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Time to rethink bioprosthetic valve guidelines?
Recent findings on the incidence and pathophysiology of bioprosthetic valve thrombosis require revisiting existing guidelines against routine echocardiography in the first 5 years after bioprosthetic valve replacement and a longer course of anticoagulation therapy than the current standard of 3 months, investigators from the Mayo Clinic said in an expert opinion article in the October issue of the Journal of Thoracic and Cardiovascular Surgery (2016;152;975-8).
In the expert commentary, Alexander C. Egbe, MBBS, of the departments of cardiovascular diseases and cardiovascular surgery at Mayo Clinic in Rochester, Minn., and coauthors explored the implications of their previous research, published in the Journal of the American College of Cardiology, that reported that bioprosthetic valve thrombosis (BPVT) is “not an uncommon cause of prosthetic valve dysfunction.” They identified BPVT in 46 of 397 (11%) bioprosthetic valves explanted at Mayo Clinic, and estimated the incidence of BPVT at 1% (J Am Coll Cardiol. 2015;66:2285-94), although Dr. Egbe and colleagues acknowledged the true incidence of BPVT is unknown, as is the time to occurrence. They noted that a different study design would be needed to determine that, along with the incidence of BPVT.
“The occurrence of BPVT is not restricted to surgically implanted bioprosthetic valves, but has also been observed after transcatheter aortic valve replacement (TAVR),” Dr. Egbe and colleagues said. They noted an association between BPVT and a lack of anticoagulation therapy in two earlier reports (N Engl J Med. 2015;373:2015-24; J Am Coll Cardiol. 2016;67:644-55). In their own study, 14 of 15 patients (93%) with diagnosed BPVT responded to anticoagulation therapy and avoided reoperation.
Dr. Egbe and coauthors did somewhat define the extent of the problem of misdiagnosis of BPVT. The diagnosis was considered in only 6 of 45 patients (13%) who had transesophageal echocardiography. “A significant proportion of the patients with BPVT were misdiagnosed as having structural failure and referred for reoperation,” Dr. Egbe and coauthors said. “This attests to the low level of awareness of the existence of BPVT and the lack of well-defined diagnostic criteria.”
They proposed a diagnostic model based on the echocardiography characteristics of three findings: a 50% increase in gradient within 5 years of implantation; increased cusp thickness; and abnormal cusp mobility. “The presence of all three echocardiographic features reliably diagnosed BPVT with a sensitivity of 72% and a specificity of 90%,” they said.
Their finding that 85% of BPVT cases occurred within 5 years of implantation flies in the face of clinical guidelines that state routine annual echocardiography is not recommended in that time frame (J Am So Echocardiogr. 2009;22;975-1014). But abnormal physical examination findings as a prerequisite for echocardiography may not be an effective method to diagnose BPVT. “In addition to transthoracic and transesophageal echocardiography, the use of other complementary imaging modalities, such as computed tomography, could be very effective in identifying subtle BPVT,” Dr. Egbe and colleagues said,
But preventing BPVT is more complicated. Clinical guidelines recommend anticoagulation of bioprosthetic valves for 3 months after implantation, but adhering to that guideline showed no protective effect against BPVT in their study, Dr. Egbe and coauthors said. Nor did antiplatelet therapy prove effective in preventing BPVT. However, a Danish study showed stopping anticoagulation within 6 months of surgical aortic valve replacement increased risk of thromboembolic complications and cardiovascular death (JAMA. 2012;308:2118-25). And the role of prosthesis type in BPVT “remains unclear.”
Dr. Egbe and coauthors acknowledged a number of questions persist with regard to BPVT in bioprosthetic valve dysfunction, including the true incidence, best screening method, risk factors, and the duration of anticoagulation, as well as the role of novel oral anticoagulants. “Answers to these questions will come from population-based prospective studies,” Dr. Egbe and colleagues said.
Dr. Egbe and his coauthors had no relationships to disclose.
Dr. Egbe and colleagues make a “provocative” case that it is the presence of thrombus on bioprosthetic valves, and not degeneration, that causes valve dysfunction, Clifford W. Barlow, MBBCh, DPhil, FRCS, of University Hospital Southampton (England) said in his invited commentary (J Thorac Cardiovasc Surg. 2016;152:978-80).
“This Expert Opinion is of particular interest because it relates to something commonly performed: conventional valve replacement,” Dr. Barlow said. Moreover, “BPVT is an under-recognized problem for which Dr. Egbe and colleagues concisely direct how future research should ascertain which diagnostic, preventive, and treatment strategies would improve long-term outcomes and avoid redo surgery.”
Dr. Egbe’s and colleagues’ recommendation of prolonged anticoagulation after bioprosthetic valve implantation complicates the selection of bioprosthetic valves – because cardiovascular surgeons frequently choose them to avoid anticoagulation, while accepting a higher risk of a reoperation because of valve degeneration, Dr. Barlow said.
And while Dr. Barlow noted this study found that porcine valves are not a predictor for BPVT, another Mayo Clinic study reported eight cases of BPVT, all in porcine valves (J Thorac Cardiovasc Surg. 2012;144:108-11). Nonetheless, the expert opinion by Dr. Egbe and colleagues is “relevant to much that is important – not only to improving outcomes with conventional valve replacement but also to these developing technologies,” Dr. Barlow said.
Dr. Egbe and colleagues make a “provocative” case that it is the presence of thrombus on bioprosthetic valves, and not degeneration, that causes valve dysfunction, Clifford W. Barlow, MBBCh, DPhil, FRCS, of University Hospital Southampton (England) said in his invited commentary (J Thorac Cardiovasc Surg. 2016;152:978-80).
“This Expert Opinion is of particular interest because it relates to something commonly performed: conventional valve replacement,” Dr. Barlow said. Moreover, “BPVT is an under-recognized problem for which Dr. Egbe and colleagues concisely direct how future research should ascertain which diagnostic, preventive, and treatment strategies would improve long-term outcomes and avoid redo surgery.”
Dr. Egbe’s and colleagues’ recommendation of prolonged anticoagulation after bioprosthetic valve implantation complicates the selection of bioprosthetic valves – because cardiovascular surgeons frequently choose them to avoid anticoagulation, while accepting a higher risk of a reoperation because of valve degeneration, Dr. Barlow said.
And while Dr. Barlow noted this study found that porcine valves are not a predictor for BPVT, another Mayo Clinic study reported eight cases of BPVT, all in porcine valves (J Thorac Cardiovasc Surg. 2012;144:108-11). Nonetheless, the expert opinion by Dr. Egbe and colleagues is “relevant to much that is important – not only to improving outcomes with conventional valve replacement but also to these developing technologies,” Dr. Barlow said.
Dr. Egbe and colleagues make a “provocative” case that it is the presence of thrombus on bioprosthetic valves, and not degeneration, that causes valve dysfunction, Clifford W. Barlow, MBBCh, DPhil, FRCS, of University Hospital Southampton (England) said in his invited commentary (J Thorac Cardiovasc Surg. 2016;152:978-80).
“This Expert Opinion is of particular interest because it relates to something commonly performed: conventional valve replacement,” Dr. Barlow said. Moreover, “BPVT is an under-recognized problem for which Dr. Egbe and colleagues concisely direct how future research should ascertain which diagnostic, preventive, and treatment strategies would improve long-term outcomes and avoid redo surgery.”
Dr. Egbe’s and colleagues’ recommendation of prolonged anticoagulation after bioprosthetic valve implantation complicates the selection of bioprosthetic valves – because cardiovascular surgeons frequently choose them to avoid anticoagulation, while accepting a higher risk of a reoperation because of valve degeneration, Dr. Barlow said.
And while Dr. Barlow noted this study found that porcine valves are not a predictor for BPVT, another Mayo Clinic study reported eight cases of BPVT, all in porcine valves (J Thorac Cardiovasc Surg. 2012;144:108-11). Nonetheless, the expert opinion by Dr. Egbe and colleagues is “relevant to much that is important – not only to improving outcomes with conventional valve replacement but also to these developing technologies,” Dr. Barlow said.
Recent findings on the incidence and pathophysiology of bioprosthetic valve thrombosis require revisiting existing guidelines against routine echocardiography in the first 5 years after bioprosthetic valve replacement and a longer course of anticoagulation therapy than the current standard of 3 months, investigators from the Mayo Clinic said in an expert opinion article in the October issue of the Journal of Thoracic and Cardiovascular Surgery (2016;152;975-8).
In the expert commentary, Alexander C. Egbe, MBBS, of the departments of cardiovascular diseases and cardiovascular surgery at Mayo Clinic in Rochester, Minn., and coauthors explored the implications of their previous research, published in the Journal of the American College of Cardiology, that reported that bioprosthetic valve thrombosis (BPVT) is “not an uncommon cause of prosthetic valve dysfunction.” They identified BPVT in 46 of 397 (11%) bioprosthetic valves explanted at Mayo Clinic, and estimated the incidence of BPVT at 1% (J Am Coll Cardiol. 2015;66:2285-94), although Dr. Egbe and colleagues acknowledged the true incidence of BPVT is unknown, as is the time to occurrence. They noted that a different study design would be needed to determine that, along with the incidence of BPVT.
“The occurrence of BPVT is not restricted to surgically implanted bioprosthetic valves, but has also been observed after transcatheter aortic valve replacement (TAVR),” Dr. Egbe and colleagues said. They noted an association between BPVT and a lack of anticoagulation therapy in two earlier reports (N Engl J Med. 2015;373:2015-24; J Am Coll Cardiol. 2016;67:644-55). In their own study, 14 of 15 patients (93%) with diagnosed BPVT responded to anticoagulation therapy and avoided reoperation.
Dr. Egbe and coauthors did somewhat define the extent of the problem of misdiagnosis of BPVT. The diagnosis was considered in only 6 of 45 patients (13%) who had transesophageal echocardiography. “A significant proportion of the patients with BPVT were misdiagnosed as having structural failure and referred for reoperation,” Dr. Egbe and coauthors said. “This attests to the low level of awareness of the existence of BPVT and the lack of well-defined diagnostic criteria.”
They proposed a diagnostic model based on the echocardiography characteristics of three findings: a 50% increase in gradient within 5 years of implantation; increased cusp thickness; and abnormal cusp mobility. “The presence of all three echocardiographic features reliably diagnosed BPVT with a sensitivity of 72% and a specificity of 90%,” they said.
Their finding that 85% of BPVT cases occurred within 5 years of implantation flies in the face of clinical guidelines that state routine annual echocardiography is not recommended in that time frame (J Am So Echocardiogr. 2009;22;975-1014). But abnormal physical examination findings as a prerequisite for echocardiography may not be an effective method to diagnose BPVT. “In addition to transthoracic and transesophageal echocardiography, the use of other complementary imaging modalities, such as computed tomography, could be very effective in identifying subtle BPVT,” Dr. Egbe and colleagues said,
But preventing BPVT is more complicated. Clinical guidelines recommend anticoagulation of bioprosthetic valves for 3 months after implantation, but adhering to that guideline showed no protective effect against BPVT in their study, Dr. Egbe and coauthors said. Nor did antiplatelet therapy prove effective in preventing BPVT. However, a Danish study showed stopping anticoagulation within 6 months of surgical aortic valve replacement increased risk of thromboembolic complications and cardiovascular death (JAMA. 2012;308:2118-25). And the role of prosthesis type in BPVT “remains unclear.”
Dr. Egbe and coauthors acknowledged a number of questions persist with regard to BPVT in bioprosthetic valve dysfunction, including the true incidence, best screening method, risk factors, and the duration of anticoagulation, as well as the role of novel oral anticoagulants. “Answers to these questions will come from population-based prospective studies,” Dr. Egbe and colleagues said.
Dr. Egbe and his coauthors had no relationships to disclose.
Recent findings on the incidence and pathophysiology of bioprosthetic valve thrombosis require revisiting existing guidelines against routine echocardiography in the first 5 years after bioprosthetic valve replacement and a longer course of anticoagulation therapy than the current standard of 3 months, investigators from the Mayo Clinic said in an expert opinion article in the October issue of the Journal of Thoracic and Cardiovascular Surgery (2016;152;975-8).
In the expert commentary, Alexander C. Egbe, MBBS, of the departments of cardiovascular diseases and cardiovascular surgery at Mayo Clinic in Rochester, Minn., and coauthors explored the implications of their previous research, published in the Journal of the American College of Cardiology, that reported that bioprosthetic valve thrombosis (BPVT) is “not an uncommon cause of prosthetic valve dysfunction.” They identified BPVT in 46 of 397 (11%) bioprosthetic valves explanted at Mayo Clinic, and estimated the incidence of BPVT at 1% (J Am Coll Cardiol. 2015;66:2285-94), although Dr. Egbe and colleagues acknowledged the true incidence of BPVT is unknown, as is the time to occurrence. They noted that a different study design would be needed to determine that, along with the incidence of BPVT.
“The occurrence of BPVT is not restricted to surgically implanted bioprosthetic valves, but has also been observed after transcatheter aortic valve replacement (TAVR),” Dr. Egbe and colleagues said. They noted an association between BPVT and a lack of anticoagulation therapy in two earlier reports (N Engl J Med. 2015;373:2015-24; J Am Coll Cardiol. 2016;67:644-55). In their own study, 14 of 15 patients (93%) with diagnosed BPVT responded to anticoagulation therapy and avoided reoperation.
Dr. Egbe and coauthors did somewhat define the extent of the problem of misdiagnosis of BPVT. The diagnosis was considered in only 6 of 45 patients (13%) who had transesophageal echocardiography. “A significant proportion of the patients with BPVT were misdiagnosed as having structural failure and referred for reoperation,” Dr. Egbe and coauthors said. “This attests to the low level of awareness of the existence of BPVT and the lack of well-defined diagnostic criteria.”
They proposed a diagnostic model based on the echocardiography characteristics of three findings: a 50% increase in gradient within 5 years of implantation; increased cusp thickness; and abnormal cusp mobility. “The presence of all three echocardiographic features reliably diagnosed BPVT with a sensitivity of 72% and a specificity of 90%,” they said.
Their finding that 85% of BPVT cases occurred within 5 years of implantation flies in the face of clinical guidelines that state routine annual echocardiography is not recommended in that time frame (J Am So Echocardiogr. 2009;22;975-1014). But abnormal physical examination findings as a prerequisite for echocardiography may not be an effective method to diagnose BPVT. “In addition to transthoracic and transesophageal echocardiography, the use of other complementary imaging modalities, such as computed tomography, could be very effective in identifying subtle BPVT,” Dr. Egbe and colleagues said,
But preventing BPVT is more complicated. Clinical guidelines recommend anticoagulation of bioprosthetic valves for 3 months after implantation, but adhering to that guideline showed no protective effect against BPVT in their study, Dr. Egbe and coauthors said. Nor did antiplatelet therapy prove effective in preventing BPVT. However, a Danish study showed stopping anticoagulation within 6 months of surgical aortic valve replacement increased risk of thromboembolic complications and cardiovascular death (JAMA. 2012;308:2118-25). And the role of prosthesis type in BPVT “remains unclear.”
Dr. Egbe and coauthors acknowledged a number of questions persist with regard to BPVT in bioprosthetic valve dysfunction, including the true incidence, best screening method, risk factors, and the duration of anticoagulation, as well as the role of novel oral anticoagulants. “Answers to these questions will come from population-based prospective studies,” Dr. Egbe and colleagues said.
Dr. Egbe and his coauthors had no relationships to disclose.
FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Key clinical point: Preoperative echocardiography can aid in the diagnosis of BPVT.
Major finding: Sixty-five percent of all reoperations for BPVT occurred more than a year after implantation and up to 15% of these reoperations occurred more than 5 years after the initial implantation.
Data source: Single-center retrospective study of 397 valve explants.
Disclosures: Dr. Egbe and his coauthors reported having no financial disclosures.
‘Stepping’ up to a better way to teach robotic lobectomy
Teaching minimally invasive robotic surgery to residents can be difficult in a health care environment obsessed with quality outcome measures and under scrutiny by hospital administrators and payers, but researchers at the University of Alabama at Birmingham may have devised a method to instruct residents in robotic lobectomy without compromising patient outcomes, according to a study published in the October issue of the Journal of Thoracic and Cardiovascular Surgery (2016;152:991-7).
