% vs. 5.8%). Both groups had higher prevalence of diabetes (45.6% and 54.5% vs. 21.7%). In addition, Native Americans had higher body mass index (35.2 vs. 30.7).
Clear cell histology was seen in 78.8% of European Americans, but in 92.6% of Hispanic Americans (odds ratio, 2.79) and 86.4% of Native Americans. African Americans more commonly had stage III or IV disease at diagnosis (77.8% vs. 35.3%; odds ratio, 6.51), but the racial/ethnic groups did not differ significantly on grade, tumor size, or presence of necrosis.
Among the Hispanic American patients undergoing radical nephrectomy, disease was more commonly of stage III or IV at diagnosis in those who were aged 65 or older (odds ratio, 10.48) and those who spoke Spanish as their primary language (odds ratios, 4.61).
The reasons for the observed racial/ethnic disparities remain unclear, according to Dr. Batai and his coinvestigators. Nonetheless, “it is necessary to better understand the clinical characteristics of these underserved Hispanic American and Native American populations with high kidney cancer burden,” they wrote.
“Our findings can direct future research toward elucidating the difference in tumor behavior among the different ethnic groups and health care issues causing poor outcomes,” they concluded. The findings also “bring ... awareness to practitioners treating patients from these racial/ethnic minority groups regarding the clinical characteristics and underlying issues in these patient populations.”
The study was supported by the American Cancer Society and the Partnership for Native American Cancer Prevention.
SOURCE: Batai K et al. Clin Genitourin Cancer. 2018 Oct 26. doi: 10.1016/j.clgc.2018.10.012.
In a southwestern U.S. population having renal cell carcinoma (RCC), patient and disease characteristics differ by race/ethnicity in ways that may have implications for prevention, diagnosis, prognosis, and treatment, finds a single-center cohort study.
Investigators led by Ken Batai, PhD, of University of Arizona, Tucson, retrospectively reviewed the medical records of 294 patients with RCC as their first cancer who underwent partial or radical nephrectomy: 151 European Americans, 95 Hispanic Americans, 22 Native Americans, 9 African Americans, and 17 other race/ethnicity. About 12% overall had metastases at presentation.
On average, compared with European Americans, Hispanic Americans were about 5 years younger at diagnosis (55.8 vs. 60.5) and had higher odds of diagnosis before the age of 50 (odds ratio, 2.77), according to results published in Clinical Genitourinary Cancer.
Native Americans were even younger (49.7) and had dramatically elevated odds of diagnosis before that age (odds ratio, 6.23).
Relative to their European American counterparts, Hispanic Americans less commonly smoked (30.5% vs 48.6%) and African Americans more commonly had chronic kidney disease (37.5% vs. 5.8%). Both groups had higher prevalence of diabetes (45.6% and 54.5% vs. 21.7%). In addition, Native Americans had higher body mass index (35.2 vs. 30.7).
Clear cell histology was seen in 78.8% of European Americans, but in 92.6% of Hispanic Americans (odds ratio, 2.79) and 86.4% of Native Americans. African Americans more commonly had stage III or IV disease at diagnosis (77.8% vs. 35.3%; odds ratio, 6.51), but the racial/ethnic groups did not differ significantly on grade, tumor size, or presence of necrosis.
Among the Hispanic American patients undergoing radical nephrectomy, disease was more commonly of stage III or IV at diagnosis in those who were aged 65 or older (odds ratio, 10.48) and those who spoke Spanish as their primary language (odds ratios, 4.61).
The reasons for the observed racial/ethnic disparities remain unclear, according to Dr. Batai and his coinvestigators. Nonetheless, “it is necessary to better understand the clinical characteristics of these underserved Hispanic American and Native American populations with high kidney cancer burden,” they wrote.
“Our findings can direct future research toward elucidating the difference in tumor behavior among the different ethnic groups and health care issues causing poor outcomes,” they concluded. The findings also “bring ... awareness to practitioners treating patients from these racial/ethnic minority groups regarding the clinical characteristics and underlying issues in these patient populations.”
The study was supported by the American Cancer Society and the Partnership for Native American Cancer Prevention.
SOURCE: Batai K et al. Clin Genitourin Cancer. 2018 Oct 26. doi: 10.1016/j.clgc.2018.10.012.
In a southwestern U.S. population having renal cell carcinoma (RCC), patient and disease characteristics differ by race/ethnicity in ways that may have implications for prevention, diagnosis, prognosis, and treatment, finds a single-center cohort study.
Investigators led by Ken Batai, PhD, of University of Arizona, Tucson, retrospectively reviewed the medical records of 294 patients with RCC as their first cancer who underwent partial or radical nephrectomy: 151 European Americans, 95 Hispanic Americans, 22 Native Americans, 9 African Americans, and 17 other race/ethnicity. About 12% overall had metastases at presentation.
On average, compared with European Americans, Hispanic Americans were about 5 years younger at diagnosis (55.8 vs. 60.5) and had higher odds of diagnosis before the age of 50 (odds ratio, 2.77), according to results published in Clinical Genitourinary Cancer.
Native Americans were even younger (49.7) and had dramatically elevated odds of diagnosis before that age (odds ratio, 6.23).
Relative to their European American counterparts, Hispanic Americans less commonly smoked (30.5% vs 48.6%) and African Americans more commonly had chronic kidney disease (37.5% vs. 5.8%). Both groups had higher prevalence of diabetes (45.6% and 54.5% vs. 21.7%). In addition, Native Americans had higher body mass index (35.2 vs. 30.7).
Clear cell histology was seen in 78.8% of European Americans, but in 92.6% of Hispanic Americans (odds ratio, 2.79) and 86.4% of Native Americans. African Americans more commonly had stage III or IV disease at diagnosis (77.8% vs. 35.3%; odds ratio, 6.51), but the racial/ethnic groups did not differ significantly on grade, tumor size, or presence of necrosis.
Among the Hispanic American patients undergoing radical nephrectomy, disease was more commonly of stage III or IV at diagnosis in those who were aged 65 or older (odds ratio, 10.48) and those who spoke Spanish as their primary language (odds ratios, 4.61).
The reasons for the observed racial/ethnic disparities remain unclear, according to Dr. Batai and his coinvestigators. Nonetheless, “it is necessary to better understand the clinical characteristics of these underserved Hispanic American and Native American populations with high kidney cancer burden,” they wrote.
“Our findings can direct future research toward elucidating the difference in tumor behavior among the different ethnic groups and health care issues causing poor outcomes,” they concluded. The findings also “bring ... awareness to practitioners treating patients from these racial/ethnic minority groups regarding the clinical characteristics and underlying issues in these patient populations.”
The study was supported by the American Cancer Society and the Partnership for Native American Cancer Prevention.
SOURCE: Batai K et al. Clin Genitourin Cancer. 2018 Oct 26. doi: 10.1016/j.clgc.2018.10.012.
FROM CLINICAL GENITOURINARY CANCER
Key clinical point: .
Major finding: Compared with European Americans, Hispanic Americans and Native Americans were younger at diagnosis (55.8 and 49.7 vs. 60.5 years) and more often had clear cell histology (92.6% and 86.4% vs. 78.8%), and African Americans more often had stage III/IV disease (77.8% vs. 35.3%).
Study details: U.S. single-center retrospective cohort study of 294 patients with RCC who underwent partial or radical nephrectomy.
Disclosures: The authors declared that they did not have any conflicts of interest. The study was supported by the American Cancer Society and the Partnership for Native American Cancer Prevention.
Source: Batai K et al. Clin Genitourin Cancer. 2018 Oct 26. doi: 10.1016/j.clgc.2018.10.012.
KPNA2 is “novel prognostic factor” in RCC
High expression of karyopherin alpha 2 (KPNA2), a carrier protein that helps shuttle cancer-associated proteins from the nucleus to the cytoplasm, is an adverse prognostic factor in patients with clear cell or papillary renal cell carcinoma (RCC), according to a retrospective cohort study.
Senior author Glen Kristiansen, MD, director of the Institute of Pathology at the University Hospital Bonn (Germany), and his colleagues assessed tumor levels of KPNA2 protein by immunohistochemistry in 240 clinic patients with RCC (217 with clear cell histology, 23 with papillary histology). They also assessed tumor levels of KPNA2 mRNA in 771 patients with RCC (481 with clear cell histology, 290 with papillary cell histology) using publicly available gene expression data from the Cancer Genome Atlas (CGA).
Overall, 19% of the clinic patients’ tumors showed high expression of KPNA2 protein, according to results reported in Clinical Genitourinary Cancer. In addition, 26% of the CGA patients’ tumors showed high expression of KPNA2 mRNA.
Among patients with clear cell RCC, those with high tumor levels of KPNA2 protein survived roughly half as long as counterparts with low levels or none (74 months vs. 171 months); the difference was significant in univariate analysis (P = .012) but not in multivariate analysis that included well-known prognostic factors (HR, 1.491; P = .237). On the other hand, those with high tumor levels of KPNA2 mRNA had an elevated risk of death in both univariate analysis (HR, 2.31; P less than .001) and multivariate analysis (HR, 1.45; P = .035).
Among patients with papillary RCC, tumor levels of KPNA2 protein were not significantly associated with survival. However, those with high tumor levels of KPNA2 mRNA had a sharply elevated risk of death in both univariate analysis (HR, 9.7; P less than .001) and multivariate analysis (HR, 6.2; P = .004).
KPNA2 expression “represents a novel prognostic factor in these subtypes of RCC,” concluded Dr. Kristiansen and his coinvestigators. Therefore, this biomarker “could be used to stratify risk groups within RCC.” Collectively, the study’s findings suggest that KPNA2 is involved in both the pathogenesis and the progression of RCC. Given evidence that it helps transport p53 and fibroblast growth factor 2 at least in tumors with clear cell histology, “investigation of the nucleocytoplasmic transport through KPNA2 in [clear cell] RCC is an important task for future studies to better understand the link between elevated KPNA2 expression and altered biological processes like proliferation, cell growth, migration, invasion and tumor formation in RCC. In addition, examination of other members of [the] karyopherin-alpha family could elucidate the role of the nucleocytoplasmic transport system in pathogenesis of RCC.”
The authors reported that they had no conflict of interests.
SOURCE: Kristiansen G et al. Clin Genitourin Cancer. 2018 Oct 22. doi: 10.1016/j.clgc.2018.10.008.
High expression of karyopherin alpha 2 (KPNA2), a carrier protein that helps shuttle cancer-associated proteins from the nucleus to the cytoplasm, is an adverse prognostic factor in patients with clear cell or papillary renal cell carcinoma (RCC), according to a retrospective cohort study.
Senior author Glen Kristiansen, MD, director of the Institute of Pathology at the University Hospital Bonn (Germany), and his colleagues assessed tumor levels of KPNA2 protein by immunohistochemistry in 240 clinic patients with RCC (217 with clear cell histology, 23 with papillary histology). They also assessed tumor levels of KPNA2 mRNA in 771 patients with RCC (481 with clear cell histology, 290 with papillary cell histology) using publicly available gene expression data from the Cancer Genome Atlas (CGA).
Overall, 19% of the clinic patients’ tumors showed high expression of KPNA2 protein, according to results reported in Clinical Genitourinary Cancer. In addition, 26% of the CGA patients’ tumors showed high expression of KPNA2 mRNA.
Among patients with clear cell RCC, those with high tumor levels of KPNA2 protein survived roughly half as long as counterparts with low levels or none (74 months vs. 171 months); the difference was significant in univariate analysis (P = .012) but not in multivariate analysis that included well-known prognostic factors (HR, 1.491; P = .237). On the other hand, those with high tumor levels of KPNA2 mRNA had an elevated risk of death in both univariate analysis (HR, 2.31; P less than .001) and multivariate analysis (HR, 1.45; P = .035).
Among patients with papillary RCC, tumor levels of KPNA2 protein were not significantly associated with survival. However, those with high tumor levels of KPNA2 mRNA had a sharply elevated risk of death in both univariate analysis (HR, 9.7; P less than .001) and multivariate analysis (HR, 6.2; P = .004).
