Interventional Cardiology & Surgery

PARIS – Fewer than half of commercial drivers who received implantable cardioverter-defibrillators (ICDs) recalled being told they should never drive professionally again, according to a recent Danish survey. Further, about a third of patients overall reported that they began driving soon after they received an ICD, during the period when guidelines recommend refraining from driving.

“These devices, they save lives – so what’s not to like?” lead investigator Jenny Bjerre, MD, asked at the annual congress of the European Society of Cardiology. “Well, if you are a patient qualifying for an ICD, you also automatically qualify for some driving restrictions.” These are put in place because of the concern for an arrhythmia causing a loss of consciousness behind the wheel, she said.

A European consensus statement calls for a 3-month driving moratorium when an ICD is implanted for secondary prevention or after an appropriate ICD shock, and a 4-week restriction when an ICD is placed for primary prevention. All these restrictions apply to personal driver’s licenses; anyone with an ICD is permanently restricted from commercial driving according to the consensus statement, said Dr. Bjerre, of the University Hospital, Copenhagen.

“As you can imagine, these restrictions are not that popular with the patients,” she said. She related the story of a patient, a taxi driver who had returned to a full range of physically taxing activities after his ICD implantation, but whose livelihood had been taken away from him.

Dr. Bjerre said she sought to understand the perspective of this patient, who said, “Sometimes I wish I hadn’t been resuscitated!” She saw that the loss of freedom and a meaningful occupation had profoundly affected the daily life of this patient, and she became curious about adherence to driving restrictions in patients with ICDs.

Using the nationwide Danish medical record database, Dr. Bjerre and her colleagues looked at a nationwide cohort of ICD patients to see they remembered hearing about restrictions on personal and commercial driving activities after ICD implantation. They also investigated adherence to restrictions, and sought to identify what factors were associated with nonadherence.

The questionnaire developed by Dr. Bjerre and her colleagues was made available to the ICD cohort both electronically and in a paper version. Questionnaires received were linked with a variety of nationwide registries through each participant’s unique national identification number, she explained. They obtained information about comorbidities, pharmacotherapies, and socioeconomic status. Not only did this linkage give more precise and complete data than would a questionnaire alone, but it also allowed the investigators to see how responders differed from nonresponders – important in questionnaire research, said Dr. Bjerre.

The investigators were able to locate and distribute questionnaires to a total of 3,913 living adults who had received first-time ICDs during the 3-year study period. In the end, even after excluding 31 responses for missing data, 2,741 responses were used for analysis – a response rate of over 70%.

The median age of respondents was 67, and 83% were male. About half – 46% – of respondents had an ICD implanted for primary prevention. Compared with those who did respond, said Dr. Bjerre, the nonresponders “were younger, sicker, more likely to be female, had lower socioeconomic status, and were less likely to be on guideline-directed therapy.”

Over 90% of respondents held a private driver’s license at the time of their ICD implantation, and just 7% were actively using a commercial license prior to implantation. Participants had a variety of commercial driving occupations, including driving trucks, buses, and taxis.

“Only 43% of primary prevention patients and 64% of secondary prevention patients stated that they had been informed about any driving restrictions,” said Dr. Bjerre. The figure was slightly better for patients after an ICD shock was delivered – 72% of these patients recalled hearing about driving restrictions.

“Among professional drivers – who are never supposed to drive again – only 45% said they had been informed about any professional driving restrictions,” she added.

What did patients report about their actual driving behaviors? Of patients receiving an ICD for primary prevention, 34% resumed driving within one week of ICD implantation. For those receiving an ICD for secondary prevention and those who had received an appropriate ICD shock, 43% and 30%, respectively, began driving before the recommended 3 months had elapsed.

The driving behavior of those with commercial licenses didn’t differ from the cohort as a whole: 35% of this group had resumed commercial driving.

In all the study’s subgroups, nonadherence to driving restrictions was more likely if the participant didn’t recall having been informed of the restrictions, with an odds ratio (OR) of 3.34 for nonadherence. However, noted Dr. Bjerre, at least 20% of patients in all subgroups who said they’d been told not to drive still resumed driving in contravention of restrictions. “So it seems that information can’t explain everything,” she said.

Additional predictors of nonadherence included male sex, with an OR of 1.53, being the only driver in the household (OR 1.29), and being at least 60 years old (OR, 1.20). Those receiving an ICD for secondary prevention had an OR of 2.20 for nonadherence, as well.

The study had a large cohort of real-life ICD patients and the response rate was high, said Dr. Bjerre. However, there was a risk of recall bias; additionally, nonresponders differed from responders, limiting full generalizability of the data. Finally, she observed that participants may have given the answers they thought were socially desirable.

“I want to get back to our friend the taxi driver,” who was adherent to restrictions, but who kept wanting to know what the actual chances were that he’d harm someone if he resumed driving. Realizing she couldn’t give him a very precise answer, Dr. Bjerre concluded, “I do think we owe it to our patients to provide more evidence on the absolute risk of traffic accidents in these patients.”

Dr. Bjerre reported that she had no conflicts of interest.

[email protected]

PARIS – Fewer than half of commercial drivers who received implantable cardioverter-defibrillators (ICDs) recalled being told they should never drive professionally again, according to a recent Danish survey. Further, about a third of patients overall reported that they began driving soon after they received an ICD, during the period when guidelines recommend refraining from driving.

“These devices, they save lives – so what’s not to like?” lead investigator Jenny Bjerre, MD, asked at the annual congress of the European Society of Cardiology. “Well, if you are a patient qualifying for an ICD, you also automatically qualify for some driving restrictions.” These are put in place because of the concern for an arrhythmia causing a loss of consciousness behind the wheel, she said.

A European consensus statement calls for a 3-month driving moratorium when an ICD is implanted for secondary prevention or after an appropriate ICD shock, and a 4-week restriction when an ICD is placed for primary prevention. All these restrictions apply to personal driver’s licenses; anyone with an ICD is permanently restricted from commercial driving according to the consensus statement, said Dr. Bjerre, of the University Hospital, Copenhagen.

“As you can imagine, these restrictions are not that popular with the patients,” she said. She related the story of a patient, a taxi driver who had returned to a full range of physically taxing activities after his ICD implantation, but whose livelihood had been taken away from him.

Dr. Bjerre said she sought to understand the perspective of this patient, who said, “Sometimes I wish I hadn’t been resuscitated!” She saw that the loss of freedom and a meaningful occupation had profoundly affected the daily life of this patient, and she became curious about adherence to driving restrictions in patients with ICDs.

Using the nationwide Danish medical record database, Dr. Bjerre and her colleagues looked at a nationwide cohort of ICD patients to see they remembered hearing about restrictions on personal and commercial driving activities after ICD implantation. They also investigated adherence to restrictions, and sought to identify what factors were associated with nonadherence.

The questionnaire developed by Dr. Bjerre and her colleagues was made available to the ICD cohort both electronically and in a paper version. Questionnaires received were linked with a variety of nationwide registries through each participant’s unique national identification number, she explained. They obtained information about comorbidities, pharmacotherapies, and socioeconomic status. Not only did this linkage give more precise and complete data than would a questionnaire alone, but it also allowed the investigators to see how responders differed from nonresponders – important in questionnaire research, said Dr. Bjerre.

The investigators were able to locate and distribute questionnaires to a total of 3,913 living adults who had received first-time ICDs during the 3-year study period. In the end, even after excluding 31 responses for missing data, 2,741 responses were used for analysis – a response rate of over 70%.

The median age of respondents was 67, and 83% were male. About half – 46% – of respondents had an ICD implanted for primary prevention. Compared with those who did respond, said Dr. Bjerre, the nonresponders “were younger, sicker, more likely to be female, had lower socioeconomic status, and were less likely to be on guideline-directed therapy.”

Over 90% of respondents held a private driver’s license at the time of their ICD implantation, and just 7% were actively using a commercial license prior to implantation. Participants had a variety of commercial driving occupations, including driving trucks, buses, and taxis.

“Only 43% of primary prevention patients and 64% of secondary prevention patients stated that they had been informed about any driving restrictions,” said Dr. Bjerre. The figure was slightly better for patients after an ICD shock was delivered – 72% of these patients recalled hearing about driving restrictions.

“Among professional drivers – who are never supposed to drive again – only 45% said they had been informed about any professional driving restrictions,” she added.

What did patients report about their actual driving behaviors? Of patients receiving an ICD for primary prevention, 34% resumed driving within one week of ICD implantation. For those receiving an ICD for secondary prevention and those who had received an appropriate ICD shock, 43% and 30%, respectively, began driving before the recommended 3 months had elapsed.

The driving behavior of those with commercial licenses didn’t differ from the cohort as a whole: 35% of this group had resumed commercial driving.

In all the study’s subgroups, nonadherence to driving restrictions was more likely if the participant didn’t recall having been informed of the restrictions, with an odds ratio (OR) of 3.34 for nonadherence. However, noted Dr. Bjerre, at least 20% of patients in all subgroups who said they’d been told not to drive still resumed driving in contravention of restrictions. “So it seems that information can’t explain everything,” she said.

Additional predictors of nonadherence included male sex, with an OR of 1.53, being the only driver in the household (OR 1.29), and being at least 60 years old (OR, 1.20). Those receiving an ICD for secondary prevention had an OR of 2.20 for nonadherence, as well.

The study had a large cohort of real-life ICD patients and the response rate was high, said Dr. Bjerre. However, there was a risk of recall bias; additionally, nonresponders differed from responders, limiting full generalizability of the data. Finally, she observed that participants may have given the answers they thought were socially desirable.

“I want to get back to our friend the taxi driver,” who was adherent to restrictions, but who kept wanting to know what the actual chances were that he’d harm someone if he resumed driving. Realizing she couldn’t give him a very precise answer, Dr. Bjerre concluded, “I do think we owe it to our patients to provide more evidence on the absolute risk of traffic accidents in these patients.”

Dr. Bjerre reported that she had no conflicts of interest.

[email protected]

PARIS – Fewer than half of commercial drivers who received implantable cardioverter-defibrillators (ICDs) recalled being told they should never drive professionally again, according to a recent Danish survey. Further, about a third of patients overall reported that they began driving soon after they received an ICD, during the period when guidelines recommend refraining from driving.

“These devices, they save lives – so what’s not to like?” lead investigator Jenny Bjerre, MD, asked at the annual congress of the European Society of Cardiology. “Well, if you are a patient qualifying for an ICD, you also automatically qualify for some driving restrictions.” These are put in place because of the concern for an arrhythmia causing a loss of consciousness behind the wheel, she said.

A European consensus statement calls for a 3-month driving moratorium when an ICD is implanted for secondary prevention or after an appropriate ICD shock, and a 4-week restriction when an ICD is placed for primary prevention. All these restrictions apply to personal driver’s licenses; anyone with an ICD is permanently restricted from commercial driving according to the consensus statement, said Dr. Bjerre, of the University Hospital, Copenhagen.

“As you can imagine, these restrictions are not that popular with the patients,” she said. She related the story of a patient, a taxi driver who had returned to a full range of physically taxing activities after his ICD implantation, but whose livelihood had been taken away from him.

Dr. Bjerre said she sought to understand the perspective of this patient, who said, “Sometimes I wish I hadn’t been resuscitated!” She saw that the loss of freedom and a meaningful occupation had profoundly affected the daily life of this patient, and she became curious about adherence to driving restrictions in patients with ICDs.

Using the nationwide Danish medical record database, Dr. Bjerre and her colleagues looked at a nationwide cohort of ICD patients to see they remembered hearing about restrictions on personal and commercial driving activities after ICD implantation. They also investigated adherence to restrictions, and sought to identify what factors were associated with nonadherence.

The questionnaire developed by Dr. Bjerre and her colleagues was made available to the ICD cohort both electronically and in a paper version. Questionnaires received were linked with a variety of nationwide registries through each participant’s unique national identification number, she explained. They obtained information about comorbidities, pharmacotherapies, and socioeconomic status. Not only did this linkage give more precise and complete data than would a questionnaire alone, but it also allowed the investigators to see how responders differed from nonresponders – important in questionnaire research, said Dr. Bjerre.

The investigators were able to locate and distribute questionnaires to a total of 3,913 living adults who had received first-time ICDs during the 3-year study period. In the end, even after excluding 31 responses for missing data, 2,741 responses were used for analysis – a response rate of over 70%.

The median age of respondents was 67, and 83% were male. About half – 46% – of respondents had an ICD implanted for primary prevention. Compared with those who did respond, said Dr. Bjerre, the nonresponders “were younger, sicker, more likely to be female, had lower socioeconomic status, and were less likely to be on guideline-directed therapy.”

Over 90% of respondents held a private driver’s license at the time of their ICD implantation, and just 7% were actively using a commercial license prior to implantation. Participants had a variety of commercial driving occupations, including driving trucks, buses, and taxis.

“Only 43% of primary prevention patients and 64% of secondary prevention patients stated that they had been informed about any driving restrictions,” said Dr. Bjerre. The figure was slightly better for patients after an ICD shock was delivered – 72% of these patients recalled hearing about driving restrictions.

“Among professional drivers – who are never supposed to drive again – only 45% said they had been informed about any professional driving restrictions,” she added.

What did patients report about their actual driving behaviors? Of patients receiving an ICD for primary prevention, 34% resumed driving within one week of ICD implantation. For those receiving an ICD for secondary prevention and those who had received an appropriate ICD shock, 43% and 30%, respectively, began driving before the recommended 3 months had elapsed.

The driving behavior of those with commercial licenses didn’t differ from the cohort as a whole: 35% of this group had resumed commercial driving.

In all the study’s subgroups, nonadherence to driving restrictions was more likely if the participant didn’t recall having been informed of the restrictions, with an odds ratio (OR) of 3.34 for nonadherence. However, noted Dr. Bjerre, at least 20% of patients in all subgroups who said they’d been told not to drive still resumed driving in contravention of restrictions. “So it seems that information can’t explain everything,” she said.

Additional predictors of nonadherence included male sex, with an OR of 1.53, being the only driver in the household (OR 1.29), and being at least 60 years old (OR, 1.20). Those receiving an ICD for secondary prevention had an OR of 2.20 for nonadherence, as well.

The study had a large cohort of real-life ICD patients and the response rate was high, said Dr. Bjerre. However, there was a risk of recall bias; additionally, nonresponders differed from responders, limiting full generalizability of the data. Finally, she observed that participants may have given the answers they thought were socially desirable.