Robert J. Cerfolio, MD, MBA, and his coauthors divided the procedure into 19 sequential, teachable steps and allowed residents to perform selected steps during operations that Dr. Cerfolio directed. “We then applied simulation training, coaching techniques, and video review of each step to help improve the steps that residents could not complete,” Dr. Cerfolio and his coauthors said. 
Surgeons in academic centers face the challenge of teaching “the art and science of surgery,” Dr. Cerfolio and his colleagues said, while maintaining quality outcomes. “Teaching minimally invasive surgery, especially robotic surgery, is challenging given the risks and the limited availability of the robot.”
The researchers acknowledged that other groups have taken a similar approach to training, but this is the first study that included video review, coaching, and instruction tied to time constraints, they said. “A major concern is that while teaching robotic surgery, patients can be injured, care is worse, and metrics that are increasingly used as surrogates for quality outcomes suffer,” they noted.
They allotted each step in the procedure a set amount of time in which the resident had to complete it, totaling 80 minutes for all 19 steps and ranging from 1 minute to inspect the pleura after placing ports (9 minutes) to 20 minutes to close the five incisions. If the resident completed the task in the allotted time, it was recorded as “performed.”
Between February 2010 and December 2010 Dr. Cerfolio performed 520 robotic lobectomies, and over time the percentage of successful steps per resident improved. For example, in the first year, 50% of thoracic surgery residents completed the first five steps (mark and place ports, inspect pleura, resect the inferior pulmonary ligament, and remove three lymph nodes), but by the last year of the study 90% of them successfully completed the five steps.
Dr. Cerfolio and coauthors acknowledged “many flaws” in their study, but the study also had strengths: It involved only one operation and corroborated the database with each resident’s own surgical logs.
“Operations such as robotic lobectomy can be successfully taught by dividing them into a series of surgical maneuvers or steps,” the researchers noted. Recording what residents can and can’t do, reviewing video, and coaching contribute to the process to improve their skills. “Further studies that scientifically measure ‘ways to teach’ and ways to coach and mentor are needed,” they said.
Dr. Cerfolio disclosed relationships with Intuitive Surgical, Ethicon, Community Health Services, KCL, Bovie and C-SATS. Coauthor Douglas Minnich, MD, is a consultant to Medtronic. The other co-authors had no financial relationships to disclose.
Inderpal S. Sarkaria, MD, of the University of Pittsburgh acknowledged in his invited commentary how “metric-driven patient outcomes” have changed cardiothoracic surgical training (J Thorac Cardiovasc Surg. 2016;152:998).
But Dr. Sarkaria questioned the validity of using time performed as a metric in this study to evaluate a trainee’s competency. “Although ‘time’ is an important component, should not the primary focus be on ‘quality’ of the trainee’s work?” Dr. Sarkaria asked. 
Despite these questions and the limitations of the study, he found the approach to surgical training “laudable.” Said Dr. Sarkaria: “It is arguable that the limitations of the study speak more to a common wisdom that certain aspects of surgical education remain an art to a greater or lesser extent, not easily amenable to our efforts to discretely compartmentalize and quantify the process.”
While the premise demands further study, Dr. Cerfolio and his coauthors “have laid a solid foundation on which further to build, explore, and potentially improve the science and art of teaching complex operations to our surgical residents,” Dr. Sarkaria said.
Dr. Sarkaria had no relationships to disclose.
Inderpal S. Sarkaria, MD, of the University of Pittsburgh acknowledged in his invited commentary how “metric-driven patient outcomes” have changed cardiothoracic surgical training (J Thorac Cardiovasc Surg. 2016;152:998).
But Dr. Sarkaria questioned the validity of using time performed as a metric in this study to evaluate a trainee’s competency. “Although ‘time’ is an important component, should not the primary focus be on ‘quality’ of the trainee’s work?” Dr. Sarkaria asked.
Despite these questions and the limitations of the study, he found the approach to surgical training “laudable.” Said Dr. Sarkaria: “It is arguable that the limitations of the study speak more to a common wisdom that certain aspects of surgical education remain an art to a greater or lesser extent, not easily amenable to our efforts to discretely compartmentalize and quantify the process.”
While the premise demands further study, Dr. Cerfolio and his coauthors “have laid a solid foundation on which further to build, explore, and potentially improve the science and art of teaching complex operations to our surgical residents,” Dr. Sarkaria said.
Dr. Sarkaria had no relationships to disclose.
Inderpal S. Sarkaria, MD, of the University of Pittsburgh acknowledged in his invited commentary how “metric-driven patient outcomes” have changed cardiothoracic surgical training (J Thorac Cardiovasc Surg. 2016;152:998).
But Dr. Sarkaria questioned the validity of using time performed as a metric in this study to evaluate a trainee’s competency. “Although ‘time’ is an important component, should not the primary focus be on ‘quality’ of the trainee’s work?” Dr. Sarkaria asked.
Despite these questions and the limitations of the study, he found the approach to surgical training “laudable.” Said Dr. Sarkaria: “It is arguable that the limitations of the study speak more to a common wisdom that certain aspects of surgical education remain an art to a greater or lesser extent, not easily amenable to our efforts to discretely compartmentalize and quantify the process.”
While the premise demands further study, Dr. Cerfolio and his coauthors “have laid a solid foundation on which further to build, explore, and potentially improve the science and art of teaching complex operations to our surgical residents,” Dr. Sarkaria said.
Dr. Sarkaria had no relationships to disclose.
Teaching minimally invasive robotic surgery to residents can be difficult in a health care environment obsessed with quality outcome measures and under scrutiny by hospital administrators and payers, but researchers at the University of Alabama at Birmingham may have devised a method to instruct residents in robotic lobectomy without compromising patient outcomes, according to a study published in the October issue of the Journal of Thoracic and Cardiovascular Surgery (2016;152:991-7).
Robert J. Cerfolio, MD, MBA, and his coauthors divided the procedure into 19 sequential, teachable steps and allowed residents to perform selected steps during operations that Dr. Cerfolio directed. “We then applied simulation training, coaching techniques, and video review of each step to help improve the steps that residents could not complete,” Dr. Cerfolio and his coauthors said.
Surgeons in academic centers face the challenge of teaching “the art and science of surgery,” Dr. Cerfolio and his colleagues said, while maintaining quality outcomes. “Teaching minimally invasive surgery, especially robotic surgery, is challenging given the risks and the limited availability of the robot.”
The researchers acknowledged that other groups have taken a similar approach to training, but this is the first study that included video review, coaching, and instruction tied to time constraints, they said. “A major concern is that while teaching robotic surgery, patients can be injured, care is worse, and metrics that are increasingly used as surrogates for quality outcomes suffer,” they noted.
They allotted each step in the procedure a set amount of time in which the resident had to complete it, totaling 80 minutes for all 19 steps and ranging from 1 minute to inspect the pleura after placing ports (9 minutes) to 20 minutes to close the five incisions. If the resident completed the task in the allotted time, it was recorded as “performed.”
Between February 2010 and December 2010 Dr. Cerfolio performed 520 robotic lobectomies, and over time the percentage of successful steps per resident improved. For example, in the first year, 50% of thoracic surgery residents completed the first five steps (mark and place ports, inspect pleura, resect the inferior pulmonary ligament, and remove three lymph nodes), but by the last year of the study 90% of them successfully completed the five steps.
Dr. Cerfolio and coauthors acknowledged “many flaws” in their study, but the study also had strengths: It involved only one operation and corroborated the database with each resident’s own surgical logs.
“Operations such as robotic lobectomy can be successfully taught by dividing them into a series of surgical maneuvers or steps,” the researchers noted. Recording what residents can and can’t do, reviewing video, and coaching contribute to the process to improve their skills. “Further studies that scientifically measure ‘ways to teach’ and ways to coach and mentor are needed,” they said.
Dr. Cerfolio disclosed relationships with Intuitive Surgical, Ethicon, Community Health Services, KCL, Bovie and C-SATS. Coauthor Douglas Minnich, MD, is a consultant to Medtronic. The other co-authors had no financial relationships to disclose.
Teaching minimally invasive robotic surgery to residents can be difficult in a health care environment obsessed with quality outcome measures and under scrutiny by hospital administrators and payers, but researchers at the University of Alabama at Birmingham may have devised a method to instruct residents in robotic lobectomy without compromising patient outcomes, according to a study published in the October issue of the Journal of Thoracic and Cardiovascular Surgery (2016;152:991-7).
Robert J. Cerfolio, MD, MBA, and his coauthors divided the procedure into 19 sequential, teachable steps and allowed residents to perform selected steps during operations that Dr. Cerfolio directed. “We then applied simulation training, coaching techniques, and video review of each step to help improve the steps that residents could not complete,” Dr. Cerfolio and his coauthors said.
Surgeons in academic centers face the challenge of teaching “the art and science of surgery,” Dr. Cerfolio and his colleagues said, while maintaining quality outcomes. “Teaching minimally invasive surgery, especially robotic surgery, is challenging given the risks and the limited availability of the robot.”
The researchers acknowledged that other groups have taken a similar approach to training, but this is the first study that included video review, coaching, and instruction tied to time constraints, they said. “A major concern is that while teaching robotic surgery, patients can be injured, care is worse, and metrics that are increasingly used as surrogates for quality outcomes suffer,” they noted.
They allotted each step in the procedure a set amount of time in which the resident had to complete it, totaling 80 minutes for all 19 steps and ranging from 1 minute to inspect the pleura after placing ports (9 minutes) to 20 minutes to close the five incisions. If the resident completed the task in the allotted time, it was recorded as “performed.”
Between February 2010 and December 2010 Dr. Cerfolio performed 520 robotic lobectomies, and over time the percentage of successful steps per resident improved. For example, in the first year, 50% of thoracic surgery residents completed the first five steps (mark and place ports, inspect pleura, resect the inferior pulmonary ligament, and remove three lymph nodes), but by the last year of the study 90% of them successfully completed the five steps.
Dr. Cerfolio and coauthors acknowledged “many flaws” in their study, but the study also had strengths: It involved only one operation and corroborated the database with each resident’s own surgical logs.
“Operations such as robotic lobectomy can be successfully taught by dividing them into a series of surgical maneuvers or steps,” the researchers noted. Recording what residents can and can’t do, reviewing video, and coaching contribute to the process to improve their skills. “Further studies that scientifically measure ‘ways to teach’ and ways to coach and mentor are needed,” they said.
Dr. Cerfolio disclosed relationships with Intuitive Surgical, Ethicon, Community Health Services, KCL, Bovie and C-SATS. Coauthor Douglas Minnich, MD, is a consultant to Medtronic. The other co-authors had no financial relationships to disclose.
FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Key clinical point: Surgical residents learn and safely perform robotic lobectomy by dividing the procedure into a series of surgical maneuvers.
Major finding: The percentage of thoracic surgery residents who completed the first 5 of 19 procedural steps of the operation improved from 50% in the first year to 90% in the fifth year.
Data source: Single-center study of 520 consecutive lobectomies over 5 years by 35 general surgery residents and 7 cardiothoracic residents from February 2010 to December 2015.
Disclosures: Dr. Cerfolio disclosed relationships with Intuitive Surgical, Ethicon, Community Health Services, KCL, Bovie and C-SATS. Coauthor Douglas Minnich, MD, is a consultant to Medtronic. The other coauthors had no financial relationships to disclose.
VIDEO: Two PCI vs. CABG trials produce conflicting results
WASHINGTON – Results from two large, multicenter comparisons of coronary stenting and coronary bypass surgery for treating patients with unprotected left main coronary disease may have superficially shown sharp differences, but the bottom line will likely be greater empowerment of percutaneous coronary intervention as an option for selected patients with less complex coronary disease.
Prior to the results from the EXCEL and NOBLE trials, reported at the Transcatheter Cardiovascular Therapeutics annual meeting, “guidelines put PCI [percutaneous coronary intervention] into a class 1, 2 or 3 status for treating left main coronary disease depending on disease complexity, but in the United States, PCI for patients eligible for CABG [coronary artery bypass grafting] has not been frequently done. I think these results, in a very circumscribed subset of patients and using a state-of-the-art stent, will affect the guidelines,” predicted Gregg W. Stone, MD, lead investigator for EXCEL and professor of medicine at Columbia University in New York.
“What the guidelines have not addressed are the patients with low- or intermediate-complexity disease who have an acceptable risk for undergoing either PCI or CABG. I think the trial results answer this question,” said David Kandzari, MD, director of interventional cardiology and chief scientific officer at the Piedmont Heart Institute in Atlanta and an EXCEL investigator.
While the EXCEL and NOBLE results don’t provide a simple answer on the relative merits of PCI and CABG, many of their outcome differences seem explicable, several experts said at the meeting.
The Nordic-Baltic-British Left Main Revascularisation (NOBLE) trial randomized 1,201 patients who had unprotected left main coronary disease and were judged by a heart team to be reasonable candidates for both PCI or CABG at 36 centers in nine European countries during 2008-2015. The primary endpoint was death from any cause, nonprocedural MIs, stroke, or repeat revascularization.
The researchers followed patients for a median of just over 3 years, but they calculated the primary endpoint based on a Kaplan-Meier estimate for 5-year outcomes, which showed the primary endpoint in 29% of the PCI patients and in 19% of the CABG patients, a statistically significant benefit in favor of CABG, Evald H. Christiansen, MD, reported at the meeting, which was sponsored by the Cardiovascular Research Foundation. Concurrently with his report, the results were published online (Lancet. 2016 Oct. 31. doi: 10.1016/S0140-6736[16]32052-9).
This difference between PCI and CABG was largely driven by an excess of postprocedural MIs and repeat revascularizations among the PCI patients, said Dr. Christiansen, an interventional cardiologist at Aarhus University Hospital in Denmark. Another notable finding was that the superior outcomes with CABG primarily occurred among patients with a SYNTAX score – a measure of coronary disease complexity – of 22 or less, which identifies patients with low complexity disease. The outcomes of patients with SYNTAX scores of 23-32, which identifies intermediate complexity disease, and of patients with scores of 33 or higher, with very complex disease, were similar in the PCI and CABG arms, he reported. This finding was “very surprising,” Dr. Christiansen said, because it reversed the finding originally made in the SYNTAX trial that PCI performed best compared with CABG in patients with the lowest scores and least-complex coronary disease.
The superiority of CABG over PCI seen in the NOBLE results, especially in patients with lower SYNTAX scores, seemed at odds with the EXCEL results, reported at the meeting by Dr. Stone and simultaneously online (N Engl J Med. 2016 Oct. 31. doi: 10.1056/NEJMoa1610227). In EXCEL, which enrolled only patients with a SYNTAX score of 32 or less (low- or intermediate-complexity coronary disease), patients had a 3-year incidence of death, stroke or MI of 15% in both the PCI and CABG arms.
But the EXCEL and NOBLE trials had several important differences, and it seemed like cumulatively these differences account for their differing results.
“One of the biggest differences” was the exclusion of procedural MIs in the NOBLE tally of adverse events, noted Dr. Stone. These were diagnosed in EXCEL using the MI definition published in 2013 by a panel of the Society for Cardiovascular Angiography and Interventions (SCAI). NOBLE disregarded procedural MIs because many of its participating hospitals did not have the laboratory resources to make these diagnoses and because the trial’s design predated the SCAI definition by several years, Dr. Christiansen explained.
Other important differences included the shorter follow-up in EXCEL, the inclusion of revascularization as an endpoint component in NOBLE but not in EXCEL, and differences in the stents used. In EXCEL, all patients undergoing PCI received Xience everolimus-eluting stents. In NOBLE, the first 11% of the enrolled patients received first-generation, sirolimus-eluting Cypher stents; the next 89% of enrollees received a biolimus-eluting Biomatrix Flex stent. Dr. Christiansen acknowledged the confounding caused by having many patients in the NOBLE PCI arm who received outmoded Cypher stents, especially because their relatively longer follow-up made them overrepresented in the primary outcome results. Plus, the Biomatrix Flex stent was disparaged by Martin B. Leon, MD, an EXCEL investigator and professor of medicine at Columbia University, who called the device “not currently widely used for PCI and more of historic interest.”
Dr. Leon added that the EXCEL and NOBLE patients also had substantially different prevalence rates of diabetes and acute coronary syndrome.
“The huge difference [between EXCEL and NOBLE] is the endpoint,” declared Marc Ruel, MD, another EXCEL investigator and head of cardiac surgery at the Ottawa Heart Institute. “The EXCEL endpoint was driven by the high rate of periprocedural MIs in the CABG arm. Once you get past 30 days, the noninferiority is not met by PCI.”