KPNA2 expression “represents a novel prognostic factor in these subtypes of RCC,” concluded Dr. Kristiansen and his coinvestigators. Therefore, this biomarker “could be used to stratify risk groups within RCC.” Collectively, the study’s findings suggest that KPNA2 is involved in both the pathogenesis and the progression of RCC. Given evidence that it helps transport p53 and fibroblast growth factor 2 at least in tumors with clear cell histology, “investigation of the nucleocytoplasmic transport through KPNA2 in [clear cell] RCC is an important task for future studies to better understand the link between elevated KPNA2 expression and altered biological processes like proliferation, cell growth, migration, invasion and tumor formation in RCC. In addition, examination of other members of [the] karyopherin-alpha family could elucidate the role of the nucleocytoplasmic transport system in pathogenesis of RCC.”
The authors reported that they had no conflict of interests.
SOURCE: Kristiansen G et al. Clin Genitourin Cancer. 2018 Oct 22. doi: 10.1016/j.clgc.2018.10.008.
High expression of karyopherin alpha 2 (KPNA2), a carrier protein that helps shuttle cancer-associated proteins from the nucleus to the cytoplasm, is an adverse prognostic factor in patients with clear cell or papillary renal cell carcinoma (RCC), according to a retrospective cohort study.
Senior author Glen Kristiansen, MD, director of the Institute of Pathology at the University Hospital Bonn (Germany), and his colleagues assessed tumor levels of KPNA2 protein by immunohistochemistry in 240 clinic patients with RCC (217 with clear cell histology, 23 with papillary histology). They also assessed tumor levels of KPNA2 mRNA in 771 patients with RCC (481 with clear cell histology, 290 with papillary cell histology) using publicly available gene expression data from the Cancer Genome Atlas (CGA).
Overall, 19% of the clinic patients’ tumors showed high expression of KPNA2 protein, according to results reported in Clinical Genitourinary Cancer. In addition, 26% of the CGA patients’ tumors showed high expression of KPNA2 mRNA.
Among patients with clear cell RCC, those with high tumor levels of KPNA2 protein survived roughly half as long as counterparts with low levels or none (74 months vs. 171 months); the difference was significant in univariate analysis (P = .012) but not in multivariate analysis that included well-known prognostic factors (HR, 1.491; P = .237). On the other hand, those with high tumor levels of KPNA2 mRNA had an elevated risk of death in both univariate analysis (HR, 2.31; P less than .001) and multivariate analysis (HR, 1.45; P = .035).
Among patients with papillary RCC, tumor levels of KPNA2 protein were not significantly associated with survival. However, those with high tumor levels of KPNA2 mRNA had a sharply elevated risk of death in both univariate analysis (HR, 9.7; P less than .001) and multivariate analysis (HR, 6.2; P = .004).
KPNA2 expression “represents a novel prognostic factor in these subtypes of RCC,” concluded Dr. Kristiansen and his coinvestigators. Therefore, this biomarker “could be used to stratify risk groups within RCC.” Collectively, the study’s findings suggest that KPNA2 is involved in both the pathogenesis and the progression of RCC. Given evidence that it helps transport p53 and fibroblast growth factor 2 at least in tumors with clear cell histology, “investigation of the nucleocytoplasmic transport through KPNA2 in [clear cell] RCC is an important task for future studies to better understand the link between elevated KPNA2 expression and altered biological processes like proliferation, cell growth, migration, invasion and tumor formation in RCC. In addition, examination of other members of [the] karyopherin-alpha family could elucidate the role of the nucleocytoplasmic transport system in pathogenesis of RCC.”
The authors reported that they had no conflict of interests.
SOURCE: Kristiansen G et al. Clin Genitourin Cancer. 2018 Oct 22. doi: 10.1016/j.clgc.2018.10.008.
FROM CLINICAL GENITOURINARY CANCER
Key clinical point:
Major finding: Survival was poorer for patients with clear cell RCC having high KPNA2 protein levels (74 vs. 171 months) or mRNA levels (hazard ratio for death, 1.45) and for patients with papillary RCC having high KPNA2 mRNA levels (HR, 6.2).
Study details: A retrospective dual cohort study of 240 clinic patients and 771 Cancer Genome Atlas patients.
Disclosures: The authors reported that they had no conflict of interests.
Source: Kristiansen G et al. Clin Genitourin Cancer. 2018 Oct 22. doi: 10.1016/j.clgc.2018.10.008.
Time reveals benefit of CABG over PCI for left main disease
SAN DIEGO – In the long run, patients with left main coronary artery disease fare better if they undergo coronary artery bypass grafting (CABG) instead of percutaneous coronary intervention (PCI) with drug-eluting stents, suggest 10-year results of the MAIN-COMPARE trial. Findings were reported at the Transcatheter Cardiovascular Therapeutics annual meeting.
Although CABG is the standard choice for revascularization in this patient population, PCI has been making inroads thanks to advances in stents, antithrombotic drugs, periprocedural management, and operator expertise, noted senior author Seung-Jung Park, MD, PhD, chairman of the Heart Institute at Asan Medical Center in Seoul and professor of medicine at University of Ulsan, South Korea. “Indeed, many studies showed that PCI using drug-eluting stents might be a good alternative for selected patients with left main coronary artery disease.”
Two large, randomized, controlled trials, EXCEL and NOBLE, have compared these treatment strategies and helped clarify outcomes at intermediate follow-up periods of 3-5 years. But long-term data, increasingly important as survival improves, are lacking.
Dr. Park reported the 10-year update of a prospective, observational cohort study that analyzed data from more than 2,000 patients with unprotected left main coronary artery disease in the MAIN-COMPARE registry, which captures revascularization procedures performed at 12 Korean cardiac centers.
In the entire cohort, about a fifth of the patients died, and roughly a fourth experienced a composite adverse outcome of death and cardiovascular events regardless of whether they received PCI or CABG, but the former yielded a rate of target vessel revascularization that was more than three times higher, according to results reported at the meeting and simultaneously published (J Am Coll Cardiol. 2018 Sep 14. doi: 10.1016/j.jacc.2018.09.012). Among the subset of patients treated in the more recent drug-eluting stent era, those who underwent PCI were more likely to die and to experience the composite outcome starting at the 5-year mark.
“Drug-eluting stents were associated with higher risks of death and serious composite outcomes compared to CABG after 5 years. The treatment benefit of CABG has diverged over time during continued follow-up,” Dr. Park noted. “The rate of target-vessel failure was consistently higher in the PCI group.”
“We used mainly first-generation drug-eluting stents,” he acknowledged. “However, many studies have demonstrated there is not too much difference between the first- and second-generation stents.”
Data worth the wait
In the same session, investigators reported the 10-year update of the European and U.S. randomized SYNTAX Extended Survival trial, called SYNTAXES. SYNTAX enrolled patients with three-vessel or left main coronary disease. That trial found no significant difference in survival between PCI with drug-eluting stents and CABG overall. In stratified analysis, mortality was higher with PCI among patients with three-vessel disease, but not among patients with left main disease.
Taken together, these trials help clarify the long-term comparative efficacy of PCI and begin to inform patient selection, according to press conference panelist Morton J. Kern, MD, a professor at the University of California, Irvine Medical Center.
“The fine subgroup analysis of who the best candidates are is still in question,” he elaborated. “The SYNTAXES study told us that surgery for left mains is still pretty good, and even though you can get good results with PCI, the event rates are higher in that three-vessel, high-SYNTAX score group, so we should be careful. Interventionalists need to know their limitations. I think that’s what both studies tell us, actually.”
Study details
The MAIN-COMPARE analyses were based on 2,240 patients with unprotected left main coronary artery disease (stenosis of more than 50% and no coronary artery bypass grafts to the left anterior descending or the left circumflex artery) treated during 2000-2006.
A total of 1,102 patients underwent PCI with stenting: 318 in the era of bare-metal stents and 784 in the era of drug-eluting stents, predominantly sirolimus-eluting stents. A total of 1,138 patients underwent CABG. The minimum follow-up was 10 years in all patients, with a median of 12 years.
In the entire study cohort, PCI and CABG yielded similar rates of death (21.1% vs. 23.2%) and the composite of death, Q-wave myocardial infarction, or stroke (23.8% vs. 26.3%), but the PCI patients had a significantly higher rate of target vessel revascularization (21.1% vs. 5.8%), according to data reported at the meeting, which was sponsored by the New York–based Cardiovascular Research Foundation.
In analyses using a propensity score weighting technique, results for the entire cohort were much the same. But on stratification, PCI with drug-eluting stents versus CABG yielded higher risks of death (hazard ratio, 1.35; P = .05) and the composite adverse outcome (HR, 1.46; P = .009) from 5 years onward, as well as a sharply higher risk of target vessel revascularization for the full duration of follow-up (HR, 5.82; P less than .001).
Dr. Park disclosed that he had no conflicts of interest. The study was supported by the Korean Society of Interventional Cardiology and the CardioVascular Research Foundation of South Korea.
SOURCE: Park SJ et al. J Am Coll Cardiol. 2018 Sep 14. doi: 10.1016/j.jacc.2018.09.012).
SAN DIEGO – In the long run, patients with left main coronary artery disease fare better if they undergo coronary artery bypass grafting (CABG) instead of percutaneous coronary intervention (PCI) with drug-eluting stents, suggest 10-year results of the MAIN-COMPARE trial. Findings were reported at the Transcatheter Cardiovascular Therapeutics annual meeting.
Although CABG is the standard choice for revascularization in this patient population, PCI has been making inroads thanks to advances in stents, antithrombotic drugs, periprocedural management, and operator expertise, noted senior author Seung-Jung Park, MD, PhD, chairman of the Heart Institute at Asan Medical Center in Seoul and professor of medicine at University of Ulsan, South Korea. “Indeed, many studies showed that PCI using drug-eluting stents might be a good alternative for selected patients with left main coronary artery disease.”
Two large, randomized, controlled trials, EXCEL and NOBLE, have compared these treatment strategies and helped clarify outcomes at intermediate follow-up periods of 3-5 years. But long-term data, increasingly important as survival improves, are lacking.
Dr. Park reported the 10-year update of a prospective, observational cohort study that analyzed data from more than 2,000 patients with unprotected left main coronary artery disease in the MAIN-COMPARE registry, which captures revascularization procedures performed at 12 Korean cardiac centers.
In the entire cohort, about a fifth of the patients died, and roughly a fourth experienced a composite adverse outcome of death and cardiovascular events regardless of whether they received PCI or CABG, but the former yielded a rate of target vessel revascularization that was more than three times higher, according to results reported at the meeting and simultaneously published (J Am Coll Cardiol. 2018 Sep 14. doi: 10.1016/j.jacc.2018.09.012). Among the subset of patients treated in the more recent drug-eluting stent era, those who underwent PCI were more likely to die and to experience the composite outcome starting at the 5-year mark.
“Drug-eluting stents were associated with higher risks of death and serious composite outcomes compared to CABG after 5 years. The treatment benefit of CABG has diverged over time during continued follow-up,” Dr. Park noted. “The rate of target-vessel failure was consistently higher in the PCI group.”
“We used mainly first-generation drug-eluting stents,” he acknowledged. “However, many studies have demonstrated there is not too much difference between the first- and second-generation stents.”
Data worth the wait
In the same session, investigators reported the 10-year update of the European and U.S. randomized SYNTAX Extended Survival trial, called SYNTAXES. SYNTAX enrolled patients with three-vessel or left main coronary disease. That trial found no significant difference in survival between PCI with drug-eluting stents and CABG overall. In stratified analysis, mortality was higher with PCI among patients with three-vessel disease, but not among patients with left main disease.
Taken together, these trials help clarify the long-term comparative efficacy of PCI and begin to inform patient selection, according to press conference panelist Morton J. Kern, MD, a professor at the University of California, Irvine Medical Center.
“The fine subgroup analysis of who the best candidates are is still in question,” he elaborated. “The SYNTAXES study told us that surgery for left mains is still pretty good, and even though you can get good results with PCI, the event rates are higher in that three-vessel, high-SYNTAX score group, so we should be careful. Interventionalists need to know their limitations. I think that’s what both studies tell us, actually.”