“I want to get back to our friend the taxi driver,” who was adherent to restrictions, but who kept wanting to know what the actual chances were that he’d harm someone if he resumed driving. Realizing she couldn’t give him a very precise answer, Dr. Bjerre concluded, “I do think we owe it to our patients to provide more evidence on the absolute risk of traffic accidents in these patients.”

Dr. Bjerre reported that she had no conflicts of interest.

[email protected]

SAN ANTONIO – Fibrinogen concentrate was noninferior to cryoprecipitate for controlling bleeding following cardiac surgery in the randomized FIBRES trial, Canadian investigators reported.

Neil Osterweil/MDedge News

Among 827 patients undergoing cardiopulmonary bypass, there were no significant differences in the use of allogenenic transfusion products within 24 hours of surgery for patients assigned to receive fibrinogen concentrate for control of bleeding, compared with patients who received cryoprecipitate, reported Jeannie Callum, MD, from Sunnybrook Health Sciences Centre in Toronto, on behalf of coinvestigators in the FIBRES trial.

Fibrinogen concentrate, commonly used to control postoperative bleeding in Europe, was associated with numerically, but not statistically, lower incidence of both adverse events and serious adverse events than cryoprecipitate, the current standard of care in North America.

“Given its safety and logistical advantages, fibrinogen concentrate may be considered in bleeding patients with acquired hypofibrinogenemia,” Dr. Callum said at the annual meeting of the AABB, the group formerly known as the American Association of Blood Banks.

Results of the FIBRES trial were published simultaneously in JAMA (2019 Oct 21. doi: 10.1001/jama.2019.17312).

Acquired hypofibrinogenemia, defined as a fibrinogen level below the range of 1.5-2.0 g/L, is a major cause of excess bleeding after cardiac surgery. European guidelines on the management of bleeding following trauma or cardiac surgery recommend the use of either cryoprecipitate or fibrinogen concentrate to control excessive bleeding in patients with acquired hypofibrinogenemia, Dr. Callum noted.

Cryoprecipitate is a pooled plasma–derived product that contains fibrinogen, but also fibronectin, platelet microparticles, coagulation factors VIII and XIII, and von Willebrand factor.

Additionally, fibrinogen levels in cryoprecipitate can range from as low as 3 g/L to as high as 30 g/L, and the product is normally kept and shipped frozen, and is then thawed for use and pooled prior to administration, with a shelf life of just 4-6 hours.

In contrast, fibrinogen concentrates “are pathogen-reduced and purified; have standardized fibrinogen content (20 g/L); are lyophilized, allowing for easy storage, reconstitution, and administration; and have longer shelf life after reconstitution (up to 24 hours),” Dr. Callum and her colleagues reported.

Despite the North American preference for cryoprecipitate and the European preference for fibrinogen concentrate, there have been few studies directly comparing the two products, which prompted the FIBRES investigators to design a head-to-head trial.

The randomized trial was conducted in 11 Canadian hospitals with adults undergoing cardiac surgery with cardiopulmonary bypass for whom fibrinogen supplementation was ordered in accordance with accepted clinical standards.

Patients were randomly assigned to received either 4 g of fibrinogen concentrate or 10 units of cryoprecipitate for 24 hours, with all patients receiving additional cryoprecipitate as needed after the first day.

Of 15,412 cardiac patients treated at the participating sites, 827 patients met the trial criteria and were randomized. Because the trial met the prespecified stopping criterion for noninferiority of fibrinogen at the interim analysis, the trial was halted, leaving the 827 patients as the final analysis population.

The mean number of allogeneic blood component units administered – the primary outcome – was 16.3 units in the fibrinogen concentrate group and 17.0 units in the cryoprecipitate group (mean ratio, 0.96; P for noninferiority less than .001; P for superiority = .50).

Fibrinogen was also noninferior for the secondary outcomes of individual 24-hour and cumulative 7-day blood component transfusions, and in a post-hoc analysis of cumulative transfusions measured from product administration to 24 hours after termination of cardiopulmonary bypass. These endpoints should be interpreted with caution, however, because they were not corrected for type 1 error, the investigators noted.

Fibrinogen concentrate also appeared to be noninferior for all defined subgroups, except for patients who underwent nonelective procedures, which included all patients in critical state before surgery.

Adverse events (AEs) of any kind occurred in 66.7% of patients with fibrinogen concentrate vs. 72.7% of those on cryoprecipitate. Serious AEs occurred in 31.5% vs. 34.7%, respectively.

Thromboembolic events – stroke or transient ischemic attack, amaurosis fugax (temporary vision loss), myocardial infarction, deep-vein thrombosis, pulmonary embolism, other-vessel thrombosis, disseminated intravascular coagulation, or thrombophlebitis – occurred in 7% vs. 9.6%, respectively.

The investigators acknowledged that the study was limited by the inability to blind the clinical team to the product used, by the adult-only population, and by the likelihood of variable dosing in the cryoprecipitate group.

Advantages of fibrinogen concentrate over cryoprecipitate are that the former is pathogen reduced and is easier to deliver, the investigators said.

“One important consideration is the cost differential that currently favors cryoprecipitate, but this varies across regions, and the most recent economic analysis failed to include the costs of future emerging pathogens and did not include comprehensive activity-based costing,” the investigators wrote in JAMA.

The trial was sponsored by Octapharma AG, which also provided fibrinogen concentrate. Cryoprecipitate was provided by the Canadian Blood Services and Héma-Québec. Dr. Callum reported receiving grants from Canadian Blood Services, Octapharma, and CSL Behring during the conduct of the study. Multiple coauthors had similar disclosures.

SOURCE: Callum J et al. JAMA. 2019 Oct 21. doi:10.1001/jama.2019.17312.

SAN ANTONIO – Fibrinogen concentrate was noninferior to cryoprecipitate for controlling bleeding following cardiac surgery in the randomized FIBRES trial, Canadian investigators reported.

Neil Osterweil/MDedge News

Among 827 patients undergoing cardiopulmonary bypass, there were no significant differences in the use of allogenenic transfusion products within 24 hours of surgery for patients assigned to receive fibrinogen concentrate for control of bleeding, compared with patients who received cryoprecipitate, reported Jeannie Callum, MD, from Sunnybrook Health Sciences Centre in Toronto, on behalf of coinvestigators in the FIBRES trial.

Fibrinogen concentrate, commonly used to control postoperative bleeding in Europe, was associated with numerically, but not statistically, lower incidence of both adverse events and serious adverse events than cryoprecipitate, the current standard of care in North America.

“Given its safety and logistical advantages, fibrinogen concentrate may be considered in bleeding patients with acquired hypofibrinogenemia,” Dr. Callum said at the annual meeting of the AABB, the group formerly known as the American Association of Blood Banks.

Results of the FIBRES trial were published simultaneously in JAMA (2019 Oct 21. doi: 10.1001/jama.2019.17312).

Acquired hypofibrinogenemia, defined as a fibrinogen level below the range of 1.5-2.0 g/L, is a major cause of excess bleeding after cardiac surgery. European guidelines on the management of bleeding following trauma or cardiac surgery recommend the use of either cryoprecipitate or fibrinogen concentrate to control excessive bleeding in patients with acquired hypofibrinogenemia, Dr. Callum noted.

Cryoprecipitate is a pooled plasma–derived product that contains fibrinogen, but also fibronectin, platelet microparticles, coagulation factors VIII and XIII, and von Willebrand factor.

Additionally, fibrinogen levels in cryoprecipitate can range from as low as 3 g/L to as high as 30 g/L, and the product is normally kept and shipped frozen, and is then thawed for use and pooled prior to administration, with a shelf life of just 4-6 hours.

In contrast, fibrinogen concentrates “are pathogen-reduced and purified; have standardized fibrinogen content (20 g/L); are lyophilized, allowing for easy storage, reconstitution, and administration; and have longer shelf life after reconstitution (up to 24 hours),” Dr. Callum and her colleagues reported.

Despite the North American preference for cryoprecipitate and the European preference for fibrinogen concentrate, there have been few studies directly comparing the two products, which prompted the FIBRES investigators to design a head-to-head trial.

The randomized trial was conducted in 11 Canadian hospitals with adults undergoing cardiac surgery with cardiopulmonary bypass for whom fibrinogen supplementation was ordered in accordance with accepted clinical standards.

Patients were randomly assigned to received either 4 g of fibrinogen concentrate or 10 units of cryoprecipitate for 24 hours, with all patients receiving additional cryoprecipitate as needed after the first day.

Of 15,412 cardiac patients treated at the participating sites, 827 patients met the trial criteria and were randomized. Because the trial met the prespecified stopping criterion for noninferiority of fibrinogen at the interim analysis, the trial was halted, leaving the 827 patients as the final analysis population.

The mean number of allogeneic blood component units administered – the primary outcome – was 16.3 units in the fibrinogen concentrate group and 17.0 units in the cryoprecipitate group (mean ratio, 0.96; P for noninferiority less than .001; P for superiority = .50).

Fibrinogen was also noninferior for the secondary outcomes of individual 24-hour and cumulative 7-day blood component transfusions, and in a post-hoc analysis of cumulative transfusions measured from product administration to 24 hours after termination of cardiopulmonary bypass. These endpoints should be interpreted with caution, however, because they were not corrected for type 1 error, the investigators noted.

Fibrinogen concentrate also appeared to be noninferior for all defined subgroups, except for patients who underwent nonelective procedures, which included all patients in critical state before surgery.

Adverse events (AEs) of any kind occurred in 66.7% of patients with fibrinogen concentrate vs. 72.7% of those on cryoprecipitate. Serious AEs occurred in 31.5% vs. 34.7%, respectively.

Thromboembolic events – stroke or transient ischemic attack, amaurosis fugax (temporary vision loss), myocardial infarction, deep-vein thrombosis, pulmonary embolism, other-vessel thrombosis, disseminated intravascular coagulation, or thrombophlebitis – occurred in 7% vs. 9.6%, respectively.

The investigators acknowledged that the study was limited by the inability to blind the clinical team to the product used, by the adult-only population, and by the likelihood of variable dosing in the cryoprecipitate group.

Advantages of fibrinogen concentrate over cryoprecipitate are that the former is pathogen reduced and is easier to deliver, the investigators said.

“One important consideration is the cost differential that currently favors cryoprecipitate, but this varies across regions, and the most recent economic analysis failed to include the costs of future emerging pathogens and did not include comprehensive activity-based costing,” the investigators wrote in JAMA.

The trial was sponsored by Octapharma AG, which also provided fibrinogen concentrate. Cryoprecipitate was provided by the Canadian Blood Services and Héma-Québec. Dr. Callum reported receiving grants from Canadian Blood Services, Octapharma, and CSL Behring during the conduct of the study. Multiple coauthors had similar disclosures.

SOURCE: Callum J et al. JAMA. 2019 Oct 21. doi:10.1001/jama.2019.17312.

SAN ANTONIO – Fibrinogen concentrate was noninferior to cryoprecipitate for controlling bleeding following cardiac surgery in the randomized FIBRES trial, Canadian investigators reported.

Neil Osterweil/MDedge News

Among 827 patients undergoing cardiopulmonary bypass, there were no significant differences in the use of allogenenic transfusion products within 24 hours of surgery for patients assigned to receive fibrinogen concentrate for control of bleeding, compared with patients who received cryoprecipitate, reported Jeannie Callum, MD, from Sunnybrook Health Sciences Centre in Toronto, on behalf of coinvestigators in the FIBRES trial.

Fibrinogen concentrate, commonly used to control postoperative bleeding in Europe, was associated with numerically, but not statistically, lower incidence of both adverse events and serious adverse events than cryoprecipitate, the current standard of care in North America.

“Given its safety and logistical advantages, fibrinogen concentrate may be considered in bleeding patients with acquired hypofibrinogenemia,” Dr. Callum said at the annual meeting of the AABB, the group formerly known as the American Association of Blood Banks.

Results of the FIBRES trial were published simultaneously in JAMA (2019 Oct 21. doi: 10.1001/jama.2019.17312).

Acquired hypofibrinogenemia, defined as a fibrinogen level below the range of 1.5-2.0 g/L, is a major cause of excess bleeding after cardiac surgery. European guidelines on the management of bleeding following trauma or cardiac surgery recommend the use of either cryoprecipitate or fibrinogen concentrate to control excessive bleeding in patients with acquired hypofibrinogenemia, Dr. Callum noted.

Cryoprecipitate is a pooled plasma–derived product that contains fibrinogen, but also fibronectin, platelet microparticles, coagulation factors VIII and XIII, and von Willebrand factor.

Additionally, fibrinogen levels in cryoprecipitate can range from as low as 3 g/L to as high as 30 g/L, and the product is normally kept and shipped frozen, and is then thawed for use and pooled prior to administration, with a shelf life of just 4-6 hours.

In contrast, fibrinogen concentrates “are pathogen-reduced and purified; have standardized fibrinogen content (20 g/L); are lyophilized, allowing for easy storage, reconstitution, and administration; and have longer shelf life after reconstitution (up to 24 hours),” Dr. Callum and her colleagues reported.

Despite the North American preference for cryoprecipitate and the European preference for fibrinogen concentrate, there have been few studies directly comparing the two products, which prompted the FIBRES investigators to design a head-to-head trial.

The randomized trial was conducted in 11 Canadian hospitals with adults undergoing cardiac surgery with cardiopulmonary bypass for whom fibrinogen supplementation was ordered in accordance with accepted clinical standards.

Patients were randomly assigned to received either 4 g of fibrinogen concentrate or 10 units of cryoprecipitate for 24 hours, with all patients receiving additional cryoprecipitate as needed after the first day.

Of 15,412 cardiac patients treated at the participating sites, 827 patients met the trial criteria and were randomized. Because the trial met the prespecified stopping criterion for noninferiority of fibrinogen at the interim analysis, the trial was halted, leaving the 827 patients as the final analysis population.

The mean number of allogeneic blood component units administered – the primary outcome – was 16.3 units in the fibrinogen concentrate group and 17.0 units in the cryoprecipitate group (mean ratio, 0.96; P for noninferiority less than .001; P for superiority = .50).

Fibrinogen was also noninferior for the secondary outcomes of individual 24-hour and cumulative 7-day blood component transfusions, and in a post-hoc analysis of cumulative transfusions measured from product administration to 24 hours after termination of cardiopulmonary bypass. These endpoints should be interpreted with caution, however, because they were not corrected for type 1 error, the investigators noted.

Fibrinogen concentrate also appeared to be noninferior for all defined subgroups, except for patients who underwent nonelective procedures, which included all patients in critical state before surgery.