Another big endpoint difference was leaving revascularizations out of the EXCEL composite. “Once you take revascularization out of the primary endpoint, the outcome [of EXCEL] was more or less preordained,” noted Craig R. Smith, MD, chairman of surgery at Columbia University and an EXCEL investigator. “It’s the slope of events [in the PCI arm] after 3 months that’s the story. I think the CABG and PCI slopes in EXCEL will continue to diverge with time” beyond the current 3-year follow-up, Dr. Smith said.
“I agree that after 30 days surgery was the more durable procedure,” said Dr. Stone. “There is a big upfront hit for patients to take with surgery compared with PCI. If patients get through that, then they have a more durable procedure. That’s the trade-off.”
Dr. Stone hinted that future reports of EXCEL data will highlight other hits that patients must endure upfront if they choose CABG over PCI. “The early difference was quite profound not only for the primary endpoint but also for renal failure, infections, arrhythmias, and blood transfusions,” he said. Choosing between PCI and CABG for patients with left main disease and a lower SYNTAX score “is a decision that should be made by the heart team and patients. Some patients will prefer surgery, and some will prefer PCI.”
The NOBLE trial received partial funding from Biosensors, the company that markets the Biomatrix Flex stent used in the trial. The EXCEL trial was sponsored by Abbott Vascular, the company that markets the Xience stent used in the trial. Dr. Stone, Dr. Kandzari, Dr. Christiansen, Dr. Ruel, and Dr. Smith had no disclosures. Dr. Leon has been a consultant to and received research support from Abbott Vascular and Boston Scientific and has also received research support from Edwards, Medtronic and St. Jude.
[email protected]
On Twitter @mitchelzoler
The results from EXCEL and NOBLE were not that different, but what was different was how the two trials were designed and how their endpoints were defined. The biggest difference between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) seemed to be in the rate of late MIs, with a little higher rate following PCI, and more repeat revascularizations with PCI, but with similar mortality rates with both treatments. There was a lot of similarity in the results despite the differences in the trials.
The evidence in both studies gives more support to the concept that, for patients with simpler left main lesions, PCI is a competitive alternative to CABG. Until now, in U.S. practice patients with left main coronary disease have been preferentially referred for CABG. These results will open us up to giving selected patients a more balanced view of the two options. After we explain differences in recovery and late events patients can decide which treatment to receive.
Despite these new findings, PCI is still not for every patient. A substantial fraction of patients with left main coronary disease were excluded from these studies because they had more complex coronary anatomy, and for patients like that, CABG remains the clear standard of care.
David J. Cohen, MD, is director of cardiovascular research and an interventional cardiologist at Saint Luke’s Health System in Kansas City, Mo. He made these comments in a video interview. He had received research support from Abbott Vascular, and is an investigator in the EXCEL trial.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The results from EXCEL and NOBLE were not that different, but what was different was how the two trials were designed and how their endpoints were defined. The biggest difference between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) seemed to be in the rate of late MIs, with a little higher rate following PCI, and more repeat revascularizations with PCI, but with similar mortality rates with both treatments. There was a lot of similarity in the results despite the differences in the trials.
The evidence in both studies gives more support to the concept that, for patients with simpler left main lesions, PCI is a competitive alternative to CABG. Until now, in U.S. practice patients with left main coronary disease have been preferentially referred for CABG. These results will open us up to giving selected patients a more balanced view of the two options. After we explain differences in recovery and late events patients can decide which treatment to receive.
Despite these new findings, PCI is still not for every patient. A substantial fraction of patients with left main coronary disease were excluded from these studies because they had more complex coronary anatomy, and for patients like that, CABG remains the clear standard of care.
David J. Cohen, MD, is director of cardiovascular research and an interventional cardiologist at Saint Luke’s Health System in Kansas City, Mo. He made these comments in a video interview. He had received research support from Abbott Vascular, and is an investigator in the EXCEL trial.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The results from EXCEL and NOBLE were not that different, but what was different was how the two trials were designed and how their endpoints were defined. The biggest difference between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) seemed to be in the rate of late MIs, with a little higher rate following PCI, and more repeat revascularizations with PCI, but with similar mortality rates with both treatments. There was a lot of similarity in the results despite the differences in the trials.
The evidence in both studies gives more support to the concept that, for patients with simpler left main lesions, PCI is a competitive alternative to CABG. Until now, in U.S. practice patients with left main coronary disease have been preferentially referred for CABG. These results will open us up to giving selected patients a more balanced view of the two options. After we explain differences in recovery and late events patients can decide which treatment to receive.
Despite these new findings, PCI is still not for every patient. A substantial fraction of patients with left main coronary disease were excluded from these studies because they had more complex coronary anatomy, and for patients like that, CABG remains the clear standard of care.
David J. Cohen, MD, is director of cardiovascular research and an interventional cardiologist at Saint Luke’s Health System in Kansas City, Mo. He made these comments in a video interview. He had received research support from Abbott Vascular, and is an investigator in the EXCEL trial.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WASHINGTON – Results from two large, multicenter comparisons of coronary stenting and coronary bypass surgery for treating patients with unprotected left main coronary disease may have superficially shown sharp differences, but the bottom line will likely be greater empowerment of percutaneous coronary intervention as an option for selected patients with less complex coronary disease.
Prior to the results from the EXCEL and NOBLE trials, reported at the Transcatheter Cardiovascular Therapeutics annual meeting, “guidelines put PCI [percutaneous coronary intervention] into a class 1, 2 or 3 status for treating left main coronary disease depending on disease complexity, but in the United States, PCI for patients eligible for CABG [coronary artery bypass grafting] has not been frequently done. I think these results, in a very circumscribed subset of patients and using a state-of-the-art stent, will affect the guidelines,” predicted Gregg W. Stone, MD, lead investigator for EXCEL and professor of medicine at Columbia University in New York.
“What the guidelines have not addressed are the patients with low- or intermediate-complexity disease who have an acceptable risk for undergoing either PCI or CABG. I think the trial results answer this question,” said David Kandzari, MD, director of interventional cardiology and chief scientific officer at the Piedmont Heart Institute in Atlanta and an EXCEL investigator.
While the EXCEL and NOBLE results don’t provide a simple answer on the relative merits of PCI and CABG, many of their outcome differences seem explicable, several experts said at the meeting.
The Nordic-Baltic-British Left Main Revascularisation (NOBLE) trial randomized 1,201 patients who had unprotected left main coronary disease and were judged by a heart team to be reasonable candidates for both PCI or CABG at 36 centers in nine European countries during 2008-2015. The primary endpoint was death from any cause, nonprocedural MIs, stroke, or repeat revascularization.
The researchers followed patients for a median of just over 3 years, but they calculated the primary endpoint based on a Kaplan-Meier estimate for 5-year outcomes, which showed the primary endpoint in 29% of the PCI patients and in 19% of the CABG patients, a statistically significant benefit in favor of CABG, Evald H. Christiansen, MD, reported at the meeting, which was sponsored by the Cardiovascular Research Foundation. Concurrently with his report, the results were published online (Lancet. 2016 Oct. 31. doi: 10.1016/S0140-6736[16]32052-9).
This difference between PCI and CABG was largely driven by an excess of postprocedural MIs and repeat revascularizations among the PCI patients, said Dr. Christiansen, an interventional cardiologist at Aarhus University Hospital in Denmark. Another notable finding was that the superior outcomes with CABG primarily occurred among patients with a SYNTAX score – a measure of coronary disease complexity – of 22 or less, which identifies patients with low complexity disease. The outcomes of patients with SYNTAX scores of 23-32, which identifies intermediate complexity disease, and of patients with scores of 33 or higher, with very complex disease, were similar in the PCI and CABG arms, he reported. This finding was “very surprising,” Dr. Christiansen said, because it reversed the finding originally made in the SYNTAX trial that PCI performed best compared with CABG in patients with the lowest scores and least-complex coronary disease.
The superiority of CABG over PCI seen in the NOBLE results, especially in patients with lower SYNTAX scores, seemed at odds with the EXCEL results, reported at the meeting by Dr. Stone and simultaneously online (N Engl J Med. 2016 Oct. 31. doi: 10.1056/NEJMoa1610227). In EXCEL, which enrolled only patients with a SYNTAX score of 32 or less (low- or intermediate-complexity coronary disease), patients had a 3-year incidence of death, stroke or MI of 15% in both the PCI and CABG arms.
But the EXCEL and NOBLE trials had several important differences, and it seemed like cumulatively these differences account for their differing results.
“One of the biggest differences” was the exclusion of procedural MIs in the NOBLE tally of adverse events, noted Dr. Stone. These were diagnosed in EXCEL using the MI definition published in 2013 by a panel of the Society for Cardiovascular Angiography and Interventions (SCAI). NOBLE disregarded procedural MIs because many of its participating hospitals did not have the laboratory resources to make these diagnoses and because the trial’s design predated the SCAI definition by several years, Dr. Christiansen explained.
Other important differences included the shorter follow-up in EXCEL, the inclusion of revascularization as an endpoint component in NOBLE but not in EXCEL, and differences in the stents used. In EXCEL, all patients undergoing PCI received Xience everolimus-eluting stents. In NOBLE, the first 11% of the enrolled patients received first-generation, sirolimus-eluting Cypher stents; the next 89% of enrollees received a biolimus-eluting Biomatrix Flex stent. Dr. Christiansen acknowledged the confounding caused by having many patients in the NOBLE PCI arm who received outmoded Cypher stents, especially because their relatively longer follow-up made them overrepresented in the primary outcome results. Plus, the Biomatrix Flex stent was disparaged by Martin B. Leon, MD, an EXCEL investigator and professor of medicine at Columbia University, who called the device “not currently widely used for PCI and more of historic interest.”
Dr. Leon added that the EXCEL and NOBLE patients also had substantially different prevalence rates of diabetes and acute coronary syndrome.
“The huge difference [between EXCEL and NOBLE] is the endpoint,” declared Marc Ruel, MD, another EXCEL investigator and head of cardiac surgery at the Ottawa Heart Institute. “The EXCEL endpoint was driven by the high rate of periprocedural MIs in the CABG arm. Once you get past 30 days, the noninferiority is not met by PCI.”
Another big endpoint difference was leaving revascularizations out of the EXCEL composite. “Once you take revascularization out of the primary endpoint, the outcome [of EXCEL] was more or less preordained,” noted Craig R. Smith, MD, chairman of surgery at Columbia University and an EXCEL investigator. “It’s the slope of events [in the PCI arm] after 3 months that’s the story. I think the CABG and PCI slopes in EXCEL will continue to diverge with time” beyond the current 3-year follow-up, Dr. Smith said.
“I agree that after 30 days surgery was the more durable procedure,” said Dr. Stone. “There is a big upfront hit for patients to take with surgery compared with PCI. If patients get through that, then they have a more durable procedure. That’s the trade-off.”
Dr. Stone hinted that future reports of EXCEL data will highlight other hits that patients must endure upfront if they choose CABG over PCI. “The early difference was quite profound not only for the primary endpoint but also for renal failure, infections, arrhythmias, and blood transfusions,” he said. Choosing between PCI and CABG for patients with left main disease and a lower SYNTAX score “is a decision that should be made by the heart team and patients. Some patients will prefer surgery, and some will prefer PCI.”
The NOBLE trial received partial funding from Biosensors, the company that markets the Biomatrix Flex stent used in the trial. The EXCEL trial was sponsored by Abbott Vascular, the company that markets the Xience stent used in the trial. Dr. Stone, Dr. Kandzari, Dr. Christiansen, Dr. Ruel, and Dr. Smith had no disclosures. Dr. Leon has been a consultant to and received research support from Abbott Vascular and Boston Scientific and has also received research support from Edwards, Medtronic and St. Jude.
[email protected]
On Twitter @mitchelzoler
WASHINGTON – Results from two large, multicenter comparisons of coronary stenting and coronary bypass surgery for treating patients with unprotected left main coronary disease may have superficially shown sharp differences, but the bottom line will likely be greater empowerment of percutaneous coronary intervention as an option for selected patients with less complex coronary disease.
Prior to the results from the EXCEL and NOBLE trials, reported at the Transcatheter Cardiovascular Therapeutics annual meeting, “guidelines put PCI [percutaneous coronary intervention] into a class 1, 2 or 3 status for treating left main coronary disease depending on disease complexity, but in the United States, PCI for patients eligible for CABG [coronary artery bypass grafting] has not been frequently done. I think these results, in a very circumscribed subset of patients and using a state-of-the-art stent, will affect the guidelines,” predicted Gregg W. Stone, MD, lead investigator for EXCEL and professor of medicine at Columbia University in New York.
“What the guidelines have not addressed are the patients with low- or intermediate-complexity disease who have an acceptable risk for undergoing either PCI or CABG. I think the trial results answer this question,” said David Kandzari, MD, director of interventional cardiology and chief scientific officer at the Piedmont Heart Institute in Atlanta and an EXCEL investigator.
While the EXCEL and NOBLE results don’t provide a simple answer on the relative merits of PCI and CABG, many of their outcome differences seem explicable, several experts said at the meeting.
The Nordic-Baltic-British Left Main Revascularisation (NOBLE) trial randomized 1,201 patients who had unprotected left main coronary disease and were judged by a heart team to be reasonable candidates for both PCI or CABG at 36 centers in nine European countries during 2008-2015. The primary endpoint was death from any cause, nonprocedural MIs, stroke, or repeat revascularization.
The researchers followed patients for a median of just over 3 years, but they calculated the primary endpoint based on a Kaplan-Meier estimate for 5-year outcomes, which showed the primary endpoint in 29% of the PCI patients and in 19% of the CABG patients, a statistically significant benefit in favor of CABG, Evald H. Christiansen, MD, reported at the meeting, which was sponsored by the Cardiovascular Research Foundation. Concurrently with his report, the results were published online (Lancet. 2016 Oct. 31. doi: 10.1016/S0140-6736[16]32052-9).
This difference between PCI and CABG was largely driven by an excess of postprocedural MIs and repeat revascularizations among the PCI patients, said Dr. Christiansen, an interventional cardiologist at Aarhus University Hospital in Denmark. Another notable finding was that the superior outcomes with CABG primarily occurred among patients with a SYNTAX score – a measure of coronary disease complexity – of 22 or less, which identifies patients with low complexity disease. The outcomes of patients with SYNTAX scores of 23-32, which identifies intermediate complexity disease, and of patients with scores of 33 or higher, with very complex disease, were similar in the PCI and CABG arms, he reported. This finding was “very surprising,” Dr. Christiansen said, because it reversed the finding originally made in the SYNTAX trial that PCI performed best compared with CABG in patients with the lowest scores and least-complex coronary disease.
The superiority of CABG over PCI seen in the NOBLE results, especially in patients with lower SYNTAX scores, seemed at odds with the EXCEL results, reported at the meeting by Dr. Stone and simultaneously online (N Engl J Med. 2016 Oct. 31. doi: 10.1056/NEJMoa1610227). In EXCEL, which enrolled only patients with a SYNTAX score of 32 or less (low- or intermediate-complexity coronary disease), patients had a 3-year incidence of death, stroke or MI of 15% in both the PCI and CABG arms.
But the EXCEL and NOBLE trials had several important differences, and it seemed like cumulatively these differences account for their differing results.
“One of the biggest differences” was the exclusion of procedural MIs in the NOBLE tally of adverse events, noted Dr. Stone. These were diagnosed in EXCEL using the MI definition published in 2013 by a panel of the Society for Cardiovascular Angiography and Interventions (SCAI). NOBLE disregarded procedural MIs because many of its participating hospitals did not have the laboratory resources to make these diagnoses and because the trial’s design predated the SCAI definition by several years, Dr. Christiansen explained.
Other important differences included the shorter follow-up in EXCEL, the inclusion of revascularization as an endpoint component in NOBLE but not in EXCEL, and differences in the stents used. In EXCEL, all patients undergoing PCI received Xience everolimus-eluting stents. In NOBLE, the first 11% of the enrolled patients received first-generation, sirolimus-eluting Cypher stents; the next 89% of enrollees received a biolimus-eluting Biomatrix Flex stent. Dr. Christiansen acknowledged the confounding caused by having many patients in the NOBLE PCI arm who received outmoded Cypher stents, especially because their relatively longer follow-up made them overrepresented in the primary outcome results. Plus, the Biomatrix Flex stent was disparaged by Martin B. Leon, MD, an EXCEL investigator and professor of medicine at Columbia University, who called the device “not currently widely used for PCI and more of historic interest.”