Study details
The MAIN-COMPARE analyses were based on 2,240 patients with unprotected left main coronary artery disease (stenosis of more than 50% and no coronary artery bypass grafts to the left anterior descending or the left circumflex artery) treated during 2000-2006.
A total of 1,102 patients underwent PCI with stenting: 318 in the era of bare-metal stents and 784 in the era of drug-eluting stents, predominantly sirolimus-eluting stents. A total of 1,138 patients underwent CABG. The minimum follow-up was 10 years in all patients, with a median of 12 years.
In the entire study cohort, PCI and CABG yielded similar rates of death (21.1% vs. 23.2%) and the composite of death, Q-wave myocardial infarction, or stroke (23.8% vs. 26.3%), but the PCI patients had a significantly higher rate of target vessel revascularization (21.1% vs. 5.8%), according to data reported at the meeting, which was sponsored by the New York–based Cardiovascular Research Foundation.
In analyses using a propensity score weighting technique, results for the entire cohort were much the same. But on stratification, PCI with drug-eluting stents versus CABG yielded higher risks of death (hazard ratio, 1.35; P = .05) and the composite adverse outcome (HR, 1.46; P = .009) from 5 years onward, as well as a sharply higher risk of target vessel revascularization for the full duration of follow-up (HR, 5.82; P less than .001).
Dr. Park disclosed that he had no conflicts of interest. The study was supported by the Korean Society of Interventional Cardiology and the CardioVascular Research Foundation of South Korea.
SOURCE: Park SJ et al. J Am Coll Cardiol. 2018 Sep 14. doi: 10.1016/j.jacc.2018.09.012).
SAN DIEGO – In the long run, patients with left main coronary artery disease fare better if they undergo coronary artery bypass grafting (CABG) instead of percutaneous coronary intervention (PCI) with drug-eluting stents, suggest 10-year results of the MAIN-COMPARE trial. Findings were reported at the Transcatheter Cardiovascular Therapeutics annual meeting.
Although CABG is the standard choice for revascularization in this patient population, PCI has been making inroads thanks to advances in stents, antithrombotic drugs, periprocedural management, and operator expertise, noted senior author Seung-Jung Park, MD, PhD, chairman of the Heart Institute at Asan Medical Center in Seoul and professor of medicine at University of Ulsan, South Korea. “Indeed, many studies showed that PCI using drug-eluting stents might be a good alternative for selected patients with left main coronary artery disease.”
Two large, randomized, controlled trials, EXCEL and NOBLE, have compared these treatment strategies and helped clarify outcomes at intermediate follow-up periods of 3-5 years. But long-term data, increasingly important as survival improves, are lacking.
Dr. Park reported the 10-year update of a prospective, observational cohort study that analyzed data from more than 2,000 patients with unprotected left main coronary artery disease in the MAIN-COMPARE registry, which captures revascularization procedures performed at 12 Korean cardiac centers.
In the entire cohort, about a fifth of the patients died, and roughly a fourth experienced a composite adverse outcome of death and cardiovascular events regardless of whether they received PCI or CABG, but the former yielded a rate of target vessel revascularization that was more than three times higher, according to results reported at the meeting and simultaneously published (J Am Coll Cardiol. 2018 Sep 14. doi: 10.1016/j.jacc.2018.09.012). Among the subset of patients treated in the more recent drug-eluting stent era, those who underwent PCI were more likely to die and to experience the composite outcome starting at the 5-year mark.
“Drug-eluting stents were associated with higher risks of death and serious composite outcomes compared to CABG after 5 years. The treatment benefit of CABG has diverged over time during continued follow-up,” Dr. Park noted. “The rate of target-vessel failure was consistently higher in the PCI group.”
“We used mainly first-generation drug-eluting stents,” he acknowledged. “However, many studies have demonstrated there is not too much difference between the first- and second-generation stents.”
Data worth the wait
In the same session, investigators reported the 10-year update of the European and U.S. randomized SYNTAX Extended Survival trial, called SYNTAXES. SYNTAX enrolled patients with three-vessel or left main coronary disease. That trial found no significant difference in survival between PCI with drug-eluting stents and CABG overall. In stratified analysis, mortality was higher with PCI among patients with three-vessel disease, but not among patients with left main disease.
Taken together, these trials help clarify the long-term comparative efficacy of PCI and begin to inform patient selection, according to press conference panelist Morton J. Kern, MD, a professor at the University of California, Irvine Medical Center.
“The fine subgroup analysis of who the best candidates are is still in question,” he elaborated. “The SYNTAXES study told us that surgery for left mains is still pretty good, and even though you can get good results with PCI, the event rates are higher in that three-vessel, high-SYNTAX score group, so we should be careful. Interventionalists need to know their limitations. I think that’s what both studies tell us, actually.”
Study details
The MAIN-COMPARE analyses were based on 2,240 patients with unprotected left main coronary artery disease (stenosis of more than 50% and no coronary artery bypass grafts to the left anterior descending or the left circumflex artery) treated during 2000-2006.
A total of 1,102 patients underwent PCI with stenting: 318 in the era of bare-metal stents and 784 in the era of drug-eluting stents, predominantly sirolimus-eluting stents. A total of 1,138 patients underwent CABG. The minimum follow-up was 10 years in all patients, with a median of 12 years.
In the entire study cohort, PCI and CABG yielded similar rates of death (21.1% vs. 23.2%) and the composite of death, Q-wave myocardial infarction, or stroke (23.8% vs. 26.3%), but the PCI patients had a significantly higher rate of target vessel revascularization (21.1% vs. 5.8%), according to data reported at the meeting, which was sponsored by the New York–based Cardiovascular Research Foundation.
In analyses using a propensity score weighting technique, results for the entire cohort were much the same. But on stratification, PCI with drug-eluting stents versus CABG yielded higher risks of death (hazard ratio, 1.35; P = .05) and the composite adverse outcome (HR, 1.46; P = .009) from 5 years onward, as well as a sharply higher risk of target vessel revascularization for the full duration of follow-up (HR, 5.82; P less than .001).
Dr. Park disclosed that he had no conflicts of interest. The study was supported by the Korean Society of Interventional Cardiology and the CardioVascular Research Foundation of South Korea.
SOURCE: Park SJ et al. J Am Coll Cardiol. 2018 Sep 14. doi: 10.1016/j.jacc.2018.09.012).
REPORTING FROM TCT 2018
Key clinical point: CABG had an edge over PCI with drug-eluting stents in patients with left main disease that became evident with longer follow-up.
Major finding: Compared with CABG, PCI with drug-eluting stents carried higher risks of death (hazard ratio, 1.35; P = .05) and a composite adverse outcome (HR, 1.46; P = .009) from 5 years onward.
Study details: Ten-year follow-up of a multicenter prospective cohort study of 2,240 patients with unprotected left main coronary artery disease who underwent either PCI with stenting or CABG (MAIN-COMPARE study).
Disclosures: Dr. Park disclosed that he had no conflicts of interest. The study was supported by the Korean Society of Interventional Cardiology and the CardioVascular Research Foundation of South Korea.
Source: Park S-J et al. J Am Coll Cardiol. 2018 Sep 14. doi: 10.1016/j.jacc.2018.09.012.
Obesity is linked to some RCC subtypes
The link between obesity and renal cell carcinoma (RCC) appears to be complex and may provide insight into differing etiologies for various histologic subtypes of this cancer, according to a nested case-control study and subsequent meta-analysis.
Investigators led by Catherine L. Callahan, PhD, a postdoctoral fellow with the Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Md., first analyzed data from the Kaiser Permanente Northern California health care network. They matched 685 patients with RCC (421 clear cell, 65 papillary, 24 chromophobe, 35 other, and 140 not otherwise specified) with 4,266 unaffected control patients on age, sex, race/ethnicity, duration of network membership, and medical center of diagnosis.
Compared with normal-weight counterparts (body mass index less than 25 kg/m2), obese patients (body mass index of at least 30 kg/m2), had a significantly elevated risk of clear cell RCC (odds ratio, 1.5) and a nonsignificantly elevated risk of chromophobe RCC (2.5), but a similar risk of papillary RCC (1.0), according to results reported in Cancer Epidemiology. Associations weakened when cases were restricted to stage II or higher RCC, suggesting potential bias from incidental diagnoses related to abdominal imaging. Patients who were overweight (body mass index of 25 to 29.9 kg/m2) did not have significantly elevated risks of any subtype of RCC.
The investigators next conducted a meta-analysis, including this new study and three others. Results showed a significant link between obesity and clear cell RCC (summary relative risk, 1.8) and chromophobe RCC (2.2), but not papillary RCC (1.2). Here, however, patients who were overweight also had elevated risks of clear cell RCC (1.3) and chromophobe RCC (1.9).
“Our results provide support for the hypothesis that histologic subtypes of RCC represent distinct etiologic pathways, and that obesity is more strongly associated with risk of clear cell RCC. Additional research to elucidate the underlying biology of specific subtypes of RCC is warranted,” wrote Dr. Callahan and her coinvestigators. “More generally, our findings underscore the importance of accounting for histologic subtype in investigations of RCC etiology.”
The investigators disclosed that they had no conflicts of interest. The research was supported by the Intramural Research Program of the NIH and the National Cancer Institute.
SOURCE: Callahan CL et al. Cancer Epidemiol. 2018 Jul 18, doi: 10.1016/j.canep.2018.07.002.
The link between obesity and renal cell carcinoma (RCC) appears to be complex and may provide insight into differing etiologies for various histologic subtypes of this cancer, according to a nested case-control study and subsequent meta-analysis.
Investigators led by Catherine L. Callahan, PhD, a postdoctoral fellow with the Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Md., first analyzed data from the Kaiser Permanente Northern California health care network. They matched 685 patients with RCC (421 clear cell, 65 papillary, 24 chromophobe, 35 other, and 140 not otherwise specified) with 4,266 unaffected control patients on age, sex, race/ethnicity, duration of network membership, and medical center of diagnosis.
Compared with normal-weight counterparts (body mass index less than 25 kg/m2), obese patients (body mass index of at least 30 kg/m2), had a significantly elevated risk of clear cell RCC (odds ratio, 1.5) and a nonsignificantly elevated risk of chromophobe RCC (2.5), but a similar risk of papillary RCC (1.0), according to results reported in Cancer Epidemiology. Associations weakened when cases were restricted to stage II or higher RCC, suggesting potential bias from incidental diagnoses related to abdominal imaging. Patients who were overweight (body mass index of 25 to 29.9 kg/m2) did not have significantly elevated risks of any subtype of RCC.
The investigators next conducted a meta-analysis, including this new study and three others. Results showed a significant link between obesity and clear cell RCC (summary relative risk, 1.8) and chromophobe RCC (2.2), but not papillary RCC (1.2). Here, however, patients who were overweight also had elevated risks of clear cell RCC (1.3) and chromophobe RCC (1.9).
“Our results provide support for the hypothesis that histologic subtypes of RCC represent distinct etiologic pathways, and that obesity is more strongly associated with risk of clear cell RCC. Additional research to elucidate the underlying biology of specific subtypes of RCC is warranted,” wrote Dr. Callahan and her coinvestigators. “More generally, our findings underscore the importance of accounting for histologic subtype in investigations of RCC etiology.”
The investigators disclosed that they had no conflicts of interest. The research was supported by the Intramural Research Program of the NIH and the National Cancer Institute.
SOURCE: Callahan CL et al. Cancer Epidemiol. 2018 Jul 18, doi: 10.1016/j.canep.2018.07.002.
The link between obesity and renal cell carcinoma (RCC) appears to be complex and may provide insight into differing etiologies for various histologic subtypes of this cancer, according to a nested case-control study and subsequent meta-analysis.
Investigators led by Catherine L. Callahan, PhD, a postdoctoral fellow with the Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Md., first analyzed data from the Kaiser Permanente Northern California health care network. They matched 685 patients with RCC (421 clear cell, 65 papillary, 24 chromophobe, 35 other, and 140 not otherwise specified) with 4,266 unaffected control patients on age, sex, race/ethnicity, duration of network membership, and medical center of diagnosis.
