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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.
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.
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The results from EXCEL and NOBLE were not that different, but what was different was how the two trials were designed and how their endpoints were defined. The biggest difference between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) seemed to be in the rate of late MIs, with a little higher rate following PCI, and more repeat revascularizations with PCI, but with similar mortality rates with both treatments. There was a lot of similarity in the results despite the differences in the trials.
The evidence in both studies gives more support to the concept that, for patients with simpler left main lesions, PCI is a competitive alternative to CABG. Until now, in U.S. practice patients with left main coronary disease have been preferentially referred for CABG. These results will open us up to giving selected patients a more balanced view of the two options. After we explain differences in recovery and late events patients can decide which treatment to receive.
Despite these new findings, PCI is still not for every patient. A substantial fraction of patients with left main coronary disease were excluded from these studies because they had more complex coronary anatomy, and for patients like that, CABG remains the clear standard of care.
David J. Cohen, MD, is director of cardiovascular research and an interventional cardiologist at Saint Luke’s Health System in Kansas City, Mo. He made these comments in a video interview. He had received research support from Abbott Vascular, and is an investigator in the EXCEL trial.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The results from EXCEL and NOBLE were not that different, but what was different was how the two trials were designed and how their endpoints were defined. The biggest difference between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) seemed to be in the rate of late MIs, with a little higher rate following PCI, and more repeat revascularizations with PCI, but with similar mortality rates with both treatments. There was a lot of similarity in the results despite the differences in the trials.
The evidence in both studies gives more support to the concept that, for patients with simpler left main lesions, PCI is a competitive alternative to CABG. Until now, in U.S. practice patients with left main coronary disease have been preferentially referred for CABG. These results will open us up to giving selected patients a more balanced view of the two options. After we explain differences in recovery and late events patients can decide which treatment to receive.
Despite these new findings, PCI is still not for every patient. A substantial fraction of patients with left main coronary disease were excluded from these studies because they had more complex coronary anatomy, and for patients like that, CABG remains the clear standard of care.
David J. Cohen, MD, is director of cardiovascular research and an interventional cardiologist at Saint Luke’s Health System in Kansas City, Mo. He made these comments in a video interview. He had received research support from Abbott Vascular, and is an investigator in the EXCEL trial.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The results from EXCEL and NOBLE were not that different, but what was different was how the two trials were designed and how their endpoints were defined. The biggest difference between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) seemed to be in the rate of late MIs, with a little higher rate following PCI, and more repeat revascularizations with PCI, but with similar mortality rates with both treatments. There was a lot of similarity in the results despite the differences in the trials.
The evidence in both studies gives more support to the concept that, for patients with simpler left main lesions, PCI is a competitive alternative to CABG. Until now, in U.S. practice patients with left main coronary disease have been preferentially referred for CABG. These results will open us up to giving selected patients a more balanced view of the two options. After we explain differences in recovery and late events patients can decide which treatment to receive.
Despite these new findings, PCI is still not for every patient. A substantial fraction of patients with left main coronary disease were excluded from these studies because they had more complex coronary anatomy, and for patients like that, CABG remains the clear standard of care.
David J. Cohen, MD, is director of cardiovascular research and an interventional cardiologist at Saint Luke’s Health System in Kansas City, Mo. He made these comments in a video interview. He had received research support from Abbott Vascular, and is an investigator in the EXCEL trial.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WASHINGTON – Results from two large, multicenter comparisons of coronary stenting and coronary bypass surgery for treating patients with unprotected left main coronary disease may have superficially shown sharp differences, but the bottom line will likely be greater empowerment of percutaneous coronary intervention as an option for selected patients with less complex coronary disease.
Prior to the results from the EXCEL and NOBLE trials, reported at the Transcatheter Cardiovascular Therapeutics annual meeting, “guidelines put PCI [percutaneous coronary intervention] into a class 1, 2 or 3 status for treating left main coronary disease depending on disease complexity, but in the United States, PCI for patients eligible for CABG [coronary artery bypass grafting] has not been frequently done. I think these results, in a very circumscribed subset of patients and using a state-of-the-art stent, will affect the guidelines,” predicted Gregg W. Stone, MD, lead investigator for EXCEL and professor of medicine at Columbia University in New York.
“What the guidelines have not addressed are the patients with low- or intermediate-complexity disease who have an acceptable risk for undergoing either PCI or CABG. I think the trial results answer this question,” said David Kandzari, MD, director of interventional cardiology and chief scientific officer at the Piedmont Heart Institute in Atlanta and an EXCEL investigator.
While the EXCEL and NOBLE results don’t provide a simple answer on the relative merits of PCI and CABG, many of their outcome differences seem explicable, several experts said at the meeting.
The Nordic-Baltic-British Left Main Revascularisation (NOBLE) trial randomized 1,201 patients who had unprotected left main coronary disease and were judged by a heart team to be reasonable candidates for both PCI or CABG at 36 centers in nine European countries during 2008-2015. The primary endpoint was death from any cause, nonprocedural MIs, stroke, or repeat revascularization.
The researchers followed patients for a median of just over 3 years, but they calculated the primary endpoint based on a Kaplan-Meier estimate for 5-year outcomes, which showed the primary endpoint in 29% of the PCI patients and in 19% of the CABG patients, a statistically significant benefit in favor of CABG, Evald H. Christiansen, MD, reported at the meeting, which was sponsored by the Cardiovascular Research Foundation. Concurrently with his report, the results were published online (Lancet. 2016 Oct. 31. doi: 10.1016/S0140-6736[16]32052-9).
This difference between PCI and CABG was largely driven by an excess of postprocedural MIs and repeat revascularizations among the PCI patients, said Dr. Christiansen, an interventional cardiologist at Aarhus University Hospital in Denmark. Another notable finding was that the superior outcomes with CABG primarily occurred among patients with a SYNTAX score – a measure of coronary disease complexity – of 22 or less, which identifies patients with low complexity disease. The outcomes of patients with SYNTAX scores of 23-32, which identifies intermediate complexity disease, and of patients with scores of 33 or higher, with very complex disease, were similar in the PCI and CABG arms, he reported. This finding was “very surprising,” Dr. Christiansen said, because it reversed the finding originally made in the SYNTAX trial that PCI performed best compared with CABG in patients with the lowest scores and least-complex coronary disease.
The superiority of CABG over PCI seen in the NOBLE results, especially in patients with lower SYNTAX scores, seemed at odds with the EXCEL results, reported at the meeting by Dr. Stone and simultaneously online (N Engl J Med. 2016 Oct. 31. doi: 10.1056/NEJMoa1610227). In EXCEL, which enrolled only patients with a SYNTAX score of 32 or less (low- or intermediate-complexity coronary disease), patients had a 3-year incidence of death, stroke or MI of 15% in both the PCI and CABG arms.
But the EXCEL and NOBLE trials had several important differences, and it seemed like cumulatively these differences account for their differing results.
“One of the biggest differences” was the exclusion of procedural MIs in the NOBLE tally of adverse events, noted Dr. Stone. These were diagnosed in EXCEL using the MI definition published in 2013 by a panel of the Society for Cardiovascular Angiography and Interventions (SCAI). NOBLE disregarded procedural MIs because many of its participating hospitals did not have the laboratory resources to make these diagnoses and because the trial’s design predated the SCAI definition by several years, Dr. Christiansen explained.
Other important differences included the shorter follow-up in EXCEL, the inclusion of revascularization as an endpoint component in NOBLE but not in EXCEL, and differences in the stents used. In EXCEL, all patients undergoing PCI received Xience everolimus-eluting stents. In NOBLE, the first 11% of the enrolled patients received first-generation, sirolimus-eluting Cypher stents; the next 89% of enrollees received a biolimus-eluting Biomatrix Flex stent. Dr. Christiansen acknowledged the confounding caused by having many patients in the NOBLE PCI arm who received outmoded Cypher stents, especially because their relatively longer follow-up made them overrepresented in the primary outcome results. Plus, the Biomatrix Flex stent was disparaged by Martin B. Leon, MD, an EXCEL investigator and professor of medicine at Columbia University, who called the device “not currently widely used for PCI and more of historic interest.”
Dr. Leon added that the EXCEL and NOBLE patients also had substantially different prevalence rates of diabetes and acute coronary syndrome.
“The huge difference [between EXCEL and NOBLE] is the endpoint,” declared Marc Ruel, MD, another EXCEL investigator and head of cardiac surgery at the Ottawa Heart Institute. “The EXCEL endpoint was driven by the high rate of periprocedural MIs in the CABG arm. Once you get past 30 days, the noninferiority is not met by PCI.”