Adverse events (AEs) of any kind occurred in 66.7% of patients with fibrinogen concentrate vs. 72.7% of those on cryoprecipitate. Serious AEs occurred in 31.5% vs. 34.7%, respectively.

Thromboembolic events – stroke or transient ischemic attack, amaurosis fugax (temporary vision loss), myocardial infarction, deep-vein thrombosis, pulmonary embolism, other-vessel thrombosis, disseminated intravascular coagulation, or thrombophlebitis – occurred in 7% vs. 9.6%, respectively.

The investigators acknowledged that the study was limited by the inability to blind the clinical team to the product used, by the adult-only population, and by the likelihood of variable dosing in the cryoprecipitate group.

Advantages of fibrinogen concentrate over cryoprecipitate are that the former is pathogen reduced and is easier to deliver, the investigators said.

“One important consideration is the cost differential that currently favors cryoprecipitate, but this varies across regions, and the most recent economic analysis failed to include the costs of future emerging pathogens and did not include comprehensive activity-based costing,” the investigators wrote in JAMA.

The trial was sponsored by Octapharma AG, which also provided fibrinogen concentrate. Cryoprecipitate was provided by the Canadian Blood Services and Héma-Québec. Dr. Callum reported receiving grants from Canadian Blood Services, Octapharma, and CSL Behring during the conduct of the study. Multiple coauthors had similar disclosures.

SOURCE: Callum J et al. JAMA. 2019 Oct 21. doi:10.1001/jama.2019.17312.

SAN FRANCISCO – At 5 years, the rates of disabling stroke or death were similar among patients with severe aortic stenosis and intermediate surgical risk who underwent transcatheter aortic valve replacement or surgical aortic valve replacement.

Doug Brunk/MDedge News

At the same time, patients who underwent TAVR using a transthoracic approach had poorer outcomes, compared with their counterparts who underwent SAVR, Vinod H. Thourani, MD, reported at the Transcatheter Cardiovascular Therapeutics annual meeting. The findings come from an analysis of the PARTNER 2A trial, the largest randomized study ever conducted in the field of TAVR and SAVR.

In an effort to compare the key clinical outcomes, bioprosthetic valve function, and quality-of-life measures at 5 years for TAVR versus surgery, Dr. Thourani and his colleagues used data from 2,032 intermediate-risk patients with severe AS assigned to either TAVR or SAVR at 57 centers in the PARTNER 2A trial. Their mean age was 82 years, and their average Society of Thoracic Surgery risk score was 5.8%. The 2-year primary endpoint was all-cause death or disabling stroke in the intention-to-treat (ITT) population. At 5 years, the researchers analyzed all primary and secondary clinical and echo endpoints in both ITT and prespecified as-treated populations.

At 5 years, the primary endpoint of death and disabling stroke at 5 years was 47.9% in the TAVR group and 43.4% in the surgery group, a difference that did not reach statistical significance (hazard ratio, 1.09; P = .21). In the transfemoral cohort, rates of the primary endpoint were also similar between TAVR and SAVR (44.5% vs. 42%, respectively; HR, 1.02; P = .80). In the transthoracic cohort, however, the researchers observed a divergence in the primary outcome starting at year 1, such that it was higher with TAVR at 5 years, compared with SAVR (59.3% vs. 48.3%; P = .03), reported Dr. Thourani, chair of cardiac surgery at Medstar Heart and Vascular Institute, Washington.

When he and his colleagues examined freedom from aortic valve reintervention at 5 years, the hazard ratios showed some difference between TAVR and SAVR (HR, 3.93; P = .003), yet clinically the freedom from reintervention rate was very high (96.8% vs. 99.4%, respectively). “The other issue we’ve been interested in is the difference between mean aortic valve gradients between the groups,” Dr. Thourani said at the meeting. “There was no difference in mean aortic valve gradients between TAVR and SAVR at 5 years (a mean of 11.4 mm Hg vs. 10.8 mm Hg, respectively; P = .23).”

Paravalvular regurgitation (PVR) was more common in the TAVR vs. SAVR group at all follow-up times (P less than .001 in all categories). By year 5, the proportion of patients with moderate to severe PVR was 6.5% in the TAVR group vs. 0.4% in the SAVR group, respectively, while the proportion of those with mild PVR was 26.8%, compared with 5.9%.

In other findings, no difference in mortality was seen in the TAVR cohort between those with mild PVR and no or trace PVR (48.7% vs. 41.1%; P = .07). However, those with moderate to severe PVR at the end of the procedure had an increased mortality at the end of 5 years (64.8%; P = .007). “If you had none or trace PVR at baseline, there was no major difference in mortality between the two groups at 2 years,” Dr. Thourani said. “That difference was maintained at 5 years.”

The overall findings, he continued, support the notion that TAVR should be considered as an alternative to surgery in intermediate-risk patients with severe aortic stenosis. “However, in patients without acceptable transfemoral access, surgery may be the preferred alternative,” he said.

Roxana Mehran, MD,, director of interventional cardiovascular research and clinical trials at Mount Sinai School of Medicine, New York, commented that the reassurance of the same outcomes at 5 years between the two approaches “makes TAVR superior. It’s a less invasive and durable result. One of the things we have yet to figure out is the need for anticoagulation to prevent stroke in these patients. We have very little data and understanding about that.”

The PARTNER 2A study was funded by Edwards Lifesciences. Dr. Thourani has received grant or research support from and participation in steering committees for Edwards Lifesciences, Abbott Vascular, Boston Scientific, Gore Vascular, JenaValve, and Cryolife.

[email protected]

SAN FRANCISCO – At 5 years, the rates of disabling stroke or death were similar among patients with severe aortic stenosis and intermediate surgical risk who underwent transcatheter aortic valve replacement or surgical aortic valve replacement.

Doug Brunk/MDedge News

At the same time, patients who underwent TAVR using a transthoracic approach had poorer outcomes, compared with their counterparts who underwent SAVR, Vinod H. Thourani, MD, reported at the Transcatheter Cardiovascular Therapeutics annual meeting. The findings come from an analysis of the PARTNER 2A trial, the largest randomized study ever conducted in the field of TAVR and SAVR.

In an effort to compare the key clinical outcomes, bioprosthetic valve function, and quality-of-life measures at 5 years for TAVR versus surgery, Dr. Thourani and his colleagues used data from 2,032 intermediate-risk patients with severe AS assigned to either TAVR or SAVR at 57 centers in the PARTNER 2A trial. Their mean age was 82 years, and their average Society of Thoracic Surgery risk score was 5.8%. The 2-year primary endpoint was all-cause death or disabling stroke in the intention-to-treat (ITT) population. At 5 years, the researchers analyzed all primary and secondary clinical and echo endpoints in both ITT and prespecified as-treated populations.

At 5 years, the primary endpoint of death and disabling stroke at 5 years was 47.9% in the TAVR group and 43.4% in the surgery group, a difference that did not reach statistical significance (hazard ratio, 1.09; P = .21). In the transfemoral cohort, rates of the primary endpoint were also similar between TAVR and SAVR (44.5% vs. 42%, respectively; HR, 1.02; P = .80). In the transthoracic cohort, however, the researchers observed a divergence in the primary outcome starting at year 1, such that it was higher with TAVR at 5 years, compared with SAVR (59.3% vs. 48.3%; P = .03), reported Dr. Thourani, chair of cardiac surgery at Medstar Heart and Vascular Institute, Washington.

When he and his colleagues examined freedom from aortic valve reintervention at 5 years, the hazard ratios showed some difference between TAVR and SAVR (HR, 3.93; P = .003), yet clinically the freedom from reintervention rate was very high (96.8% vs. 99.4%, respectively). “The other issue we’ve been interested in is the difference between mean aortic valve gradients between the groups,” Dr. Thourani said at the meeting. “There was no difference in mean aortic valve gradients between TAVR and SAVR at 5 years (a mean of 11.4 mm Hg vs. 10.8 mm Hg, respectively; P = .23).”

Paravalvular regurgitation (PVR) was more common in the TAVR vs. SAVR group at all follow-up times (P less than .001 in all categories). By year 5, the proportion of patients with moderate to severe PVR was 6.5% in the TAVR group vs. 0.4% in the SAVR group, respectively, while the proportion of those with mild PVR was 26.8%, compared with 5.9%.

In other findings, no difference in mortality was seen in the TAVR cohort between those with mild PVR and no or trace PVR (48.7% vs. 41.1%; P = .07). However, those with moderate to severe PVR at the end of the procedure had an increased mortality at the end of 5 years (64.8%; P = .007). “If you had none or trace PVR at baseline, there was no major difference in mortality between the two groups at 2 years,” Dr. Thourani said. “That difference was maintained at 5 years.”

The overall findings, he continued, support the notion that TAVR should be considered as an alternative to surgery in intermediate-risk patients with severe aortic stenosis. “However, in patients without acceptable transfemoral access, surgery may be the preferred alternative,” he said.

Roxana Mehran, MD,, director of interventional cardiovascular research and clinical trials at Mount Sinai School of Medicine, New York, commented that the reassurance of the same outcomes at 5 years between the two approaches “makes TAVR superior. It’s a less invasive and durable result. One of the things we have yet to figure out is the need for anticoagulation to prevent stroke in these patients. We have very little data and understanding about that.”

The PARTNER 2A study was funded by Edwards Lifesciences. Dr. Thourani has received grant or research support from and participation in steering committees for Edwards Lifesciences, Abbott Vascular, Boston Scientific, Gore Vascular, JenaValve, and Cryolife.

[email protected]

SAN FRANCISCO – At 5 years, the rates of disabling stroke or death were similar among patients with severe aortic stenosis and intermediate surgical risk who underwent transcatheter aortic valve replacement or surgical aortic valve replacement.

Doug Brunk/MDedge News

At the same time, patients who underwent TAVR using a transthoracic approach had poorer outcomes, compared with their counterparts who underwent SAVR, Vinod H. Thourani, MD, reported at the Transcatheter Cardiovascular Therapeutics annual meeting. The findings come from an analysis of the PARTNER 2A trial, the largest randomized study ever conducted in the field of TAVR and SAVR.

In an effort to compare the key clinical outcomes, bioprosthetic valve function, and quality-of-life measures at 5 years for TAVR versus surgery, Dr. Thourani and his colleagues used data from 2,032 intermediate-risk patients with severe AS assigned to either TAVR or SAVR at 57 centers in the PARTNER 2A trial. Their mean age was 82 years, and their average Society of Thoracic Surgery risk score was 5.8%. The 2-year primary endpoint was all-cause death or disabling stroke in the intention-to-treat (ITT) population. At 5 years, the researchers analyzed all primary and secondary clinical and echo endpoints in both ITT and prespecified as-treated populations.

At 5 years, the primary endpoint of death and disabling stroke at 5 years was 47.9% in the TAVR group and 43.4% in the surgery group, a difference that did not reach statistical significance (hazard ratio, 1.09; P = .21). In the transfemoral cohort, rates of the primary endpoint were also similar between TAVR and SAVR (44.5% vs. 42%, respectively; HR, 1.02; P = .80). In the transthoracic cohort, however, the researchers observed a divergence in the primary outcome starting at year 1, such that it was higher with TAVR at 5 years, compared with SAVR (59.3% vs. 48.3%; P = .03), reported Dr. Thourani, chair of cardiac surgery at Medstar Heart and Vascular Institute, Washington.

When he and his colleagues examined freedom from aortic valve reintervention at 5 years, the hazard ratios showed some difference between TAVR and SAVR (HR, 3.93; P = .003), yet clinically the freedom from reintervention rate was very high (96.8% vs. 99.4%, respectively). “The other issue we’ve been interested in is the difference between mean aortic valve gradients between the groups,” Dr. Thourani said at the meeting. “There was no difference in mean aortic valve gradients between TAVR and SAVR at 5 years (a mean of 11.4 mm Hg vs. 10.8 mm Hg, respectively; P = .23).”

Paravalvular regurgitation (PVR) was more common in the TAVR vs. SAVR group at all follow-up times (P less than .001 in all categories). By year 5, the proportion of patients with moderate to severe PVR was 6.5% in the TAVR group vs. 0.4% in the SAVR group, respectively, while the proportion of those with mild PVR was 26.8%, compared with 5.9%.

In other findings, no difference in mortality was seen in the TAVR cohort between those with mild PVR and no or trace PVR (48.7% vs. 41.1%; P = .07). However, those with moderate to severe PVR at the end of the procedure had an increased mortality at the end of 5 years (64.8%; P = .007). “If you had none or trace PVR at baseline, there was no major difference in mortality between the two groups at 2 years,” Dr. Thourani said. “That difference was maintained at 5 years.”

The overall findings, he continued, support the notion that TAVR should be considered as an alternative to surgery in intermediate-risk patients with severe aortic stenosis. “However, in patients without acceptable transfemoral access, surgery may be the preferred alternative,” he said.

Roxana Mehran, MD,, director of interventional cardiovascular research and clinical trials at Mount Sinai School of Medicine, New York, commented that the reassurance of the same outcomes at 5 years between the two approaches “makes TAVR superior. It’s a less invasive and durable result. One of the things we have yet to figure out is the need for anticoagulation to prevent stroke in these patients. We have very little data and understanding about that.”

The PARTNER 2A study was funded by Edwards Lifesciences. Dr. Thourani has received grant or research support from and participation in steering committees for Edwards Lifesciences, Abbott Vascular, Boston Scientific, Gore Vascular, JenaValve, and Cryolife.

[email protected]

SAN FRANCISCO – A urine flow rate (UFR)–guided approach was superior to the left ventricular end-diastolic pressure (LVEDP)-guided hydration regimen in preventing contrast-induced acute kidney injury and acute pulmonary edema in high-risk patients.

The results come from a randomized, multicenter, investigator-initiated trial designed to compare two hydration strategies for reducing the risk of acute kidney injury that Carlo Briguori, MD, PhD, presented at the Transcatheter Cardiovascular Therapeutics annual meeting.

Between July 15, 2015 and June 6, 2019, Dr. Briguori, chief of the laboratory of interventional cardiology at the Mediterranea Cardiocentro in Naples, Italy, and his colleagues enrolled 708 patients with an estimated glomerular filtration rate of 45 mL/min per 1.73 m^{2 or less} and/or with a Mehran’s score greater of at least 11 and/or a Gurm’s score greater than 7. Of these, 355 were assigned to LVEDP-guided hydration with normal saline, while 353 were assigned to UFR-guided hydration controlled by the RenalGuard system. Iobitridol, a low-osmolar, nonionic contrast agent, was administered in all cases.