Compared with normal-weight counterparts (body mass index less than 25 kg/m2), obese patients (body mass index of at least 30 kg/m2), had a significantly elevated risk of clear cell RCC (odds ratio, 1.5) and a nonsignificantly elevated risk of chromophobe RCC (2.5), but a similar risk of papillary RCC (1.0), according to results reported in Cancer Epidemiology. Associations weakened when cases were restricted to stage II or higher RCC, suggesting potential bias from incidental diagnoses related to abdominal imaging. Patients who were overweight (body mass index of 25 to 29.9 kg/m2) did not have significantly elevated risks of any subtype of RCC.
The investigators next conducted a meta-analysis, including this new study and three others. Results showed a significant link between obesity and clear cell RCC (summary relative risk, 1.8) and chromophobe RCC (2.2), but not papillary RCC (1.2). Here, however, patients who were overweight also had elevated risks of clear cell RCC (1.3) and chromophobe RCC (1.9).
“Our results provide support for the hypothesis that histologic subtypes of RCC represent distinct etiologic pathways, and that obesity is more strongly associated with risk of clear cell RCC. Additional research to elucidate the underlying biology of specific subtypes of RCC is warranted,” wrote Dr. Callahan and her coinvestigators. “More generally, our findings underscore the importance of accounting for histologic subtype in investigations of RCC etiology.”
The investigators disclosed that they had no conflicts of interest. The research was supported by the Intramural Research Program of the NIH and the National Cancer Institute.
SOURCE: Callahan CL et al. Cancer Epidemiol. 2018 Jul 18, doi: 10.1016/j.canep.2018.07.002.
FROM CANCER EPIDEMIOLOGY
Key clinical point: Obesity is a risk factor for only certain histologic subtypes of RCC.
Major finding: Obese individuals had a significantly elevated risk of clear cell RCC (odds ratio, 1.5) and a nonsignificantly elevated risk of chromophobe RCC (OR, 2.5), but a similar risk of papillary RCC (OR, 1.0).
Study details: A nested case-control study of 685 patients with RCC and 4,266 unaffected matched control patients.
Disclosures: The investigators disclosed that they had no conflicts of interest. The research was supported by the Intramural Research Program of the NIH and the National Cancer Institute.
Source: Callahan CL et al. Cancer Epidemiol. 2018 Jul 18. doi: 10.1016/j.canep.2018.07.002.
Pazopanib is active against renal, other neoplasms of von Hippel-Lindau disease
The oral, multitargeted tyrosine kinase inhibitor pazopanib (Votrient) is active and safe in patients with renal cell carcinoma and other neoplasms caused by von Hippel-Lindau disease, a phase 2 trial has found.
Eric Jonasch, MD, and his coinvestigators at the University of Texas MD Anderson Cancer Center, Houston, conducted the single-arm trial among 31 adult patients with clinical manifestations of von Hippel-Lindau disease, an autosomal dominant disorder that currently has no approved treatment.
All patients were treated with open-label pazopanib (800 mg daily with dose reductions permitted) for 24 weeks, with an option to continue thereafter. Pazopanib derives its antiangiogenic and antineoplastic activity from its selective inhibition of vascular endothelial growth factor receptors (VEGFR)–1, –2, and –3; c-KIT; and platelet-derived growth factor receptor (PDGFR). It is currently approved by the FDA for treatment of advanced renal cell carcinoma and advanced soft-tissue sarcoma.
The trial was stopped before attaining planned enrollment because accrual slowed and it met a prespecified toxicity stopping threshold, according to results reported in Lancet Oncology.
At a median follow-up of 12 months, 42% of patients overall had an objective response to pazopanib. By site, response was seen in 52% of 59 renal cell carcinomas, 53% of 17 pancreatic lesions (mainly serous cystadenomas), and 4% of 49 CNS hemangioblastomas; the median reduction in tumor size was 40.5%, 30.5%, and 13%, respectively.
Slightly more than half of patients, 52%, opted to stay on pazopanib after 24 weeks, with the longest duration being 60 months at data cutoff.
Some 13% of patients withdrew from the study because of grade 3 or 4 transaminitis, and 10% stopped treatment because of general intolerance related to multiple grade 1 and 2 toxicities. There were three treatment-related serious adverse events: one case of appendicitis, one case of gastritis, and one case of fatal CNS bleeding after a fall.
“Pazopanib was associated with encouraging preliminary activity in von Hippel-Lindau disease, with a side effect profile consistent with that seen in previous trials,” the investigators concluded. “Pazopanib could be considered as a treatment choice for patients with von Hippel-Lindau disease and growing lesions, or to reduce the size of unresectable lesions in these patients.”
Dr. Jonasch disclosed that he receives research support and honoraria from Novartis. The study was funded by Novartis and by a National Institutes of Health National Cancer Institute core grant.
SOURCE: Jonasch E et al. Lancet Oncol. 2018 Sep 17. doi: 10.1016/S1470-2045(18)30487-X,
The oral, multitargeted tyrosine kinase inhibitor pazopanib (Votrient) is active and safe in patients with renal cell carcinoma and other neoplasms caused by von Hippel-Lindau disease, a phase 2 trial has found.
Eric Jonasch, MD, and his coinvestigators at the University of Texas MD Anderson Cancer Center, Houston, conducted the single-arm trial among 31 adult patients with clinical manifestations of von Hippel-Lindau disease, an autosomal dominant disorder that currently has no approved treatment.
All patients were treated with open-label pazopanib (800 mg daily with dose reductions permitted) for 24 weeks, with an option to continue thereafter. Pazopanib derives its antiangiogenic and antineoplastic activity from its selective inhibition of vascular endothelial growth factor receptors (VEGFR)–1, –2, and –3; c-KIT; and platelet-derived growth factor receptor (PDGFR). It is currently approved by the FDA for treatment of advanced renal cell carcinoma and advanced soft-tissue sarcoma.
The trial was stopped before attaining planned enrollment because accrual slowed and it met a prespecified toxicity stopping threshold, according to results reported in Lancet Oncology.
At a median follow-up of 12 months, 42% of patients overall had an objective response to pazopanib. By site, response was seen in 52% of 59 renal cell carcinomas, 53% of 17 pancreatic lesions (mainly serous cystadenomas), and 4% of 49 CNS hemangioblastomas; the median reduction in tumor size was 40.5%, 30.5%, and 13%, respectively.
Slightly more than half of patients, 52%, opted to stay on pazopanib after 24 weeks, with the longest duration being 60 months at data cutoff.
Some 13% of patients withdrew from the study because of grade 3 or 4 transaminitis, and 10% stopped treatment because of general intolerance related to multiple grade 1 and 2 toxicities. There were three treatment-related serious adverse events: one case of appendicitis, one case of gastritis, and one case of fatal CNS bleeding after a fall.
“Pazopanib was associated with encouraging preliminary activity in von Hippel-Lindau disease, with a side effect profile consistent with that seen in previous trials,” the investigators concluded. “Pazopanib could be considered as a treatment choice for patients with von Hippel-Lindau disease and growing lesions, or to reduce the size of unresectable lesions in these patients.”
Dr. Jonasch disclosed that he receives research support and honoraria from Novartis. The study was funded by Novartis and by a National Institutes of Health National Cancer Institute core grant.
SOURCE: Jonasch E et al. Lancet Oncol. 2018 Sep 17. doi: 10.1016/S1470-2045(18)30487-X,
The oral, multitargeted tyrosine kinase inhibitor pazopanib (Votrient) is active and safe in patients with renal cell carcinoma and other neoplasms caused by von Hippel-Lindau disease, a phase 2 trial has found.
Eric Jonasch, MD, and his coinvestigators at the University of Texas MD Anderson Cancer Center, Houston, conducted the single-arm trial among 31 adult patients with clinical manifestations of von Hippel-Lindau disease, an autosomal dominant disorder that currently has no approved treatment.
All patients were treated with open-label pazopanib (800 mg daily with dose reductions permitted) for 24 weeks, with an option to continue thereafter. Pazopanib derives its antiangiogenic and antineoplastic activity from its selective inhibition of vascular endothelial growth factor receptors (VEGFR)–1, –2, and –3; c-KIT; and platelet-derived growth factor receptor (PDGFR). It is currently approved by the FDA for treatment of advanced renal cell carcinoma and advanced soft-tissue sarcoma.
The trial was stopped before attaining planned enrollment because accrual slowed and it met a prespecified toxicity stopping threshold, according to results reported in Lancet Oncology.
At a median follow-up of 12 months, 42% of patients overall had an objective response to pazopanib. By site, response was seen in 52% of 59 renal cell carcinomas, 53% of 17 pancreatic lesions (mainly serous cystadenomas), and 4% of 49 CNS hemangioblastomas; the median reduction in tumor size was 40.5%, 30.5%, and 13%, respectively.
Slightly more than half of patients, 52%, opted to stay on pazopanib after 24 weeks, with the longest duration being 60 months at data cutoff.
Some 13% of patients withdrew from the study because of grade 3 or 4 transaminitis, and 10% stopped treatment because of general intolerance related to multiple grade 1 and 2 toxicities. There were three treatment-related serious adverse events: one case of appendicitis, one case of gastritis, and one case of fatal CNS bleeding after a fall.
“Pazopanib was associated with encouraging preliminary activity in von Hippel-Lindau disease, with a side effect profile consistent with that seen in previous trials,” the investigators concluded. “Pazopanib could be considered as a treatment choice for patients with von Hippel-Lindau disease and growing lesions, or to reduce the size of unresectable lesions in these patients.”
Dr. Jonasch disclosed that he receives research support and honoraria from Novartis. The study was funded by Novartis and by a National Institutes of Health National Cancer Institute core grant.
SOURCE: Jonasch E et al. Lancet Oncol. 2018 Sep 17. doi: 10.1016/S1470-2045(18)30487-X,
FROM LANCET ONCOLOGY
Key clinical point: Pazopanib appears efficacious and safe for treating neoplasms associated with von Hippel-Lindau disease.
Major finding: The objective response rate was 42% overall, with response seen in 52% of renal cell carcinomas.
Study details: Single-center, single-arm, open-label, phase 2 trial among 31 adult patients with clinical manifestations of von Hippel-Lindau disease who were treated with pazopanib for at least 24 weeks.
Disclosures: Dr. Jonasch disclosed that he receives research support and honoraria from Novartis. The study was funded by Novartis and by a National Institutes of Health National Cancer Institute core grant.
Source: Jonasch E et al. Lancet Oncol. 2018 Sep 17. doi: 10.1016/S1470-2045(18)30487-X.
Pulmonary artery denervation boosts walking capacity in left heart failure
SAN DIEGO – Pulmonary artery denervation is efficacious for treating combined pre- and postcapillary pulmonary hypertension attributable to left heart failure, based on results of the Chinese PADN-5 trial reported at the Transcatheter Cardiovascular Therapeutics annual meeting.
This ablative treatment has been studied among patients with pulmonary hypertension attributable to other etiologies, but not in randomized fashion among this population, noted lead investigator Shao-Liang Chen, MD, of Nanjing (China) First Hospital, Nanjing Medical University. The treatment is an attractive one, as medications recommended for pulmonary arterial hypertension are not recommended for joint pre- and postcapillary pulmonary hypertension (group II pulmonary hypertension).
In PADN-5, 98 patients were randomized to pulmonary artery denervation or to sham denervation plus open-label sildenafil (Viagra), which at the time of trial initiation was thought to be safe and potentially beneficial.
The trial’s main outcome, 6-minute walk distance at 6 months, improved in both groups, according to data reported at the meeting and simultaneously published in JACC Cardiovascular Interventions. But the improvement was about four times greater in the pulmonary artery denervation group. Secondary efficacy outcomes also favored that group, and the rate of fatal pulmonary embolism did not differ for the two groups.
“The PADN-5 trial demonstrates the benefits of pulmonary artery denervation for patients with combined pre- and postcapillary pulmonary hypertension. Patients with preserved and with reduced ejection fraction equally benefited,” summarized Dr. Chen, who pioneered this procedure about 7 years ago. “There was no sign of any harm of sildenafil in patients with combined pre- and postcapillary pulmonary hypertension.”
Trial critique
“This is a very difficult study to conduct, being able to recruit patients and actually have these procedures done,” commented press conference moderator Ori Ben-Yehuda, MD, professor of clinical medicine and director, coronary care unit, UC San Diego Medical Center.