Another big endpoint difference was leaving revascularizations out of the EXCEL composite. “Once you take revascularization out of the primary endpoint, the outcome [of EXCEL] was more or less preordained,” noted Craig R. Smith, MD, chairman of surgery at Columbia University and an EXCEL investigator. “It’s the slope of events [in the PCI arm] after 3 months that’s the story. I think the CABG and PCI slopes in EXCEL will continue to diverge with time” beyond the current 3-year follow-up, Dr. Smith said.
“I agree that after 30 days surgery was the more durable procedure,” said Dr. Stone. “There is a big upfront hit for patients to take with surgery compared with PCI. If patients get through that, then they have a more durable procedure. That’s the trade-off.”
Dr. Stone hinted that future reports of EXCEL data will highlight other hits that patients must endure upfront if they choose CABG over PCI. “The early difference was quite profound not only for the primary endpoint but also for renal failure, infections, arrhythmias, and blood transfusions,” he said. Choosing between PCI and CABG for patients with left main disease and a lower SYNTAX score “is a decision that should be made by the heart team and patients. Some patients will prefer surgery, and some will prefer PCI.”
The NOBLE trial received partial funding from Biosensors, the company that markets the Biomatrix Flex stent used in the trial. The EXCEL trial was sponsored by Abbott Vascular, the company that markets the Xience stent used in the trial. Dr. Stone, Dr. Kandzari, Dr. Christiansen, Dr. Ruel, and Dr. Smith had no disclosures. Dr. Leon has been a consultant to and received research support from Abbott Vascular and Boston Scientific and has also received research support from Edwards, Medtronic and St. Jude.
[email protected]
On Twitter @mitchelzoler
WASHINGTON – Results from two large, multicenter comparisons of coronary stenting and coronary bypass surgery for treating patients with unprotected left main coronary disease may have superficially shown sharp differences, but the bottom line will likely be greater empowerment of percutaneous coronary intervention as an option for selected patients with less complex coronary disease.
Prior to the results from the EXCEL and NOBLE trials, reported at the Transcatheter Cardiovascular Therapeutics annual meeting, “guidelines put PCI [percutaneous coronary intervention] into a class 1, 2 or 3 status for treating left main coronary disease depending on disease complexity, but in the United States, PCI for patients eligible for CABG [coronary artery bypass grafting] has not been frequently done. I think these results, in a very circumscribed subset of patients and using a state-of-the-art stent, will affect the guidelines,” predicted Gregg W. Stone, MD, lead investigator for EXCEL and professor of medicine at Columbia University in New York.
“What the guidelines have not addressed are the patients with low- or intermediate-complexity disease who have an acceptable risk for undergoing either PCI or CABG. I think the trial results answer this question,” said David Kandzari, MD, director of interventional cardiology and chief scientific officer at the Piedmont Heart Institute in Atlanta and an EXCEL investigator.
While the EXCEL and NOBLE results don’t provide a simple answer on the relative merits of PCI and CABG, many of their outcome differences seem explicable, several experts said at the meeting.
The Nordic-Baltic-British Left Main Revascularisation (NOBLE) trial randomized 1,201 patients who had unprotected left main coronary disease and were judged by a heart team to be reasonable candidates for both PCI or CABG at 36 centers in nine European countries during 2008-2015. The primary endpoint was death from any cause, nonprocedural MIs, stroke, or repeat revascularization.
The researchers followed patients for a median of just over 3 years, but they calculated the primary endpoint based on a Kaplan-Meier estimate for 5-year outcomes, which showed the primary endpoint in 29% of the PCI patients and in 19% of the CABG patients, a statistically significant benefit in favor of CABG, Evald H. Christiansen, MD, reported at the meeting, which was sponsored by the Cardiovascular Research Foundation. Concurrently with his report, the results were published online (Lancet. 2016 Oct. 31. doi: 10.1016/S0140-6736[16]32052-9).
This difference between PCI and CABG was largely driven by an excess of postprocedural MIs and repeat revascularizations among the PCI patients, said Dr. Christiansen, an interventional cardiologist at Aarhus University Hospital in Denmark. Another notable finding was that the superior outcomes with CABG primarily occurred among patients with a SYNTAX score – a measure of coronary disease complexity – of 22 or less, which identifies patients with low complexity disease. The outcomes of patients with SYNTAX scores of 23-32, which identifies intermediate complexity disease, and of patients with scores of 33 or higher, with very complex disease, were similar in the PCI and CABG arms, he reported. This finding was “very surprising,” Dr. Christiansen said, because it reversed the finding originally made in the SYNTAX trial that PCI performed best compared with CABG in patients with the lowest scores and least-complex coronary disease.
The superiority of CABG over PCI seen in the NOBLE results, especially in patients with lower SYNTAX scores, seemed at odds with the EXCEL results, reported at the meeting by Dr. Stone and simultaneously online (N Engl J Med. 2016 Oct. 31. doi: 10.1056/NEJMoa1610227). In EXCEL, which enrolled only patients with a SYNTAX score of 32 or less (low- or intermediate-complexity coronary disease), patients had a 3-year incidence of death, stroke or MI of 15% in both the PCI and CABG arms.
But the EXCEL and NOBLE trials had several important differences, and it seemed like cumulatively these differences account for their differing results.
“One of the biggest differences” was the exclusion of procedural MIs in the NOBLE tally of adverse events, noted Dr. Stone. These were diagnosed in EXCEL using the MI definition published in 2013 by a panel of the Society for Cardiovascular Angiography and Interventions (SCAI). NOBLE disregarded procedural MIs because many of its participating hospitals did not have the laboratory resources to make these diagnoses and because the trial’s design predated the SCAI definition by several years, Dr. Christiansen explained.
Other important differences included the shorter follow-up in EXCEL, the inclusion of revascularization as an endpoint component in NOBLE but not in EXCEL, and differences in the stents used. In EXCEL, all patients undergoing PCI received Xience everolimus-eluting stents. In NOBLE, the first 11% of the enrolled patients received first-generation, sirolimus-eluting Cypher stents; the next 89% of enrollees received a biolimus-eluting Biomatrix Flex stent. Dr. Christiansen acknowledged the confounding caused by having many patients in the NOBLE PCI arm who received outmoded Cypher stents, especially because their relatively longer follow-up made them overrepresented in the primary outcome results. Plus, the Biomatrix Flex stent was disparaged by Martin B. Leon, MD, an EXCEL investigator and professor of medicine at Columbia University, who called the device “not currently widely used for PCI and more of historic interest.”
Dr. Leon added that the EXCEL and NOBLE patients also had substantially different prevalence rates of diabetes and acute coronary syndrome.
“The huge difference [between EXCEL and NOBLE] is the endpoint,” declared Marc Ruel, MD, another EXCEL investigator and head of cardiac surgery at the Ottawa Heart Institute. “The EXCEL endpoint was driven by the high rate of periprocedural MIs in the CABG arm. Once you get past 30 days, the noninferiority is not met by PCI.”
Another big endpoint difference was leaving revascularizations out of the EXCEL composite. “Once you take revascularization out of the primary endpoint, the outcome [of EXCEL] was more or less preordained,” noted Craig R. Smith, MD, chairman of surgery at Columbia University and an EXCEL investigator. “It’s the slope of events [in the PCI arm] after 3 months that’s the story. I think the CABG and PCI slopes in EXCEL will continue to diverge with time” beyond the current 3-year follow-up, Dr. Smith said.
“I agree that after 30 days surgery was the more durable procedure,” said Dr. Stone. “There is a big upfront hit for patients to take with surgery compared with PCI. If patients get through that, then they have a more durable procedure. That’s the trade-off.”
Dr. Stone hinted that future reports of EXCEL data will highlight other hits that patients must endure upfront if they choose CABG over PCI. “The early difference was quite profound not only for the primary endpoint but also for renal failure, infections, arrhythmias, and blood transfusions,” he said. Choosing between PCI and CABG for patients with left main disease and a lower SYNTAX score “is a decision that should be made by the heart team and patients. Some patients will prefer surgery, and some will prefer PCI.”
The NOBLE trial received partial funding from Biosensors, the company that markets the Biomatrix Flex stent used in the trial. The EXCEL trial was sponsored by Abbott Vascular, the company that markets the Xience stent used in the trial. Dr. Stone, Dr. Kandzari, Dr. Christiansen, Dr. Ruel, and Dr. Smith had no disclosures. Dr. Leon has been a consultant to and received research support from Abbott Vascular and Boston Scientific and has also received research support from Edwards, Medtronic and St. Jude.