Dr. Leon added that the EXCEL and NOBLE patients also had substantially different prevalence rates of diabetes and acute coronary syndrome.
“The huge difference [between EXCEL and NOBLE] is the endpoint,” declared Marc Ruel, MD, another EXCEL investigator and head of cardiac surgery at the Ottawa Heart Institute. “The EXCEL endpoint was driven by the high rate of periprocedural MIs in the CABG arm. Once you get past 30 days, the noninferiority is not met by PCI.”
Another big endpoint difference was leaving revascularizations out of the EXCEL composite. “Once you take revascularization out of the primary endpoint, the outcome [of EXCEL] was more or less preordained,” noted Craig R. Smith, MD, chairman of surgery at Columbia University and an EXCEL investigator. “It’s the slope of events [in the PCI arm] after 3 months that’s the story. I think the CABG and PCI slopes in EXCEL will continue to diverge with time” beyond the current 3-year follow-up, Dr. Smith said.
“I agree that after 30 days surgery was the more durable procedure,” said Dr. Stone. “There is a big upfront hit for patients to take with surgery compared with PCI. If patients get through that, then they have a more durable procedure. That’s the trade-off.”
Dr. Stone hinted that future reports of EXCEL data will highlight other hits that patients must endure upfront if they choose CABG over PCI. “The early difference was quite profound not only for the primary endpoint but also for renal failure, infections, arrhythmias, and blood transfusions,” he said. Choosing between PCI and CABG for patients with left main disease and a lower SYNTAX score “is a decision that should be made by the heart team and patients. Some patients will prefer surgery, and some will prefer PCI.”
The NOBLE trial received partial funding from Biosensors, the company that markets the Biomatrix Flex stent used in the trial. The EXCEL trial was sponsored by Abbott Vascular, the company that markets the Xience stent used in the trial. Dr. Stone, Dr. Kandzari, Dr. Christiansen, Dr. Ruel, and Dr. Smith had no disclosures. Dr. Leon has been a consultant to and received research support from Abbott Vascular and Boston Scientific and has also received research support from Edwards, Medtronic and St. Jude.
[email protected]
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM TCT 2016
Results puzzling for embolic protection during TAVR
The largest randomized clinical trial to assess the safety and efficacy of cerebral embolic protection systems during transcatheter aortic valve replacement yielded puzzling and somewhat contradictory results, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology.
Virtually every device in this industry-sponsored study involving 363 elderly patients (mean age, 83.4 years) with severe aortic stenosis trapped particulate debris as intended, the mean volume of new lesions in the protected areas of the brain was reduced by 42%, and the number and volume of new lesions correlated with neurocognitive outcomes at 30 days.
However, the reduction in lesion volume did not achieve statistical significance, and the improvement in neurocognitive function also did not reach statistical significance.
In addition, “the sample size was clearly too low to assess clinical outcomes, and in retrospect, was also too low to evaluate follow-up MRI findings or neurocognitive outcomes.” Nevertheless, the trial “provides reassuring evidence of device safety,” said Samir R. Kapadia, MD, of the Cleveland Clinic (J Am Coll Cardiol. 2016 Nov 1. doi: 10.1016/j.jacc.2016.10.023).
In this prospective study, the investigators assessed patients at 17 medical centers in the United States and 2 in Germany. In addition to being elderly, the study patients were at high risk because of frequent comorbidities, including atrial fibrillation (31.7%) and prior stroke (5.8%).
The remaining 123 patients underwent TAVR but not MRI in a safety arm of the trial.
The protection devices were placed “without safety concerns” in most patients. The rate of major adverse events with the device was 7.3%, markedly less than the 18.3% prespecified performance goal for this outcome. Total procedure time was lengthened by only 13 minutes when the device was used, and total fluoroscopy time was increased by only 3 minutes. These findings demonstrate the overall safety of using the device, Dr. Kapadia said.
Debris including thrombus with tissue elements, artery wall particles, calcifications, valve tissue, and foreign materials was retrieved from the filters in 99% of patients.
The mean volume of new cerebral lesions in areas of the brain protected by the device was reduced by 42%, compared with that in patients who underwent TAVR without the protection device. However, this reduction was not statistically significant, so the primary efficacy endpoint of the study was not met.
Similarly, neurocognitive testing at 30 days showed that the volume of new lesions correlated with poorer outcomes. However, the difference in neurocognitive function between the intervention group and the control group did not reach statistical significance.
Several limitations likely contributed to this lack of statistical significance, Dr. Kapadia said.
First, the 5-day “window” for MRI assessment was too long. Both the number and the volume of new lesions rapidly changed over time, which led to marked variance in MRI findings depending on when the images were taken.
In addition, only one TAVR device was available at the time the trial was designed, so the study wasn’t stratified by type of valve device. But several new devices became available during the study, and the study investigators were permitted to use any of them. Both pre- and postimplantation techniques differ among these TAVR devices, but these differences could not be accounted for, given the study design.
Also, certain risk factors for stroke, especially certain findings on baseline MRI, were not understood when the trial was designed, and those factors also were not accounted for, Dr. Kapadia said.
Claret Medical funded the study. Dr. Kapadia reported having no relevant financial disclosures; his associates reported numerous ties to industry sources. The meeting was sponsored by the Cardiovascular Research Foundation.
From a logical standpoint, a device that collects cerebral embolic material in 99% of cases should prevent ischemic brain injury, yet the findings from this randomized trial don’t appear to support the routine use of such devices. But it would be inappropriate and unfair to close the book on cerebral protection after this chapter.
The authors acknowledge that an MRI “window” of 5 days creates too much heterogeneity in the data, that multiple TAVR devices requiring different implantation techniques further muddy the picture, and that in retrospect the sample size was inadequate and the study was underpowered. In addition, rigorous neurocognitive assessment can be challenging in elderly, recovering patients, and results can depend on the time of day and the patient’s alertness.
Despite the negative findings regarding both primary and secondary endpoints, the data do show the overall safety of embolic protection devices. We are dealing with a potential benefit that cannot be ignored as TAVR shifts to younger and lower-risk patients.
Azeem Latib, MD, is in the interventional cardiology unit at San Raffaele Scientific Institute in Milan. Matteo Pagnesi, MD, is in the interventional cardiology unit at EMO-GVM Centro Cuore Columbus in Milan. San Raffaele Scientific Institute has been involved in clinical studies of embolic protection devices made by Claret Medical, Innovative Cardiovascular Solutions, and Keystone Heart. Dr. Latib and Dr. Pagnesi reported having no other relevant financial disclosures. They made these remarks in an editorial accompanying Dr. Kapadia’s report (J Am Coll Cardiol. 2016 Nov 1. doi: 10.1016/j.jacc.2016.10.036).
From a logical standpoint, a device that collects cerebral embolic material in 99% of cases should prevent ischemic brain injury, yet the findings from this randomized trial don’t appear to support the routine use of such devices. But it would be inappropriate and unfair to close the book on cerebral protection after this chapter.
The authors acknowledge that an MRI “window” of 5 days creates too much heterogeneity in the data, that multiple TAVR devices requiring different implantation techniques further muddy the picture, and that in retrospect the sample size was inadequate and the study was underpowered. In addition, rigorous neurocognitive assessment can be challenging in elderly, recovering patients, and results can depend on the time of day and the patient’s alertness.
Despite the negative findings regarding both primary and secondary endpoints, the data do show the overall safety of embolic protection devices. We are dealing with a potential benefit that cannot be ignored as TAVR shifts to younger and lower-risk patients.
Azeem Latib, MD, is in the interventional cardiology unit at San Raffaele Scientific Institute in Milan. Matteo Pagnesi, MD, is in the interventional cardiology unit at EMO-GVM Centro Cuore Columbus in Milan. San Raffaele Scientific Institute has been involved in clinical studies of embolic protection devices made by Claret Medical, Innovative Cardiovascular Solutions, and Keystone Heart. Dr. Latib and Dr. Pagnesi reported having no other relevant financial disclosures. They made these remarks in an editorial accompanying Dr. Kapadia’s report (J Am Coll Cardiol. 2016 Nov 1. doi: 10.1016/j.jacc.2016.10.036).
From a logical standpoint, a device that collects cerebral embolic material in 99% of cases should prevent ischemic brain injury, yet the findings from this randomized trial don’t appear to support the routine use of such devices. But it would be inappropriate and unfair to close the book on cerebral protection after this chapter.
The authors acknowledge that an MRI “window” of 5 days creates too much heterogeneity in the data, that multiple TAVR devices requiring different implantation techniques further muddy the picture, and that in retrospect the sample size was inadequate and the study was underpowered. In addition, rigorous neurocognitive assessment can be challenging in elderly, recovering patients, and results can depend on the time of day and the patient’s alertness.
Despite the negative findings regarding both primary and secondary endpoints, the data do show the overall safety of embolic protection devices. We are dealing with a potential benefit that cannot be ignored as TAVR shifts to younger and lower-risk patients.
Azeem Latib, MD, is in the interventional cardiology unit at San Raffaele Scientific Institute in Milan. Matteo Pagnesi, MD, is in the interventional cardiology unit at EMO-GVM Centro Cuore Columbus in Milan. San Raffaele Scientific Institute has been involved in clinical studies of embolic protection devices made by Claret Medical, Innovative Cardiovascular Solutions, and Keystone Heart. Dr. Latib and Dr. Pagnesi reported having no other relevant financial disclosures. They made these remarks in an editorial accompanying Dr. Kapadia’s report (J Am Coll Cardiol. 2016 Nov 1. doi: 10.1016/j.jacc.2016.10.036).
The largest randomized clinical trial to assess the safety and efficacy of cerebral embolic protection systems during transcatheter aortic valve replacement yielded puzzling and somewhat contradictory results, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology.
Virtually every device in this industry-sponsored study involving 363 elderly patients (mean age, 83.4 years) with severe aortic stenosis trapped particulate debris as intended, the mean volume of new lesions in the protected areas of the brain was reduced by 42%, and the number and volume of new lesions correlated with neurocognitive outcomes at 30 days.
However, the reduction in lesion volume did not achieve statistical significance, and the improvement in neurocognitive function also did not reach statistical significance.
In addition, “the sample size was clearly too low to assess clinical outcomes, and in retrospect, was also too low to evaluate follow-up MRI findings or neurocognitive outcomes.” Nevertheless, the trial “provides reassuring evidence of device safety,” said Samir R. Kapadia, MD, of the Cleveland Clinic (J Am Coll Cardiol. 2016 Nov 1. doi: 10.1016/j.jacc.2016.10.023).
In this prospective study, the investigators assessed patients at 17 medical centers in the United States and 2 in Germany. In addition to being elderly, the study patients were at high risk because of frequent comorbidities, including atrial fibrillation (31.7%) and prior stroke (5.8%).
The remaining 123 patients underwent TAVR but not MRI in a safety arm of the trial.
The protection devices were placed “without safety concerns” in most patients. The rate of major adverse events with the device was 7.3%, markedly less than the 18.3% prespecified performance goal for this outcome. Total procedure time was lengthened by only 13 minutes when the device was used, and total fluoroscopy time was increased by only 3 minutes. These findings demonstrate the overall safety of using the device, Dr. Kapadia said.
Debris including thrombus with tissue elements, artery wall particles, calcifications, valve tissue, and foreign materials was retrieved from the filters in 99% of patients.
The mean volume of new cerebral lesions in areas of the brain protected by the device was reduced by 42%, compared with that in patients who underwent TAVR without the protection device. However, this reduction was not statistically significant, so the primary efficacy endpoint of the study was not met.
Similarly, neurocognitive testing at 30 days showed that the volume of new lesions correlated with poorer outcomes. However, the difference in neurocognitive function between the intervention group and the control group did not reach statistical significance.
Several limitations likely contributed to this lack of statistical significance, Dr. Kapadia said.
First, the 5-day “window” for MRI assessment was too long. Both the number and the volume of new lesions rapidly changed over time, which led to marked variance in MRI findings depending on when the images were taken.
In addition, only one TAVR device was available at the time the trial was designed, so the study wasn’t stratified by type of valve device. But several new devices became available during the study, and the study investigators were permitted to use any of them. Both pre- and postimplantation techniques differ among these TAVR devices, but these differences could not be accounted for, given the study design.
Also, certain risk factors for stroke, especially certain findings on baseline MRI, were not understood when the trial was designed, and those factors also were not accounted for, Dr. Kapadia said.
Claret Medical funded the study. Dr. Kapadia reported having no relevant financial disclosures; his associates reported numerous ties to industry sources. The meeting was sponsored by the Cardiovascular Research Foundation.
The largest randomized clinical trial to assess the safety and efficacy of cerebral embolic protection systems during transcatheter aortic valve replacement yielded puzzling and somewhat contradictory results, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology.
Virtually every device in this industry-sponsored study involving 363 elderly patients (mean age, 83.4 years) with severe aortic stenosis trapped particulate debris as intended, the mean volume of new lesions in the protected areas of the brain was reduced by 42%, and the number and volume of new lesions correlated with neurocognitive outcomes at 30 days.
However, the reduction in lesion volume did not achieve statistical significance, and the improvement in neurocognitive function also did not reach statistical significance.
In addition, “the sample size was clearly too low to assess clinical outcomes, and in retrospect, was also too low to evaluate follow-up MRI findings or neurocognitive outcomes.” Nevertheless, the trial “provides reassuring evidence of device safety,” said Samir R. Kapadia, MD, of the Cleveland Clinic (J Am Coll Cardiol. 2016 Nov 1. doi: 10.1016/j.jacc.2016.10.023).
In this prospective study, the investigators assessed patients at 17 medical centers in the United States and 2 in Germany. In addition to being elderly, the study patients were at high risk because of frequent comorbidities, including atrial fibrillation (31.7%) and prior stroke (5.8%).
The remaining 123 patients underwent TAVR but not MRI in a safety arm of the trial.
The protection devices were placed “without safety concerns” in most patients. The rate of major adverse events with the device was 7.3%, markedly less than the 18.3% prespecified performance goal for this outcome. Total procedure time was lengthened by only 13 minutes when the device was used, and total fluoroscopy time was increased by only 3 minutes. These findings demonstrate the overall safety of using the device, Dr. Kapadia said.
Debris including thrombus with tissue elements, artery wall particles, calcifications, valve tissue, and foreign materials was retrieved from the filters in 99% of patients.
The mean volume of new cerebral lesions in areas of the brain protected by the device was reduced by 42%, compared with that in patients who underwent TAVR without the protection device. However, this reduction was not statistically significant, so the primary efficacy endpoint of the study was not met.
Similarly, neurocognitive testing at 30 days showed that the volume of new lesions correlated with poorer outcomes. However, the difference in neurocognitive function between the intervention group and the control group did not reach statistical significance.
Several limitations likely contributed to this lack of statistical significance, Dr. Kapadia said.
First, the 5-day “window” for MRI assessment was too long. Both the number and the volume of new lesions rapidly changed over time, which led to marked variance in MRI findings depending on when the images were taken.
In addition, only one TAVR device was available at the time the trial was designed, so the study wasn’t stratified by type of valve device. But several new devices became available during the study, and the study investigators were permitted to use any of them. Both pre- and postimplantation techniques differ among these TAVR devices, but these differences could not be accounted for, given the study design.
Also, certain risk factors for stroke, especially certain findings on baseline MRI, were not understood when the trial was designed, and those factors also were not accounted for, Dr. Kapadia said.
Claret Medical funded the study. Dr. Kapadia reported having no relevant financial disclosures; his associates reported numerous ties to industry sources. The meeting was sponsored by the Cardiovascular Research Foundation.
Key clinical point: The largest randomized clinical trial to assess the safety and efficacy of cerebral embolic protection systems during TAVR yielded puzzling and contradictory results.
Major finding: Debris including thrombus with tissue elements, artery wall particles, calcifications, valve tissue, and foreign materials was retrieved from the cerebral protection filters in 99% of patients.
Data source: A prospective, international, randomized trial involving 363 elderly patients undergoing TAVR for severe aortic stenosis.
Disclosures: Claret Medical funded the study. Dr. Kapadia reported having no relevant financial disclosures; his associates reported numerous ties to industry sources.