The primary endpoint for the trial, known as Renal Insufficiency Following Contrast Media Administration Trial III (REMEDIAL III), was the composite of contrast-induced acute kidney injury (defined as a serum creatinine increase of at least 25% and/or at least 0.5 mg/dL from baseline to 48 hours) and/or acute pulmonary edema. That endpoint occurred in 5.7% of patients in the UFR-guided group and in 10.3% of patients in the LVEDP-guided group (relative risk, 0.56; P = .036). As for side effects, three patients in the UFR-guided group (0.8%) experienced complications related to Foley insertion, including one case of hematuria and two cases of pain on micturition. No patients developed a urinary tract infection, Dr. Briguori reported at the meeting, which was sponsored by the Cardiovascular Research Foundation.

Hypokalemia occurred in 6.2% of patients in the UFR-guided group and 2.3% of patients in the LVEDP-guided group (RR, 2.70; P = .013), while potassium replacement was required in 5.1% of patients in the UFR-guided group, compared with 1.4% of LVEDP-guided patients (RR, 3.74; P = .009). Meanwhile, hypernatremia was observed in 1.2% of patients in both groups (P = 1.00).

“For the longest time, the interventional field has been trying to find ways to minimize acute kidney injury related to interventional procedures,” Juan F. Granada, MD, president and CEO of the Cardiovascular Research Foundation said in a media briefing. “We have a lot of data with multiple approaches with different results – mostly negative. This is important because, as procedures get more complex, longer, and contrast media is used, there is continuous interest in minimizing the potential kidney injury.”

A discussant at the briefing, Gary S. Mintz, MD, a senior medical adviser for the CRF, suggested a different approach to preventing contrast-induced nephropathy. “If you do imaging-guided zero-contrast percutaneous coronary intervention, you do not get contrast-induced nephropathy, period,” he said. “If you get rid of contrast, you get rid of contrast nephropathy. Anybody who has worked with patients who transition to dialysis understands that once you go on dialysis, your life changes for the worse no matter what you do. There has been no improvement in dialysis therapy in decades. But to me, the solution is to get rid of contrast, which can be done if you think differently and plan differently.”

For his part, Dr. Briguori said that he and his colleagues in REMEDIAL III “tried to use the least amount of contrast possible. The mean volume of contrast media in this trial was 70 mL, which is very low.”

The RenalGuard device (RenalGuard Solutions) is CE-marked for sale in Europe and is under investigation in the United States. The REMEDIAL III study was supported by an unrestricted grant from Guerbet (Villepinte, France) provided to the Mediterranea Cardiocentro. Dr. Briguori reported having no relevant disclosures.

[email protected]

SOURCE: Briguori C. TCT 2019, Late Breaking Trials 4 Session.

SAN FRANCISCO – A urine flow rate (UFR)–guided approach was superior to the left ventricular end-diastolic pressure (LVEDP)-guided hydration regimen in preventing contrast-induced acute kidney injury and acute pulmonary edema in high-risk patients.

The results come from a randomized, multicenter, investigator-initiated trial designed to compare two hydration strategies for reducing the risk of acute kidney injury that Carlo Briguori, MD, PhD, presented at the Transcatheter Cardiovascular Therapeutics annual meeting.

Between July 15, 2015 and June 6, 2019, Dr. Briguori, chief of the laboratory of interventional cardiology at the Mediterranea Cardiocentro in Naples, Italy, and his colleagues enrolled 708 patients with an estimated glomerular filtration rate of 45 mL/min per 1.73 m^{2 or less} and/or with a Mehran’s score greater of at least 11 and/or a Gurm’s score greater than 7. Of these, 355 were assigned to LVEDP-guided hydration with normal saline, while 353 were assigned to UFR-guided hydration controlled by the RenalGuard system. Iobitridol, a low-osmolar, nonionic contrast agent, was administered in all cases.

The primary endpoint for the trial, known as Renal Insufficiency Following Contrast Media Administration Trial III (REMEDIAL III), was the composite of contrast-induced acute kidney injury (defined as a serum creatinine increase of at least 25% and/or at least 0.5 mg/dL from baseline to 48 hours) and/or acute pulmonary edema. That endpoint occurred in 5.7% of patients in the UFR-guided group and in 10.3% of patients in the LVEDP-guided group (relative risk, 0.56; P = .036). As for side effects, three patients in the UFR-guided group (0.8%) experienced complications related to Foley insertion, including one case of hematuria and two cases of pain on micturition. No patients developed a urinary tract infection, Dr. Briguori reported at the meeting, which was sponsored by the Cardiovascular Research Foundation.

Hypokalemia occurred in 6.2% of patients in the UFR-guided group and 2.3% of patients in the LVEDP-guided group (RR, 2.70; P = .013), while potassium replacement was required in 5.1% of patients in the UFR-guided group, compared with 1.4% of LVEDP-guided patients (RR, 3.74; P = .009). Meanwhile, hypernatremia was observed in 1.2% of patients in both groups (P = 1.00).

“For the longest time, the interventional field has been trying to find ways to minimize acute kidney injury related to interventional procedures,” Juan F. Granada, MD, president and CEO of the Cardiovascular Research Foundation said in a media briefing. “We have a lot of data with multiple approaches with different results – mostly negative. This is important because, as procedures get more complex, longer, and contrast media is used, there is continuous interest in minimizing the potential kidney injury.”

A discussant at the briefing, Gary S. Mintz, MD, a senior medical adviser for the CRF, suggested a different approach to preventing contrast-induced nephropathy. “If you do imaging-guided zero-contrast percutaneous coronary intervention, you do not get contrast-induced nephropathy, period,” he said. “If you get rid of contrast, you get rid of contrast nephropathy. Anybody who has worked with patients who transition to dialysis understands that once you go on dialysis, your life changes for the worse no matter what you do. There has been no improvement in dialysis therapy in decades. But to me, the solution is to get rid of contrast, which can be done if you think differently and plan differently.”

For his part, Dr. Briguori said that he and his colleagues in REMEDIAL III “tried to use the least amount of contrast possible. The mean volume of contrast media in this trial was 70 mL, which is very low.”

The RenalGuard device (RenalGuard Solutions) is CE-marked for sale in Europe and is under investigation in the United States. The REMEDIAL III study was supported by an unrestricted grant from Guerbet (Villepinte, France) provided to the Mediterranea Cardiocentro. Dr. Briguori reported having no relevant disclosures.

[email protected]

SOURCE: Briguori C. TCT 2019, Late Breaking Trials 4 Session.

SAN FRANCISCO – A urine flow rate (UFR)–guided approach was superior to the left ventricular end-diastolic pressure (LVEDP)-guided hydration regimen in preventing contrast-induced acute kidney injury and acute pulmonary edema in high-risk patients.

The results come from a randomized, multicenter, investigator-initiated trial designed to compare two hydration strategies for reducing the risk of acute kidney injury that Carlo Briguori, MD, PhD, presented at the Transcatheter Cardiovascular Therapeutics annual meeting.

Between July 15, 2015 and June 6, 2019, Dr. Briguori, chief of the laboratory of interventional cardiology at the Mediterranea Cardiocentro in Naples, Italy, and his colleagues enrolled 708 patients with an estimated glomerular filtration rate of 45 mL/min per 1.73 m^{2 or less} and/or with a Mehran’s score greater of at least 11 and/or a Gurm’s score greater than 7. Of these, 355 were assigned to LVEDP-guided hydration with normal saline, while 353 were assigned to UFR-guided hydration controlled by the RenalGuard system. Iobitridol, a low-osmolar, nonionic contrast agent, was administered in all cases.

The primary endpoint for the trial, known as Renal Insufficiency Following Contrast Media Administration Trial III (REMEDIAL III), was the composite of contrast-induced acute kidney injury (defined as a serum creatinine increase of at least 25% and/or at least 0.5 mg/dL from baseline to 48 hours) and/or acute pulmonary edema. That endpoint occurred in 5.7% of patients in the UFR-guided group and in 10.3% of patients in the LVEDP-guided group (relative risk, 0.56; P = .036). As for side effects, three patients in the UFR-guided group (0.8%) experienced complications related to Foley insertion, including one case of hematuria and two cases of pain on micturition. No patients developed a urinary tract infection, Dr. Briguori reported at the meeting, which was sponsored by the Cardiovascular Research Foundation.

Hypokalemia occurred in 6.2% of patients in the UFR-guided group and 2.3% of patients in the LVEDP-guided group (RR, 2.70; P = .013), while potassium replacement was required in 5.1% of patients in the UFR-guided group, compared with 1.4% of LVEDP-guided patients (RR, 3.74; P = .009). Meanwhile, hypernatremia was observed in 1.2% of patients in both groups (P = 1.00).

“For the longest time, the interventional field has been trying to find ways to minimize acute kidney injury related to interventional procedures,” Juan F. Granada, MD, president and CEO of the Cardiovascular Research Foundation said in a media briefing. “We have a lot of data with multiple approaches with different results – mostly negative. This is important because, as procedures get more complex, longer, and contrast media is used, there is continuous interest in minimizing the potential kidney injury.”

A discussant at the briefing, Gary S. Mintz, MD, a senior medical adviser for the CRF, suggested a different approach to preventing contrast-induced nephropathy. “If you do imaging-guided zero-contrast percutaneous coronary intervention, you do not get contrast-induced nephropathy, period,” he said. “If you get rid of contrast, you get rid of contrast nephropathy. Anybody who has worked with patients who transition to dialysis understands that once you go on dialysis, your life changes for the worse no matter what you do. There has been no improvement in dialysis therapy in decades. But to me, the solution is to get rid of contrast, which can be done if you think differently and plan differently.”

For his part, Dr. Briguori said that he and his colleagues in REMEDIAL III “tried to use the least amount of contrast possible. The mean volume of contrast media in this trial was 70 mL, which is very low.”

The RenalGuard device (RenalGuard Solutions) is CE-marked for sale in Europe and is under investigation in the United States. The REMEDIAL III study was supported by an unrestricted grant from Guerbet (Villepinte, France) provided to the Mediterranea Cardiocentro. Dr. Briguori reported having no relevant disclosures.

[email protected]

SOURCE: Briguori C. TCT 2019, Late Breaking Trials 4 Session.

SAN FRANCISCO – An investigational device exemption trial of the Portico valve with FlexNav delivery system showed 1-year clinical results on par with commercially available valves, Gregory P. Fontana, MD, reported at the Transcatheter Cardiovascular Therapeutics annual meeting.

Doug Brunk/MDedge News

In a prospective, open-label study conducted at 52 sites known as PORTICO, Dr. Fontana and colleagues conducted a noninferiority intention-to-treat evaluation of the safety and effectiveness of the self-expanding Portico transcatheter aortic valve replacement system, compared with Food and Drug Administration–approved and commercially available TAVR systems for patients with severe aortic stenosis at high or extreme risk for surgery. Between May 2014 and June 2019, 750 patients from 69 sites were randomized 1:1 to each group. The prespecified primary safety composite endpoint was all-cause mortality, disabling stroke, life-threatening bleeding requiring blood transfusion, acute kidney injury requiring dialysis, or major vascular complications at 30 days, while the primary effectiveness composite endpoint was all-cause mortality or disabling stroke at 1 year.

The mean baseline age of patients was 83 years, 53% were female, and their mean Society of Thoracic Surgeons score was 6.5%. Dr. Fontana, director and chairman of cardiothoracic surgery at the CardioVascular Institute of Los Robles Regional Medical Center, Thousand Oaks, Calif., reported at the meeting sponsored by the Cardiovascular Research Foundation that procedural success was comparable between groups (96.5% for Portico vs, 98.3% for commercially available TAVR, respectively). In addition, patients in both groups met the prespecified primary safety composite endpoint (13.8% vs. 9.6%; P for noninferiority = .03) and the primary effectiveness composite endpoint (14.9% vs. 13.4%, P for noninferiority = .006).

However, the rate of moderate to severe paravalvular leak at 30 days was 6.3% among patients in the Portico valve group, compared with 2.1% of their counterparts in the commercially available TAVR group, a difference that did not reach noninferiority. Dr. Fontana said that a next-generation valve with design modifications to reduce paravalvular leak is being tested in clinical trials.

PORTICO included a separate cohort of 100 patients who underwent Portico valve implantation using the FlexNav Delivery System, which became available after the trial had launched. The primary safety endpoint for the FlexNav cohort was major vascular complication rate at 30 days. This cohort demonstrated no deaths or strokes, low rates of major vascular complications (7.0%) and new permanent pacemaker implants (14.6%), as well as a safety profile comparable with the commercially available valve group in the randomized study (8.0% vs. 9.6%).

“My sense of this device is that presumably it will be another valve we have available to us in the United States,” Pinak B. Shah, MD, a cardiologist at Brigham and Women’s Hospital, Boston, said during a media briefing. “The challenge to all of us is to figure out where it fits in our armamentarium. Is it going to be worth individuals to learn a whole new device when at this point it’s hard to say if there’s a major difference compared to the other self-expanding devices we have now?”

With the new FlexNav delivery system, the Portico valve is characterized by “a very calm, slow delivery,” said Dr. Fontana, who was the study’s coprincipal investigator, along with Raj R. Makkar, MD, director of interventional cardiology at Cedars-Sinai Medical Center, Los Angeles. “The operator can land the valve exactly where they want it. If they’re not happy, they can make some adjustments. I haven’t yet a system in my hands that is as stable as this. The option of having excellent hemodynamics and large cells to engage the coronary system is a unique combination for us in the United States.”

The Portico valve is not currently FDA approved. The PORTICO study was funded by Abbott. Dr. Fontana disclosed grant/research support from Abbott and Medtronic and consulting fees/honoraria from Abbott, Medtronic, and LivaNova.

[email protected]

SAN FRANCISCO – An investigational device exemption trial of the Portico valve with FlexNav delivery system showed 1-year clinical results on par with commercially available valves, Gregory P. Fontana, MD, reported at the Transcatheter Cardiovascular Therapeutics annual meeting.

Doug Brunk/MDedge News

In a prospective, open-label study conducted at 52 sites known as PORTICO, Dr. Fontana and colleagues conducted a noninferiority intention-to-treat evaluation of the safety and effectiveness of the self-expanding Portico transcatheter aortic valve replacement system, compared with Food and Drug Administration–approved and commercially available TAVR systems for patients with severe aortic stenosis at high or extreme risk for surgery. Between May 2014 and June 2019, 750 patients from 69 sites were randomized 1:1 to each group. The prespecified primary safety composite endpoint was all-cause mortality, disabling stroke, life-threatening bleeding requiring blood transfusion, acute kidney injury requiring dialysis, or major vascular complications at 30 days, while the primary effectiveness composite endpoint was all-cause mortality or disabling stroke at 1 year.