[email protected]
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM TCT 2016
ReACT: No benefit from routine coronary angiography after PCI
Routine follow-up coronary angiography after percutaneous coronary intervention leads to increased rates of coronary revascularization but without any significant benefits for outcomes, according to a study presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously on Nov. 1 in the Journal of the American College of Cardiology: Cardiovascular Interventions.
Hiroki Shiomi, MD, from Kyoto University, and his coauthors reported on ReACT, a prospective, open-label randomized controlled trial of routine follow-up coronary angiography in 700 patients who underwent successful percutaneous coronary intervention (PCI).
Among the 349 patients randomized to follow-up coronary angiography (FUCAG), 12.8% underwent any coronary revascularization within the first year after PCI, compared with 3.8% of the 351 patients randomized to standard clinical follow-up. The routine angiography group also had a higher incidence of target lesion revascularization in the first year after the index PCI (7.0% vs. 1.7%).
In both these cases, the cumulative 5-year incidence of coronary or target lesion revascularization was not significantly different between the routine angiography and control groups. However researchers saw no significant benefit from routine FUCAG in terms of the cumulative 5-year incidence of all-cause death, myocardial infarction, stroke, or emergency hospitalizations for acute coronary syndrome or heart failure, compared with clinical follow-up (22.4% vs. 24.7%; P = 0.70).
Nor were there any significant differences between the two groups in these individual components, or in the cumulative 5-year incidence of major bleeding (JACC Cardiovasc Interv. 2016 Nov 1.)
The authors commented that several previous studies have shown that routine FUCAG does not improve clinical outcomes, although it is still commonly performed in Japan after PCI.
“However, previous studies in the drug-eluting stents (DES) era were conducted in the context of pivotal randomized trials of DES and there have been no randomized clinical trials evaluating long-term clinical impact of routine FUCAG after PCI in the real world clinical practice including high-risk patients for cardiovascular events risk such as complex coronary artery disease and acute myocardial infarction (AMI) presentation,” the authors wrote.
Overall, 85.4% of patients in the routine angiography group and 12% of those in the clinical care group underwent coronary angiography in the first year, including for clinical reasons.
In the clinical follow-up group, coronary angiography was performed because of acute coronary syndrome (14%), recurrence of angina (60%), other clinical reasons (14%), or no clinical reason (12%). The control group also had more noninvasive physiological stress testing such as treadmill exercise test and stress nuclear study.
“Considering the invasive nature of coronary angiography and increased medical expenses, routine FUCAG after PCI would not be allowed as the usual clinical practice, unless patients have recurrent symptoms or objective evidence of ischemia,” the authors wrote.
“On the other hand, there was no excess of adverse clinical events with routine angiographic follow-up strategy except for the increased rate of 1-year repeat coronary revascularization.”
Given this, they suggested that scheduled angiographic follow-up might still be considered acceptable for early in vivo or significant coronary device trials.
While the authors said the trial ended up being underpowered because of a reduced final sample size and lower-than-anticipated event rate, it did warrant further larger-scale studies. In particular, they highlighted the question of what impact routine follow-up angiography might have in higher-risk patients, such as those with left main or multivessel coronary artery disease.
“Finally, because patient demographics, practice patterns including the indication of coronary revascularization, and clinical outcomes in Japan may be different from those outside Japan, generalizing the present study results to populations outside Japan should be done with caution.”
This study was supported by an educational grant from the Research Institute for Production Development (Kyoto). One author declared honoraria for education consulting from Boston Scientific Corporation.
Routine follow-up coronary angiography after percutaneous coronary intervention leads to increased rates of coronary revascularization but without any significant benefits for outcomes, according to a study presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously on Nov. 1 in the Journal of the American College of Cardiology: Cardiovascular Interventions.
Hiroki Shiomi, MD, from Kyoto University, and his coauthors reported on ReACT, a prospective, open-label randomized controlled trial of routine follow-up coronary angiography in 700 patients who underwent successful percutaneous coronary intervention (PCI).
Among the 349 patients randomized to follow-up coronary angiography (FUCAG), 12.8% underwent any coronary revascularization within the first year after PCI, compared with 3.8% of the 351 patients randomized to standard clinical follow-up. The routine angiography group also had a higher incidence of target lesion revascularization in the first year after the index PCI (7.0% vs. 1.7%).
In both these cases, the cumulative 5-year incidence of coronary or target lesion revascularization was not significantly different between the routine angiography and control groups. However researchers saw no significant benefit from routine FUCAG in terms of the cumulative 5-year incidence of all-cause death, myocardial infarction, stroke, or emergency hospitalizations for acute coronary syndrome or heart failure, compared with clinical follow-up (22.4% vs. 24.7%; P = 0.70).
Nor were there any significant differences between the two groups in these individual components, or in the cumulative 5-year incidence of major bleeding (JACC Cardiovasc Interv. 2016 Nov 1.)
The authors commented that several previous studies have shown that routine FUCAG does not improve clinical outcomes, although it is still commonly performed in Japan after PCI.
“However, previous studies in the drug-eluting stents (DES) era were conducted in the context of pivotal randomized trials of DES and there have been no randomized clinical trials evaluating long-term clinical impact of routine FUCAG after PCI in the real world clinical practice including high-risk patients for cardiovascular events risk such as complex coronary artery disease and acute myocardial infarction (AMI) presentation,” the authors wrote.
Overall, 85.4% of patients in the routine angiography group and 12% of those in the clinical care group underwent coronary angiography in the first year, including for clinical reasons.
In the clinical follow-up group, coronary angiography was performed because of acute coronary syndrome (14%), recurrence of angina (60%), other clinical reasons (14%), or no clinical reason (12%). The control group also had more noninvasive physiological stress testing such as treadmill exercise test and stress nuclear study.
“Considering the invasive nature of coronary angiography and increased medical expenses, routine FUCAG after PCI would not be allowed as the usual clinical practice, unless patients have recurrent symptoms or objective evidence of ischemia,” the authors wrote.
“On the other hand, there was no excess of adverse clinical events with routine angiographic follow-up strategy except for the increased rate of 1-year repeat coronary revascularization.”
Given this, they suggested that scheduled angiographic follow-up might still be considered acceptable for early in vivo or significant coronary device trials.
While the authors said the trial ended up being underpowered because of a reduced final sample size and lower-than-anticipated event rate, it did warrant further larger-scale studies. In particular, they highlighted the question of what impact routine follow-up angiography might have in higher-risk patients, such as those with left main or multivessel coronary artery disease.
“Finally, because patient demographics, practice patterns including the indication of coronary revascularization, and clinical outcomes in Japan may be different from those outside Japan, generalizing the present study results to populations outside Japan should be done with caution.”
This study was supported by an educational grant from the Research Institute for Production Development (Kyoto). One author declared honoraria for education consulting from Boston Scientific Corporation.
Routine follow-up coronary angiography after percutaneous coronary intervention leads to increased rates of coronary revascularization but without any significant benefits for outcomes, according to a study presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously on Nov. 1 in the Journal of the American College of Cardiology: Cardiovascular Interventions.
Hiroki Shiomi, MD, from Kyoto University, and his coauthors reported on ReACT, a prospective, open-label randomized controlled trial of routine follow-up coronary angiography in 700 patients who underwent successful percutaneous coronary intervention (PCI).
Among the 349 patients randomized to follow-up coronary angiography (FUCAG), 12.8% underwent any coronary revascularization within the first year after PCI, compared with 3.8% of the 351 patients randomized to standard clinical follow-up. The routine angiography group also had a higher incidence of target lesion revascularization in the first year after the index PCI (7.0% vs. 1.7%).
In both these cases, the cumulative 5-year incidence of coronary or target lesion revascularization was not significantly different between the routine angiography and control groups. However researchers saw no significant benefit from routine FUCAG in terms of the cumulative 5-year incidence of all-cause death, myocardial infarction, stroke, or emergency hospitalizations for acute coronary syndrome or heart failure, compared with clinical follow-up (22.4% vs. 24.7%; P = 0.70).
Nor were there any significant differences between the two groups in these individual components, or in the cumulative 5-year incidence of major bleeding (JACC Cardiovasc Interv. 2016 Nov 1.)
The authors commented that several previous studies have shown that routine FUCAG does not improve clinical outcomes, although it is still commonly performed in Japan after PCI.
“However, previous studies in the drug-eluting stents (DES) era were conducted in the context of pivotal randomized trials of DES and there have been no randomized clinical trials evaluating long-term clinical impact of routine FUCAG after PCI in the real world clinical practice including high-risk patients for cardiovascular events risk such as complex coronary artery disease and acute myocardial infarction (AMI) presentation,” the authors wrote.
Overall, 85.4% of patients in the routine angiography group and 12% of those in the clinical care group underwent coronary angiography in the first year, including for clinical reasons.