At the same time, he expressed some reservations about the trial. “Sildenafil in the control group might actually be expected to ... decrease your effect size. Also, particularly in men, perhaps even in women, it might unblind them to which group they are in and undermine your sham design,” he noted. In addition, some hemodynamic changes after pulmonary artery denervation – a decrease in wedge pressure and an increase in ejection fraction – were puzzling.
“We need a lot more data here. There are some issues with this trial in terms of design, and we haven’t even gotten into the issue of whether there were core labs, whether the echoes, the hemodynamics, were read blindly,” Dr. Ben-Yehuda maintained. “This issue of secondary or group II pulmonary hypertension due to left heart failure is one that has been very frustrating in terms of actual PA-specific therapies. So this is an important step further, but it needs confirmation in truly sham-controlled trials that have no potential for unblinding.”
The catheter used in PADN-5 is available in China but has not received clearance in the United States, he pointed out. “There are alternative or competing technologies, one using ultrasound, for example, that has a very similar approach. … We’ll have to see how it ends up [performing].”
Trial details
Patients in the PADN-5 pulmonary artery denervation group underwent ablation only in the periconjunctional area between the distal main trunk and the left ostial branch with a multifunction catheter having premounted electrodes. Those in the control group underwent a sham procedure, with catheter positioning at the target sites and connection to a generator but no ablation, and were given open-label sildenafil. All additionally received standard heart failure medical therapy. (No sildenafil placebo was used in the denervation group.)
Trial results reported at the meeting, which is sponsored by the Cardiovascular Research Foundation, showed that most echocardiographic and hemodynamic measures improved more in the pulmonary artery denervation group.
The greater improvement in 6-minute walk test with denervation versus sham sildenafil at 6 months was evident in a variety of measures: absolute median distance walked (432.5 m vs. 358 m) and mean distance walked (434.6 m vs. 359.4 m), and absolute increase (80 m vs. 17.5 m) and relative increase (21.4% vs. 4.9%) The difference was significant for all measures at P less than .001.
The denervation group had a comparatively greater reduction of pulmonary vascular resistance (29.8% vs. 3.4%; P less than .001) and were less likely to experience clinical worsening (16.7% vs. 40.0%; P = .014).
There was a single fatal pulmonary embolism in each treatment group. Of the seven total deaths, two occurred in the denervation group (one attributable to pump failure, one a sudden death) and five occurred in the sham sildenafil group (all but one attributable to pump failure).
Dr. Chen disclosed that he had no relevant conflicts of interest. The trial was sponsored by Nanjing First Hospital, Nanjing Medical University.
SOURCE: Chen S-J et al. TCT 2018. JACC Cardiovasc Interv. 2018 Sep 23.
SAN DIEGO – Pulmonary artery denervation is efficacious for treating combined pre- and postcapillary pulmonary hypertension attributable to left heart failure, based on results of the Chinese PADN-5 trial reported at the Transcatheter Cardiovascular Therapeutics annual meeting.
This ablative treatment has been studied among patients with pulmonary hypertension attributable to other etiologies, but not in randomized fashion among this population, noted lead investigator Shao-Liang Chen, MD, of Nanjing (China) First Hospital, Nanjing Medical University. The treatment is an attractive one, as medications recommended for pulmonary arterial hypertension are not recommended for joint pre- and postcapillary pulmonary hypertension (group II pulmonary hypertension).
In PADN-5, 98 patients were randomized to pulmonary artery denervation or to sham denervation plus open-label sildenafil (Viagra), which at the time of trial initiation was thought to be safe and potentially beneficial.
The trial’s main outcome, 6-minute walk distance at 6 months, improved in both groups, according to data reported at the meeting and simultaneously published in JACC Cardiovascular Interventions. But the improvement was about four times greater in the pulmonary artery denervation group. Secondary efficacy outcomes also favored that group, and the rate of fatal pulmonary embolism did not differ for the two groups.
“The PADN-5 trial demonstrates the benefits of pulmonary artery denervation for patients with combined pre- and postcapillary pulmonary hypertension. Patients with preserved and with reduced ejection fraction equally benefited,” summarized Dr. Chen, who pioneered this procedure about 7 years ago. “There was no sign of any harm of sildenafil in patients with combined pre- and postcapillary pulmonary hypertension.”
Trial critique
“This is a very difficult study to conduct, being able to recruit patients and actually have these procedures done,” commented press conference moderator Ori Ben-Yehuda, MD, professor of clinical medicine and director, coronary care unit, UC San Diego Medical Center.
At the same time, he expressed some reservations about the trial. “Sildenafil in the control group might actually be expected to ... decrease your effect size. Also, particularly in men, perhaps even in women, it might unblind them to which group they are in and undermine your sham design,” he noted. In addition, some hemodynamic changes after pulmonary artery denervation – a decrease in wedge pressure and an increase in ejection fraction – were puzzling.
“We need a lot more data here. There are some issues with this trial in terms of design, and we haven’t even gotten into the issue of whether there were core labs, whether the echoes, the hemodynamics, were read blindly,” Dr. Ben-Yehuda maintained. “This issue of secondary or group II pulmonary hypertension due to left heart failure is one that has been very frustrating in terms of actual PA-specific therapies. So this is an important step further, but it needs confirmation in truly sham-controlled trials that have no potential for unblinding.”
The catheter used in PADN-5 is available in China but has not received clearance in the United States, he pointed out. “There are alternative or competing technologies, one using ultrasound, for example, that has a very similar approach. … We’ll have to see how it ends up [performing].”
Trial details
Patients in the PADN-5 pulmonary artery denervation group underwent ablation only in the periconjunctional area between the distal main trunk and the left ostial branch with a multifunction catheter having premounted electrodes. Those in the control group underwent a sham procedure, with catheter positioning at the target sites and connection to a generator but no ablation, and were given open-label sildenafil. All additionally received standard heart failure medical therapy. (No sildenafil placebo was used in the denervation group.)
Trial results reported at the meeting, which is sponsored by the Cardiovascular Research Foundation, showed that most echocardiographic and hemodynamic measures improved more in the pulmonary artery denervation group.
The greater improvement in 6-minute walk test with denervation versus sham sildenafil at 6 months was evident in a variety of measures: absolute median distance walked (432.5 m vs. 358 m) and mean distance walked (434.6 m vs. 359.4 m), and absolute increase (80 m vs. 17.5 m) and relative increase (21.4% vs. 4.9%) The difference was significant for all measures at P less than .001.
The denervation group had a comparatively greater reduction of pulmonary vascular resistance (29.8% vs. 3.4%; P less than .001) and were less likely to experience clinical worsening (16.7% vs. 40.0%; P = .014).
There was a single fatal pulmonary embolism in each treatment group. Of the seven total deaths, two occurred in the denervation group (one attributable to pump failure, one a sudden death) and five occurred in the sham sildenafil group (all but one attributable to pump failure).
Dr. Chen disclosed that he had no relevant conflicts of interest. The trial was sponsored by Nanjing First Hospital, Nanjing Medical University.
SOURCE: Chen S-J et al. TCT 2018. JACC Cardiovasc Interv. 2018 Sep 23.
SAN DIEGO – Pulmonary artery denervation is efficacious for treating combined pre- and postcapillary pulmonary hypertension attributable to left heart failure, based on results of the Chinese PADN-5 trial reported at the Transcatheter Cardiovascular Therapeutics annual meeting.
This ablative treatment has been studied among patients with pulmonary hypertension attributable to other etiologies, but not in randomized fashion among this population, noted lead investigator Shao-Liang Chen, MD, of Nanjing (China) First Hospital, Nanjing Medical University. The treatment is an attractive one, as medications recommended for pulmonary arterial hypertension are not recommended for joint pre- and postcapillary pulmonary hypertension (group II pulmonary hypertension).
In PADN-5, 98 patients were randomized to pulmonary artery denervation or to sham denervation plus open-label sildenafil (Viagra), which at the time of trial initiation was thought to be safe and potentially beneficial.
The trial’s main outcome, 6-minute walk distance at 6 months, improved in both groups, according to data reported at the meeting and simultaneously published in JACC Cardiovascular Interventions. But the improvement was about four times greater in the pulmonary artery denervation group. Secondary efficacy outcomes also favored that group, and the rate of fatal pulmonary embolism did not differ for the two groups.
“The PADN-5 trial demonstrates the benefits of pulmonary artery denervation for patients with combined pre- and postcapillary pulmonary hypertension. Patients with preserved and with reduced ejection fraction equally benefited,” summarized Dr. Chen, who pioneered this procedure about 7 years ago. “There was no sign of any harm of sildenafil in patients with combined pre- and postcapillary pulmonary hypertension.”
Trial critique
“This is a very difficult study to conduct, being able to recruit patients and actually have these procedures done,” commented press conference moderator Ori Ben-Yehuda, MD, professor of clinical medicine and director, coronary care unit, UC San Diego Medical Center.
At the same time, he expressed some reservations about the trial. “Sildenafil in the control group might actually be expected to ... decrease your effect size. Also, particularly in men, perhaps even in women, it might unblind them to which group they are in and undermine your sham design,” he noted. In addition, some hemodynamic changes after pulmonary artery denervation – a decrease in wedge pressure and an increase in ejection fraction – were puzzling.
“We need a lot more data here. There are some issues with this trial in terms of design, and we haven’t even gotten into the issue of whether there were core labs, whether the echoes, the hemodynamics, were read blindly,” Dr. Ben-Yehuda maintained. “This issue of secondary or group II pulmonary hypertension due to left heart failure is one that has been very frustrating in terms of actual PA-specific therapies. So this is an important step further, but it needs confirmation in truly sham-controlled trials that have no potential for unblinding.”
The catheter used in PADN-5 is available in China but has not received clearance in the United States, he pointed out. “There are alternative or competing technologies, one using ultrasound, for example, that has a very similar approach. … We’ll have to see how it ends up [performing].”
Trial details
Patients in the PADN-5 pulmonary artery denervation group underwent ablation only in the periconjunctional area between the distal main trunk and the left ostial branch with a multifunction catheter having premounted electrodes. Those in the control group underwent a sham procedure, with catheter positioning at the target sites and connection to a generator but no ablation, and were given open-label sildenafil. All additionally received standard heart failure medical therapy. (No sildenafil placebo was used in the denervation group.)
Trial results reported at the meeting, which is sponsored by the Cardiovascular Research Foundation, showed that most echocardiographic and hemodynamic measures improved more in the pulmonary artery denervation group.
The greater improvement in 6-minute walk test with denervation versus sham sildenafil at 6 months was evident in a variety of measures: absolute median distance walked (432.5 m vs. 358 m) and mean distance walked (434.6 m vs. 359.4 m), and absolute increase (80 m vs. 17.5 m) and relative increase (21.4% vs. 4.9%) The difference was significant for all measures at P less than .001.
The denervation group had a comparatively greater reduction of pulmonary vascular resistance (29.8% vs. 3.4%; P less than .001) and were less likely to experience clinical worsening (16.7% vs. 40.0%; P = .014).
There was a single fatal pulmonary embolism in each treatment group. Of the seven total deaths, two occurred in the denervation group (one attributable to pump failure, one a sudden death) and five occurred in the sham sildenafil group (all but one attributable to pump failure).
Dr. Chen disclosed that he had no relevant conflicts of interest. The trial was sponsored by Nanjing First Hospital, Nanjing Medical University.
SOURCE: Chen S-J et al. TCT 2018. JACC Cardiovasc Interv. 2018 Sep 23.
REPORTING FROM TCT 2018
Key clinical point: Pulmonary artery denervation is efficacious for treating pulmonary hypertension related to heart failure.
Major finding: Improvement in 6-minute walk distance was greater with pulmonary artery denervation than with sham denervation plus sildenafil (21.4% vs. 4.9%; P less than .001).
Study details: PADN-5 is a randomized controlled trial among 98 patients with combined pre- and postcapillary pulmonary hypertension secondary to left heart failure (group II pulmonary hypertension).
Disclosures: Dr. Chen disclosed that he had no relevant conflicts of interest. The trial was sponsored by Nanjing First Hospital, Nanjing Medical University.