The mean baseline age of patients was 83 years, 53% were female, and their mean Society of Thoracic Surgeons score was 6.5%. Dr. Fontana, director and chairman of cardiothoracic surgery at the CardioVascular Institute of Los Robles Regional Medical Center, Thousand Oaks, Calif., reported at the meeting sponsored by the Cardiovascular Research Foundation that procedural success was comparable between groups (96.5% for Portico vs, 98.3% for commercially available TAVR, respectively). In addition, patients in both groups met the prespecified primary safety composite endpoint (13.8% vs. 9.6%; P for noninferiority = .03) and the primary effectiveness composite endpoint (14.9% vs. 13.4%, P for noninferiority = .006).

However, the rate of moderate to severe paravalvular leak at 30 days was 6.3% among patients in the Portico valve group, compared with 2.1% of their counterparts in the commercially available TAVR group, a difference that did not reach noninferiority. Dr. Fontana said that a next-generation valve with design modifications to reduce paravalvular leak is being tested in clinical trials.

PORTICO included a separate cohort of 100 patients who underwent Portico valve implantation using the FlexNav Delivery System, which became available after the trial had launched. The primary safety endpoint for the FlexNav cohort was major vascular complication rate at 30 days. This cohort demonstrated no deaths or strokes, low rates of major vascular complications (7.0%) and new permanent pacemaker implants (14.6%), as well as a safety profile comparable with the commercially available valve group in the randomized study (8.0% vs. 9.6%).

“My sense of this device is that presumably it will be another valve we have available to us in the United States,” Pinak B. Shah, MD, a cardiologist at Brigham and Women’s Hospital, Boston, said during a media briefing. “The challenge to all of us is to figure out where it fits in our armamentarium. Is it going to be worth individuals to learn a whole new device when at this point it’s hard to say if there’s a major difference compared to the other self-expanding devices we have now?”

With the new FlexNav delivery system, the Portico valve is characterized by “a very calm, slow delivery,” said Dr. Fontana, who was the study’s coprincipal investigator, along with Raj R. Makkar, MD, director of interventional cardiology at Cedars-Sinai Medical Center, Los Angeles. “The operator can land the valve exactly where they want it. If they’re not happy, they can make some adjustments. I haven’t yet a system in my hands that is as stable as this. The option of having excellent hemodynamics and large cells to engage the coronary system is a unique combination for us in the United States.”

The Portico valve is not currently FDA approved. The PORTICO study was funded by Abbott. Dr. Fontana disclosed grant/research support from Abbott and Medtronic and consulting fees/honoraria from Abbott, Medtronic, and LivaNova.

[email protected]

SAN FRANCISCO – An investigational device exemption trial of the Portico valve with FlexNav delivery system showed 1-year clinical results on par with commercially available valves, Gregory P. Fontana, MD, reported at the Transcatheter Cardiovascular Therapeutics annual meeting.

Doug Brunk/MDedge News

In a prospective, open-label study conducted at 52 sites known as PORTICO, Dr. Fontana and colleagues conducted a noninferiority intention-to-treat evaluation of the safety and effectiveness of the self-expanding Portico transcatheter aortic valve replacement system, compared with Food and Drug Administration–approved and commercially available TAVR systems for patients with severe aortic stenosis at high or extreme risk for surgery. Between May 2014 and June 2019, 750 patients from 69 sites were randomized 1:1 to each group. The prespecified primary safety composite endpoint was all-cause mortality, disabling stroke, life-threatening bleeding requiring blood transfusion, acute kidney injury requiring dialysis, or major vascular complications at 30 days, while the primary effectiveness composite endpoint was all-cause mortality or disabling stroke at 1 year.

The mean baseline age of patients was 83 years, 53% were female, and their mean Society of Thoracic Surgeons score was 6.5%. Dr. Fontana, director and chairman of cardiothoracic surgery at the CardioVascular Institute of Los Robles Regional Medical Center, Thousand Oaks, Calif., reported at the meeting sponsored by the Cardiovascular Research Foundation that procedural success was comparable between groups (96.5% for Portico vs, 98.3% for commercially available TAVR, respectively). In addition, patients in both groups met the prespecified primary safety composite endpoint (13.8% vs. 9.6%; P for noninferiority = .03) and the primary effectiveness composite endpoint (14.9% vs. 13.4%, P for noninferiority = .006).

However, the rate of moderate to severe paravalvular leak at 30 days was 6.3% among patients in the Portico valve group, compared with 2.1% of their counterparts in the commercially available TAVR group, a difference that did not reach noninferiority. Dr. Fontana said that a next-generation valve with design modifications to reduce paravalvular leak is being tested in clinical trials.

PORTICO included a separate cohort of 100 patients who underwent Portico valve implantation using the FlexNav Delivery System, which became available after the trial had launched. The primary safety endpoint for the FlexNav cohort was major vascular complication rate at 30 days. This cohort demonstrated no deaths or strokes, low rates of major vascular complications (7.0%) and new permanent pacemaker implants (14.6%), as well as a safety profile comparable with the commercially available valve group in the randomized study (8.0% vs. 9.6%).

“My sense of this device is that presumably it will be another valve we have available to us in the United States,” Pinak B. Shah, MD, a cardiologist at Brigham and Women’s Hospital, Boston, said during a media briefing. “The challenge to all of us is to figure out where it fits in our armamentarium. Is it going to be worth individuals to learn a whole new device when at this point it’s hard to say if there’s a major difference compared to the other self-expanding devices we have now?”

With the new FlexNav delivery system, the Portico valve is characterized by “a very calm, slow delivery,” said Dr. Fontana, who was the study’s coprincipal investigator, along with Raj R. Makkar, MD, director of interventional cardiology at Cedars-Sinai Medical Center, Los Angeles. “The operator can land the valve exactly where they want it. If they’re not happy, they can make some adjustments. I haven’t yet a system in my hands that is as stable as this. The option of having excellent hemodynamics and large cells to engage the coronary system is a unique combination for us in the United States.”

The Portico valve is not currently FDA approved. The PORTICO study was funded by Abbott. Dr. Fontana disclosed grant/research support from Abbott and Medtronic and consulting fees/honoraria from Abbott, Medtronic, and LivaNova.

[email protected]

SAN FRANCISCO – Among patients with left main coronary artery disease and low or intermediate coronary disease complexity, no significant differences were observed between percutaneous coronary intervention and coronary artery bypass graft surgery with respect to the composite rate of death, stroke, or myocardial infarction at 5 years.

Doug Brunk/MDedge News

The findings come from an analysis of data from the EXCEL trial, which lead investigator Gregg W. Stone, MD, presented at the Transcatheter Cardiovascular Therapeutics annual meeting.

“PCI may be considered an acceptable revascularization modality for selected patients with left main coronary artery disease, a decision which should be made after heart team discussion, taking into account each patient’s individual risk factors and preferences,” said Dr. Stone, professor of medicine and professor of population health sciences and policy at the Icahn School of Medicine at Mount Sinai, New York.

Between September 2010 and March 2014, Dr. Stone and his colleagues at 126 sites in 17 countries enrolled 1,905 patients with left main CAD and site-assessed low or intermediate CAD complexity (SYNTAX score of up to 32) for randomization into one of two arms: 948 to revascularization with the Xience everolimus-eluting stent and 957 to coronary artery bypass graft surgery (CABG). The primary outcome was the composite of death, stroke, or myocardial infarction at 5 years. Long-term additional secondary outcomes included their components at 5 years, as well as therapy failure (definite stent thrombosis or symptomatic graft stenosis or occlusion), all revascularizations, and all cerebrovascular events (stroke or transient ischemic attack).

Dr. Stone reported that at 5 years, the primary composite of death, stroke, or MI occurred in 22.0% of patients in the PCI group and 19.2% of patients in the CABG group, a nonsignificant difference at P = 0.13).

However, when the researchers broke the results into three distinct risk periods within the 5-year time frame, they found that, with longer follow-up, came more of an advantage for CABG. The relative risk of PCI vs. CABG for the primary outcome favored PCI over CABG in the first 30 days (4.9% vs. 8%; hazard ratio, 0.61; P = .008), was neutral at 30 days to 1 year (4.1 vs. 3.8%; HR, 1.07; P = .76), and reversed at 1-5 years (15.1% vs. 9.7%; HR, 1.61; P less than .001). Using restricted mean survival time analysis, Dr. Stone and his colleagues found that, at the end of the 5-year follow-up period, event-free survival time was 5.2 days longer after PCI, compared with CABG. This translates into “a very similar event-free survival of a burden of disease from these two therapies at the end of 5 years,” he said.

In their analysis of secondary endpoints, some differences were noted, including an elevated risk of all-cause mortality in the PCI group, compared with the CABG group (13% vs. 9.9%, respectively; odds ratio, 1.38), yet no differences in definite cardiovascular mortality (5% vs. 4.5%; OR, 1.13) or in MI (10.6% vs. 9.1%; OR 1.14). In addition, there were fewer cerebrovascular events in the PCI vs. CABG groups (3.3% vs. 5.2%; OR, 0.61). “Overall, all of these differences were relatively small given the 5-year perspective,” Dr. Stone said at the meeting sponsored by the Cardiovascular Research Foundation. He concluded that the early benefits of PCI attributable to reduced periprocedural risk “were attenuated by the greater number of events occurring during follow-up with CABG, such that at 5 years the cumulative mean time free from adverse events was similar with both treatments.” He noted that a 10-year or longer follow-up is required to characterize the very late safety profile of PCI and CABG as both stents and bypass grafts progressively fail over time.

Discussant Dharam Kumbhani, MD, an interventional cardiologist at UT Southwestern Medical Center, Dallas, said that the findings from EXCEL “help us move the field forward and help us understand this concept of risk with PCI versus CABG. It really does help inform shared decision-making with patients.”

Results of the study were published online at the time of presentation (N Engl J Med. 2019 Sep 28. doi: 10.1056/NEJMoa1909406). The EXCEL trial was funded by Abbott Vascular. Dr. Stone disclosed having relationships with numerous device and pharmaceutical companies but had no relevant disclosures for this study.

[email protected]

SOURCE: Stone G et al. TCT 2019. N Engl J Med. 2019 Sep 28. doi: 10.1056/NEJMoa1909406.
 

SAN FRANCISCO – Among patients with left main coronary artery disease and low or intermediate coronary disease complexity, no significant differences were observed between percutaneous coronary intervention and coronary artery bypass graft surgery with respect to the composite rate of death, stroke, or myocardial infarction at 5 years.

Doug Brunk/MDedge News

The findings come from an analysis of data from the EXCEL trial, which lead investigator Gregg W. Stone, MD, presented at the Transcatheter Cardiovascular Therapeutics annual meeting.

“PCI may be considered an acceptable revascularization modality for selected patients with left main coronary artery disease, a decision which should be made after heart team discussion, taking into account each patient’s individual risk factors and preferences,” said Dr. Stone, professor of medicine and professor of population health sciences and policy at the Icahn School of Medicine at Mount Sinai, New York.

Between September 2010 and March 2014, Dr. Stone and his colleagues at 126 sites in 17 countries enrolled 1,905 patients with left main CAD and site-assessed low or intermediate CAD complexity (SYNTAX score of up to 32) for randomization into one of two arms: 948 to revascularization with the Xience everolimus-eluting stent and 957 to coronary artery bypass graft surgery (CABG). The primary outcome was the composite of death, stroke, or myocardial infarction at 5 years. Long-term additional secondary outcomes included their components at 5 years, as well as therapy failure (definite stent thrombosis or symptomatic graft stenosis or occlusion), all revascularizations, and all cerebrovascular events (stroke or transient ischemic attack).

Dr. Stone reported that at 5 years, the primary composite of death, stroke, or MI occurred in 22.0% of patients in the PCI group and 19.2% of patients in the CABG group, a nonsignificant difference at P = 0.13).

However, when the researchers broke the results into three distinct risk periods within the 5-year time frame, they found that, with longer follow-up, came more of an advantage for CABG. The relative risk of PCI vs. CABG for the primary outcome favored PCI over CABG in the first 30 days (4.9% vs. 8%; hazard ratio, 0.61; P = .008), was neutral at 30 days to 1 year (4.1 vs. 3.8%; HR, 1.07; P = .76), and reversed at 1-5 years (15.1% vs. 9.7%; HR, 1.61; P less than .001). Using restricted mean survival time analysis, Dr. Stone and his colleagues found that, at the end of the 5-year follow-up period, event-free survival time was 5.2 days longer after PCI, compared with CABG. This translates into “a very similar event-free survival of a burden of disease from these two therapies at the end of 5 years,” he said.

In their analysis of secondary endpoints, some differences were noted, including an elevated risk of all-cause mortality in the PCI group, compared with the CABG group (13% vs. 9.9%, respectively; odds ratio, 1.38), yet no differences in definite cardiovascular mortality (5% vs. 4.5%; OR, 1.13) or in MI (10.6% vs. 9.1%; OR 1.14). In addition, there were fewer cerebrovascular events in the PCI vs. CABG groups (3.3% vs. 5.2%; OR, 0.61). “Overall, all of these differences were relatively small given the 5-year perspective,” Dr. Stone said at the meeting sponsored by the Cardiovascular Research Foundation. He concluded that the early benefits of PCI attributable to reduced periprocedural risk “were attenuated by the greater number of events occurring during follow-up with CABG, such that at 5 years the cumulative mean time free from adverse events was similar with both treatments.” He noted that a 10-year or longer follow-up is required to characterize the very late safety profile of PCI and CABG as both stents and bypass grafts progressively fail over time.

Discussant Dharam Kumbhani, MD, an interventional cardiologist at UT Southwestern Medical Center, Dallas, said that the findings from EXCEL “help us move the field forward and help us understand this concept of risk with PCI versus CABG. It really does help inform shared decision-making with patients.”

Results of the study were published online at the time of presentation (N Engl J Med. 2019 Sep 28. doi: 10.1056/NEJMoa1909406). The EXCEL trial was funded by Abbott Vascular. Dr. Stone disclosed having relationships with numerous device and pharmaceutical companies but had no relevant disclosures for this study.