In the clinical follow-up group, coronary angiography was performed because of acute coronary syndrome (14%), recurrence of angina (60%), other clinical reasons (14%), or no clinical reason (12%). The control group also had more noninvasive physiological stress testing such as treadmill exercise test and stress nuclear study.
“Considering the invasive nature of coronary angiography and increased medical expenses, routine FUCAG after PCI would not be allowed as the usual clinical practice, unless patients have recurrent symptoms or objective evidence of ischemia,” the authors wrote.
“On the other hand, there was no excess of adverse clinical events with routine angiographic follow-up strategy except for the increased rate of 1-year repeat coronary revascularization.”
Given this, they suggested that scheduled angiographic follow-up might still be considered acceptable for early in vivo or significant coronary device trials.
While the authors said the trial ended up being underpowered because of a reduced final sample size and lower-than-anticipated event rate, it did warrant further larger-scale studies. In particular, they highlighted the question of what impact routine follow-up angiography might have in higher-risk patients, such as those with left main or multivessel coronary artery disease.
“Finally, because patient demographics, practice patterns including the indication of coronary revascularization, and clinical outcomes in Japan may be different from those outside Japan, generalizing the present study results to populations outside Japan should be done with caution.”
This study was supported by an educational grant from the Research Institute for Production Development (Kyoto). One author declared honoraria for education consulting from Boston Scientific Corporation.
Key clinical point: Routine follow-up coronary angiography after percutaneous coronary intervention increases rates of coronary revascularization but does not improve outcomes.
Major finding: Patients who underwent routine angiographic follow-up had a similar cumulative 5-year incidence of all-cause death, myocardial infarction, stroke, or emergency hospitalizations for acute coronary syndrome or heart failure as those who had standard clinical follow-up.
Data source: ReACT: a prospective, open-label randomized controlled trial in 700 patients after percutaneous coronary intervention.
Disclosures: This study was supported by an educational grant from the Research Institute for Production Development (Kyoto). One author declared honoraria for education consulting from Boston Scientific Corporation.
Results puzzling for embolic protection during TAVR
The largest randomized clinical trial to assess the safety and efficacy of cerebral embolic protection systems during transcatheter aortic valve replacement yielded puzzling and somewhat contradictory results, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology.
Virtually every device in this industry-sponsored study involving 363 elderly patients (mean age, 83.4 years) with severe aortic stenosis trapped particulate debris as intended, the mean volume of new lesions in the protected areas of the brain was reduced by 42%, and the number and volume of new lesions correlated with neurocognitive outcomes at 30 days.
However, the reduction in lesion volume did not achieve statistical significance, and the improvement in neurocognitive function also did not reach statistical significance.
In addition, “the sample size was clearly too low to assess clinical outcomes, and in retrospect, was also too low to evaluate follow-up MRI findings or neurocognitive outcomes.” Nevertheless, the trial “provides reassuring evidence of device safety,” said Samir R. Kapadia, MD, of the Cleveland Clinic (J Am Coll Cardiol. 2016 Nov 1. doi: 10.1016/j.jacc.2016.10.023).
In this prospective study, the investigators assessed patients at 17 medical centers in the United States and 2 in Germany. In addition to being elderly, the study patients were at high risk because of frequent comorbidities, including atrial fibrillation (31.7%) and prior stroke (5.8%).
The remaining 123 patients underwent TAVR but not MRI in a safety arm of the trial.
The protection devices were placed “without safety concerns” in most patients. The rate of major adverse events with the device was 7.3%, markedly less than the 18.3% prespecified performance goal for this outcome. Total procedure time was lengthened by only 13 minutes when the device was used, and total fluoroscopy time was increased by only 3 minutes. These findings demonstrate the overall safety of using the device, Dr. Kapadia said.
Debris including thrombus with tissue elements, artery wall particles, calcifications, valve tissue, and foreign materials was retrieved from the filters in 99% of patients.
The mean volume of new cerebral lesions in areas of the brain protected by the device was reduced by 42%, compared with that in patients who underwent TAVR without the protection device. However, this reduction was not statistically significant, so the primary efficacy endpoint of the study was not met.
Similarly, neurocognitive testing at 30 days showed that the volume of new lesions correlated with poorer outcomes. However, the difference in neurocognitive function between the intervention group and the control group did not reach statistical significance.
Several limitations likely contributed to this lack of statistical significance, Dr. Kapadia said.
First, the 5-day “window” for MRI assessment was too long. Both the number and the volume of new lesions rapidly changed over time, which led to marked variance in MRI findings depending on when the images were taken.
In addition, only one TAVR device was available at the time the trial was designed, so the study wasn’t stratified by type of valve device. But several new devices became available during the study, and the study investigators were permitted to use any of them. Both pre- and postimplantation techniques differ among these TAVR devices, but these differences could not be accounted for, given the study design.
Also, certain risk factors for stroke, especially certain findings on baseline MRI, were not understood when the trial was designed, and those factors also were not accounted for, Dr. Kapadia said.
Claret Medical funded the study. Dr. Kapadia reported having no relevant financial disclosures; his associates reported numerous ties to industry sources. The meeting was sponsored by the Cardiovascular Research Foundation.
From a logical standpoint, a device that collects cerebral embolic material in 99% of cases should prevent ischemic brain injury, yet the findings from this randomized trial don’t appear to support the routine use of such devices. But it would be inappropriate and unfair to close the book on cerebral protection after this chapter.
The authors acknowledge that an MRI “window” of 5 days creates too much heterogeneity in the data, that multiple TAVR devices requiring different implantation techniques further muddy the picture, and that in retrospect the sample size was inadequate and the study was underpowered. In addition, rigorous neurocognitive assessment can be challenging in elderly, recovering patients, and results can depend on the time of day and the patient’s alertness.
Despite the negative findings regarding both primary and secondary endpoints, the data do show the overall safety of embolic protection devices. We are dealing with a potential benefit that cannot be ignored as TAVR shifts to younger and lower-risk patients.
Azeem Latib, MD, is in the interventional cardiology unit at San Raffaele Scientific Institute in Milan. Matteo Pagnesi, MD, is in the interventional cardiology unit at EMO-GVM Centro Cuore Columbus in Milan. San Raffaele Scientific Institute has been involved in clinical studies of embolic protection devices made by Claret Medical, Innovative Cardiovascular Solutions, and Keystone Heart. Dr. Latib and Dr. Pagnesi reported having no other relevant financial disclosures. They made these remarks in an editorial accompanying Dr. Kapadia’s report (J Am Coll Cardiol. 2016 Nov 1. doi: 10.1016/j.jacc.2016.10.036).
From a logical standpoint, a device that collects cerebral embolic material in 99% of cases should prevent ischemic brain injury, yet the findings from this randomized trial don’t appear to support the routine use of such devices. But it would be inappropriate and unfair to close the book on cerebral protection after this chapter.
The authors acknowledge that an MRI “window” of 5 days creates too much heterogeneity in the data, that multiple TAVR devices requiring different implantation techniques further muddy the picture, and that in retrospect the sample size was inadequate and the study was underpowered. In addition, rigorous neurocognitive assessment can be challenging in elderly, recovering patients, and results can depend on the time of day and the patient’s alertness.
Despite the negative findings regarding both primary and secondary endpoints, the data do show the overall safety of embolic protection devices. We are dealing with a potential benefit that cannot be ignored as TAVR shifts to younger and lower-risk patients.
Azeem Latib, MD, is in the interventional cardiology unit at San Raffaele Scientific Institute in Milan. Matteo Pagnesi, MD, is in the interventional cardiology unit at EMO-GVM Centro Cuore Columbus in Milan. San Raffaele Scientific Institute has been involved in clinical studies of embolic protection devices made by Claret Medical, Innovative Cardiovascular Solutions, and Keystone Heart. Dr. Latib and Dr. Pagnesi reported having no other relevant financial disclosures. They made these remarks in an editorial accompanying Dr. Kapadia’s report (J Am Coll Cardiol. 2016 Nov 1. doi: 10.1016/j.jacc.2016.10.036).
From a logical standpoint, a device that collects cerebral embolic material in 99% of cases should prevent ischemic brain injury, yet the findings from this randomized trial don’t appear to support the routine use of such devices. But it would be inappropriate and unfair to close the book on cerebral protection after this chapter.
The authors acknowledge that an MRI “window” of 5 days creates too much heterogeneity in the data, that multiple TAVR devices requiring different implantation techniques further muddy the picture, and that in retrospect the sample size was inadequate and the study was underpowered. In addition, rigorous neurocognitive assessment can be challenging in elderly, recovering patients, and results can depend on the time of day and the patient’s alertness.