Source: Chen S-L et al. TCT 2018. JACC Cardiovasc Interv. 2018 Sep 23.
Rotablation aids in prepping highly calcified lesions: PREPARE-CALC
SAN DIEGO – When it comes to preparing highly calcified coronary lesions for drug-eluting stents, rotational atherectomy has an early procedural advantage over modified balloons that cut or score the lesion, but yields similar clinical outcomes over time, according to results of the randomized PREPARE-CALC trial.
“Because severe calcification is mostly excluded from randomized PCI [percutaneous coronary intervention] trials, there is poor evidence for best PCI practice,” commented presenter Gert Richardt, MD, PhD, chief of cardiology and angiology at the Heart Center Segeberger Kliniken, Bad Segeberg, Germany. “Most interventional cardiologists will agree it is essential to facilitate stent delivery and adequate stent expansion in severely calcified lesions.”
Compared with standard balloon preparation, rotational atherectomy (rotablation) achieves a higher stenting success rate and better acute luminal gain, but its stimulatory effect leads to neointima formation that translates to late lumen loss, he noted. New balloons and drug-eluting stents may alter that calculus, however.
The 200 patients in PREPARE-CALC were randomized evenly to undergo preparation of their severely calcified coronary lesions with rotational atherectomy or a modified cutting/scoring balloon, each followed by placement of drug-eluting stents.
Compared with modified balloons, rotational atherectomy yielded a higher rate of successful stent delivery and expansion, according to data reported at the Transcatheter Cardiovascular Therapeutics annual meeting and simultaneously published online (Circ Cardiovasc Interv. 2018;11:e007415). The two methods did not differ significantly with respect to the 9-month magnitude of restenosis or rate of target vessel failure, at 6% with rotational atherectomy and 8% with modified balloons.
Importantly, about one in six patients in the modified balloon group had to cross over to rotational atherectomy because the balloon could not pass or sufficiently dilate the lesion.
“In patients with severely calcified coronary lesions, elective rotablation is feasible in nearly all patients, and the acute success rate is superior to modified balloons. Both approaches, elective rotational atherectomy and balloon plus bailout rotational atherectomy, are equally safe and effective,” Dr. Richardt summarized at the meeting sponsored by the Cardiovascular Research Foundation. “Use of rotablation is no longer associated with excessive late lumen loss in the era of modern drug-eluting stents.”
An underused tool
“This is a little bit ‘back to the future’ for me,” commented press conference panelist Mark Reisman, MD, director of the Center for Emerging Cardiovascular Therapies and head of UW Cardiology, Seattle. The PREPARE-CALC results are not surprising, but low uptake of rotablation in Europe, at just 1%-2%, is surprising and unexplained.
Importantly, the trial allows a sound comparison of rotational atherectomy with the best available alternatives, he said. “This may significantly impact the behavior and maybe some of the reimbursement in Europe. ... I’m sure that drives a lot of the decisions: cost as well as technique.”
Many of the original rotational atherectomy studies used larger burrs and multiple burrs, whereas the trial investigators applied less aggressive, more refined parameters. It will be interesting to look at their technique as it may have contributed to the favorable findings, according to Dr. Reisman.
“Based on what we just heard, there are very complex lesions that were maybe not being approached historically, which now people will feel a lot more confident in approaching, looking at the durable outcome with the Rotablator [Boston Scientific],” he summarized.
“From the practice of a clinician, it’s very frustrating to hit a calcified lesion and attempt to work on it up front and find you can’t cross it,” commented press conference panelist Morton J. Kern, MD, professor of medicine at the school of medicine and chief of medicine, VA Long Beach Health Care System, University of California, Irvine Medical Center. The high rate of crossover to rotablation in PREPARE-CALC speaks to this problem. Having to resort to this tool after failure of other lesional interventions often translates to a rockier overall procedure and clinical course.
“Lesion preparation is underestimated. I know from my own experience that [in] those calcified long lesions where I didn’t use the Rotablator, I regretted it in a fair number of cases,” Dr. Kern said. “So my view is that we probably don’t use it enough. This trial suggests that you can get away [without it], but I think ultimately, we are going to need this tool, even though it’s not used in a huge number of patients.”
Trial details
Patients enrolled in PREPARE-CALC had severely calcified coronary lesions according to angiographic criteria. For lesion preparation, half underwent high-speed rotational atherectomy (Rotablator), and half underwent treatment with either a cutting balloon (Flextome, Boston Scientific) or a scoring balloon (AngioSculpt, AngioScore, or Scoreflex, OrbusNeich Medical). Thereafter, all received sirolimus-eluting stents (Orsiro, Biotronik).
Results reported at the meeting, which is sponsored by the Cardiovascular Research Foundation, showed that, compared with the modified balloons, rotational atherectomy yielded a higher rate of strategy success, defined as successful stent delivery and expansion with less than 20% in-stent residual stenosis and TIMI 3 flow, without crossover to the other arm or stent failure. The rotational atherectomy patients had a success rate of 98%, compared with 81% for the balloon patients (P = .0001).
“This difference was mainly driven by a high rate of crossovers from balloon to rotablation,” Dr. Richardt, noted, with 16% of patients assigned to the former modality ultimately receiving the latter. “These crossovers were due to noncrossable or nondilated lesions.”
Analyses suggested three subgroups did not benefit from rotational atherectomy when it came to strategy success: women, patients in whom the left anterior descending artery was the target, and patients not having type C lesions.
Quantitative coronary analysis showed that the acute lumen gain, whether in-stent or in-segment, did not differ significantly between the two preparation methods. “This is different from what we know from historical studies where the Rotablator was always achieving more acute gain than standard balloons,” Dr. Richardt commented.
Rotational atherectomy and modified balloons were similar with respect to the magnitude of in-stent late lumen loss (0.22 vs. 0.16 mm, P = .021 for superiority; P = .01 for noninferiority) and the rate of target-vessel failure (6% vs. 8%) at 9 months. Those failure rates were lower than the 10% expected from previous trials, he pointed out. “This might increase over time, but it’s not so far away from what we see in contemporary drug-eluting stent trials.”
Fluoroscopy time was about 4 minutes longer with rotational atherectomy than with modified balloons. “You may say that’s a lot. I would say in these 75-year-old patients, it is acceptable,” Dr. Richardt commented. “But to be honest, we had some cases where we had to place a pacemaker, and this increases the duration of the fluoroscopy time.”
The PREPARE-CALC findings should improve the rate of rotational atherectomy use in Europe, he said. “If you believe my data, then the rate should go up to 10% or 12%.”
Dr. Richardt disclosed that he receives speaker’s honoraria from Boston Scientific and Biotronik. The trial was sponsored by the Herz-Kreislauf-Zentrum Segeberger Kliniken GmbH.
SAN DIEGO – When it comes to preparing highly calcified coronary lesions for drug-eluting stents, rotational atherectomy has an early procedural advantage over modified balloons that cut or score the lesion, but yields similar clinical outcomes over time, according to results of the randomized PREPARE-CALC trial.
“Because severe calcification is mostly excluded from randomized PCI [percutaneous coronary intervention] trials, there is poor evidence for best PCI practice,” commented presenter Gert Richardt, MD, PhD, chief of cardiology and angiology at the Heart Center Segeberger Kliniken, Bad Segeberg, Germany. “Most interventional cardiologists will agree it is essential to facilitate stent delivery and adequate stent expansion in severely calcified lesions.”
Compared with standard balloon preparation, rotational atherectomy (rotablation) achieves a higher stenting success rate and better acute luminal gain, but its stimulatory effect leads to neointima formation that translates to late lumen loss, he noted. New balloons and drug-eluting stents may alter that calculus, however.
The 200 patients in PREPARE-CALC were randomized evenly to undergo preparation of their severely calcified coronary lesions with rotational atherectomy or a modified cutting/scoring balloon, each followed by placement of drug-eluting stents.
Compared with modified balloons, rotational atherectomy yielded a higher rate of successful stent delivery and expansion, according to data reported at the Transcatheter Cardiovascular Therapeutics annual meeting and simultaneously published online (Circ Cardiovasc Interv. 2018;11:e007415). The two methods did not differ significantly with respect to the 9-month magnitude of restenosis or rate of target vessel failure, at 6% with rotational atherectomy and 8% with modified balloons.
Importantly, about one in six patients in the modified balloon group had to cross over to rotational atherectomy because the balloon could not pass or sufficiently dilate the lesion.
“In patients with severely calcified coronary lesions, elective rotablation is feasible in nearly all patients, and the acute success rate is superior to modified balloons. Both approaches, elective rotational atherectomy and balloon plus bailout rotational atherectomy, are equally safe and effective,” Dr. Richardt summarized at the meeting sponsored by the Cardiovascular Research Foundation. “Use of rotablation is no longer associated with excessive late lumen loss in the era of modern drug-eluting stents.”
An underused tool
“This is a little bit ‘back to the future’ for me,” commented press conference panelist Mark Reisman, MD, director of the Center for Emerging Cardiovascular Therapies and head of UW Cardiology, Seattle. The PREPARE-CALC results are not surprising, but low uptake of rotablation in Europe, at just 1%-2%, is surprising and unexplained.
Importantly, the trial allows a sound comparison of rotational atherectomy with the best available alternatives, he said. “This may significantly impact the behavior and maybe some of the reimbursement in Europe. ... I’m sure that drives a lot of the decisions: cost as well as technique.”
Many of the original rotational atherectomy studies used larger burrs and multiple burrs, whereas the trial investigators applied less aggressive, more refined parameters. It will be interesting to look at their technique as it may have contributed to the favorable findings, according to Dr. Reisman.
“Based on what we just heard, there are very complex lesions that were maybe not being approached historically, which now people will feel a lot more confident in approaching, looking at the durable outcome with the Rotablator [Boston Scientific],” he summarized.
“From the practice of a clinician, it’s very frustrating to hit a calcified lesion and attempt to work on it up front and find you can’t cross it,” commented press conference panelist Morton J. Kern, MD, professor of medicine at the school of medicine and chief of medicine, VA Long Beach Health Care System, University of California, Irvine Medical Center. The high rate of crossover to rotablation in PREPARE-CALC speaks to this problem. Having to resort to this tool after failure of other lesional interventions often translates to a rockier overall procedure and clinical course.
“Lesion preparation is underestimated. I know from my own experience that [in] those calcified long lesions where I didn’t use the Rotablator, I regretted it in a fair number of cases,” Dr. Kern said. “So my view is that we probably don’t use it enough. This trial suggests that you can get away [without it], but I think ultimately, we are going to need this tool, even though it’s not used in a huge number of patients.”
Trial details
Patients enrolled in PREPARE-CALC had severely calcified coronary lesions according to angiographic criteria. For lesion preparation, half underwent high-speed rotational atherectomy (Rotablator), and half underwent treatment with either a cutting balloon (Flextome, Boston Scientific) or a scoring balloon (AngioSculpt, AngioScore, or Scoreflex, OrbusNeich Medical). Thereafter, all received sirolimus-eluting stents (Orsiro, Biotronik).
Results reported at the meeting, which is sponsored by the Cardiovascular Research Foundation, showed that, compared with the modified balloons, rotational atherectomy yielded a higher rate of strategy success, defined as successful stent delivery and expansion with less than 20% in-stent residual stenosis and TIMI 3 flow, without crossover to the other arm or stent failure. The rotational atherectomy patients had a success rate of 98%, compared with 81% for the balloon patients (P = .0001).
“This difference was mainly driven by a high rate of crossovers from balloon to rotablation,” Dr. Richardt, noted, with 16% of patients assigned to the former modality ultimately receiving the latter. “These crossovers were due to noncrossable or nondilated lesions.”
Analyses suggested three subgroups did not benefit from rotational atherectomy when it came to strategy success: women, patients in whom the left anterior descending artery was the target, and patients not having type C lesions.
Quantitative coronary analysis showed that the acute lumen gain, whether in-stent or in-segment, did not differ significantly between the two preparation methods. “This is different from what we know from historical studies where the Rotablator was always achieving more acute gain than standard balloons,” Dr. Richardt commented.