Resorbable scaffold appears safe, effective in diabetes patients
An everolimus-eluting resorbable scaffold appeared to be safe and effective for percutaneous coronary intervention (PCI) in patients with diabetes and noncomplex coronary lesions, according to a study presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology: Cardiovascular Interventions.
Patients with diabetes constitute an important and increasingly prevalent subgroup of PCI patients, who are at high risk of adverse clinical and angiographic outcomes such as MI, stent thrombosis, restenosis, and death. This is thought to be due to diabetic patients’ greater level of vascular inflammation and tendency toward a prothrombotic state and more complex angiographic features, said Dean J. Kereiakes, MD, of the Christ Hospital Heart and Vascular Center, Lindner Research Center, Cincinnati.
The substudy participants all received at least one resorbable scaffold in at least one target lesion. A total of 27.3% were insulin dependent and nearly 60% had HbA1c levels exceeding 7.0%. Notably, 18% of all the treated lesions in this analysis were less than 2.25 mm in diameter as assessed by quantitative coronary angiography, and approximately 60% had moderately to severely complex morphology.
The primary endpoint – the rate of target-lesion failure at 1-year follow-up – was 8.3%, which was well below the prespecified performance goal of 12.7%. This rate ranged from 4.4% to 10.9% across the different trials. A sensitivity analysis confirmed that the 1-year rate of target-lesion failure was significantly lower than the prespecified performance goal.
The rates of target-lesion failure, target-vessel MI, ischemia-driven target-lesion revascularization, and scaffold thrombosis were significantly higher in diabetic patients who required insulin than in those who did not. Older patient age, insulin dependency, and small target-vessel diameter all were independent predictors of target-lesion failure at 1 year.
The overall 1-year rate of scaffold thrombosis in this study was 2.3%, which is not surprising given the study population’s risk factors. For diabetic patients with appropriately sized vessels of greater than 2.25 mm diameter, the scaffold thrombosis rate was lower (1.3%).
In addition to being underpowered to assess rare adverse events, this study was limited in that it reported outcomes at 1 year, before resorption of the device was complete. It also reflects the first-time clinical experience with a resorbable scaffold for most of the participating investigators, “and one would expect that as with all new medical procedures, results will improve over time with increased operator experience,” the coauthors wrote.
Dr. Kereiakes reported being a consultant to Abbott Vascular, and his associates also reported ties to the company and to other industry sources.
An everolimus-eluting resorbable scaffold appeared to be safe and effective for percutaneous coronary intervention (PCI) in patients with diabetes and noncomplex coronary lesions, according to a study presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology: Cardiovascular Interventions.
Patients with diabetes constitute an important and increasingly prevalent subgroup of PCI patients, who are at high risk of adverse clinical and angiographic outcomes such as MI, stent thrombosis, restenosis, and death. This is thought to be due to diabetic patients’ greater level of vascular inflammation and tendency toward a prothrombotic state and more complex angiographic features, said Dean J. Kereiakes, MD, of the Christ Hospital Heart and Vascular Center, Lindner Research Center, Cincinnati.
The substudy participants all received at least one resorbable scaffold in at least one target lesion. A total of 27.3% were insulin dependent and nearly 60% had HbA1c levels exceeding 7.0%. Notably, 18% of all the treated lesions in this analysis were less than 2.25 mm in diameter as assessed by quantitative coronary angiography, and approximately 60% had moderately to severely complex morphology.
The primary endpoint – the rate of target-lesion failure at 1-year follow-up – was 8.3%, which was well below the prespecified performance goal of 12.7%. This rate ranged from 4.4% to 10.9% across the different trials. A sensitivity analysis confirmed that the 1-year rate of target-lesion failure was significantly lower than the prespecified performance goal.
The rates of target-lesion failure, target-vessel MI, ischemia-driven target-lesion revascularization, and scaffold thrombosis were significantly higher in diabetic patients who required insulin than in those who did not. Older patient age, insulin dependency, and small target-vessel diameter all were independent predictors of target-lesion failure at 1 year.
The overall 1-year rate of scaffold thrombosis in this study was 2.3%, which is not surprising given the study population’s risk factors. For diabetic patients with appropriately sized vessels of greater than 2.25 mm diameter, the scaffold thrombosis rate was lower (1.3%).
In addition to being underpowered to assess rare adverse events, this study was limited in that it reported outcomes at 1 year, before resorption of the device was complete. It also reflects the first-time clinical experience with a resorbable scaffold for most of the participating investigators, “and one would expect that as with all new medical procedures, results will improve over time with increased operator experience,” the coauthors wrote.
Dr. Kereiakes reported being a consultant to Abbott Vascular, and his associates also reported ties to the company and to other industry sources.
An everolimus-eluting resorbable scaffold appeared to be safe and effective for percutaneous coronary intervention (PCI) in patients with diabetes and noncomplex coronary lesions, according to a study presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology: Cardiovascular Interventions.
Patients with diabetes constitute an important and increasingly prevalent subgroup of PCI patients, who are at high risk of adverse clinical and angiographic outcomes such as MI, stent thrombosis, restenosis, and death. This is thought to be due to diabetic patients’ greater level of vascular inflammation and tendency toward a prothrombotic state and more complex angiographic features, said Dean J. Kereiakes, MD, of the Christ Hospital Heart and Vascular Center, Lindner Research Center, Cincinnati.
The substudy participants all received at least one resorbable scaffold in at least one target lesion. A total of 27.3% were insulin dependent and nearly 60% had HbA1c levels exceeding 7.0%. Notably, 18% of all the treated lesions in this analysis were less than 2.25 mm in diameter as assessed by quantitative coronary angiography, and approximately 60% had moderately to severely complex morphology.
The primary endpoint – the rate of target-lesion failure at 1-year follow-up – was 8.3%, which was well below the prespecified performance goal of 12.7%. This rate ranged from 4.4% to 10.9% across the different trials. A sensitivity analysis confirmed that the 1-year rate of target-lesion failure was significantly lower than the prespecified performance goal.
The rates of target-lesion failure, target-vessel MI, ischemia-driven target-lesion revascularization, and scaffold thrombosis were significantly higher in diabetic patients who required insulin than in those who did not. Older patient age, insulin dependency, and small target-vessel diameter all were independent predictors of target-lesion failure at 1 year.
The overall 1-year rate of scaffold thrombosis in this study was 2.3%, which is not surprising given the study population’s risk factors. For diabetic patients with appropriately sized vessels of greater than 2.25 mm diameter, the scaffold thrombosis rate was lower (1.3%).
In addition to being underpowered to assess rare adverse events, this study was limited in that it reported outcomes at 1 year, before resorption of the device was complete. It also reflects the first-time clinical experience with a resorbable scaffold for most of the participating investigators, “and one would expect that as with all new medical procedures, results will improve over time with increased operator experience,” the coauthors wrote.
Dr. Kereiakes reported being a consultant to Abbott Vascular, and his associates also reported ties to the company and to other industry sources.
Key clinical point:
Major finding: The primary endpoint – the rate of target-lesion failure at 1 year follow-up – was 8.3%, which was well below the prespecified performance goal of 12.7%.
Data source: A prespecified formal substudy of 754 patients with diabetes who participated in three clinical trials and one device registry, assessing 1-year outcomes after PCI.
Disclosures: This pooled analysis, plus all the contributing trials and the device registry, were funded by Abbott Vascular, maker of the resorbable scaffold. Dr. Kereiakes reported being a consultant to Abbott Vascular, and his associates also reported ties to the company and to other industry sources.
PCI noninferior to CABG for certain left main CAD
Percutaneous coronary intervention (PCI) using everolimus-eluting stents was found noninferior to coronary artery bypass grafting (CABG) with respect to the composite end point of death, stroke, or myocardial infarction at 3 years among patients with left main coronary artery disease and low or intermediate anatomical complexity, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the New England Journal of Medicine.
The rate of this composite outcome was lower with PCI than with CABG during the first 30 days following the procedure, but higher between day 30 and year 3. In addition, the 3-year rate of revascularization was slightly higher with PCI (23.1% vs 19.1%), but the rate of periprocedural MI and major adverse events was lower (8.1% vs 23.0%).
Taken together, these results “suggest that PCI with everolimus-eluting stents is an acceptable or perhaps preferred alternative to CABG in selected patients with left main CAD who are candidates for either procedure,” said Gregg W. Stone, MD, of Columbia University Medical Center, New York, and his associates in the EXCEL (Evaluation of XIENCE versus CABG for Effectiveness of Left Main Revascularization) trial.
This study was funded by Abbott Vascular, maker of the everolimus-eluting stent (the XIENCE). The company also participated in the design of the trial and in the selection and management of the treatment sites.
Until now, it was generally agreed that most patients with left main CAD would have better outcomes with CABG than with PCI, based on the results of earlier trials comparing the two approaches. But contemporary drug-eluting stents have better safety and efficacy profiles than first-generation stents, and surgical techniques have also improved over time, so a study comparing the current standards of care was warranted, Dr. Stone and his associates said (New Engl J Med. 2016 Oct 31. doi:10.1056/NEJMoa1610227).
They assessed 1,905 patients at 126 medical centers in 17 countries in the open-label noninferiority trial. Participants had left main coronary artery stenosis of 70% or more (estimated visually) or of 50%-70% (estimated by invasive or noninvasive testing) if the stenosis was judged to be hemodynamically significant. The study participants also were required to have low or intermediate anatomical complexity of the involved portion of the coronary artery, as defined by a SYNTAX score of 32 or lower. A total of 948 patients were randomly assigned to PCI and 957 to CABG.
The primary composite end point – the rate of death, stroke, or MI assessed at a median of 3 years of follow-up – was 15.4% with PCI and 14.7% with CABG, a nonsignificant difference (Hazard Ratio, 1.00) that demonstrates the noninferiority of PCI. This rate was consistently noninferior across all subgroups of patients, regardless of age, sex, and the presence or absence of diabetes or chronic kidney disease.
At 30 days, the rate of the composite end point was 4.9% with PCI and 7.9% with CABG, which also demonstrates the noninferiority of PCI. At 3 years, secondary end points including the rate of ischemia-driven revascularization also showed the noninferiority of PCI, as did each of the individual components of the primary composite end point.
The rate of death, stroke, or MI was lower at 30 days with PCI than with CABG, mainly because there were fewer MIs with PCI. But a post-hoc analysis showed that this rate was higher with PCI than with CABG after 30 days.
During follow-up, ischemia-driven revascularization was more common after PCI (12.6%) than after CABG (7.5%). However, symptomatic graft occlusion after CABG (5.4%) was more frequent than definite stent thrombosis after PCI (0.7%).
Periprocedural major adverse events developed in 8.1% of the PCI group and 23.0% of the CABG group, and the difference was attributed mainly to fewer arrhythmias, infections, and blood transfusions in the PCI group. Cardiovascular mortality was similar between the two study groups, though all-cause mortality was higher with PCI due to an excess of fatal infections and malignancies in that group.
The investigators noted several limitations with the EXCEL trial. First, treatment blinding wasn’t possible, so some degree of bias may have resulted.
Second, prerandomization SYNTAX scores estimating the anatomical complexity of the affected vessels weren’t always accurate, and 24% of the patients in this study proved to have complex lesions when their procedures were undertaken. However, the rate of the primary composite end point was the same in this subgroup of patients as in the overall patient population.
Third, long-term medications after PCI differ from those after CABG, and the investigators said further study is needed to determine how these differences may have contributed to patient outcomes. And finally, longer follow-up is needed to assess whether more differences between the two study groups emerge over time. Five-year follow-up of this study population is now under way.
Dr. Stone and his associates reported ties to numerous industry sources.
The well-designed and rigorously conducted EXCEL trial’s take-home message is that most patients with left main CAD can now be managed equally well using either PCI or CABG, provided that their treatment team is as experienced as those participating in the study.
PCI may be favored in some patients because of its greater periprocedural safety, shorter hospital stay, and more rapid recovery. However, the composite rate of death, stroke, or MI after 30 days was higher with PCI (11.5% vs 7.9%). It is reassuring that these study participants will be followed for another 2 years so that longer-term events can be assessed.
Eugene Braunwald, MD, is in the Thrombolysis in Myocardial Infarction Study Group, in the cardiovascular division at Brigham and Women’s Hospital, and in the department of medicine at Harvard Medical School. He reported having no relevant financial disclosures. Dr. Braunwald made these remarks in an editorial accompanying Dr. Stone’s report (New Engl J Med. 2016 Oct 31. doi:10.1056/NEJMe1612570).
The well-designed and rigorously conducted EXCEL trial’s take-home message is that most patients with left main CAD can now be managed equally well using either PCI or CABG, provided that their treatment team is as experienced as those participating in the study.
PCI may be favored in some patients because of its greater periprocedural safety, shorter hospital stay, and more rapid recovery. However, the composite rate of death, stroke, or MI after 30 days was higher with PCI (11.5% vs 7.9%). It is reassuring that these study participants will be followed for another 2 years so that longer-term events can be assessed.
Eugene Braunwald, MD, is in the Thrombolysis in Myocardial Infarction Study Group, in the cardiovascular division at Brigham and Women’s Hospital, and in the department of medicine at Harvard Medical School. He reported having no relevant financial disclosures. Dr. Braunwald made these remarks in an editorial accompanying Dr. Stone’s report (New Engl J Med. 2016 Oct 31. doi:10.1056/NEJMe1612570).
The well-designed and rigorously conducted EXCEL trial’s take-home message is that most patients with left main CAD can now be managed equally well using either PCI or CABG, provided that their treatment team is as experienced as those participating in the study.
PCI may be favored in some patients because of its greater periprocedural safety, shorter hospital stay, and more rapid recovery. However, the composite rate of death, stroke, or MI after 30 days was higher with PCI (11.5% vs 7.9%). It is reassuring that these study participants will be followed for another 2 years so that longer-term events can be assessed.
Eugene Braunwald, MD, is in the Thrombolysis in Myocardial Infarction Study Group, in the cardiovascular division at Brigham and Women’s Hospital, and in the department of medicine at Harvard Medical School. He reported having no relevant financial disclosures. Dr. Braunwald made these remarks in an editorial accompanying Dr. Stone’s report (New Engl J Med. 2016 Oct 31. doi:10.1056/NEJMe1612570).
Percutaneous coronary intervention (PCI) using everolimus-eluting stents was found noninferior to coronary artery bypass grafting (CABG) with respect to the composite end point of death, stroke, or myocardial infarction at 3 years among patients with left main coronary artery disease and low or intermediate anatomical complexity, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the New England Journal of Medicine.
The rate of this composite outcome was lower with PCI than with CABG during the first 30 days following the procedure, but higher between day 30 and year 3. In addition, the 3-year rate of revascularization was slightly higher with PCI (23.1% vs 19.1%), but the rate of periprocedural MI and major adverse events was lower (8.1% vs 23.0%).
Taken together, these results “suggest that PCI with everolimus-eluting stents is an acceptable or perhaps preferred alternative to CABG in selected patients with left main CAD who are candidates for either procedure,” said Gregg W. Stone, MD, of Columbia University Medical Center, New York, and his associates in the EXCEL (Evaluation of XIENCE versus CABG for Effectiveness of Left Main Revascularization) trial.
This study was funded by Abbott Vascular, maker of the everolimus-eluting stent (the XIENCE). The company also participated in the design of the trial and in the selection and management of the treatment sites.
Until now, it was generally agreed that most patients with left main CAD would have better outcomes with CABG than with PCI, based on the results of earlier trials comparing the two approaches. But contemporary drug-eluting stents have better safety and efficacy profiles than first-generation stents, and surgical techniques have also improved over time, so a study comparing the current standards of care was warranted, Dr. Stone and his associates said (New Engl J Med. 2016 Oct 31. doi:10.1056/NEJMoa1610227).
They assessed 1,905 patients at 126 medical centers in 17 countries in the open-label noninferiority trial. Participants had left main coronary artery stenosis of 70% or more (estimated visually) or of 50%-70% (estimated by invasive or noninvasive testing) if the stenosis was judged to be hemodynamically significant. The study participants also were required to have low or intermediate anatomical complexity of the involved portion of the coronary artery, as defined by a SYNTAX score of 32 or lower. A total of 948 patients were randomly assigned to PCI and 957 to CABG.
The primary composite end point – the rate of death, stroke, or MI assessed at a median of 3 years of follow-up – was 15.4% with PCI and 14.7% with CABG, a nonsignificant difference (Hazard Ratio, 1.00) that demonstrates the noninferiority of PCI. This rate was consistently noninferior across all subgroups of patients, regardless of age, sex, and the presence or absence of diabetes or chronic kidney disease.