Despite the negative findings regarding both primary and secondary endpoints, the data do show the overall safety of embolic protection devices. We are dealing with a potential benefit that cannot be ignored as TAVR shifts to younger and lower-risk patients.
Azeem Latib, MD, is in the interventional cardiology unit at San Raffaele Scientific Institute in Milan. Matteo Pagnesi, MD, is in the interventional cardiology unit at EMO-GVM Centro Cuore Columbus in Milan. San Raffaele Scientific Institute has been involved in clinical studies of embolic protection devices made by Claret Medical, Innovative Cardiovascular Solutions, and Keystone Heart. Dr. Latib and Dr. Pagnesi reported having no other relevant financial disclosures. They made these remarks in an editorial accompanying Dr. Kapadia’s report (J Am Coll Cardiol. 2016 Nov 1. doi: 10.1016/j.jacc.2016.10.036).
The largest randomized clinical trial to assess the safety and efficacy of cerebral embolic protection systems during transcatheter aortic valve replacement yielded puzzling and somewhat contradictory results, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology.
Virtually every device in this industry-sponsored study involving 363 elderly patients (mean age, 83.4 years) with severe aortic stenosis trapped particulate debris as intended, the mean volume of new lesions in the protected areas of the brain was reduced by 42%, and the number and volume of new lesions correlated with neurocognitive outcomes at 30 days.
However, the reduction in lesion volume did not achieve statistical significance, and the improvement in neurocognitive function also did not reach statistical significance.
In addition, “the sample size was clearly too low to assess clinical outcomes, and in retrospect, was also too low to evaluate follow-up MRI findings or neurocognitive outcomes.” Nevertheless, the trial “provides reassuring evidence of device safety,” said Samir R. Kapadia, MD, of the Cleveland Clinic (J Am Coll Cardiol. 2016 Nov 1. doi: 10.1016/j.jacc.2016.10.023).
In this prospective study, the investigators assessed patients at 17 medical centers in the United States and 2 in Germany. In addition to being elderly, the study patients were at high risk because of frequent comorbidities, including atrial fibrillation (31.7%) and prior stroke (5.8%).
The remaining 123 patients underwent TAVR but not MRI in a safety arm of the trial.
The protection devices were placed “without safety concerns” in most patients. The rate of major adverse events with the device was 7.3%, markedly less than the 18.3% prespecified performance goal for this outcome. Total procedure time was lengthened by only 13 minutes when the device was used, and total fluoroscopy time was increased by only 3 minutes. These findings demonstrate the overall safety of using the device, Dr. Kapadia said.
Debris including thrombus with tissue elements, artery wall particles, calcifications, valve tissue, and foreign materials was retrieved from the filters in 99% of patients.
The mean volume of new cerebral lesions in areas of the brain protected by the device was reduced by 42%, compared with that in patients who underwent TAVR without the protection device. However, this reduction was not statistically significant, so the primary efficacy endpoint of the study was not met.
Similarly, neurocognitive testing at 30 days showed that the volume of new lesions correlated with poorer outcomes. However, the difference in neurocognitive function between the intervention group and the control group did not reach statistical significance.
Several limitations likely contributed to this lack of statistical significance, Dr. Kapadia said.
First, the 5-day “window” for MRI assessment was too long. Both the number and the volume of new lesions rapidly changed over time, which led to marked variance in MRI findings depending on when the images were taken.
In addition, only one TAVR device was available at the time the trial was designed, so the study wasn’t stratified by type of valve device. But several new devices became available during the study, and the study investigators were permitted to use any of them. Both pre- and postimplantation techniques differ among these TAVR devices, but these differences could not be accounted for, given the study design.
Also, certain risk factors for stroke, especially certain findings on baseline MRI, were not understood when the trial was designed, and those factors also were not accounted for, Dr. Kapadia said.
Claret Medical funded the study. Dr. Kapadia reported having no relevant financial disclosures; his associates reported numerous ties to industry sources. The meeting was sponsored by the Cardiovascular Research Foundation.
The largest randomized clinical trial to assess the safety and efficacy of cerebral embolic protection systems during transcatheter aortic valve replacement yielded puzzling and somewhat contradictory results, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology.
Virtually every device in this industry-sponsored study involving 363 elderly patients (mean age, 83.4 years) with severe aortic stenosis trapped particulate debris as intended, the mean volume of new lesions in the protected areas of the brain was reduced by 42%, and the number and volume of new lesions correlated with neurocognitive outcomes at 30 days.
However, the reduction in lesion volume did not achieve statistical significance, and the improvement in neurocognitive function also did not reach statistical significance.
In addition, “the sample size was clearly too low to assess clinical outcomes, and in retrospect, was also too low to evaluate follow-up MRI findings or neurocognitive outcomes.” Nevertheless, the trial “provides reassuring evidence of device safety,” said Samir R. Kapadia, MD, of the Cleveland Clinic (J Am Coll Cardiol. 2016 Nov 1. doi: 10.1016/j.jacc.2016.10.023).
In this prospective study, the investigators assessed patients at 17 medical centers in the United States and 2 in Germany. In addition to being elderly, the study patients were at high risk because of frequent comorbidities, including atrial fibrillation (31.7%) and prior stroke (5.8%).
The remaining 123 patients underwent TAVR but not MRI in a safety arm of the trial.
The protection devices were placed “without safety concerns” in most patients. The rate of major adverse events with the device was 7.3%, markedly less than the 18.3% prespecified performance goal for this outcome. Total procedure time was lengthened by only 13 minutes when the device was used, and total fluoroscopy time was increased by only 3 minutes. These findings demonstrate the overall safety of using the device, Dr. Kapadia said.
Debris including thrombus with tissue elements, artery wall particles, calcifications, valve tissue, and foreign materials was retrieved from the filters in 99% of patients.
The mean volume of new cerebral lesions in areas of the brain protected by the device was reduced by 42%, compared with that in patients who underwent TAVR without the protection device. However, this reduction was not statistically significant, so the primary efficacy endpoint of the study was not met.
Similarly, neurocognitive testing at 30 days showed that the volume of new lesions correlated with poorer outcomes. However, the difference in neurocognitive function between the intervention group and the control group did not reach statistical significance.
Several limitations likely contributed to this lack of statistical significance, Dr. Kapadia said.
First, the 5-day “window” for MRI assessment was too long. Both the number and the volume of new lesions rapidly changed over time, which led to marked variance in MRI findings depending on when the images were taken.
In addition, only one TAVR device was available at the time the trial was designed, so the study wasn’t stratified by type of valve device. But several new devices became available during the study, and the study investigators were permitted to use any of them. Both pre- and postimplantation techniques differ among these TAVR devices, but these differences could not be accounted for, given the study design.
Also, certain risk factors for stroke, especially certain findings on baseline MRI, were not understood when the trial was designed, and those factors also were not accounted for, Dr. Kapadia said.
Claret Medical funded the study. Dr. Kapadia reported having no relevant financial disclosures; his associates reported numerous ties to industry sources. The meeting was sponsored by the Cardiovascular Research Foundation.
Key clinical point: The largest randomized clinical trial to assess the safety and efficacy of cerebral embolic protection systems during TAVR yielded puzzling and contradictory results.
Major finding: Debris including thrombus with tissue elements, artery wall particles, calcifications, valve tissue, and foreign materials was retrieved from the cerebral protection filters in 99% of patients.
Data source: A prospective, international, randomized trial involving 363 elderly patients undergoing TAVR for severe aortic stenosis.
Disclosures: Claret Medical funded the study. Dr. Kapadia reported having no relevant financial disclosures; his associates reported numerous ties to industry sources.
ECMO patients need less sedation, pain meds than previously reported
Patients on extracorporeal membrane oxygenation (ECMO) received relatively low doses of sedatives and analgesics while at a light level of sedation in a single-center prospective study of 32 patients.
In addition, patients rarely required neuromuscular blockade, investigators reported online in the Journal of Critical Care.
This finding contrasts with current guidelines on the management of pain, agitation, and delirium in patients on ECMO. The guidelines are based upon previous research that indicated the need for significant increases in sedative and analgesic doses, as well as the need for neuromuscular blockade, wrote Jeremy R. DeGrado, PharmD, of the department of pharmacy at Brigham and Women’s Hospital, Boston, and his colleagues (J Crit Care. 2016 Aug 10;37:1-6. doi: 10.1016/j.jcrc.2016.07.020).
“Patients required significantly lower doses of opioids and sedatives than previously reported in the literature and did not demonstrate a need for increasing doses throughout the study period,” the investigators said. “Continuous infusions of opioids were utilized on most ECMO days, but continuous infusions of benzodiazepines were used on less than half of all ECMO days.”