[email protected]

SOURCE: Stone G et al. TCT 2019. N Engl J Med. 2019 Sep 28. doi: 10.1056/NEJMoa1909406.
 

SAN FRANCISCO – Among patients with left main coronary artery disease and low or intermediate coronary disease complexity, no significant differences were observed between percutaneous coronary intervention and coronary artery bypass graft surgery with respect to the composite rate of death, stroke, or myocardial infarction at 5 years.

Doug Brunk/MDedge News

The findings come from an analysis of data from the EXCEL trial, which lead investigator Gregg W. Stone, MD, presented at the Transcatheter Cardiovascular Therapeutics annual meeting.

“PCI may be considered an acceptable revascularization modality for selected patients with left main coronary artery disease, a decision which should be made after heart team discussion, taking into account each patient’s individual risk factors and preferences,” said Dr. Stone, professor of medicine and professor of population health sciences and policy at the Icahn School of Medicine at Mount Sinai, New York.

Between September 2010 and March 2014, Dr. Stone and his colleagues at 126 sites in 17 countries enrolled 1,905 patients with left main CAD and site-assessed low or intermediate CAD complexity (SYNTAX score of up to 32) for randomization into one of two arms: 948 to revascularization with the Xience everolimus-eluting stent and 957 to coronary artery bypass graft surgery (CABG). The primary outcome was the composite of death, stroke, or myocardial infarction at 5 years. Long-term additional secondary outcomes included their components at 5 years, as well as therapy failure (definite stent thrombosis or symptomatic graft stenosis or occlusion), all revascularizations, and all cerebrovascular events (stroke or transient ischemic attack).

Dr. Stone reported that at 5 years, the primary composite of death, stroke, or MI occurred in 22.0% of patients in the PCI group and 19.2% of patients in the CABG group, a nonsignificant difference at P = 0.13).

However, when the researchers broke the results into three distinct risk periods within the 5-year time frame, they found that, with longer follow-up, came more of an advantage for CABG. The relative risk of PCI vs. CABG for the primary outcome favored PCI over CABG in the first 30 days (4.9% vs. 8%; hazard ratio, 0.61; P = .008), was neutral at 30 days to 1 year (4.1 vs. 3.8%; HR, 1.07; P = .76), and reversed at 1-5 years (15.1% vs. 9.7%; HR, 1.61; P less than .001). Using restricted mean survival time analysis, Dr. Stone and his colleagues found that, at the end of the 5-year follow-up period, event-free survival time was 5.2 days longer after PCI, compared with CABG. This translates into “a very similar event-free survival of a burden of disease from these two therapies at the end of 5 years,” he said.

In their analysis of secondary endpoints, some differences were noted, including an elevated risk of all-cause mortality in the PCI group, compared with the CABG group (13% vs. 9.9%, respectively; odds ratio, 1.38), yet no differences in definite cardiovascular mortality (5% vs. 4.5%; OR, 1.13) or in MI (10.6% vs. 9.1%; OR 1.14). In addition, there were fewer cerebrovascular events in the PCI vs. CABG groups (3.3% vs. 5.2%; OR, 0.61). “Overall, all of these differences were relatively small given the 5-year perspective,” Dr. Stone said at the meeting sponsored by the Cardiovascular Research Foundation. He concluded that the early benefits of PCI attributable to reduced periprocedural risk “were attenuated by the greater number of events occurring during follow-up with CABG, such that at 5 years the cumulative mean time free from adverse events was similar with both treatments.” He noted that a 10-year or longer follow-up is required to characterize the very late safety profile of PCI and CABG as both stents and bypass grafts progressively fail over time.

Discussant Dharam Kumbhani, MD, an interventional cardiologist at UT Southwestern Medical Center, Dallas, said that the findings from EXCEL “help us move the field forward and help us understand this concept of risk with PCI versus CABG. It really does help inform shared decision-making with patients.”

Results of the study were published online at the time of presentation (N Engl J Med. 2019 Sep 28. doi: 10.1056/NEJMoa1909406). The EXCEL trial was funded by Abbott Vascular. Dr. Stone disclosed having relationships with numerous device and pharmaceutical companies but had no relevant disclosures for this study.

[email protected]

SOURCE: Stone G et al. TCT 2019. N Engl J Med. 2019 Sep 28. doi: 10.1056/NEJMoa1909406.
 

SAN FRANCISCO – Reducing the dual antiplatelet therapy period to 3 months after implantation of Ultimaster sirolimus-eluting stent was noninferior to a longer duration of DAPT in a historical cohort, results from a prospective study showed.

Doug Brunk/MDedge News

In addition, P2Y12 inhibitor monotherapy was almost equivalent to aspirin monotherapy after 3 months in terms of both bleeding and thrombotic events.

“Recent guidelines recommend short DAPT up to 3 months, only in high bleeding risk patients,” lead investigator Ken Kozuma, MD, said during a media briefing at the Transcatheter Cardiovascular Therapeutics annual meeting. “However, short-term DAPT may be beneficial for any patients. Aspirin may be more associated with bleeding complication than P2Y12 receptor inhibitors.”

In a single-arm registry trial known as MODEL U-SES, Dr. Kozuma, of Teikyo University Hospital in Tokyo, and colleagues at 65 sites in Japan prospectively evaluated the safety of 3-month DAPT after implantation of the Ultimaster bioresorbable polymer sirolimus-eluting stent (BP-SES). The secondary objective was to investigate the appropriateness of P2Y12 receptor inhibitor monotherapy compared with aspirin monotherapy after 3 months. The researchers enrolled 1,695 patients with a mean age of 70 years who were treated with U-SES and considered appropriate for 3-month DAPT after implantation.

The primary endpoint was a composite endpoint of all-cause death, myocardial infarction, stroke (ischemic and hemorrhagic), Academic Research Consortium (ARC) definite/probable stent thrombosis, and serious bleeding (Bleeding Academic Research Consortium [BARC] 3 or 5) during the 12 months after stent implantation. Major secondary endpoints included a comparison of the incidence of each event for each continued antiplatelet drug.

Of the 1,695 patients enrolled, 1,686 completed 3-month clinical follow-up while 1,616 completed 1-year clinical follow-up. Patient-level adjusted historical data from 542 subjects in the CENTURY II cohort was used as the control group. Patients in that trial received the same stent but took DAPT for 1 year.

Dr. Kozuma reported that the primary endpoint occurred in 4.3% of patients in the MODEL U-SES group, compared with 5.7% of patients in the CENTURY II BP-SES group, a difference of –3.17%, which demonstrated noninferiority of the trial (P less than .001). At 3 months, P2Y12 inhibitor monotherapy was equivalent to aspirin monotherapy in terms of both bleeding and thrombotic events (2.5% in each modality; hazard ratio, 1.14; P = 0.71).

Dr. Kozuma acknowledged certain limitations of the trial, including the fact that propensity score adjusted analysis “may not compensate the selection bias of this study sufficiently, since considerable baseline difference was observed. Also, comparison between aspirin and P2Y12 receptor inhibitors was not randomized so that the safety and efficacy of each antiplatelet monotherapy cannot be conclusive.”

Despite these limitations, he concluded that the trial “demonstrated that 3-month DAPT was noninferior to an adjusted cohort of longer DAPT after BP-SES implantation in net adverse clinical events. Direct comparison between P2Y12 inhibitor and aspirin would be necessary to confirm the efficacy and safety of P2Y12 inhibitor monotherapy in a randomized fashion.”

The meeting was sponsored by the Cardiovascular Research Foundation.

Terumo sponsored the trial. Dr. Kozuma disclosed that he serves on the scientific advisory boards for and has received honoraria from Terumo, Abbott Vascular Japan, Boston Scientific Japan, Daiichi-Sankyo, Sanofi, Bayer, Boehringer Ingelheim and Bristol-Meyers Squibb.

[email protected]

SOURCE: Kozuma K et al. TCT 2019, late-breaking presentation.

SAN FRANCISCO – Reducing the dual antiplatelet therapy period to 3 months after implantation of Ultimaster sirolimus-eluting stent was noninferior to a longer duration of DAPT in a historical cohort, results from a prospective study showed.

Doug Brunk/MDedge News

In addition, P2Y12 inhibitor monotherapy was almost equivalent to aspirin monotherapy after 3 months in terms of both bleeding and thrombotic events.

“Recent guidelines recommend short DAPT up to 3 months, only in high bleeding risk patients,” lead investigator Ken Kozuma, MD, said during a media briefing at the Transcatheter Cardiovascular Therapeutics annual meeting. “However, short-term DAPT may be beneficial for any patients. Aspirin may be more associated with bleeding complication than P2Y12 receptor inhibitors.”

In a single-arm registry trial known as MODEL U-SES, Dr. Kozuma, of Teikyo University Hospital in Tokyo, and colleagues at 65 sites in Japan prospectively evaluated the safety of 3-month DAPT after implantation of the Ultimaster bioresorbable polymer sirolimus-eluting stent (BP-SES). The secondary objective was to investigate the appropriateness of P2Y12 receptor inhibitor monotherapy compared with aspirin monotherapy after 3 months. The researchers enrolled 1,695 patients with a mean age of 70 years who were treated with U-SES and considered appropriate for 3-month DAPT after implantation.

The primary endpoint was a composite endpoint of all-cause death, myocardial infarction, stroke (ischemic and hemorrhagic), Academic Research Consortium (ARC) definite/probable stent thrombosis, and serious bleeding (Bleeding Academic Research Consortium [BARC] 3 or 5) during the 12 months after stent implantation. Major secondary endpoints included a comparison of the incidence of each event for each continued antiplatelet drug.

Of the 1,695 patients enrolled, 1,686 completed 3-month clinical follow-up while 1,616 completed 1-year clinical follow-up. Patient-level adjusted historical data from 542 subjects in the CENTURY II cohort was used as the control group. Patients in that trial received the same stent but took DAPT for 1 year.

Dr. Kozuma reported that the primary endpoint occurred in 4.3% of patients in the MODEL U-SES group, compared with 5.7% of patients in the CENTURY II BP-SES group, a difference of –3.17%, which demonstrated noninferiority of the trial (P less than .001). At 3 months, P2Y12 inhibitor monotherapy was equivalent to aspirin monotherapy in terms of both bleeding and thrombotic events (2.5% in each modality; hazard ratio, 1.14; P = 0.71).

Dr. Kozuma acknowledged certain limitations of the trial, including the fact that propensity score adjusted analysis “may not compensate the selection bias of this study sufficiently, since considerable baseline difference was observed. Also, comparison between aspirin and P2Y12 receptor inhibitors was not randomized so that the safety and efficacy of each antiplatelet monotherapy cannot be conclusive.”

Despite these limitations, he concluded that the trial “demonstrated that 3-month DAPT was noninferior to an adjusted cohort of longer DAPT after BP-SES implantation in net adverse clinical events. Direct comparison between P2Y12 inhibitor and aspirin would be necessary to confirm the efficacy and safety of P2Y12 inhibitor monotherapy in a randomized fashion.”

The meeting was sponsored by the Cardiovascular Research Foundation.

Terumo sponsored the trial. Dr. Kozuma disclosed that he serves on the scientific advisory boards for and has received honoraria from Terumo, Abbott Vascular Japan, Boston Scientific Japan, Daiichi-Sankyo, Sanofi, Bayer, Boehringer Ingelheim and Bristol-Meyers Squibb.

[email protected]

SOURCE: Kozuma K et al. TCT 2019, late-breaking presentation.

SAN FRANCISCO – Reducing the dual antiplatelet therapy period to 3 months after implantation of Ultimaster sirolimus-eluting stent was noninferior to a longer duration of DAPT in a historical cohort, results from a prospective study showed.

Doug Brunk/MDedge News

In addition, P2Y12 inhibitor monotherapy was almost equivalent to aspirin monotherapy after 3 months in terms of both bleeding and thrombotic events.

“Recent guidelines recommend short DAPT up to 3 months, only in high bleeding risk patients,” lead investigator Ken Kozuma, MD, said during a media briefing at the Transcatheter Cardiovascular Therapeutics annual meeting. “However, short-term DAPT may be beneficial for any patients. Aspirin may be more associated with bleeding complication than P2Y12 receptor inhibitors.”

In a single-arm registry trial known as MODEL U-SES, Dr. Kozuma, of Teikyo University Hospital in Tokyo, and colleagues at 65 sites in Japan prospectively evaluated the safety of 3-month DAPT after implantation of the Ultimaster bioresorbable polymer sirolimus-eluting stent (BP-SES). The secondary objective was to investigate the appropriateness of P2Y12 receptor inhibitor monotherapy compared with aspirin monotherapy after 3 months. The researchers enrolled 1,695 patients with a mean age of 70 years who were treated with U-SES and considered appropriate for 3-month DAPT after implantation.

The primary endpoint was a composite endpoint of all-cause death, myocardial infarction, stroke (ischemic and hemorrhagic), Academic Research Consortium (ARC) definite/probable stent thrombosis, and serious bleeding (Bleeding Academic Research Consortium [BARC] 3 or 5) during the 12 months after stent implantation. Major secondary endpoints included a comparison of the incidence of each event for each continued antiplatelet drug.

Of the 1,695 patients enrolled, 1,686 completed 3-month clinical follow-up while 1,616 completed 1-year clinical follow-up. Patient-level adjusted historical data from 542 subjects in the CENTURY II cohort was used as the control group. Patients in that trial received the same stent but took DAPT for 1 year.

Dr. Kozuma reported that the primary endpoint occurred in 4.3% of patients in the MODEL U-SES group, compared with 5.7% of patients in the CENTURY II BP-SES group, a difference of –3.17%, which demonstrated noninferiority of the trial (P less than .001). At 3 months, P2Y12 inhibitor monotherapy was equivalent to aspirin monotherapy in terms of both bleeding and thrombotic events (2.5% in each modality; hazard ratio, 1.14; P = 0.71).

Dr. Kozuma acknowledged certain limitations of the trial, including the fact that propensity score adjusted analysis “may not compensate the selection bias of this study sufficiently, since considerable baseline difference was observed. Also, comparison between aspirin and P2Y12 receptor inhibitors was not randomized so that the safety and efficacy of each antiplatelet monotherapy cannot be conclusive.”

Despite these limitations, he concluded that the trial “demonstrated that 3-month DAPT was noninferior to an adjusted cohort of longer DAPT after BP-SES implantation in net adverse clinical events. Direct comparison between P2Y12 inhibitor and aspirin would be necessary to confirm the efficacy and safety of P2Y12 inhibitor monotherapy in a randomized fashion.”