At 30 days, the rate of the composite end point was 4.9% with PCI and 7.9% with CABG, which also demonstrates the noninferiority of PCI. At 3 years, secondary end points including the rate of ischemia-driven revascularization also showed the noninferiority of PCI, as did each of the individual components of the primary composite end point.
The rate of death, stroke, or MI was lower at 30 days with PCI than with CABG, mainly because there were fewer MIs with PCI. But a post-hoc analysis showed that this rate was higher with PCI than with CABG after 30 days.
During follow-up, ischemia-driven revascularization was more common after PCI (12.6%) than after CABG (7.5%). However, symptomatic graft occlusion after CABG (5.4%) was more frequent than definite stent thrombosis after PCI (0.7%).
Periprocedural major adverse events developed in 8.1% of the PCI group and 23.0% of the CABG group, and the difference was attributed mainly to fewer arrhythmias, infections, and blood transfusions in the PCI group. Cardiovascular mortality was similar between the two study groups, though all-cause mortality was higher with PCI due to an excess of fatal infections and malignancies in that group.
The investigators noted several limitations with the EXCEL trial. First, treatment blinding wasn’t possible, so some degree of bias may have resulted.
Second, prerandomization SYNTAX scores estimating the anatomical complexity of the affected vessels weren’t always accurate, and 24% of the patients in this study proved to have complex lesions when their procedures were undertaken. However, the rate of the primary composite end point was the same in this subgroup of patients as in the overall patient population.
Third, long-term medications after PCI differ from those after CABG, and the investigators said further study is needed to determine how these differences may have contributed to patient outcomes. And finally, longer follow-up is needed to assess whether more differences between the two study groups emerge over time. Five-year follow-up of this study population is now under way.
Dr. Stone and his associates reported ties to numerous industry sources.
Percutaneous coronary intervention (PCI) using everolimus-eluting stents was found noninferior to coronary artery bypass grafting (CABG) with respect to the composite end point of death, stroke, or myocardial infarction at 3 years among patients with left main coronary artery disease and low or intermediate anatomical complexity, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the New England Journal of Medicine.
The rate of this composite outcome was lower with PCI than with CABG during the first 30 days following the procedure, but higher between day 30 and year 3. In addition, the 3-year rate of revascularization was slightly higher with PCI (23.1% vs 19.1%), but the rate of periprocedural MI and major adverse events was lower (8.1% vs 23.0%).
Taken together, these results “suggest that PCI with everolimus-eluting stents is an acceptable or perhaps preferred alternative to CABG in selected patients with left main CAD who are candidates for either procedure,” said Gregg W. Stone, MD, of Columbia University Medical Center, New York, and his associates in the EXCEL (Evaluation of XIENCE versus CABG for Effectiveness of Left Main Revascularization) trial.
This study was funded by Abbott Vascular, maker of the everolimus-eluting stent (the XIENCE). The company also participated in the design of the trial and in the selection and management of the treatment sites.
Until now, it was generally agreed that most patients with left main CAD would have better outcomes with CABG than with PCI, based on the results of earlier trials comparing the two approaches. But contemporary drug-eluting stents have better safety and efficacy profiles than first-generation stents, and surgical techniques have also improved over time, so a study comparing the current standards of care was warranted, Dr. Stone and his associates said (New Engl J Med. 2016 Oct 31. doi:10.1056/NEJMoa1610227).
They assessed 1,905 patients at 126 medical centers in 17 countries in the open-label noninferiority trial. Participants had left main coronary artery stenosis of 70% or more (estimated visually) or of 50%-70% (estimated by invasive or noninvasive testing) if the stenosis was judged to be hemodynamically significant. The study participants also were required to have low or intermediate anatomical complexity of the involved portion of the coronary artery, as defined by a SYNTAX score of 32 or lower. A total of 948 patients were randomly assigned to PCI and 957 to CABG.
The primary composite end point – the rate of death, stroke, or MI assessed at a median of 3 years of follow-up – was 15.4% with PCI and 14.7% with CABG, a nonsignificant difference (Hazard Ratio, 1.00) that demonstrates the noninferiority of PCI. This rate was consistently noninferior across all subgroups of patients, regardless of age, sex, and the presence or absence of diabetes or chronic kidney disease.
At 30 days, the rate of the composite end point was 4.9% with PCI and 7.9% with CABG, which also demonstrates the noninferiority of PCI. At 3 years, secondary end points including the rate of ischemia-driven revascularization also showed the noninferiority of PCI, as did each of the individual components of the primary composite end point.
The rate of death, stroke, or MI was lower at 30 days with PCI than with CABG, mainly because there were fewer MIs with PCI. But a post-hoc analysis showed that this rate was higher with PCI than with CABG after 30 days.
During follow-up, ischemia-driven revascularization was more common after PCI (12.6%) than after CABG (7.5%). However, symptomatic graft occlusion after CABG (5.4%) was more frequent than definite stent thrombosis after PCI (0.7%).
Periprocedural major adverse events developed in 8.1% of the PCI group and 23.0% of the CABG group, and the difference was attributed mainly to fewer arrhythmias, infections, and blood transfusions in the PCI group. Cardiovascular mortality was similar between the two study groups, though all-cause mortality was higher with PCI due to an excess of fatal infections and malignancies in that group.
The investigators noted several limitations with the EXCEL trial. First, treatment blinding wasn’t possible, so some degree of bias may have resulted.
Second, prerandomization SYNTAX scores estimating the anatomical complexity of the affected vessels weren’t always accurate, and 24% of the patients in this study proved to have complex lesions when their procedures were undertaken. However, the rate of the primary composite end point was the same in this subgroup of patients as in the overall patient population.
Third, long-term medications after PCI differ from those after CABG, and the investigators said further study is needed to determine how these differences may have contributed to patient outcomes. And finally, longer follow-up is needed to assess whether more differences between the two study groups emerge over time. Five-year follow-up of this study population is now under way.
Dr. Stone and his associates reported ties to numerous industry sources.
Key clinical point: PCI was found noninferior to CABG regarding the composite end point of death, stroke, or myocardial infarction in certain patients with left main CAD.
Major finding: The primary composite end point – the rate of death, stroke, or MI assessed at a median of 3 years of follow-up – was 15.4% with PCI and 14.7% with CABG, a nonsignificant difference (HR, 1.00) that demonstrates the noninferiority of PCI.
Data source: An international open-label randomized trial involving 1,905 patients followed for 3 years.
Disclosures: The EXCEL trial was funded by Abbott Vascular, maker of the everolimus-eluting stent used in this study. The company participated in the design of the trial and in selection and management of the treatment sites, but was not involved in managing or analyzing the data or writing the manuscript. Dr. Stone and his associates reported ties to numerous industry sources.
Surgical treatment tops medical management of prosthetic valve endocarditis
NEW ORLEANS – Over the years patients with prosthetic valve endocarditis treated at Cleveland Clinic tended to fare better with surgery compared to medical management, some clinicians noted. However, there was no data to confirm their observations.
“It was not recognized widely. A lot of our colleagues continued to believe it could be adequately treated with the right antibiotic,” Nabin K. Shrestha, MD, said at the IDWeek 2016 annual meeting on infectious diseases.
So Dr Shrestha and his colleagues conducted a retrospective cohort study to compare outcomes between 253 surgically treated adults and 77 others treated medically between April 2008 and December 2012. Survival from the time of treatment decision was the primary outcome.
The groups differed on some demographic and clinical factors. For example, the medically treated group was older, had fewer men, and more patients with mitral valves. “We might think the medical patients might be too sick for surgery, and that could certainly be true, but … they could have been too well for surgery too,” Dr. Shrestha said. To control for these differences between groups, the investigators performed a number of statistical analyses, including a propensity score adjusted model and reduced Cox proportion hazards model.
“Patients with PVE have a high hazard of death if treated medically,” Dr. Shrestha said, based on a 6.68 hazard ratio. The higher risk of death associated with medical treatment remained significant when adjusted for age, sex, and other factors. “Compared to surgical treatment, medical treatment was associated with a seven-fold higher hazard of death overall,” Dr. Shrestha said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
The medical treatment group also fared worse on a number of secondary outcomes. For example, this group had a five-fold higher risk of death during hospitalization compared to the surgery group (odds ratio, 4.65); a 12-fold higher risk of death within one year (OR, 11.70); a seven-fold higher risk of subsequent surgery for infective endocarditis (OR, 6.57); and an eight-fold higher odds of surgery for the same episode of infective endocarditis at a subsequent hospitalization (OR, 8.02).
A large sample size and setting the date of management decision as time zero to avoid survival selection bias “give us confidence in our findings.” Limitations include an inability to look at some important variables because of the retrospective design.
A meeting attendee commented that surgeons often request a patient be optimized medically prior to surgery, and asked if investigators looked at time from hospitalization to the operation.
“The median date from admission to surgery was six days in our database,” said Dr. Shrestha, who is a staff physician at the Cleveland Clinic in Ohio.
“Medical treatment overall is associated with significantly poorer outcomes in patients with PVE compared with surgical treatment,” Dr. Shrestha said. “Although some patients are not candidates for surgery, a definite diagnosis of PVE should prompt a surgical evaluation in the majority of patients.”
Dr. Shrestha reported having no disclosures.
NEW ORLEANS – Over the years patients with prosthetic valve endocarditis treated at Cleveland Clinic tended to fare better with surgery compared to medical management, some clinicians noted. However, there was no data to confirm their observations.
“It was not recognized widely. A lot of our colleagues continued to believe it could be adequately treated with the right antibiotic,” Nabin K. Shrestha, MD, said at the IDWeek 2016 annual meeting on infectious diseases.
So Dr Shrestha and his colleagues conducted a retrospective cohort study to compare outcomes between 253 surgically treated adults and 77 others treated medically between April 2008 and December 2012. Survival from the time of treatment decision was the primary outcome.
The groups differed on some demographic and clinical factors. For example, the medically treated group was older, had fewer men, and more patients with mitral valves. “We might think the medical patients might be too sick for surgery, and that could certainly be true, but … they could have been too well for surgery too,” Dr. Shrestha said. To control for these differences between groups, the investigators performed a number of statistical analyses, including a propensity score adjusted model and reduced Cox proportion hazards model.
“Patients with PVE have a high hazard of death if treated medically,” Dr. Shrestha said, based on a 6.68 hazard ratio. The higher risk of death associated with medical treatment remained significant when adjusted for age, sex, and other factors. “Compared to surgical treatment, medical treatment was associated with a seven-fold higher hazard of death overall,” Dr. Shrestha said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
The medical treatment group also fared worse on a number of secondary outcomes. For example, this group had a five-fold higher risk of death during hospitalization compared to the surgery group (odds ratio, 4.65); a 12-fold higher risk of death within one year (OR, 11.70); a seven-fold higher risk of subsequent surgery for infective endocarditis (OR, 6.57); and an eight-fold higher odds of surgery for the same episode of infective endocarditis at a subsequent hospitalization (OR, 8.02).
A large sample size and setting the date of management decision as time zero to avoid survival selection bias “give us confidence in our findings.” Limitations include an inability to look at some important variables because of the retrospective design.
A meeting attendee commented that surgeons often request a patient be optimized medically prior to surgery, and asked if investigators looked at time from hospitalization to the operation.
“The median date from admission to surgery was six days in our database,” said Dr. Shrestha, who is a staff physician at the Cleveland Clinic in Ohio.
“Medical treatment overall is associated with significantly poorer outcomes in patients with PVE compared with surgical treatment,” Dr. Shrestha said. “Although some patients are not candidates for surgery, a definite diagnosis of PVE should prompt a surgical evaluation in the majority of patients.”
Dr. Shrestha reported having no disclosures.
NEW ORLEANS – Over the years patients with prosthetic valve endocarditis treated at Cleveland Clinic tended to fare better with surgery compared to medical management, some clinicians noted. However, there was no data to confirm their observations.
“It was not recognized widely. A lot of our colleagues continued to believe it could be adequately treated with the right antibiotic,” Nabin K. Shrestha, MD, said at the IDWeek 2016 annual meeting on infectious diseases.
So Dr Shrestha and his colleagues conducted a retrospective cohort study to compare outcomes between 253 surgically treated adults and 77 others treated medically between April 2008 and December 2012. Survival from the time of treatment decision was the primary outcome.
The groups differed on some demographic and clinical factors. For example, the medically treated group was older, had fewer men, and more patients with mitral valves. “We might think the medical patients might be too sick for surgery, and that could certainly be true, but … they could have been too well for surgery too,” Dr. Shrestha said. To control for these differences between groups, the investigators performed a number of statistical analyses, including a propensity score adjusted model and reduced Cox proportion hazards model.
“Patients with PVE have a high hazard of death if treated medically,” Dr. Shrestha said, based on a 6.68 hazard ratio. The higher risk of death associated with medical treatment remained significant when adjusted for age, sex, and other factors. “Compared to surgical treatment, medical treatment was associated with a seven-fold higher hazard of death overall,” Dr. Shrestha said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
The medical treatment group also fared worse on a number of secondary outcomes. For example, this group had a five-fold higher risk of death during hospitalization compared to the surgery group (odds ratio, 4.65); a 12-fold higher risk of death within one year (OR, 11.70); a seven-fold higher risk of subsequent surgery for infective endocarditis (OR, 6.57); and an eight-fold higher odds of surgery for the same episode of infective endocarditis at a subsequent hospitalization (OR, 8.02).
A large sample size and setting the date of management decision as time zero to avoid survival selection bias “give us confidence in our findings.” Limitations include an inability to look at some important variables because of the retrospective design.
A meeting attendee commented that surgeons often request a patient be optimized medically prior to surgery, and asked if investigators looked at time from hospitalization to the operation.
“The median date from admission to surgery was six days in our database,” said Dr. Shrestha, who is a staff physician at the Cleveland Clinic in Ohio.
“Medical treatment overall is associated with significantly poorer outcomes in patients with PVE compared with surgical treatment,” Dr. Shrestha said. “Although some patients are not candidates for surgery, a definite diagnosis of PVE should prompt a surgical evaluation in the majority of patients.”
Dr. Shrestha reported having no disclosures.
Key clinical point:
Major finding: Compared to surgery, odds of death within one year higher were almost 7 times greater with medical treatment (hazard ratio, 6.68).
Data source: Presentation at IDWeek 2016
Disclosures: Dr. Nabin K. Shrestha had no relevant disclosures.
Ezetimibe’s ACS benefit centers on high-risk, post-CABG patients
ROME – Patients who have undergone coronary artery bypass surgery and who later have an acute coronary syndrome event gain the most from an aggressive lipid-lowering regimen, according to an exploratory analysis of data from more than 18,000 patients enrolled in the IMPROVE-IT trial that tested the incremental benefit from ezetimibe treatment when added to a statin.
Additional exploratory analyses further showed that high-risk acute coronary syndrome (ACS) patients without a history of coronary artery bypass grafting (CABG) also benefited from adding ezetimibe to a background regimen of simvastatin, but the benefit from adding ezetimibe completely disappeared in low-risk ACS patients, Alon Eisen, MD, said at the annual congress of the European Society of Cardiology.
‘The benefit of adding ezetimibe to a statin was enhanced in patients with prior CABG and in other high-risk patients with no prior CABG, supporting the use of more intensive lipid-lowering therapy in these high-risk patients,” said Dr. Eisen, a cardiologist at Brigham and Women’s Hospital in Boston. He also highlighted that ezetimibe is “a safe drug that is coming off patent.” Adding ezetimibe had a moderate effect on LDL cholesterol levels, cutting them from a median of 70 mg/dL in patients in the placebo arm to a median of 54 mg/dL in the group who received ezetimibe.
These results “show that if we pick the right patients, a very benign drug can have a great benefit,” said Eugene Braunwald, MD, a coinvestigator on the IMPROVE-IT trial and a collaborator with Dr. Eisen on the new analysis. The new findings “emphasize that the higher a patient’s risk, the more effect they get from cholesterol-lowering treatment,” said Dr. Braunwald, professor of medicine at Harvard University and a cardiologist at Brigham and Women’s Hospital, both in Boston.