Their 2-year, prospective, observational study assessed 32 adult intensive care unit patients on ECMO support for more than 48 hours. A total of 15 patients received VA (venoarterial) ECMO and 17 received VV (venovenous) ECMO. Patients received a median daily dose of benzodiazepines (midazolam equivalents) of 24 mg and a median daily dose of opioids (fentanyl equivalents) of 3,875 mcg.
The primary indication for VA ECMO was cardiogenic shock, while VV ECMO was mainly used as a bridge to lung transplant or in patients with severe acute respiratory distress syndrome. The researchers evaluated a total of 475 ECMO days: 110 VA ECMO and 365 VV ECMO.
On average, patients were sedated to Richmond Agitation Sedation Scale scores between 0 and −1. Across all 475 ECMO days, patients were treated with continuous infusions of opioids (on 85% of ECMO days), benzodiazepines (42%), propofol (20%), dexmedetomidine (7%), and neuromuscular blocking agents (13%).
In total, patients who received VV ECMO had a higher median dose of opioids and trended toward a lower dose of benzodiazepines than those who received VA ECMO, Dr. DeGrado and his associates reported.
In total, patients in the VA arm, compared with those in the VV arm, more frequently received a continuous infusion opioid (96% vs. 82% of days) and a benzodiazepine (58% vs. 37% of days). These differences were statistically significant.
Adjunctive therapies, including antipsychotics and clonidine, were administered frequently, according to the report.
“We did not observe an increase in dose requirement over time during ECMO support, possibly due to a multi-modal pharmacologic approach. Overall, patients were not deeply sedated and rarely required neuromuscular blockade. The hypothesis that patients on ECMO require high doses of sedatives and analgesics should be further investigated,” the researchers concluded.
The authors reported that they had no disclosures.
Patients on extracorporeal membrane oxygenation (ECMO) received relatively low doses of sedatives and analgesics while at a light level of sedation in a single-center prospective study of 32 patients.
In addition, patients rarely required neuromuscular blockade, investigators reported online in the Journal of Critical Care.
This finding contrasts with current guidelines on the management of pain, agitation, and delirium in patients on ECMO. The guidelines are based upon previous research that indicated the need for significant increases in sedative and analgesic doses, as well as the need for neuromuscular blockade, wrote Jeremy R. DeGrado, PharmD, of the department of pharmacy at Brigham and Women’s Hospital, Boston, and his colleagues (J Crit Care. 2016 Aug 10;37:1-6. doi: 10.1016/j.jcrc.2016.07.020).
“Patients required significantly lower doses of opioids and sedatives than previously reported in the literature and did not demonstrate a need for increasing doses throughout the study period,” the investigators said. “Continuous infusions of opioids were utilized on most ECMO days, but continuous infusions of benzodiazepines were used on less than half of all ECMO days.”
Their 2-year, prospective, observational study assessed 32 adult intensive care unit patients on ECMO support for more than 48 hours. A total of 15 patients received VA (venoarterial) ECMO and 17 received VV (venovenous) ECMO. Patients received a median daily dose of benzodiazepines (midazolam equivalents) of 24 mg and a median daily dose of opioids (fentanyl equivalents) of 3,875 mcg.
The primary indication for VA ECMO was cardiogenic shock, while VV ECMO was mainly used as a bridge to lung transplant or in patients with severe acute respiratory distress syndrome. The researchers evaluated a total of 475 ECMO days: 110 VA ECMO and 365 VV ECMO.
On average, patients were sedated to Richmond Agitation Sedation Scale scores between 0 and −1. Across all 475 ECMO days, patients were treated with continuous infusions of opioids (on 85% of ECMO days), benzodiazepines (42%), propofol (20%), dexmedetomidine (7%), and neuromuscular blocking agents (13%).
In total, patients who received VV ECMO had a higher median dose of opioids and trended toward a lower dose of benzodiazepines than those who received VA ECMO, Dr. DeGrado and his associates reported.
In total, patients in the VA arm, compared with those in the VV arm, more frequently received a continuous infusion opioid (96% vs. 82% of days) and a benzodiazepine (58% vs. 37% of days). These differences were statistically significant.
Adjunctive therapies, including antipsychotics and clonidine, were administered frequently, according to the report.
“We did not observe an increase in dose requirement over time during ECMO support, possibly due to a multi-modal pharmacologic approach. Overall, patients were not deeply sedated and rarely required neuromuscular blockade. The hypothesis that patients on ECMO require high doses of sedatives and analgesics should be further investigated,” the researchers concluded.
The authors reported that they had no disclosures.
Patients on extracorporeal membrane oxygenation (ECMO) received relatively low doses of sedatives and analgesics while at a light level of sedation in a single-center prospective study of 32 patients.
In addition, patients rarely required neuromuscular blockade, investigators reported online in the Journal of Critical Care.
This finding contrasts with current guidelines on the management of pain, agitation, and delirium in patients on ECMO. The guidelines are based upon previous research that indicated the need for significant increases in sedative and analgesic doses, as well as the need for neuromuscular blockade, wrote Jeremy R. DeGrado, PharmD, of the department of pharmacy at Brigham and Women’s Hospital, Boston, and his colleagues (J Crit Care. 2016 Aug 10;37:1-6. doi: 10.1016/j.jcrc.2016.07.020).
“Patients required significantly lower doses of opioids and sedatives than previously reported in the literature and did not demonstrate a need for increasing doses throughout the study period,” the investigators said. “Continuous infusions of opioids were utilized on most ECMO days, but continuous infusions of benzodiazepines were used on less than half of all ECMO days.”
Their 2-year, prospective, observational study assessed 32 adult intensive care unit patients on ECMO support for more than 48 hours. A total of 15 patients received VA (venoarterial) ECMO and 17 received VV (venovenous) ECMO. Patients received a median daily dose of benzodiazepines (midazolam equivalents) of 24 mg and a median daily dose of opioids (fentanyl equivalents) of 3,875 mcg.
The primary indication for VA ECMO was cardiogenic shock, while VV ECMO was mainly used as a bridge to lung transplant or in patients with severe acute respiratory distress syndrome. The researchers evaluated a total of 475 ECMO days: 110 VA ECMO and 365 VV ECMO.
On average, patients were sedated to Richmond Agitation Sedation Scale scores between 0 and −1. Across all 475 ECMO days, patients were treated with continuous infusions of opioids (on 85% of ECMO days), benzodiazepines (42%), propofol (20%), dexmedetomidine (7%), and neuromuscular blocking agents (13%).
In total, patients who received VV ECMO had a higher median dose of opioids and trended toward a lower dose of benzodiazepines than those who received VA ECMO, Dr. DeGrado and his associates reported.
In total, patients in the VA arm, compared with those in the VV arm, more frequently received a continuous infusion opioid (96% vs. 82% of days) and a benzodiazepine (58% vs. 37% of days). These differences were statistically significant.
Adjunctive therapies, including antipsychotics and clonidine, were administered frequently, according to the report.
“We did not observe an increase in dose requirement over time during ECMO support, possibly due to a multi-modal pharmacologic approach. Overall, patients were not deeply sedated and rarely required neuromuscular blockade. The hypothesis that patients on ECMO require high doses of sedatives and analgesics should be further investigated,” the researchers concluded.
The authors reported that they had no disclosures.
FROM JOURNAL OF CRITICAL CARE
Key clinical point:
Major finding: Patients required lower doses of opioids and sedatives than previously reported and did not need increasing doses.
Data source: A single-institution, prospective study of 32 patients on extracorporeal membrane oxygenation.
Disclosures: Dr. DeGrado reported having no financial disclosures.
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.
Mediterranean diet for secondary prevention cuts all-cause mortality
ROME – Adherence to the traditional Mediterranean diet by patients with known heart or cerebrovascular disease was independently linked with a marked reduction in their risk of all-cause mortality in the Italian Moli-Sani Study, Giovanni de Gaetano, MD, reported at the annual congress of the European Society of Cardiology.
Subjects in the top tertile in terms of food intake consistent with the Mediterranean diet were 37% less likely to die during more than 7 years of follow-up than were those in the bottom tertile, according to Dr. de Gaetano, head of the department of epidemiology and prevention at the IRCCS Mediterranean Neurologic Institute in Pozzilli, Italy.
The Moli-Sani Study is an ongoing population-based epidemiologic study of 25,000 adults in the mountainous, heavily agricultural Molise region of southern Italy. Dr. de Gaetano, who directs the study, presented a substudy involving 1,197 participants with established coronary heart disease or cerebrovascular disease at entry. Their average age at enrollment was 66 years. Subjects with coronary heart disease outnumbered those with cerebrovascular disease by roughly 2:1.