Rotational atherectomy and modified balloons were similar with respect to the magnitude of in-stent late lumen loss (0.22 vs. 0.16 mm, P = .021 for superiority; P = .01 for noninferiority) and the rate of target-vessel failure (6% vs. 8%) at 9 months. Those failure rates were lower than the 10% expected from previous trials, he pointed out. “This might increase over time, but it’s not so far away from what we see in contemporary drug-eluting stent trials.”
Fluoroscopy time was about 4 minutes longer with rotational atherectomy than with modified balloons. “You may say that’s a lot. I would say in these 75-year-old patients, it is acceptable,” Dr. Richardt commented. “But to be honest, we had some cases where we had to place a pacemaker, and this increases the duration of the fluoroscopy time.”
The PREPARE-CALC findings should improve the rate of rotational atherectomy use in Europe, he said. “If you believe my data, then the rate should go up to 10% or 12%.”
Dr. Richardt disclosed that he receives speaker’s honoraria from Boston Scientific and Biotronik. The trial was sponsored by the Herz-Kreislauf-Zentrum Segeberger Kliniken GmbH.
SAN DIEGO – When it comes to preparing highly calcified coronary lesions for drug-eluting stents, rotational atherectomy has an early procedural advantage over modified balloons that cut or score the lesion, but yields similar clinical outcomes over time, according to results of the randomized PREPARE-CALC trial.
“Because severe calcification is mostly excluded from randomized PCI [percutaneous coronary intervention] trials, there is poor evidence for best PCI practice,” commented presenter Gert Richardt, MD, PhD, chief of cardiology and angiology at the Heart Center Segeberger Kliniken, Bad Segeberg, Germany. “Most interventional cardiologists will agree it is essential to facilitate stent delivery and adequate stent expansion in severely calcified lesions.”
Compared with standard balloon preparation, rotational atherectomy (rotablation) achieves a higher stenting success rate and better acute luminal gain, but its stimulatory effect leads to neointima formation that translates to late lumen loss, he noted. New balloons and drug-eluting stents may alter that calculus, however.
The 200 patients in PREPARE-CALC were randomized evenly to undergo preparation of their severely calcified coronary lesions with rotational atherectomy or a modified cutting/scoring balloon, each followed by placement of drug-eluting stents.
Compared with modified balloons, rotational atherectomy yielded a higher rate of successful stent delivery and expansion, according to data reported at the Transcatheter Cardiovascular Therapeutics annual meeting and simultaneously published online (Circ Cardiovasc Interv. 2018;11:e007415). The two methods did not differ significantly with respect to the 9-month magnitude of restenosis or rate of target vessel failure, at 6% with rotational atherectomy and 8% with modified balloons.
Importantly, about one in six patients in the modified balloon group had to cross over to rotational atherectomy because the balloon could not pass or sufficiently dilate the lesion.
“In patients with severely calcified coronary lesions, elective rotablation is feasible in nearly all patients, and the acute success rate is superior to modified balloons. Both approaches, elective rotational atherectomy and balloon plus bailout rotational atherectomy, are equally safe and effective,” Dr. Richardt summarized at the meeting sponsored by the Cardiovascular Research Foundation. “Use of rotablation is no longer associated with excessive late lumen loss in the era of modern drug-eluting stents.”
An underused tool
“This is a little bit ‘back to the future’ for me,” commented press conference panelist Mark Reisman, MD, director of the Center for Emerging Cardiovascular Therapies and head of UW Cardiology, Seattle. The PREPARE-CALC results are not surprising, but low uptake of rotablation in Europe, at just 1%-2%, is surprising and unexplained.
Importantly, the trial allows a sound comparison of rotational atherectomy with the best available alternatives, he said. “This may significantly impact the behavior and maybe some of the reimbursement in Europe. ... I’m sure that drives a lot of the decisions: cost as well as technique.”
Many of the original rotational atherectomy studies used larger burrs and multiple burrs, whereas the trial investigators applied less aggressive, more refined parameters. It will be interesting to look at their technique as it may have contributed to the favorable findings, according to Dr. Reisman.
“Based on what we just heard, there are very complex lesions that were maybe not being approached historically, which now people will feel a lot more confident in approaching, looking at the durable outcome with the Rotablator [Boston Scientific],” he summarized.
“From the practice of a clinician, it’s very frustrating to hit a calcified lesion and attempt to work on it up front and find you can’t cross it,” commented press conference panelist Morton J. Kern, MD, professor of medicine at the school of medicine and chief of medicine, VA Long Beach Health Care System, University of California, Irvine Medical Center. The high rate of crossover to rotablation in PREPARE-CALC speaks to this problem. Having to resort to this tool after failure of other lesional interventions often translates to a rockier overall procedure and clinical course.
“Lesion preparation is underestimated. I know from my own experience that [in] those calcified long lesions where I didn’t use the Rotablator, I regretted it in a fair number of cases,” Dr. Kern said. “So my view is that we probably don’t use it enough. This trial suggests that you can get away [without it], but I think ultimately, we are going to need this tool, even though it’s not used in a huge number of patients.”
Trial details
Patients enrolled in PREPARE-CALC had severely calcified coronary lesions according to angiographic criteria. For lesion preparation, half underwent high-speed rotational atherectomy (Rotablator), and half underwent treatment with either a cutting balloon (Flextome, Boston Scientific) or a scoring balloon (AngioSculpt, AngioScore, or Scoreflex, OrbusNeich Medical). Thereafter, all received sirolimus-eluting stents (Orsiro, Biotronik).
Results reported at the meeting, which is sponsored by the Cardiovascular Research Foundation, showed that, compared with the modified balloons, rotational atherectomy yielded a higher rate of strategy success, defined as successful stent delivery and expansion with less than 20% in-stent residual stenosis and TIMI 3 flow, without crossover to the other arm or stent failure. The rotational atherectomy patients had a success rate of 98%, compared with 81% for the balloon patients (P = .0001).
“This difference was mainly driven by a high rate of crossovers from balloon to rotablation,” Dr. Richardt, noted, with 16% of patients assigned to the former modality ultimately receiving the latter. “These crossovers were due to noncrossable or nondilated lesions.”
Analyses suggested three subgroups did not benefit from rotational atherectomy when it came to strategy success: women, patients in whom the left anterior descending artery was the target, and patients not having type C lesions.
Quantitative coronary analysis showed that the acute lumen gain, whether in-stent or in-segment, did not differ significantly between the two preparation methods. “This is different from what we know from historical studies where the Rotablator was always achieving more acute gain than standard balloons,” Dr. Richardt commented.
Rotational atherectomy and modified balloons were similar with respect to the magnitude of in-stent late lumen loss (0.22 vs. 0.16 mm, P = .021 for superiority; P = .01 for noninferiority) and the rate of target-vessel failure (6% vs. 8%) at 9 months. Those failure rates were lower than the 10% expected from previous trials, he pointed out. “This might increase over time, but it’s not so far away from what we see in contemporary drug-eluting stent trials.”
Fluoroscopy time was about 4 minutes longer with rotational atherectomy than with modified balloons. “You may say that’s a lot. I would say in these 75-year-old patients, it is acceptable,” Dr. Richardt commented. “But to be honest, we had some cases where we had to place a pacemaker, and this increases the duration of the fluoroscopy time.”
The PREPARE-CALC findings should improve the rate of rotational atherectomy use in Europe, he said. “If you believe my data, then the rate should go up to 10% or 12%.”
Dr. Richardt disclosed that he receives speaker’s honoraria from Boston Scientific and Biotronik. The trial was sponsored by the Herz-Kreislauf-Zentrum Segeberger Kliniken GmbH.
REPORTING FROM TCT 2018
Key clinical point:
Major finding: Rotational atherectomy preparation and cutting/scoring balloon preparation did not differ significantly with respect to 9-month in-stent late lumen loss (0.22 vs. 0.16 mm) and target vessel failure (6% vs. 8%).
Study details: PREPARE-CALC, an open-label, randomized, controlled trial in 200 patients with severely calcified coronary lesions undergoing implantation of drug-eluting stents.
Disclosures: Dr. Richardt disclosed that he receives speaker’s honoraria from Boston Scientific and Biotronik. The trial was sponsored by the Herz-Kreislauf-Zentrum Segeberger Kliniken GmbH.
Prosthesis-patient mismatch post TAVR ups death risk 19%
SAN DIEGO – Severe prosthesis-patient mismatch (PPM) after transcatheter aortic valve replacement (TAVR) increases risk of adverse outcomes and may be preventable in some cases with careful preprocedural planning, suggests a registry-based retrospective cohort study of 62,125 patients treated in the contemporary era.
The study – the largest to date of this patient population – determined that about one in every eight patients undergoing TAVR ultimately had a severe mismatch between the hemodynamics of the valve prosthesis and the requirements for cardiac output. Compared with counterparts that have moderate or no PPM, these patients with severe PPM had a 12% higher adjusted risk of heart failure rehospitalization and a 19% higher adjusted risk of death, according to results reported at the Transcatheter Cardiovascular Therapeutics annual meeting and simultaneously published online (J Am Coll Cardiol. 2018 Sep 23. doi: 10.1016/j.jacc.2018.09.001).
Notably, some of the predictors of severe PPM, such as use of smaller-diameter valves and performance of a valve-in-valve procedure, were potentially modifiable.
“Our findings suggest that efforts should be made to identify this problem and limit the risk for PPM after TAVR,” concluded lead investigator Howard C. Herrmann, MD, a professor at the University of Pennsylvania and director of the cardiac catheterization laboratories, Hospital of the University of Pennsylvania, both in Philadelphia. “Awareness is really the first step in trying to fix it.”
“We spend a lot of time in the heart-team meetings looking at the CT scans for annular dimensions and the vascular access, but we don’t really talk too much about severe PPM or the risk of that,” he elaborated. “This [study] allows us to start to predict it, based on patient factors and what prosthesis we might be choosing for a patient, and it allows us to have that conversation and think about alternatives.
“There are alternatives to try to avoid PPM, everything from which prosthesis we choose to the size of the prosthesis, to whether we fracture a patient’s valve if we are doing a valve-in-valve procedure. In the future, in some situations, we might even choose a low-risk or low-intermediate-risk patient for surgery with an enlargement operation in order to get a larger effective orifice area. So there are choices that we can make, and we should start thinking about that in the heart-team approach.”
Findings in context
The new study reinforces the message “that hemodynamics matter,” he said. “To the extent that we can get larger valves in and get better results from those valves, it will reduce the frequency of PPM. That’s something as operators we don’t spend as much time focusing on, and this will refocus our attention in trying to prevent PPM by being more diligent in terms of prosthesis choice and some operator characteristics, to try to reduce the gradients and improve the effective orifice areas as much as we can.”
Panelist Jeffrey J. Popma, MD, an interventional cardiologist at Beth Israel Deaconess Medical Center, Boston, noted that he and his colleagues have observed similar trends in their smaller studies but had difficulty teasing out contributors. “It really goes back to the preprocedural planning about what valve you can get in, and larger orifice area is certainly better,” he concurred. “So I do think that this is a phenomenal addition.”
Study details
For the study, Dr. Herrmann and his colleagues analyzed 2014-2107 data from the STS/ACC Transcatheter Valve Therapy Registry, a national surveillance and quality improvement system. They identified enrollees aged 65 years or older at the time of their TAVR procedure who had fee-for-service Medicare and linked them to Centers for Medicare & Medicaid Services claims data to assess outcomes.
Overall, 12.1% of patients had severe PPM, defined as an effective valve orifice area indexed to body surface area of less than 0.65 cm2/m2 on discharge echocardiography, and another 24.6% had moderate PPM, Dr. Herrmann reported at the meeting, sponsored by the Cardiovascular Research Foundation.
The strongest multivariate predictors of severe PPM were small prosthetic valve size (up to 23 mm in diameter) (odds ratio, 2.77), a valve-in-valve procedure (OR, 2.78), larger body surface area (OR, 1.71 per 0.2-U increase), and female sex (OR, 1.46). Odds also increased with decreasing age and were elevated for patients of nonwhite/Hispanic race and those having a lower ejection fraction, atrial fibrillation or flutter, or severe mitral or tricuspid regurgitation.