The meeting was sponsored by the Cardiovascular Research Foundation.

Terumo sponsored the trial. Dr. Kozuma disclosed that he serves on the scientific advisory boards for and has received honoraria from Terumo, Abbott Vascular Japan, Boston Scientific Japan, Daiichi-Sankyo, Sanofi, Bayer, Boehringer Ingelheim and Bristol-Meyers Squibb.

[email protected]

SOURCE: Kozuma K et al. TCT 2019, late-breaking presentation.

CHICAGO – The need for additional intervention after repair of the ascending aorta in extended type A aortic dissection has been thought to follow the practice for type B dissection and favor preemptive thoracic endovascular aortic repair. However, preemptive TEVAR may, at least in the midterm, provide no benefit in patients with extended type A dissections, according to results reported at the annual meeting of the Midwestern Vascular Surgery Society.

DAJ/Thinkstock

“TEVAR does not appear to be indicated in patients with extended type A dissections after acute aortic repair,” said Amy B. Reed, MD, of the University of Minnesota.

The study’s hypothesis was that growth rates of dissection and the need for additional intervention in the descending thoracic aorta are similar between extended type A (ExTA) and type B aortic dissection after initial repair of the ascending aorta. Dr. Reed noted that investigators from the INSTEAD-XL trial reported that preemptive TEVAR improved outcomes in patients with type B dissections (Circ Cardiovasc Interv. 2013;6:407-16). “The thinking has been that patients with uncomplicated ExTA would also benefit from early TEVAR,” Dr. Reed said.

The study evaluated 87 consecutive patients from 2011 to 2018, 43 with ExTA and 44 with type B dissections. Characteristics of both groups were similar, except the type B group had a significantly higher rate of coronary artery disease, 16% vs. 0% (P = .01). The distal extent of the dissection was beyond the aortic bifurcation in 75% of the ExTA patients and 52% of the type B group, “so we felt that these groups were really well matched,” Dr. Reed said.

Of the 43 ExTA patients, five had repair and 38 had no intervention. At an average follow-up of 33 months, 23 of the no-intervention patients showed no growth of their dissection, Dr. Reed said. In the type B group, 15 had no repair, and of those nine showed no growth (one patient died early and five did show growth).

“When we look at intervention-free survival, there’s a significant difference between our ExTA patients vs. our type B patients over time, with significantly more type B patients requiring intervention,” she said. At 28 months, 88% of ExTA were intervention free, whereas at 9 months 35% of type B patients were.

“We feel that, following the repair of ascending acute aortic dissection, in those patients with ExTA dissections, there does appear to be a slow progression of distal aortic disease,” Dr. Reed said. “Rarely do these patients develop complications such as dissection needing intervention either in the acute hospital period or delayed.”

Because the findings are based on medium-term follow-up, she said, “We certainly need further follow-up to confirm these midterm findings.”

Dr. Reed had no relevant financial relationships to disclose.

CHICAGO – The need for additional intervention after repair of the ascending aorta in extended type A aortic dissection has been thought to follow the practice for type B dissection and favor preemptive thoracic endovascular aortic repair. However, preemptive TEVAR may, at least in the midterm, provide no benefit in patients with extended type A dissections, according to results reported at the annual meeting of the Midwestern Vascular Surgery Society.

DAJ/Thinkstock

“TEVAR does not appear to be indicated in patients with extended type A dissections after acute aortic repair,” said Amy B. Reed, MD, of the University of Minnesota.

The study’s hypothesis was that growth rates of dissection and the need for additional intervention in the descending thoracic aorta are similar between extended type A (ExTA) and type B aortic dissection after initial repair of the ascending aorta. Dr. Reed noted that investigators from the INSTEAD-XL trial reported that preemptive TEVAR improved outcomes in patients with type B dissections (Circ Cardiovasc Interv. 2013;6:407-16). “The thinking has been that patients with uncomplicated ExTA would also benefit from early TEVAR,” Dr. Reed said.

The study evaluated 87 consecutive patients from 2011 to 2018, 43 with ExTA and 44 with type B dissections. Characteristics of both groups were similar, except the type B group had a significantly higher rate of coronary artery disease, 16% vs. 0% (P = .01). The distal extent of the dissection was beyond the aortic bifurcation in 75% of the ExTA patients and 52% of the type B group, “so we felt that these groups were really well matched,” Dr. Reed said.

Of the 43 ExTA patients, five had repair and 38 had no intervention. At an average follow-up of 33 months, 23 of the no-intervention patients showed no growth of their dissection, Dr. Reed said. In the type B group, 15 had no repair, and of those nine showed no growth (one patient died early and five did show growth).

“When we look at intervention-free survival, there’s a significant difference between our ExTA patients vs. our type B patients over time, with significantly more type B patients requiring intervention,” she said. At 28 months, 88% of ExTA were intervention free, whereas at 9 months 35% of type B patients were.

“We feel that, following the repair of ascending acute aortic dissection, in those patients with ExTA dissections, there does appear to be a slow progression of distal aortic disease,” Dr. Reed said. “Rarely do these patients develop complications such as dissection needing intervention either in the acute hospital period or delayed.”

Because the findings are based on medium-term follow-up, she said, “We certainly need further follow-up to confirm these midterm findings.”

Dr. Reed had no relevant financial relationships to disclose.

CHICAGO – The need for additional intervention after repair of the ascending aorta in extended type A aortic dissection has been thought to follow the practice for type B dissection and favor preemptive thoracic endovascular aortic repair. However, preemptive TEVAR may, at least in the midterm, provide no benefit in patients with extended type A dissections, according to results reported at the annual meeting of the Midwestern Vascular Surgery Society.

DAJ/Thinkstock

“TEVAR does not appear to be indicated in patients with extended type A dissections after acute aortic repair,” said Amy B. Reed, MD, of the University of Minnesota.

The study’s hypothesis was that growth rates of dissection and the need for additional intervention in the descending thoracic aorta are similar between extended type A (ExTA) and type B aortic dissection after initial repair of the ascending aorta. Dr. Reed noted that investigators from the INSTEAD-XL trial reported that preemptive TEVAR improved outcomes in patients with type B dissections (Circ Cardiovasc Interv. 2013;6:407-16). “The thinking has been that patients with uncomplicated ExTA would also benefit from early TEVAR,” Dr. Reed said.

The study evaluated 87 consecutive patients from 2011 to 2018, 43 with ExTA and 44 with type B dissections. Characteristics of both groups were similar, except the type B group had a significantly higher rate of coronary artery disease, 16% vs. 0% (P = .01). The distal extent of the dissection was beyond the aortic bifurcation in 75% of the ExTA patients and 52% of the type B group, “so we felt that these groups were really well matched,” Dr. Reed said.

Of the 43 ExTA patients, five had repair and 38 had no intervention. At an average follow-up of 33 months, 23 of the no-intervention patients showed no growth of their dissection, Dr. Reed said. In the type B group, 15 had no repair, and of those nine showed no growth (one patient died early and five did show growth).

“When we look at intervention-free survival, there’s a significant difference between our ExTA patients vs. our type B patients over time, with significantly more type B patients requiring intervention,” she said. At 28 months, 88% of ExTA were intervention free, whereas at 9 months 35% of type B patients were.

“We feel that, following the repair of ascending acute aortic dissection, in those patients with ExTA dissections, there does appear to be a slow progression of distal aortic disease,” Dr. Reed said. “Rarely do these patients develop complications such as dissection needing intervention either in the acute hospital period or delayed.”

Because the findings are based on medium-term follow-up, she said, “We certainly need further follow-up to confirm these midterm findings.”

Dr. Reed had no relevant financial relationships to disclose.

PARIS – The risk of infective endocarditis following transcatheter aortic valve replacement (TAVR) for the treatment of severe aortic stenosis proved to be the same as after surgical replacement in a French national propensity score–matched study.

This finding from what is believed to be the largest-ever study of infective endocarditis following TAVR will come as a surprise to many physicians. It’s easy to mistakenly assume the risk of this feared complication is lower – and perhaps even negligible – in TAVR patients since the procedure doesn’t involve a significant surgical wound, it’s briefer, the hospital length of stay is shorter, and recovery time is markedly less than with surgical aortic valve replacement (SAVR).

Not so, Laurent Fauchier, MD, PhD, said in presenting the study findings at the annual congress of the European Society of Cardiology.

“Do not think there is a lower risk of infective endocarditis. Be aware, be careful, and provide appropriate antibiotic prophylaxis, just as surgeons do in SAVR. Don’t think, as I did, that with TAVR with no pacemaker implantation there is no risk of infective endocarditis. The TAVR valve is a device, it’s a prosthesis, and the risk is very similar to that of surgery,” advised Dr. Fauchier, a cardiologist at Francois Rabelais University in Tours, France.

He presented a study of all of the nearly 108,000 patients who underwent isolated TAVR or SAVR in France during 2010-2018. The data source was the French national administrative hospital discharge record system. Since the TAVR patients were overall markedly older and sicker than the SAVR patients, especially during the first years of the study, he and his coinvestigators performed propensity score matching using 30 variables, which enabled them to narrow the field of inquiry down to a carefully selected study population of 16,291 TAVR patients and an equal number of closely similar SAVR patients.

A total of 1,070 cases of infective endocarditis occurred during a mean follow-up of just over 2 years. The rate of hospital admission for this complication was 1.89% per year in the TAVR group and similar at 1.71% per year in the SAVR cohort.

Of note, all-cause mortality in TAVR patients who developed infective endocarditis was 1.32-fold greater than it was in SAVR patients with infective endocarditis, a statistically significant difference. The explanation for the increased mortality risk in the TAVR group probably has to do at least in part with an inability on the part of the investigators to fully capture and control for the TAVR group’s greater frailty, according to the cardiologist.

Risk factors for infective endocarditis shared in common by TAVR and SAVR patients included male gender, a higher Charlson Comorbidity Index score, and a greater frailty index. The main predictors unique to the TAVR patients were atrial fibrillation, anemia, and tricuspid regurgitation. And although pacemaker and defibrillator implantation were risk factors for infective endocarditis in the SAVR patients, it wasn’t predictive of increased risk in the TAVR population. Dr. Fauchier called this finding “quite reassuring” given that roughly 20% of the TAVR group received a pacemaker.

The causative microorganisms for infective endocarditis were essentially the same in the TAVR and SAVR groups, simplifying antimicrobial prophylaxis decision making.

Dr. Fauchier reported having no financial conflicts regarding the study, conducted free of commercial support. He serves as a consultant to and/or on speakers’ bureaus for Bayer, BMS Pfizer, Boehringer Ingelheim, Medtronic, and Novartis.

[email protected]

PARIS – The risk of infective endocarditis following transcatheter aortic valve replacement (TAVR) for the treatment of severe aortic stenosis proved to be the same as after surgical replacement in a French national propensity score–matched study.

This finding from what is believed to be the largest-ever study of infective endocarditis following TAVR will come as a surprise to many physicians. It’s easy to mistakenly assume the risk of this feared complication is lower – and perhaps even negligible – in TAVR patients since the procedure doesn’t involve a significant surgical wound, it’s briefer, the hospital length of stay is shorter, and recovery time is markedly less than with surgical aortic valve replacement (SAVR).

Not so, Laurent Fauchier, MD, PhD, said in presenting the study findings at the annual congress of the European Society of Cardiology.

“Do not think there is a lower risk of infective endocarditis. Be aware, be careful, and provide appropriate antibiotic prophylaxis, just as surgeons do in SAVR. Don’t think, as I did, that with TAVR with no pacemaker implantation there is no risk of infective endocarditis. The TAVR valve is a device, it’s a prosthesis, and the risk is very similar to that of surgery,” advised Dr. Fauchier, a cardiologist at Francois Rabelais University in Tours, France.

He presented a study of all of the nearly 108,000 patients who underwent isolated TAVR or SAVR in France during 2010-2018. The data source was the French national administrative hospital discharge record system. Since the TAVR patients were overall markedly older and sicker than the SAVR patients, especially during the first years of the study, he and his coinvestigators performed propensity score matching using 30 variables, which enabled them to narrow the field of inquiry down to a carefully selected study population of 16,291 TAVR patients and an equal number of closely similar SAVR patients.

A total of 1,070 cases of infective endocarditis occurred during a mean follow-up of just over 2 years. The rate of hospital admission for this complication was 1.89% per year in the TAVR group and similar at 1.71% per year in the SAVR cohort.

Of note, all-cause mortality in TAVR patients who developed infective endocarditis was 1.32-fold greater than it was in SAVR patients with infective endocarditis, a statistically significant difference. The explanation for the increased mortality risk in the TAVR group probably has to do at least in part with an inability on the part of the investigators to fully capture and control for the TAVR group’s greater frailty, according to the cardiologist.

Risk factors for infective endocarditis shared in common by TAVR and SAVR patients included male gender, a higher Charlson Comorbidity Index score, and a greater frailty index. The main predictors unique to the TAVR patients were atrial fibrillation, anemia, and tricuspid regurgitation. And although pacemaker and defibrillator implantation were risk factors for infective endocarditis in the SAVR patients, it wasn’t predictive of increased risk in the TAVR population. Dr. Fauchier called this finding “quite reassuring” given that roughly 20% of the TAVR group received a pacemaker.

The causative microorganisms for infective endocarditis were essentially the same in the TAVR and SAVR groups, simplifying antimicrobial prophylaxis decision making.

Dr. Fauchier reported having no financial conflicts regarding the study, conducted free of commercial support. He serves as a consultant to and/or on speakers’ bureaus for Bayer, BMS Pfizer, Boehringer Ingelheim, Medtronic, and Novartis.

[email protected]

PARIS – The risk of infective endocarditis following transcatheter aortic valve replacement (TAVR) for the treatment of severe aortic stenosis proved to be the same as after surgical replacement in a French national propensity score–matched study.

This finding from what is believed to be the largest-ever study of infective endocarditis following TAVR will come as a surprise to many physicians. It’s easy to mistakenly assume the risk of this feared complication is lower – and perhaps even negligible – in TAVR patients since the procedure doesn’t involve a significant surgical wound, it’s briefer, the hospital length of stay is shorter, and recovery time is markedly less than with surgical aortic valve replacement (SAVR).

Not so, Laurent Fauchier, MD, PhD, said in presenting the study findings at the annual congress of the European Society of Cardiology.