Food intake was recorded using the European Prospective Investigation into Cancer (EPIC) food-frequency questionnaire. Dr. de Gaetano and his coinvestigators assessed adherence to the traditional Mediterranean diet using the Mediterranean Diet Score (MDS), a validated 0-9 scoring system developed as part of the famous Seven Countries Study pioneered by the late Ancel Keys.
During a median 7.3 years of prospective follow-up, 208 deaths occurred in the study population. A 2-point increase in the MDS was independently associated with a 21% reduction in the risk of mortality in a multivariate Cox proportional hazards analysis adjusted for “everything we could think of,” according to Dr. de Gaetano, including baseline demographics, socioeconomic status, energy intake, body mass index, leisure time physical activity, waist-to-hip ratio, smoking status, diabetes, standard cardiovascular risk factors, and use of cardiovascular medications.
Subjects in the top tertile for adherence to the Mediterranean diet, with an MDS of 6-9, had an adjusted 37% relative risk reduction in all-cause mortality, compared with those having an MDS of 0-3.
The number of deaths is too small at this point in the prospective study to permit analysis of specific causes of death in a statistically valid manner. With another 3 years or so of follow-up, that analysis can and will be done, Dr. de Gaetano said.
The traditional Mediterranean diet is an eating pattern characteristic of the Mediterranean basin, he explained. It encourages large intake of vegetables, legumes, fruits, nuts, and cereals, along with moderately high consumption of fish, olive oil as the primary fat source, and moderate alcohol intake during meals, but low-to-moderate intake of dairy products and low consumption of meat and poultry.
As a sobering aside, he said that in the Molise region, far and away the biggest obstacle to adherence to the Mediterranean diet is economic.
“There was no difference in adherence to the Mediterranean diet between different socioeconomic classes in the Moli-Sani Study until 2007-2008, when the Italian economic crisis began. Since then there are significant differences according to socioeconomic condition. Poor people are obliged to follow the Mediterranean diet less,” Dr. de Gaetano said.
Telling a patient with cardiovascular disease who is in a low-income family of four to eat fish at least twice per week is impractical advice, he explained.
The ongoing Moli-Sani Study is funded by the Italian government. Dr. de Gaetano reported having no financial conflicts of interest.
ROME – Adherence to the traditional Mediterranean diet by patients with known heart or cerebrovascular disease was independently linked with a marked reduction in their risk of all-cause mortality in the Italian Moli-Sani Study, Giovanni de Gaetano, MD, reported at the annual congress of the European Society of Cardiology.
Subjects in the top tertile in terms of food intake consistent with the Mediterranean diet were 37% less likely to die during more than 7 years of follow-up than were those in the bottom tertile, according to Dr. de Gaetano, head of the department of epidemiology and prevention at the IRCCS Mediterranean Neurologic Institute in Pozzilli, Italy.
The Moli-Sani Study is an ongoing population-based epidemiologic study of 25,000 adults in the mountainous, heavily agricultural Molise region of southern Italy. Dr. de Gaetano, who directs the study, presented a substudy involving 1,197 participants with established coronary heart disease or cerebrovascular disease at entry. Their average age at enrollment was 66 years. Subjects with coronary heart disease outnumbered those with cerebrovascular disease by roughly 2:1.
Food intake was recorded using the European Prospective Investigation into Cancer (EPIC) food-frequency questionnaire. Dr. de Gaetano and his coinvestigators assessed adherence to the traditional Mediterranean diet using the Mediterranean Diet Score (MDS), a validated 0-9 scoring system developed as part of the famous Seven Countries Study pioneered by the late Ancel Keys.
During a median 7.3 years of prospective follow-up, 208 deaths occurred in the study population. A 2-point increase in the MDS was independently associated with a 21% reduction in the risk of mortality in a multivariate Cox proportional hazards analysis adjusted for “everything we could think of,” according to Dr. de Gaetano, including baseline demographics, socioeconomic status, energy intake, body mass index, leisure time physical activity, waist-to-hip ratio, smoking status, diabetes, standard cardiovascular risk factors, and use of cardiovascular medications.
Subjects in the top tertile for adherence to the Mediterranean diet, with an MDS of 6-9, had an adjusted 37% relative risk reduction in all-cause mortality, compared with those having an MDS of 0-3.
The number of deaths is too small at this point in the prospective study to permit analysis of specific causes of death in a statistically valid manner. With another 3 years or so of follow-up, that analysis can and will be done, Dr. de Gaetano said.
The traditional Mediterranean diet is an eating pattern characteristic of the Mediterranean basin, he explained. It encourages large intake of vegetables, legumes, fruits, nuts, and cereals, along with moderately high consumption of fish, olive oil as the primary fat source, and moderate alcohol intake during meals, but low-to-moderate intake of dairy products and low consumption of meat and poultry.
As a sobering aside, he said that in the Molise region, far and away the biggest obstacle to adherence to the Mediterranean diet is economic.
“There was no difference in adherence to the Mediterranean diet between different socioeconomic classes in the Moli-Sani Study until 2007-2008, when the Italian economic crisis began. Since then there are significant differences according to socioeconomic condition. Poor people are obliged to follow the Mediterranean diet less,” Dr. de Gaetano said.
Telling a patient with cardiovascular disease who is in a low-income family of four to eat fish at least twice per week is impractical advice, he explained.
The ongoing Moli-Sani Study is funded by the Italian government. Dr. de Gaetano reported having no financial conflicts of interest.
ROME – Adherence to the traditional Mediterranean diet by patients with known heart or cerebrovascular disease was independently linked with a marked reduction in their risk of all-cause mortality in the Italian Moli-Sani Study, Giovanni de Gaetano, MD, reported at the annual congress of the European Society of Cardiology.
Subjects in the top tertile in terms of food intake consistent with the Mediterranean diet were 37% less likely to die during more than 7 years of follow-up than were those in the bottom tertile, according to Dr. de Gaetano, head of the department of epidemiology and prevention at the IRCCS Mediterranean Neurologic Institute in Pozzilli, Italy.
The Moli-Sani Study is an ongoing population-based epidemiologic study of 25,000 adults in the mountainous, heavily agricultural Molise region of southern Italy. Dr. de Gaetano, who directs the study, presented a substudy involving 1,197 participants with established coronary heart disease or cerebrovascular disease at entry. Their average age at enrollment was 66 years. Subjects with coronary heart disease outnumbered those with cerebrovascular disease by roughly 2:1.
Food intake was recorded using the European Prospective Investigation into Cancer (EPIC) food-frequency questionnaire. Dr. de Gaetano and his coinvestigators assessed adherence to the traditional Mediterranean diet using the Mediterranean Diet Score (MDS), a validated 0-9 scoring system developed as part of the famous Seven Countries Study pioneered by the late Ancel Keys.
During a median 7.3 years of prospective follow-up, 208 deaths occurred in the study population. A 2-point increase in the MDS was independently associated with a 21% reduction in the risk of mortality in a multivariate Cox proportional hazards analysis adjusted for “everything we could think of,” according to Dr. de Gaetano, including baseline demographics, socioeconomic status, energy intake, body mass index, leisure time physical activity, waist-to-hip ratio, smoking status, diabetes, standard cardiovascular risk factors, and use of cardiovascular medications.
Subjects in the top tertile for adherence to the Mediterranean diet, with an MDS of 6-9, had an adjusted 37% relative risk reduction in all-cause mortality, compared with those having an MDS of 0-3.
The number of deaths is too small at this point in the prospective study to permit analysis of specific causes of death in a statistically valid manner. With another 3 years or so of follow-up, that analysis can and will be done, Dr. de Gaetano said.
The traditional Mediterranean diet is an eating pattern characteristic of the Mediterranean basin, he explained. It encourages large intake of vegetables, legumes, fruits, nuts, and cereals, along with moderately high consumption of fish, olive oil as the primary fat source, and moderate alcohol intake during meals, but low-to-moderate intake of dairy products and low consumption of meat and poultry.
As a sobering aside, he said that in the Molise region, far and away the biggest obstacle to adherence to the Mediterranean diet is economic.
“There was no difference in adherence to the Mediterranean diet between different socioeconomic classes in the Moli-Sani Study until 2007-2008, when the Italian economic crisis began. Since then there are significant differences according to socioeconomic condition. Poor people are obliged to follow the Mediterranean diet less,” Dr. de Gaetano said.
Telling a patient with cardiovascular disease who is in a low-income family of four to eat fish at least twice per week is impractical advice, he explained.
The ongoing Moli-Sani Study is funded by the Italian government. Dr. de Gaetano reported having no financial conflicts of interest.