The second exploratory analysis reported by Dr. Eisen looked at the more than 16,000 patients in IMPROVE-IT without history of CABG. The analysis applied a newly developed, nine-item formula for stratifying atherothrombotic risk (Circulation. 2016 July 26;134[4];304-13) to divide these patients into low-, intermediate- and high-risk subgroups. Patients in the high-risk subgroup (20% of the IMPROVE-IT subgroup) had a 6–percentage point reduction in their primary endpoint event rate with added ezetimibe treatment, while those at intermediate risk (31%) got a 2–percentage point decrease in endpoint events, and low-risk patients (49%) actually showed a small, less than 1–percentage point increase in endpoint events with added ezetimibe, Dr. Eisen reported.
IMPROVE-IT was funded by MERCK, the company that markets ezetimibe (Zetia). Dr. Eisen had no disclosures. Dr. Braunwald has been a consultant to Merck as well as to Bayer, Daiichi Sankyo, The Medicines Company, Novartis, and Sanofi.
[email protected]
On Twitter @mitchelzoler
I suspect that the patients in IMPROVE-IT with a history of coronary artery bypass graft surgery were more likely than the other enrolled acute coronary syndrome patients to have more extensive and systemic atherosclerotic disease. Although coronary artery bypass addresses the most acute obstructions to coronary flow that exist at the time of surgery, the procedure does not cure the patient’s underlying vascular disease. We know that a substantial majority of coronary events occur in arteries that are not heavily stenosed.
Another important limitation to keep in mind about the IMPROVE-IT trial was that the background statin treatment all patients received was modest – 40 mg of simvastatin daily. In real-world practice, high-risk patients should go on the most potent statin regimen they can tolerate – ideally, 40 mg daily of rosuvastatin. The need for additional lipid-lowering interventions, with ezetimibe or other drugs, can then be considered as an add-on to aggressive statin therapy.
Richard A. Chazal, MD, is an invasive cardiologist and medical director of the Heart and Vascular Institute of Lee Memorial Health System in Fort Myers, Fla. He is also the current president of the American College of Cardiology. He had no disclosures. He made these comments in an interview.
I suspect that the patients in IMPROVE-IT with a history of coronary artery bypass graft surgery were more likely than the other enrolled acute coronary syndrome patients to have more extensive and systemic atherosclerotic disease. Although coronary artery bypass addresses the most acute obstructions to coronary flow that exist at the time of surgery, the procedure does not cure the patient’s underlying vascular disease. We know that a substantial majority of coronary events occur in arteries that are not heavily stenosed.
Another important limitation to keep in mind about the IMPROVE-IT trial was that the background statin treatment all patients received was modest – 40 mg of simvastatin daily. In real-world practice, high-risk patients should go on the most potent statin regimen they can tolerate – ideally, 40 mg daily of rosuvastatin. The need for additional lipid-lowering interventions, with ezetimibe or other drugs, can then be considered as an add-on to aggressive statin therapy.
Richard A. Chazal, MD, is an invasive cardiologist and medical director of the Heart and Vascular Institute of Lee Memorial Health System in Fort Myers, Fla. He is also the current president of the American College of Cardiology. He had no disclosures. He made these comments in an interview.
I suspect that the patients in IMPROVE-IT with a history of coronary artery bypass graft surgery were more likely than the other enrolled acute coronary syndrome patients to have more extensive and systemic atherosclerotic disease. Although coronary artery bypass addresses the most acute obstructions to coronary flow that exist at the time of surgery, the procedure does not cure the patient’s underlying vascular disease. We know that a substantial majority of coronary events occur in arteries that are not heavily stenosed.
Another important limitation to keep in mind about the IMPROVE-IT trial was that the background statin treatment all patients received was modest – 40 mg of simvastatin daily. In real-world practice, high-risk patients should go on the most potent statin regimen they can tolerate – ideally, 40 mg daily of rosuvastatin. The need for additional lipid-lowering interventions, with ezetimibe or other drugs, can then be considered as an add-on to aggressive statin therapy.
Richard A. Chazal, MD, is an invasive cardiologist and medical director of the Heart and Vascular Institute of Lee Memorial Health System in Fort Myers, Fla. He is also the current president of the American College of Cardiology. He had no disclosures. He made these comments in an interview.
ROME – Patients who have undergone coronary artery bypass surgery and who later have an acute coronary syndrome event gain the most from an aggressive lipid-lowering regimen, according to an exploratory analysis of data from more than 18,000 patients enrolled in the IMPROVE-IT trial that tested the incremental benefit from ezetimibe treatment when added to a statin.
Additional exploratory analyses further showed that high-risk acute coronary syndrome (ACS) patients without a history of coronary artery bypass grafting (CABG) also benefited from adding ezetimibe to a background regimen of simvastatin, but the benefit from adding ezetimibe completely disappeared in low-risk ACS patients, Alon Eisen, MD, said at the annual congress of the European Society of Cardiology.
‘The benefit of adding ezetimibe to a statin was enhanced in patients with prior CABG and in other high-risk patients with no prior CABG, supporting the use of more intensive lipid-lowering therapy in these high-risk patients,” said Dr. Eisen, a cardiologist at Brigham and Women’s Hospital in Boston. He also highlighted that ezetimibe is “a safe drug that is coming off patent.” Adding ezetimibe had a moderate effect on LDL cholesterol levels, cutting them from a median of 70 mg/dL in patients in the placebo arm to a median of 54 mg/dL in the group who received ezetimibe.
These results “show that if we pick the right patients, a very benign drug can have a great benefit,” said Eugene Braunwald, MD, a coinvestigator on the IMPROVE-IT trial and a collaborator with Dr. Eisen on the new analysis. The new findings “emphasize that the higher a patient’s risk, the more effect they get from cholesterol-lowering treatment,” said Dr. Braunwald, professor of medicine at Harvard University and a cardiologist at Brigham and Women’s Hospital, both in Boston.
The second exploratory analysis reported by Dr. Eisen looked at the more than 16,000 patients in IMPROVE-IT without history of CABG. The analysis applied a newly developed, nine-item formula for stratifying atherothrombotic risk (Circulation. 2016 July 26;134[4];304-13) to divide these patients into low-, intermediate- and high-risk subgroups. Patients in the high-risk subgroup (20% of the IMPROVE-IT subgroup) had a 6–percentage point reduction in their primary endpoint event rate with added ezetimibe treatment, while those at intermediate risk (31%) got a 2–percentage point decrease in endpoint events, and low-risk patients (49%) actually showed a small, less than 1–percentage point increase in endpoint events with added ezetimibe, Dr. Eisen reported.
IMPROVE-IT was funded by MERCK, the company that markets ezetimibe (Zetia). Dr. Eisen had no disclosures. Dr. Braunwald has been a consultant to Merck as well as to Bayer, Daiichi Sankyo, The Medicines Company, Novartis, and Sanofi.
[email protected]
On Twitter @mitchelzoler
ROME – Patients who have undergone coronary artery bypass surgery and who later have an acute coronary syndrome event gain the most from an aggressive lipid-lowering regimen, according to an exploratory analysis of data from more than 18,000 patients enrolled in the IMPROVE-IT trial that tested the incremental benefit from ezetimibe treatment when added to a statin.
Additional exploratory analyses further showed that high-risk acute coronary syndrome (ACS) patients without a history of coronary artery bypass grafting (CABG) also benefited from adding ezetimibe to a background regimen of simvastatin, but the benefit from adding ezetimibe completely disappeared in low-risk ACS patients, Alon Eisen, MD, said at the annual congress of the European Society of Cardiology.
‘The benefit of adding ezetimibe to a statin was enhanced in patients with prior CABG and in other high-risk patients with no prior CABG, supporting the use of more intensive lipid-lowering therapy in these high-risk patients,” said Dr. Eisen, a cardiologist at Brigham and Women’s Hospital in Boston. He also highlighted that ezetimibe is “a safe drug that is coming off patent.” Adding ezetimibe had a moderate effect on LDL cholesterol levels, cutting them from a median of 70 mg/dL in patients in the placebo arm to a median of 54 mg/dL in the group who received ezetimibe.
These results “show that if we pick the right patients, a very benign drug can have a great benefit,” said Eugene Braunwald, MD, a coinvestigator on the IMPROVE-IT trial and a collaborator with Dr. Eisen on the new analysis. The new findings “emphasize that the higher a patient’s risk, the more effect they get from cholesterol-lowering treatment,” said Dr. Braunwald, professor of medicine at Harvard University and a cardiologist at Brigham and Women’s Hospital, both in Boston.
The second exploratory analysis reported by Dr. Eisen looked at the more than 16,000 patients in IMPROVE-IT without history of CABG. The analysis applied a newly developed, nine-item formula for stratifying atherothrombotic risk (Circulation. 2016 July 26;134[4];304-13) to divide these patients into low-, intermediate- and high-risk subgroups. Patients in the high-risk subgroup (20% of the IMPROVE-IT subgroup) had a 6–percentage point reduction in their primary endpoint event rate with added ezetimibe treatment, while those at intermediate risk (31%) got a 2–percentage point decrease in endpoint events, and low-risk patients (49%) actually showed a small, less than 1–percentage point increase in endpoint events with added ezetimibe, Dr. Eisen reported.
IMPROVE-IT was funded by MERCK, the company that markets ezetimibe (Zetia). Dr. Eisen had no disclosures. Dr. Braunwald has been a consultant to Merck as well as to Bayer, Daiichi Sankyo, The Medicines Company, Novartis, and Sanofi.
[email protected]
On Twitter @mitchelzoler
AT THE ESC CONGRESS 2016
Key clinical point:
Major finding: The absolute primary-event risk reduction was 9% in post-CABG patients and 1% in all other patients.
Data source: An exploratory, post-hoc analysis of data collected in IMPROVE-IT, a multicenter trial with 18,144 patients.
Disclosures: IMPROVE-IT was funded by MERCK, the company that markets ezetimibe (Zetia). Dr. Eisen had no disclosures. Dr. Braunwald has been a consultant to Merck as well as to Bayer, Daiichi Sankyo, The Medicines Company, Novartis, and Sanofi.
SAVR for radiation-induced aortic stenosis has high late mortality
ROME – Radiation-induced aortic stenosis is associated with markedly worse long-term outcome after surgical aortic valve replacement than when the operation is performed in patients without a history of radiotherapy, Milind Y. Desai, MD, reported at the annual congress of the European Society of Cardiology.
Moreover, the Society of Thoracic Surgeons (STS) score isn’t good at risk-stratifying patients with radiation-induced aortic stenosis who are under consideration for surgical aortic valve replacement (SAVR).
Radiation-induced heart disease is a late complication of thoracic radiotherapy. It’s particularly common in patients who got radiation for lymphomas or breast cancer. It can affect any cardiac structure, including the myocardium, pericardium, valves, coronary arteries, and the conduction system.
Aortic stenosis is the most common valvular manifestation, present in roughly 80% of patients with radiation-induced heart disease. At the Cleveland Clinic, the average time from radiotherapy to development of radiation-induced aortic stenosis (RIAS) is about 20 years. The condition is characterized by thickening of the junction between the base of the anterior mitral leaflet and aortic root, known as the aortomitral curtain, Dr. Desai explained.
He presented a retrospective observational cohort study involving 172 patients who underwent SAVR for RIAS and an equal number of SAVR patients with no such history. The groups were matched by age, sex, aortic valve area, and type and timing of SAVR. Of note, the group with RIAS had a mean preoperative STS score of 11, and the control group averaged a similar score of 10.
The key finding: During a mean follow-up of 6 years, the all-cause mortality rate was a hefty 48% in patients with RIAS, compared with just 7% in matched controls. Only about 5% of deaths in the group with RIAS were from recurrent malignancy. The low figure is not surprising given the average 20-year lag between radiotherapy and development of radiation-induced heart disease.
“In our experience, most of these patients develop a recurrent pleural effusion and nasty cardiopulmonary issues that result in their death,” according to Dr. Desai.
In a multivariate Cox proportional hazards analysis, a history of chest radiation therapy was by far the strongest predictor of all-cause mortality, conferring an 8.5-fold increase in risk.
The only other statistically significant predictor of mortality during follow-up in multivariate analysis was a high STS score, with an associated weak albeit statistically significant 1.15-fold increased risk. A total of 30 of 78 (39%) RIAS patients with an STS score below 4 died during follow-up, compared with none of 91 controls.
Thirty-four of 92 (37%) RIAS patients under age 65 died during follow-up, whereas none of 83 control SAVR patients did so.
Having coronary artery bypass surgery or other cardiac surgery at the time of SAVR was not associated with significantly increased risk of mortality compared with solo SAVR.
In-hospital outcomes were consistently worse after SAVR in the RIAS group. Half of the RIAS patients experienced in-hospital atrial fibrillation and 29% developed persistent atrial fibrillation, compared with 30% and 24% of controls. About 22% of RIAS patients were readmitted within 3 months after surgery, as were only 8% of controls. In-hospital mortality occurred in 2% of SAVR patients with RIAS; none of the matched controls did.
Dr. Desai reported having no financial interests relative to this study.
ROME – Radiation-induced aortic stenosis is associated with markedly worse long-term outcome after surgical aortic valve replacement than when the operation is performed in patients without a history of radiotherapy, Milind Y. Desai, MD, reported at the annual congress of the European Society of Cardiology.
Moreover, the Society of Thoracic Surgeons (STS) score isn’t good at risk-stratifying patients with radiation-induced aortic stenosis who are under consideration for surgical aortic valve replacement (SAVR).
Radiation-induced heart disease is a late complication of thoracic radiotherapy. It’s particularly common in patients who got radiation for lymphomas or breast cancer. It can affect any cardiac structure, including the myocardium, pericardium, valves, coronary arteries, and the conduction system.
Aortic stenosis is the most common valvular manifestation, present in roughly 80% of patients with radiation-induced heart disease. At the Cleveland Clinic, the average time from radiotherapy to development of radiation-induced aortic stenosis (RIAS) is about 20 years. The condition is characterized by thickening of the junction between the base of the anterior mitral leaflet and aortic root, known as the aortomitral curtain, Dr. Desai explained.
He presented a retrospective observational cohort study involving 172 patients who underwent SAVR for RIAS and an equal number of SAVR patients with no such history. The groups were matched by age, sex, aortic valve area, and type and timing of SAVR. Of note, the group with RIAS had a mean preoperative STS score of 11, and the control group averaged a similar score of 10.
The key finding: During a mean follow-up of 6 years, the all-cause mortality rate was a hefty 48% in patients with RIAS, compared with just 7% in matched controls. Only about 5% of deaths in the group with RIAS were from recurrent malignancy. The low figure is not surprising given the average 20-year lag between radiotherapy and development of radiation-induced heart disease.
“In our experience, most of these patients develop a recurrent pleural effusion and nasty cardiopulmonary issues that result in their death,” according to Dr. Desai.
In a multivariate Cox proportional hazards analysis, a history of chest radiation therapy was by far the strongest predictor of all-cause mortality, conferring an 8.5-fold increase in risk.
The only other statistically significant predictor of mortality during follow-up in multivariate analysis was a high STS score, with an associated weak albeit statistically significant 1.15-fold increased risk. A total of 30 of 78 (39%) RIAS patients with an STS score below 4 died during follow-up, compared with none of 91 controls.
Thirty-four of 92 (37%) RIAS patients under age 65 died during follow-up, whereas none of 83 control SAVR patients did so.
Having coronary artery bypass surgery or other cardiac surgery at the time of SAVR was not associated with significantly increased risk of mortality compared with solo SAVR.
In-hospital outcomes were consistently worse after SAVR in the RIAS group. Half of the RIAS patients experienced in-hospital atrial fibrillation and 29% developed persistent atrial fibrillation, compared with 30% and 24% of controls. About 22% of RIAS patients were readmitted within 3 months after surgery, as were only 8% of controls. In-hospital mortality occurred in 2% of SAVR patients with RIAS; none of the matched controls did.
Dr. Desai reported having no financial interests relative to this study.
ROME – Radiation-induced aortic stenosis is associated with markedly worse long-term outcome after surgical aortic valve replacement than when the operation is performed in patients without a history of radiotherapy, Milind Y. Desai, MD, reported at the annual congress of the European Society of Cardiology.
Moreover, the Society of Thoracic Surgeons (STS) score isn’t good at risk-stratifying patients with radiation-induced aortic stenosis who are under consideration for surgical aortic valve replacement (SAVR).
Radiation-induced heart disease is a late complication of thoracic radiotherapy. It’s particularly common in patients who got radiation for lymphomas or breast cancer. It can affect any cardiac structure, including the myocardium, pericardium, valves, coronary arteries, and the conduction system.