It was not possible to assess specific valves as predictors of mismatch because the registry prohibits comparisons across manufacturers, according to Dr. Herrmann.
One-year mortality, the study’s primary endpoint, was 17.2% in patients with severe PPM, compared with 15.8% in patients with moderate or no PPM (adjusted hazard ratio, 1.19; P less than .001). Findings were similar across subgroups.
The 1-year rate of heart failure rehospitalization was 14.7% in patients with severe PPM, compared with 12.2% in patients with moderate or no PPM (AHR, 1.12; P = .017).
“I would point out that these [outcome] curves are divergent at 1 year,” Dr. Herrmann noted. “So if we look at low-intermediate-risk and low-risk patients and younger patients, who may be more active and who see the effects of PPM more commonly and who are going to be living more than 1 year, we are going to have to consider this going forward in a more important way.”
Severe PPM did not significantly influence the rate of stroke (which stood at about 4% in each group) or worsen quality of life score at 1 year.
Dr. Herrmann disclosed receiving institutional grant/research support from Abbott Vascular, Bayer, Boston Scientific, Corvia Medical, Edwards Lifesciences, Medtronic, and St. Jude Medical, as well as consulting fees/honoraria from Edwards, Medtronic, and Siemens Healthineers.
SAN DIEGO – Severe prosthesis-patient mismatch (PPM) after transcatheter aortic valve replacement (TAVR) increases risk of adverse outcomes and may be preventable in some cases with careful preprocedural planning, suggests a registry-based retrospective cohort study of 62,125 patients treated in the contemporary era.
The study – the largest to date of this patient population – determined that about one in every eight patients undergoing TAVR ultimately had a severe mismatch between the hemodynamics of the valve prosthesis and the requirements for cardiac output. Compared with counterparts that have moderate or no PPM, these patients with severe PPM had a 12% higher adjusted risk of heart failure rehospitalization and a 19% higher adjusted risk of death, according to results reported at the Transcatheter Cardiovascular Therapeutics annual meeting and simultaneously published online (J Am Coll Cardiol. 2018 Sep 23. doi: 10.1016/j.jacc.2018.09.001).
Notably, some of the predictors of severe PPM, such as use of smaller-diameter valves and performance of a valve-in-valve procedure, were potentially modifiable.
“Our findings suggest that efforts should be made to identify this problem and limit the risk for PPM after TAVR,” concluded lead investigator Howard C. Herrmann, MD, a professor at the University of Pennsylvania and director of the cardiac catheterization laboratories, Hospital of the University of Pennsylvania, both in Philadelphia. “Awareness is really the first step in trying to fix it.”
“We spend a lot of time in the heart-team meetings looking at the CT scans for annular dimensions and the vascular access, but we don’t really talk too much about severe PPM or the risk of that,” he elaborated. “This [study] allows us to start to predict it, based on patient factors and what prosthesis we might be choosing for a patient, and it allows us to have that conversation and think about alternatives.
“There are alternatives to try to avoid PPM, everything from which prosthesis we choose to the size of the prosthesis, to whether we fracture a patient’s valve if we are doing a valve-in-valve procedure. In the future, in some situations, we might even choose a low-risk or low-intermediate-risk patient for surgery with an enlargement operation in order to get a larger effective orifice area. So there are choices that we can make, and we should start thinking about that in the heart-team approach.”
Findings in context
The new study reinforces the message “that hemodynamics matter,” he said. “To the extent that we can get larger valves in and get better results from those valves, it will reduce the frequency of PPM. That’s something as operators we don’t spend as much time focusing on, and this will refocus our attention in trying to prevent PPM by being more diligent in terms of prosthesis choice and some operator characteristics, to try to reduce the gradients and improve the effective orifice areas as much as we can.”
Panelist Jeffrey J. Popma, MD, an interventional cardiologist at Beth Israel Deaconess Medical Center, Boston, noted that he and his colleagues have observed similar trends in their smaller studies but had difficulty teasing out contributors. “It really goes back to the preprocedural planning about what valve you can get in, and larger orifice area is certainly better,” he concurred. “So I do think that this is a phenomenal addition.”
Study details
For the study, Dr. Herrmann and his colleagues analyzed 2014-2107 data from the STS/ACC Transcatheter Valve Therapy Registry, a national surveillance and quality improvement system. They identified enrollees aged 65 years or older at the time of their TAVR procedure who had fee-for-service Medicare and linked them to Centers for Medicare & Medicaid Services claims data to assess outcomes.
Overall, 12.1% of patients had severe PPM, defined as an effective valve orifice area indexed to body surface area of less than 0.65 cm2/m2 on discharge echocardiography, and another 24.6% had moderate PPM, Dr. Herrmann reported at the meeting, sponsored by the Cardiovascular Research Foundation.
The strongest multivariate predictors of severe PPM were small prosthetic valve size (up to 23 mm in diameter) (odds ratio, 2.77), a valve-in-valve procedure (OR, 2.78), larger body surface area (OR, 1.71 per 0.2-U increase), and female sex (OR, 1.46). Odds also increased with decreasing age and were elevated for patients of nonwhite/Hispanic race and those having a lower ejection fraction, atrial fibrillation or flutter, or severe mitral or tricuspid regurgitation.
It was not possible to assess specific valves as predictors of mismatch because the registry prohibits comparisons across manufacturers, according to Dr. Herrmann.
One-year mortality, the study’s primary endpoint, was 17.2% in patients with severe PPM, compared with 15.8% in patients with moderate or no PPM (adjusted hazard ratio, 1.19; P less than .001). Findings were similar across subgroups.
The 1-year rate of heart failure rehospitalization was 14.7% in patients with severe PPM, compared with 12.2% in patients with moderate or no PPM (AHR, 1.12; P = .017).
“I would point out that these [outcome] curves are divergent at 1 year,” Dr. Herrmann noted. “So if we look at low-intermediate-risk and low-risk patients and younger patients, who may be more active and who see the effects of PPM more commonly and who are going to be living more than 1 year, we are going to have to consider this going forward in a more important way.”
Severe PPM did not significantly influence the rate of stroke (which stood at about 4% in each group) or worsen quality of life score at 1 year.
Dr. Herrmann disclosed receiving institutional grant/research support from Abbott Vascular, Bayer, Boston Scientific, Corvia Medical, Edwards Lifesciences, Medtronic, and St. Jude Medical, as well as consulting fees/honoraria from Edwards, Medtronic, and Siemens Healthineers.
SAN DIEGO – Severe prosthesis-patient mismatch (PPM) after transcatheter aortic valve replacement (TAVR) increases risk of adverse outcomes and may be preventable in some cases with careful preprocedural planning, suggests a registry-based retrospective cohort study of 62,125 patients treated in the contemporary era.
The study – the largest to date of this patient population – determined that about one in every eight patients undergoing TAVR ultimately had a severe mismatch between the hemodynamics of the valve prosthesis and the requirements for cardiac output. Compared with counterparts that have moderate or no PPM, these patients with severe PPM had a 12% higher adjusted risk of heart failure rehospitalization and a 19% higher adjusted risk of death, according to results reported at the Transcatheter Cardiovascular Therapeutics annual meeting and simultaneously published online (J Am Coll Cardiol. 2018 Sep 23. doi: 10.1016/j.jacc.2018.09.001).
Notably, some of the predictors of severe PPM, such as use of smaller-diameter valves and performance of a valve-in-valve procedure, were potentially modifiable.
“Our findings suggest that efforts should be made to identify this problem and limit the risk for PPM after TAVR,” concluded lead investigator Howard C. Herrmann, MD, a professor at the University of Pennsylvania and director of the cardiac catheterization laboratories, Hospital of the University of Pennsylvania, both in Philadelphia. “Awareness is really the first step in trying to fix it.”
“We spend a lot of time in the heart-team meetings looking at the CT scans for annular dimensions and the vascular access, but we don’t really talk too much about severe PPM or the risk of that,” he elaborated. “This [study] allows us to start to predict it, based on patient factors and what prosthesis we might be choosing for a patient, and it allows us to have that conversation and think about alternatives.
“There are alternatives to try to avoid PPM, everything from which prosthesis we choose to the size of the prosthesis, to whether we fracture a patient’s valve if we are doing a valve-in-valve procedure. In the future, in some situations, we might even choose a low-risk or low-intermediate-risk patient for surgery with an enlargement operation in order to get a larger effective orifice area. So there are choices that we can make, and we should start thinking about that in the heart-team approach.”
Findings in context
The new study reinforces the message “that hemodynamics matter,” he said. “To the extent that we can get larger valves in and get better results from those valves, it will reduce the frequency of PPM. That’s something as operators we don’t spend as much time focusing on, and this will refocus our attention in trying to prevent PPM by being more diligent in terms of prosthesis choice and some operator characteristics, to try to reduce the gradients and improve the effective orifice areas as much as we can.”
Panelist Jeffrey J. Popma, MD, an interventional cardiologist at Beth Israel Deaconess Medical Center, Boston, noted that he and his colleagues have observed similar trends in their smaller studies but had difficulty teasing out contributors. “It really goes back to the preprocedural planning about what valve you can get in, and larger orifice area is certainly better,” he concurred. “So I do think that this is a phenomenal addition.”
Study details
For the study, Dr. Herrmann and his colleagues analyzed 2014-2107 data from the STS/ACC Transcatheter Valve Therapy Registry, a national surveillance and quality improvement system. They identified enrollees aged 65 years or older at the time of their TAVR procedure who had fee-for-service Medicare and linked them to Centers for Medicare & Medicaid Services claims data to assess outcomes.
Overall, 12.1% of patients had severe PPM, defined as an effective valve orifice area indexed to body surface area of less than 0.65 cm2/m2 on discharge echocardiography, and another 24.6% had moderate PPM, Dr. Herrmann reported at the meeting, sponsored by the Cardiovascular Research Foundation.
The strongest multivariate predictors of severe PPM were small prosthetic valve size (up to 23 mm in diameter) (odds ratio, 2.77), a valve-in-valve procedure (OR, 2.78), larger body surface area (OR, 1.71 per 0.2-U increase), and female sex (OR, 1.46). Odds also increased with decreasing age and were elevated for patients of nonwhite/Hispanic race and those having a lower ejection fraction, atrial fibrillation or flutter, or severe mitral or tricuspid regurgitation.
It was not possible to assess specific valves as predictors of mismatch because the registry prohibits comparisons across manufacturers, according to Dr. Herrmann.
One-year mortality, the study’s primary endpoint, was 17.2% in patients with severe PPM, compared with 15.8% in patients with moderate or no PPM (adjusted hazard ratio, 1.19; P less than .001). Findings were similar across subgroups.
The 1-year rate of heart failure rehospitalization was 14.7% in patients with severe PPM, compared with 12.2% in patients with moderate or no PPM (AHR, 1.12; P = .017).
“I would point out that these [outcome] curves are divergent at 1 year,” Dr. Herrmann noted. “So if we look at low-intermediate-risk and low-risk patients and younger patients, who may be more active and who see the effects of PPM more commonly and who are going to be living more than 1 year, we are going to have to consider this going forward in a more important way.”
Severe PPM did not significantly influence the rate of stroke (which stood at about 4% in each group) or worsen quality of life score at 1 year.
Dr. Herrmann disclosed receiving institutional grant/research support from Abbott Vascular, Bayer, Boston Scientific, Corvia Medical, Edwards Lifesciences, Medtronic, and St. Jude Medical, as well as consulting fees/honoraria from Edwards, Medtronic, and Siemens Healthineers.
REPORTING FROM TCT 2018
Key clinical point:
Major finding: Patients with severe PPM after TAVR had elevated risks of heart failure rehospitalization (adjusted hazard ratio, 1.12) and death (AHR, 1.19).
Study details: A retrospective cohort study of 62,125 patients aged 65 years or older who underwent TAVR and were captured in the national STS/ACC Transcatheter Valve Therapy Registry.
Disclosures: Dr. Herrmann disclosed receiving institutional grant/research support from Abbott Vascular, Bayer, Boston Scientific, Corvia Medical, Edwards Lifesciences, Medtronic, and St. Jude Medical, as well as consulting fees/honoraria from Edwards, Medtronic, and Siemens Healthineers.