Key clinical point:
Major finding: Italian patients with known cardiovascular disease who were in the top third in terms of adherence to the traditional Mediterranean diet were a fully adjusted 37% less likely to die of any cause during follow-up than those in the bottom tertile.
Data source: This substudy of the prospective, observational Italian Moli-Sani Study included 1,197 participants with coronary heart disease or cerebrovascular disease at baseline who were followed for a median of 7.3 years.
Disclosures: The ongoing Moli-Sani Study is funded by the Italian government. The presenter reported having no financial conflicts of interest.
MIs in pregnancy have worse prognosis
ROME – It’s fortunate that pregnancy-associated acute MIs are infrequent, because the associated in-hospital mortality is markedly higher than in similar-age nonchildbearing women, Reza Masoomi, MD, said at the annual congress of the European Society of Cardiology.
One likely contributor to the disparity in outcome is that current management appears to feature underutilization of percutaneous intervention in women who experience pregnancy-associated MI, according to Dr. Masoomi of the University of Kansas in Kansas City.
He presented an analysis of the U.S. National Inpatient Sample database for the years 2008-2012. The NIS is a nationally representative sample of hospitalizations drawn from all of the country’s nonfederal acute-care hospitals.
A total of 55,315 hospitalizations with a discharge diagnosis of acute MI were recorded in women aged 15-54 years during the study years, of which 453 involved an ante- or postpartum MI. Extrapolating from those figures, nearly 262,000 women aged 15-54 years across the U.S. had an acute MI during the study years, of whom an estimated 2,153 experienced a pregnancy-associated MI.
In-hospital mortality among women with peripregnancy MI was 7.2%, significantly higher than the 5.2% rate in women who weren’t pregnant.
Women with peripregnancy MI had a significantly higher rate of ST-elevation MI (STEMI) than did nonpregnant women with MI in their reproductive years, by a margin of 35.3% to 32.8%. They were younger, too: an average age of 34.9 years, compared with 47.3 years in nonpregnant patients with an MI. Nearly two-thirds of women with peripregnancy MI were nonwhite, compared with 47.3% of the comparison group.
Regardless of whether women with peripregnancy MI had a STEMI or non-STEMI, they had significantly lower rates of diagnostic coronary angiography and percutaneous intervention. They were also far less likely to receive drug-eluting stents.
Diagnostic coronary angiography was performed in 59% of women with pregnancy-associated STEMI, compared with 73% of nonpregnant women with a STEMI. Only 34% of patients with peripregnancy STEMI underwent PCI, compared with 61% of nonpregnant women with a STEMI. Drug-eluting stents were implanted in 12% of peripregnancy STEMI patients and in 35% of nonpregnant patients. In contrast, 10% of patients with a pregnancy-related STEMI underwent coronary artery bypass surgery, compared with 5% of nonpregnant women with a STEMI.
The PCI rate among women with a peripregnancy non-STEMI was 7.8%, compared with 28.7% in nonpregnant women with a non-STEMI. However, CABG was utilized less frequently in the peripregnancy non-STEMI group, by a margin of 4.4% to 5.9%.
Dr. Masoomi reported having no financial conflicts regarding his study.
ROME – It’s fortunate that pregnancy-associated acute MIs are infrequent, because the associated in-hospital mortality is markedly higher than in similar-age nonchildbearing women, Reza Masoomi, MD, said at the annual congress of the European Society of Cardiology.
One likely contributor to the disparity in outcome is that current management appears to feature underutilization of percutaneous intervention in women who experience pregnancy-associated MI, according to Dr. Masoomi of the University of Kansas in Kansas City.
He presented an analysis of the U.S. National Inpatient Sample database for the years 2008-2012. The NIS is a nationally representative sample of hospitalizations drawn from all of the country’s nonfederal acute-care hospitals.
A total of 55,315 hospitalizations with a discharge diagnosis of acute MI were recorded in women aged 15-54 years during the study years, of which 453 involved an ante- or postpartum MI. Extrapolating from those figures, nearly 262,000 women aged 15-54 years across the U.S. had an acute MI during the study years, of whom an estimated 2,153 experienced a pregnancy-associated MI.
In-hospital mortality among women with peripregnancy MI was 7.2%, significantly higher than the 5.2% rate in women who weren’t pregnant.
Women with peripregnancy MI had a significantly higher rate of ST-elevation MI (STEMI) than did nonpregnant women with MI in their reproductive years, by a margin of 35.3% to 32.8%. They were younger, too: an average age of 34.9 years, compared with 47.3 years in nonpregnant patients with an MI. Nearly two-thirds of women with peripregnancy MI were nonwhite, compared with 47.3% of the comparison group.
Regardless of whether women with peripregnancy MI had a STEMI or non-STEMI, they had significantly lower rates of diagnostic coronary angiography and percutaneous intervention. They were also far less likely to receive drug-eluting stents.
Diagnostic coronary angiography was performed in 59% of women with pregnancy-associated STEMI, compared with 73% of nonpregnant women with a STEMI. Only 34% of patients with peripregnancy STEMI underwent PCI, compared with 61% of nonpregnant women with a STEMI. Drug-eluting stents were implanted in 12% of peripregnancy STEMI patients and in 35% of nonpregnant patients. In contrast, 10% of patients with a pregnancy-related STEMI underwent coronary artery bypass surgery, compared with 5% of nonpregnant women with a STEMI.
The PCI rate among women with a peripregnancy non-STEMI was 7.8%, compared with 28.7% in nonpregnant women with a non-STEMI. However, CABG was utilized less frequently in the peripregnancy non-STEMI group, by a margin of 4.4% to 5.9%.
Dr. Masoomi reported having no financial conflicts regarding his study.
ROME – It’s fortunate that pregnancy-associated acute MIs are infrequent, because the associated in-hospital mortality is markedly higher than in similar-age nonchildbearing women, Reza Masoomi, MD, said at the annual congress of the European Society of Cardiology.
One likely contributor to the disparity in outcome is that current management appears to feature underutilization of percutaneous intervention in women who experience pregnancy-associated MI, according to Dr. Masoomi of the University of Kansas in Kansas City.
He presented an analysis of the U.S. National Inpatient Sample database for the years 2008-2012. The NIS is a nationally representative sample of hospitalizations drawn from all of the country’s nonfederal acute-care hospitals.
A total of 55,315 hospitalizations with a discharge diagnosis of acute MI were recorded in women aged 15-54 years during the study years, of which 453 involved an ante- or postpartum MI. Extrapolating from those figures, nearly 262,000 women aged 15-54 years across the U.S. had an acute MI during the study years, of whom an estimated 2,153 experienced a pregnancy-associated MI.
In-hospital mortality among women with peripregnancy MI was 7.2%, significantly higher than the 5.2% rate in women who weren’t pregnant.
Women with peripregnancy MI had a significantly higher rate of ST-elevation MI (STEMI) than did nonpregnant women with MI in their reproductive years, by a margin of 35.3% to 32.8%. They were younger, too: an average age of 34.9 years, compared with 47.3 years in nonpregnant patients with an MI. Nearly two-thirds of women with peripregnancy MI were nonwhite, compared with 47.3% of the comparison group.
Regardless of whether women with peripregnancy MI had a STEMI or non-STEMI, they had significantly lower rates of diagnostic coronary angiography and percutaneous intervention. They were also far less likely to receive drug-eluting stents.
Diagnostic coronary angiography was performed in 59% of women with pregnancy-associated STEMI, compared with 73% of nonpregnant women with a STEMI. Only 34% of patients with peripregnancy STEMI underwent PCI, compared with 61% of nonpregnant women with a STEMI. Drug-eluting stents were implanted in 12% of peripregnancy STEMI patients and in 35% of nonpregnant patients. In contrast, 10% of patients with a pregnancy-related STEMI underwent coronary artery bypass surgery, compared with 5% of nonpregnant women with a STEMI.
The PCI rate among women with a peripregnancy non-STEMI was 7.8%, compared with 28.7% in nonpregnant women with a non-STEMI. However, CABG was utilized less frequently in the peripregnancy non-STEMI group, by a margin of 4.4% to 5.9%.
Dr. Masoomi reported having no financial conflicts regarding his study.
Key clinical point:
Major finding: In-hospital mortality among U.S. women with peripregnancy MI was 7.2% during 2008-2012, significantly higher than the 5.2% rate in women of reproductive age who weren’t pregnant.
Data source: This analysis of data from the U.S. National Inpatient Sample concluded that of an estimated 261,806 U.S. women aged 15-54 years who had an acute MI during 2008-2012, a total of 2,153 of them had an ante- or postpartum-associated MI.
Disclosures: The study presenter reported having no financial conflicts of interest.