“Do not think there is a lower risk of infective endocarditis. Be aware, be careful, and provide appropriate antibiotic prophylaxis, just as surgeons do in SAVR. Don’t think, as I did, that with TAVR with no pacemaker implantation there is no risk of infective endocarditis. The TAVR valve is a device, it’s a prosthesis, and the risk is very similar to that of surgery,” advised Dr. Fauchier, a cardiologist at Francois Rabelais University in Tours, France.

He presented a study of all of the nearly 108,000 patients who underwent isolated TAVR or SAVR in France during 2010-2018. The data source was the French national administrative hospital discharge record system. Since the TAVR patients were overall markedly older and sicker than the SAVR patients, especially during the first years of the study, he and his coinvestigators performed propensity score matching using 30 variables, which enabled them to narrow the field of inquiry down to a carefully selected study population of 16,291 TAVR patients and an equal number of closely similar SAVR patients.

A total of 1,070 cases of infective endocarditis occurred during a mean follow-up of just over 2 years. The rate of hospital admission for this complication was 1.89% per year in the TAVR group and similar at 1.71% per year in the SAVR cohort.

Of note, all-cause mortality in TAVR patients who developed infective endocarditis was 1.32-fold greater than it was in SAVR patients with infective endocarditis, a statistically significant difference. The explanation for the increased mortality risk in the TAVR group probably has to do at least in part with an inability on the part of the investigators to fully capture and control for the TAVR group’s greater frailty, according to the cardiologist.

Risk factors for infective endocarditis shared in common by TAVR and SAVR patients included male gender, a higher Charlson Comorbidity Index score, and a greater frailty index. The main predictors unique to the TAVR patients were atrial fibrillation, anemia, and tricuspid regurgitation. And although pacemaker and defibrillator implantation were risk factors for infective endocarditis in the SAVR patients, it wasn’t predictive of increased risk in the TAVR population. Dr. Fauchier called this finding “quite reassuring” given that roughly 20% of the TAVR group received a pacemaker.

The causative microorganisms for infective endocarditis were essentially the same in the TAVR and SAVR groups, simplifying antimicrobial prophylaxis decision making.

Dr. Fauchier reported having no financial conflicts regarding the study, conducted free of commercial support. He serves as a consultant to and/or on speakers’ bureaus for Bayer, BMS Pfizer, Boehringer Ingelheim, Medtronic, and Novartis.

[email protected]

PARIS – The 5-year mortality rate associated with untreated moderate aortic stenosis is just as grim as it is for severe aortic stenosis, according to new findings from the largest-ever study of the natural history of aortic stenosis.

“These data provide a clear signal of the expected adverse outcomes for individuals presenting across the globe with a mean aortic valve gradient greater than 20.0 mm Hg or a peak aortic valve velocity above 3.0 m/sec,” Geoff Strange, PhD, said in presenting an analysis from NEDA, the National Echocardiography Database of Australia, at the annual congress of the European Society of Cardiology.

These results, if confirmed in other large datasets, could potentially have enormous implications for the use of transcatheter and surgical aortic valve replacement, interventions which until now have been restricted to patients with severe aortic stenosis (AS) as defined by an aortic valve (AV) mean gradient in excess of 40 mm Hg or a peak AV velocity greater than 4.0 m/sec. This restriction was based on what Dr. Strange considers rather limited and flimsy evidence suggesting that the mortality associated with AS was negligible except in severe AS.

“Cut points used to stratify for interventional strategies are based on very small numbers,” observed Dr. Strange, professor of medicine at the University of Notre Dame in Fremantle, Australia.

The NEDA findings, he added, constitute a call to action: “These data provide the impetus for a contemporary evaluation of the risk-to-benefit ratio of intervention in the moderate AS population,” Dr. Strange declared.

He and his NEDA coinvestigators analyzed echocardiographic data on 241,303 individuals in the Australian database, zeroing in on the 25,827 with untreated mild, moderate, or severe native valve AS. To place the size and scope of this project into perspective, the next-largest study of the natural history of untreated AS included 1,375 individuals – and that study was in turn roughly 10-fold bigger than the handful of other published studies addressing this issue.

A key finding in the NEDA study was that the 5-year all-cause mortality rate of 61.4% in the group with moderate AS wasn’t significantly different from the 64.6% rate in those with severe AS (see graphic).

The investigators performed additional analyses, analyzing peak velocity and mean gradient as continuous variables and stratifying patients into quintiles on that basis. They found that the top quintile for AV velocity started very low, at 1.73 m/sec, while the top quintile for mean AV gradient also started at a surprisingly low level: greater than 9.6 mm Hg. They noted that both all-cause and cardiovascular-specific mortality rates were basically flat until taking what Dr. Strange described as “a sharp pivot point upward” right around 20 mm Hg or 3 m/sec.

“No matter how we looked at these data – whether we looked at patients with or without left heart disease, whether we used the dimensionless index, whether we adjusted for stroke volume index, whether we stratified between age above or below 65, whether we used the gradient, the velocity, or the AV area – this threshold of increasing mortality at around 20 mm Hg or 3 m/sec continued to emerge,” according to Dr. Strange.

He noted that this study used real-world data with hard endpoints – actuarial patient mortality outcomes obtained through linkage to the national database – rather than hypothetical projections based upon Kaplan-Meier curves. A study limitation was that comorbidity data couldn’t be obtained for the AS patients.

Session cochair Patrizio Lancellotti, MD, PhD, commented, “I think this study will change a bit our consideration about patients with moderate AS.”

However, Dr. Lancellotti, who was lead author of the second-largest study of the natural history of aortic stenosis (JAMA Cardiol. 2018 Nov 1;3[11]:1060-8), expressed misgivings about the NEDA system’s lack of a core echocardiographic laboratory for imaging adjudication. That’s a study weakness given that image quality and the accuracy of echocardiographic interpretation are so highly dependent upon an individual cardiologist’s skill, observed Dr. Lancellotti, who is head of cardiology at the University of Liege (Belgium).

Dr. Strange replied that he and his coinvestigators analyzed a random subset of the NEDA data and found very little interlaboratory variability in results.

“All I can say is that the labs that contributed to this study are the most eminent labs across Australia,” he added.

Simultaneously with Dr. Strange’s presentation at the congress, the NEDA study results were published online (J Am Coll Cardiol. Sep 2019. doi: 10.1016/j.jacc.2019.08.004).

Dr. Strange reported having no financial conflicts of interest regarding the NEDA project, which is funded by GlaxoSmithKline, Bayer, and Actelion.

[email protected]

PARIS – The 5-year mortality rate associated with untreated moderate aortic stenosis is just as grim as it is for severe aortic stenosis, according to new findings from the largest-ever study of the natural history of aortic stenosis.

“These data provide a clear signal of the expected adverse outcomes for individuals presenting across the globe with a mean aortic valve gradient greater than 20.0 mm Hg or a peak aortic valve velocity above 3.0 m/sec,” Geoff Strange, PhD, said in presenting an analysis from NEDA, the National Echocardiography Database of Australia, at the annual congress of the European Society of Cardiology.

These results, if confirmed in other large datasets, could potentially have enormous implications for the use of transcatheter and surgical aortic valve replacement, interventions which until now have been restricted to patients with severe aortic stenosis (AS) as defined by an aortic valve (AV) mean gradient in excess of 40 mm Hg or a peak AV velocity greater than 4.0 m/sec. This restriction was based on what Dr. Strange considers rather limited and flimsy evidence suggesting that the mortality associated with AS was negligible except in severe AS.

“Cut points used to stratify for interventional strategies are based on very small numbers,” observed Dr. Strange, professor of medicine at the University of Notre Dame in Fremantle, Australia.

The NEDA findings, he added, constitute a call to action: “These data provide the impetus for a contemporary evaluation of the risk-to-benefit ratio of intervention in the moderate AS population,” Dr. Strange declared.

He and his NEDA coinvestigators analyzed echocardiographic data on 241,303 individuals in the Australian database, zeroing in on the 25,827 with untreated mild, moderate, or severe native valve AS. To place the size and scope of this project into perspective, the next-largest study of the natural history of untreated AS included 1,375 individuals – and that study was in turn roughly 10-fold bigger than the handful of other published studies addressing this issue.

A key finding in the NEDA study was that the 5-year all-cause mortality rate of 61.4% in the group with moderate AS wasn’t significantly different from the 64.6% rate in those with severe AS (see graphic).

The investigators performed additional analyses, analyzing peak velocity and mean gradient as continuous variables and stratifying patients into quintiles on that basis. They found that the top quintile for AV velocity started very low, at 1.73 m/sec, while the top quintile for mean AV gradient also started at a surprisingly low level: greater than 9.6 mm Hg. They noted that both all-cause and cardiovascular-specific mortality rates were basically flat until taking what Dr. Strange described as “a sharp pivot point upward” right around 20 mm Hg or 3 m/sec.

“No matter how we looked at these data – whether we looked at patients with or without left heart disease, whether we used the dimensionless index, whether we adjusted for stroke volume index, whether we stratified between age above or below 65, whether we used the gradient, the velocity, or the AV area – this threshold of increasing mortality at around 20 mm Hg or 3 m/sec continued to emerge,” according to Dr. Strange.

He noted that this study used real-world data with hard endpoints – actuarial patient mortality outcomes obtained through linkage to the national database – rather than hypothetical projections based upon Kaplan-Meier curves. A study limitation was that comorbidity data couldn’t be obtained for the AS patients.

Session cochair Patrizio Lancellotti, MD, PhD, commented, “I think this study will change a bit our consideration about patients with moderate AS.”

However, Dr. Lancellotti, who was lead author of the second-largest study of the natural history of aortic stenosis (JAMA Cardiol. 2018 Nov 1;3[11]:1060-8), expressed misgivings about the NEDA system’s lack of a core echocardiographic laboratory for imaging adjudication. That’s a study weakness given that image quality and the accuracy of echocardiographic interpretation are so highly dependent upon an individual cardiologist’s skill, observed Dr. Lancellotti, who is head of cardiology at the University of Liege (Belgium).

Dr. Strange replied that he and his coinvestigators analyzed a random subset of the NEDA data and found very little interlaboratory variability in results.

“All I can say is that the labs that contributed to this study are the most eminent labs across Australia,” he added.

Simultaneously with Dr. Strange’s presentation at the congress, the NEDA study results were published online (J Am Coll Cardiol. Sep 2019. doi: 10.1016/j.jacc.2019.08.004).

Dr. Strange reported having no financial conflicts of interest regarding the NEDA project, which is funded by GlaxoSmithKline, Bayer, and Actelion.

[email protected]

PARIS – The 5-year mortality rate associated with untreated moderate aortic stenosis is just as grim as it is for severe aortic stenosis, according to new findings from the largest-ever study of the natural history of aortic stenosis.

“These data provide a clear signal of the expected adverse outcomes for individuals presenting across the globe with a mean aortic valve gradient greater than 20.0 mm Hg or a peak aortic valve velocity above 3.0 m/sec,” Geoff Strange, PhD, said in presenting an analysis from NEDA, the National Echocardiography Database of Australia, at the annual congress of the European Society of Cardiology.

These results, if confirmed in other large datasets, could potentially have enormous implications for the use of transcatheter and surgical aortic valve replacement, interventions which until now have been restricted to patients with severe aortic stenosis (AS) as defined by an aortic valve (AV) mean gradient in excess of 40 mm Hg or a peak AV velocity greater than 4.0 m/sec. This restriction was based on what Dr. Strange considers rather limited and flimsy evidence suggesting that the mortality associated with AS was negligible except in severe AS.

“Cut points used to stratify for interventional strategies are based on very small numbers,” observed Dr. Strange, professor of medicine at the University of Notre Dame in Fremantle, Australia.

The NEDA findings, he added, constitute a call to action: “These data provide the impetus for a contemporary evaluation of the risk-to-benefit ratio of intervention in the moderate AS population,” Dr. Strange declared.

He and his NEDA coinvestigators analyzed echocardiographic data on 241,303 individuals in the Australian database, zeroing in on the 25,827 with untreated mild, moderate, or severe native valve AS. To place the size and scope of this project into perspective, the next-largest study of the natural history of untreated AS included 1,375 individuals – and that study was in turn roughly 10-fold bigger than the handful of other published studies addressing this issue.

A key finding in the NEDA study was that the 5-year all-cause mortality rate of 61.4% in the group with moderate AS wasn’t significantly different from the 64.6% rate in those with severe AS (see graphic).

The investigators performed additional analyses, analyzing peak velocity and mean gradient as continuous variables and stratifying patients into quintiles on that basis. They found that the top quintile for AV velocity started very low, at 1.73 m/sec, while the top quintile for mean AV gradient also started at a surprisingly low level: greater than 9.6 mm Hg. They noted that both all-cause and cardiovascular-specific mortality rates were basically flat until taking what Dr. Strange described as “a sharp pivot point upward” right around 20 mm Hg or 3 m/sec.

“No matter how we looked at these data – whether we looked at patients with or without left heart disease, whether we used the dimensionless index, whether we adjusted for stroke volume index, whether we stratified between age above or below 65, whether we used the gradient, the velocity, or the AV area – this threshold of increasing mortality at around 20 mm Hg or 3 m/sec continued to emerge,” according to Dr. Strange.

He noted that this study used real-world data with hard endpoints – actuarial patient mortality outcomes obtained through linkage to the national database – rather than hypothetical projections based upon Kaplan-Meier curves. A study limitation was that comorbidity data couldn’t be obtained for the AS patients.

Session cochair Patrizio Lancellotti, MD, PhD, commented, “I think this study will change a bit our consideration about patients with moderate AS.”

However, Dr. Lancellotti, who was lead author of the second-largest study of the natural history of aortic stenosis (JAMA Cardiol. 2018 Nov 1;3[11]:1060-8), expressed misgivings about the NEDA system’s lack of a core echocardiographic laboratory for imaging adjudication. That’s a study weakness given that image quality and the accuracy of echocardiographic interpretation are so highly dependent upon an individual cardiologist’s skill, observed Dr. Lancellotti, who is head of cardiology at the University of Liege (Belgium).

Dr. Strange replied that he and his coinvestigators analyzed a random subset of the NEDA data and found very little interlaboratory variability in results.

“All I can say is that the labs that contributed to this study are the most eminent labs across Australia,” he added.

Simultaneously with Dr. Strange’s presentation at the congress, the NEDA study results were published online (J Am Coll Cardiol. Sep 2019. doi: 10.1016/j.jacc.2019.08.004).

Dr. Strange reported having no financial conflicts of interest regarding the NEDA project, which is funded by GlaxoSmithKline, Bayer, and Actelion.

[email protected]