Aortic stenosis is the most common valvular manifestation, present in roughly 80% of patients with radiation-induced heart disease. At the Cleveland Clinic, the average time from radiotherapy to development of radiation-induced aortic stenosis (RIAS) is about 20 years. The condition is characterized by thickening of the junction between the base of the anterior mitral leaflet and aortic root, known as the aortomitral curtain, Dr. Desai explained.
He presented a retrospective observational cohort study involving 172 patients who underwent SAVR for RIAS and an equal number of SAVR patients with no such history. The groups were matched by age, sex, aortic valve area, and type and timing of SAVR. Of note, the group with RIAS had a mean preoperative STS score of 11, and the control group averaged a similar score of 10.
The key finding: During a mean follow-up of 6 years, the all-cause mortality rate was a hefty 48% in patients with RIAS, compared with just 7% in matched controls. Only about 5% of deaths in the group with RIAS were from recurrent malignancy. The low figure is not surprising given the average 20-year lag between radiotherapy and development of radiation-induced heart disease.
“In our experience, most of these patients develop a recurrent pleural effusion and nasty cardiopulmonary issues that result in their death,” according to Dr. Desai.
In a multivariate Cox proportional hazards analysis, a history of chest radiation therapy was by far the strongest predictor of all-cause mortality, conferring an 8.5-fold increase in risk.
The only other statistically significant predictor of mortality during follow-up in multivariate analysis was a high STS score, with an associated weak albeit statistically significant 1.15-fold increased risk. A total of 30 of 78 (39%) RIAS patients with an STS score below 4 died during follow-up, compared with none of 91 controls.
Thirty-four of 92 (37%) RIAS patients under age 65 died during follow-up, whereas none of 83 control SAVR patients did so.
Having coronary artery bypass surgery or other cardiac surgery at the time of SAVR was not associated with significantly increased risk of mortality compared with solo SAVR.
In-hospital outcomes were consistently worse after SAVR in the RIAS group. Half of the RIAS patients experienced in-hospital atrial fibrillation and 29% developed persistent atrial fibrillation, compared with 30% and 24% of controls. About 22% of RIAS patients were readmitted within 3 months after surgery, as were only 8% of controls. In-hospital mortality occurred in 2% of SAVR patients with RIAS; none of the matched controls did.
Dr. Desai reported having no financial interests relative to this study.
AT THE ESC CONGRESS 2016
Key clinical point:
Major finding: All-cause mortality occurred in 48% of 172 patients with radiation-induced severe aortic stenosis during a mean follow-up of 6 years after surgical aortic valve replacement, compared with just 7% of matched controls.
Data source: This was a retrospective observational study involving 172 closely matched pairs of surgical aortic valve replacement patients.
Disclosures: The presenter reported having no financial conflicts of interest regarding this study.
More restrictive hemoglobin threshold recommended for transfusion
New guidelines on red blood cell blood transfusion recommend a restrictive threshold in which transfusion is not indicated until the hemoglobin level is 7-8 g/dL for most patients, finding that it is safe in most clinical settings.
The updated clinical practice guidelines on transfusion thresholds and storage from the AABB (formerly known as the American Association of Blood Banks), also note that red blood cell units can be used at any time within their licensed dating period, rather than a preference being given to fresher units less than 10 days old.
The guidelines, published online Oct. 12 in JAMA, are an update of the 2012 transfusion guidelines, and are a response to a more than doubling of the number of patients since enrolled in randomized controlled trials of red blood cell transfusions.
The AABB’s clinical transfusion medicine committee, led by Jeffrey L. Carson, MD, of Robert Wood Johnson Medical School, New Brunswick, N.J., analyzed data from 31 randomized controlled trials of 12,587 participants, which compared restrictive transfusion thresholds of 7-8 g/dL to more liberal thresholds of 9-10 g/dL.
This analysis showed that the use of restrictive transfusion protocols was associated with an absolute difference in 30-day mortality of three fewer deaths compared to the more liberal thresholds. There was no significant difference in 30-day mortality in trials that compared a threshold of 8-9 g/dL to a threshold of less than 7 g/dL (JAMA 2016, Oct 12. doi: 10.1001/jama.2016.9185).
“For all other outcomes evaluated, there was no evidence to suggest that patients were harmed by restrictive transfusion protocols, although the quality of the evidence was low for the outcomes of congestive heart failure and rebleeding,” the authors reported.
Based on these findings, they recommended a restrictive red blood cell transfusion threshold, in which transfusion is not indicated until the hemoglobin level is 7 g/dL for hospitalized adult patients who are hemodynamically stable, including critically ill patients.
However for patients undergoing orthopedic or cardiac surgery, or those with preexisting cardiovascular disease, they advised a threshold of 8 g/dL for initiating a red blood cell transfusion.
They also stressed that these recommendations did not apply to patients with acute coronary syndrome, those with severe thrombocytopenia, those treated for hematologic or oncologic disorders who at risk of bleeding, and those with chronic transfusion–dependent anemia, citing a lack of quality randomized controlled trial evidence.
The guideline authors examined the issue of the optimal length of time that red blood cell units should be stored, pointing out that there is currently no formal guidance on the optimal period of red blood cell storage prior to transfusion.
While units of red blood cells can be stored for up to 42 days, the committee said there was some evidence that longer storage may be associated with adverse transfusion outcomes.
“The RBCs stored for longer periods have decreased ability to deliver oxygen due to decreased levels of 2,3-diphsophoglycerate, decreased nitric oxide metabolism, alterations of the RBC membrane leading to increased rigidity, and increased RBC endothelial adherence,” they wrote.
Despite this, the review of 13 randomized controlled trials examining the effect of storage duration found no evidence that fresher units had any impact on mortality compared to standard issue units, nor were there any more adverse events with the standard issue units.
The absolute difference in 30-day mortality was four more deaths per 1,000 with fresher blood, and there was a higher risk of nosocomial infections among patients who received fresher red blood cell units although the authors said the quality of evidence was low.
They therefore recommended that no preference be given to fresher red blood cell units, and that all patients be treated with units chosen at any point within their licensed dating period.
Guideline development was supported by AABB. Four authors declared grants, fees, stock options or consultancies from pharmaceutical companies, but no other conflicts of interest were declared.
The two-tiered approach of this important update to the red blood cell transfusion guidelines acknowledges the current state of the evidence and also provides support for making more individualized transfusion decisions.
These new guidelines represent medicine at its best in that they are evidence based, derived from randomized controlled trials, reflect important clinical perspectives, and are definitive for conditions in which data are substantial, but provide greater flexibility for conditions in which data are less certain.
One major limitation of these guidelines is that they are based on hemoglobin level as the transfusion trigger, when good clinical practice dictates that the decision to transfuse should also be based on clinical factors, availability of alternative therapies, and patient preferences.
Mark H. Yazer, MD and Darrell J. Triulzi, MD, are in the division of transfusion medicine at the University of Pittsburgh Medical Center. These comments are adapted from an editorial (JAMA 2016, Oct 12. doi: 10.1001/jama.2016.10887 ). Dr Triulzi reported receiving grants from the National Heart, Lung, and Blood Institute; and receiving personal fees for serving on an advisory board for Fresenius Kabi.
The two-tiered approach of this important update to the red blood cell transfusion guidelines acknowledges the current state of the evidence and also provides support for making more individualized transfusion decisions.
These new guidelines represent medicine at its best in that they are evidence based, derived from randomized controlled trials, reflect important clinical perspectives, and are definitive for conditions in which data are substantial, but provide greater flexibility for conditions in which data are less certain.
One major limitation of these guidelines is that they are based on hemoglobin level as the transfusion trigger, when good clinical practice dictates that the decision to transfuse should also be based on clinical factors, availability of alternative therapies, and patient preferences.
Mark H. Yazer, MD and Darrell J. Triulzi, MD, are in the division of transfusion medicine at the University of Pittsburgh Medical Center. These comments are adapted from an editorial (JAMA 2016, Oct 12. doi: 10.1001/jama.2016.10887 ). Dr Triulzi reported receiving grants from the National Heart, Lung, and Blood Institute; and receiving personal fees for serving on an advisory board for Fresenius Kabi.
The two-tiered approach of this important update to the red blood cell transfusion guidelines acknowledges the current state of the evidence and also provides support for making more individualized transfusion decisions.
These new guidelines represent medicine at its best in that they are evidence based, derived from randomized controlled trials, reflect important clinical perspectives, and are definitive for conditions in which data are substantial, but provide greater flexibility for conditions in which data are less certain.
One major limitation of these guidelines is that they are based on hemoglobin level as the transfusion trigger, when good clinical practice dictates that the decision to transfuse should also be based on clinical factors, availability of alternative therapies, and patient preferences.
Mark H. Yazer, MD and Darrell J. Triulzi, MD, are in the division of transfusion medicine at the University of Pittsburgh Medical Center. These comments are adapted from an editorial (JAMA 2016, Oct 12. doi: 10.1001/jama.2016.10887 ). Dr Triulzi reported receiving grants from the National Heart, Lung, and Blood Institute; and receiving personal fees for serving on an advisory board for Fresenius Kabi.
New guidelines on red blood cell blood transfusion recommend a restrictive threshold in which transfusion is not indicated until the hemoglobin level is 7-8 g/dL for most patients, finding that it is safe in most clinical settings.
The updated clinical practice guidelines on transfusion thresholds and storage from the AABB (formerly known as the American Association of Blood Banks), also note that red blood cell units can be used at any time within their licensed dating period, rather than a preference being given to fresher units less than 10 days old.
The guidelines, published online Oct. 12 in JAMA, are an update of the 2012 transfusion guidelines, and are a response to a more than doubling of the number of patients since enrolled in randomized controlled trials of red blood cell transfusions.
The AABB’s clinical transfusion medicine committee, led by Jeffrey L. Carson, MD, of Robert Wood Johnson Medical School, New Brunswick, N.J., analyzed data from 31 randomized controlled trials of 12,587 participants, which compared restrictive transfusion thresholds of 7-8 g/dL to more liberal thresholds of 9-10 g/dL.
This analysis showed that the use of restrictive transfusion protocols was associated with an absolute difference in 30-day mortality of three fewer deaths compared to the more liberal thresholds. There was no significant difference in 30-day mortality in trials that compared a threshold of 8-9 g/dL to a threshold of less than 7 g/dL (JAMA 2016, Oct 12. doi: 10.1001/jama.2016.9185).
“For all other outcomes evaluated, there was no evidence to suggest that patients were harmed by restrictive transfusion protocols, although the quality of the evidence was low for the outcomes of congestive heart failure and rebleeding,” the authors reported.
Based on these findings, they recommended a restrictive red blood cell transfusion threshold, in which transfusion is not indicated until the hemoglobin level is 7 g/dL for hospitalized adult patients who are hemodynamically stable, including critically ill patients.
However for patients undergoing orthopedic or cardiac surgery, or those with preexisting cardiovascular disease, they advised a threshold of 8 g/dL for initiating a red blood cell transfusion.
They also stressed that these recommendations did not apply to patients with acute coronary syndrome, those with severe thrombocytopenia, those treated for hematologic or oncologic disorders who at risk of bleeding, and those with chronic transfusion–dependent anemia, citing a lack of quality randomized controlled trial evidence.
The guideline authors examined the issue of the optimal length of time that red blood cell units should be stored, pointing out that there is currently no formal guidance on the optimal period of red blood cell storage prior to transfusion.
While units of red blood cells can be stored for up to 42 days, the committee said there was some evidence that longer storage may be associated with adverse transfusion outcomes.
“The RBCs stored for longer periods have decreased ability to deliver oxygen due to decreased levels of 2,3-diphsophoglycerate, decreased nitric oxide metabolism, alterations of the RBC membrane leading to increased rigidity, and increased RBC endothelial adherence,” they wrote.
Despite this, the review of 13 randomized controlled trials examining the effect of storage duration found no evidence that fresher units had any impact on mortality compared to standard issue units, nor were there any more adverse events with the standard issue units.
The absolute difference in 30-day mortality was four more deaths per 1,000 with fresher blood, and there was a higher risk of nosocomial infections among patients who received fresher red blood cell units although the authors said the quality of evidence was low.
They therefore recommended that no preference be given to fresher red blood cell units, and that all patients be treated with units chosen at any point within their licensed dating period.
Guideline development was supported by AABB. Four authors declared grants, fees, stock options or consultancies from pharmaceutical companies, but no other conflicts of interest were declared.
New guidelines on red blood cell blood transfusion recommend a restrictive threshold in which transfusion is not indicated until the hemoglobin level is 7-8 g/dL for most patients, finding that it is safe in most clinical settings.
The updated clinical practice guidelines on transfusion thresholds and storage from the AABB (formerly known as the American Association of Blood Banks), also note that red blood cell units can be used at any time within their licensed dating period, rather than a preference being given to fresher units less than 10 days old.
The guidelines, published online Oct. 12 in JAMA, are an update of the 2012 transfusion guidelines, and are a response to a more than doubling of the number of patients since enrolled in randomized controlled trials of red blood cell transfusions.
The AABB’s clinical transfusion medicine committee, led by Jeffrey L. Carson, MD, of Robert Wood Johnson Medical School, New Brunswick, N.J., analyzed data from 31 randomized controlled trials of 12,587 participants, which compared restrictive transfusion thresholds of 7-8 g/dL to more liberal thresholds of 9-10 g/dL.
This analysis showed that the use of restrictive transfusion protocols was associated with an absolute difference in 30-day mortality of three fewer deaths compared to the more liberal thresholds. There was no significant difference in 30-day mortality in trials that compared a threshold of 8-9 g/dL to a threshold of less than 7 g/dL (JAMA 2016, Oct 12. doi: 10.1001/jama.2016.9185).
“For all other outcomes evaluated, there was no evidence to suggest that patients were harmed by restrictive transfusion protocols, although the quality of the evidence was low for the outcomes of congestive heart failure and rebleeding,” the authors reported.
Based on these findings, they recommended a restrictive red blood cell transfusion threshold, in which transfusion is not indicated until the hemoglobin level is 7 g/dL for hospitalized adult patients who are hemodynamically stable, including critically ill patients.
However for patients undergoing orthopedic or cardiac surgery, or those with preexisting cardiovascular disease, they advised a threshold of 8 g/dL for initiating a red blood cell transfusion.
They also stressed that these recommendations did not apply to patients with acute coronary syndrome, those with severe thrombocytopenia, those treated for hematologic or oncologic disorders who at risk of bleeding, and those with chronic transfusion–dependent anemia, citing a lack of quality randomized controlled trial evidence.
The guideline authors examined the issue of the optimal length of time that red blood cell units should be stored, pointing out that there is currently no formal guidance on the optimal period of red blood cell storage prior to transfusion.
While units of red blood cells can be stored for up to 42 days, the committee said there was some evidence that longer storage may be associated with adverse transfusion outcomes.
“The RBCs stored for longer periods have decreased ability to deliver oxygen due to decreased levels of 2,3-diphsophoglycerate, decreased nitric oxide metabolism, alterations of the RBC membrane leading to increased rigidity, and increased RBC endothelial adherence,” they wrote.
Despite this, the review of 13 randomized controlled trials examining the effect of storage duration found no evidence that fresher units had any impact on mortality compared to standard issue units, nor were there any more adverse events with the standard issue units.
The absolute difference in 30-day mortality was four more deaths per 1,000 with fresher blood, and there was a higher risk of nosocomial infections among patients who received fresher red blood cell units although the authors said the quality of evidence was low.
They therefore recommended that no preference be given to fresher red blood cell units, and that all patients be treated with units chosen at any point within their licensed dating period.
Guideline development was supported by AABB. Four authors declared grants, fees, stock options or consultancies from pharmaceutical companies, but no other conflicts of interest were declared.
FROM JAMA
Key clinical point: A restrictive threshold for red blood cell transfusion, in which transfusion is not indicated until the hemoglobin level is 7-8 g/dL, is now recommended for most patients.
Major finding: A more restrictive threshold for red blood cell transfusion is not associated with an increased risk of mortality or other adverse outcomes from transfusion.
Data source: Updated guidelines from the AABB (formerly known as the American Association of Blood Banks).
Disclosures: Guideline development was supported by AABB. Four authors declared grants, fees, stock options or consultancies from pharmaceutical companies including CSL and Fresenius Kabi, but no other conflicts of interest were declared.