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Atrial fibrillation boosts VTE risk
BARCELONA – Atrial fibrillation is at least as strong a risk factor for venous thromboembolism as for ischemic stroke, Bjorn Hornestam, MD, asserted at the annual congress of the European Society of Cardiology.
This novel finding from a Swedish national registry study suggests it’s time for thoughtful consideration of a revision of risk scores in patients with atrial fibrillation (AF), according to Dr. Hornestam, director of cardiology at Sahlgrenska University Hospital in Gothenburg, Sweden.
“VTE risk is not included as an outcome in the CHA2DS2-VASc score, so we underestimate the total thromboembolic risk in AF patients,” he said.
Dr. Hornestam presented a Swedish registry study of 1.36 million patients, including 470,738 patients with new-onset AF and no previous diagnosis of VTE or ischemic stroke and twice as many controls without AF who were matched to the AF patients by age, gender, and county. 
The VTE risk was highest during the first 30 days after diagnosis of AF. Women with new-onset AF had an 8.3-fold increased risk of VTE compared with controls during this early period, by a margin of 55.8 versus 6.4 cases per 1,000 person-years. Men with newly diagnosed AF had a 7.2-fold increased risk of VTE in the first 30 days, reflecting a rate of 40.1 per 1,000 person-years compared to 5.6 per 1,000 in controls.
The VTE risk dropped off precipitously in men after the first month. The rate was cut in half by 2 months after AF diagnosis and was no different from that of controls by 9 months.
In women, too, the early elevated VTE risk was halved by 2 months out, but thereafter the rate of decline in VTE risk slowed. Even 10 years after AF diagnosis, women had a 21% greater VTE risk than did matched controls.
Of note, the risk of VTE during the first 12 months after diagnosis of AF was nearly twice as great in both men and women under age 65 than in those older than 75.
These data raise the question of whether standard therapy in AF patients needs to be modified, especially during what now appears to be the critical time frame of the first 3-6 months after diagnosis of the arrhythmia, Dr. Hornestam said.
He reported having no financial conflicts of interest regarding this study.
BARCELONA – Atrial fibrillation is at least as strong a risk factor for venous thromboembolism as for ischemic stroke, Bjorn Hornestam, MD, asserted at the annual congress of the European Society of Cardiology.
This novel finding from a Swedish national registry study suggests it’s time for thoughtful consideration of a revision of risk scores in patients with atrial fibrillation (AF), according to Dr. Hornestam, director of cardiology at Sahlgrenska University Hospital in Gothenburg, Sweden.
“VTE risk is not included as an outcome in the CHA2DS2-VASc score, so we underestimate the total thromboembolic risk in AF patients,” he said.
Dr. Hornestam presented a Swedish registry study of 1.36 million patients, including 470,738 patients with new-onset AF and no previous diagnosis of VTE or ischemic stroke and twice as many controls without AF who were matched to the AF patients by age, gender, and county.
The VTE risk was highest during the first 30 days after diagnosis of AF. Women with new-onset AF had an 8.3-fold increased risk of VTE compared with controls during this early period, by a margin of 55.8 versus 6.4 cases per 1,000 person-years. Men with newly diagnosed AF had a 7.2-fold increased risk of VTE in the first 30 days, reflecting a rate of 40.1 per 1,000 person-years compared to 5.6 per 1,000 in controls.
The VTE risk dropped off precipitously in men after the first month. The rate was cut in half by 2 months after AF diagnosis and was no different from that of controls by 9 months.
In women, too, the early elevated VTE risk was halved by 2 months out, but thereafter the rate of decline in VTE risk slowed. Even 10 years after AF diagnosis, women had a 21% greater VTE risk than did matched controls.
Of note, the risk of VTE during the first 12 months after diagnosis of AF was nearly twice as great in both men and women under age 65 than in those older than 75.
These data raise the question of whether standard therapy in AF patients needs to be modified, especially during what now appears to be the critical time frame of the first 3-6 months after diagnosis of the arrhythmia, Dr. Hornestam said.
He reported having no financial conflicts of interest regarding this study.
BARCELONA – Atrial fibrillation is at least as strong a risk factor for venous thromboembolism as for ischemic stroke, Bjorn Hornestam, MD, asserted at the annual congress of the European Society of Cardiology.
This novel finding from a Swedish national registry study suggests it’s time for thoughtful consideration of a revision of risk scores in patients with atrial fibrillation (AF), according to Dr. Hornestam, director of cardiology at Sahlgrenska University Hospital in Gothenburg, Sweden.
“VTE risk is not included as an outcome in the CHA2DS2-VASc score, so we underestimate the total thromboembolic risk in AF patients,” he said.
Dr. Hornestam presented a Swedish registry study of 1.36 million patients, including 470,738 patients with new-onset AF and no previous diagnosis of VTE or ischemic stroke and twice as many controls without AF who were matched to the AF patients by age, gender, and county.
The VTE risk was highest during the first 30 days after diagnosis of AF. Women with new-onset AF had an 8.3-fold increased risk of VTE compared with controls during this early period, by a margin of 55.8 versus 6.4 cases per 1,000 person-years. Men with newly diagnosed AF had a 7.2-fold increased risk of VTE in the first 30 days, reflecting a rate of 40.1 per 1,000 person-years compared to 5.6 per 1,000 in controls.
The VTE risk dropped off precipitously in men after the first month. The rate was cut in half by 2 months after AF diagnosis and was no different from that of controls by 9 months.
In women, too, the early elevated VTE risk was halved by 2 months out, but thereafter the rate of decline in VTE risk slowed. Even 10 years after AF diagnosis, women had a 21% greater VTE risk than did matched controls.
Of note, the risk of VTE during the first 12 months after diagnosis of AF was nearly twice as great in both men and women under age 65 than in those older than 75.
These data raise the question of whether standard therapy in AF patients needs to be modified, especially during what now appears to be the critical time frame of the first 3-6 months after diagnosis of the arrhythmia, Dr. Hornestam said.
He reported having no financial conflicts of interest regarding this study.
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: The risk of a first venous thromboembolism is increased 7.2- to 8.3-fold during the first 30 days following diagnosis of AF and remains moderately elevated in women even 10 years later.
Data source: An observational Swedish national registry study of more than 1.3 million patients, including 470,738 with newly diagnosed atrial fibrillation and their matched controls.
Disclosures: The presenter reported having no financial conflicts of interest regarding this study, which was conducted free of commercial support.
Bag-mask ventilation for CPR deflates in large RCT
BARCELONA – Bag-mask ventilation for airway management during resuscitation of patients with out-of-hospital cardiac arrest was considerably less safe and yet no more effective than endotracheal intubation in a large randomized trial, Frederic Adnet, MD, reported at the annual congress of the European Society of Cardiology.
This was an unexpected result.
Several large, well-respected observational registry studies had strongly suggested that bag-mask ventilation is associated with a superior survival rate with good neurologic outcome. As a result, many in the resuscitation science field have been moving closer to replacing endotracheal intubation as the standard of care in favor of bag-mask ventilation. But this first-of-its-kind, large, randomized trial to formally address the issue showed virtually identical rates of day-28 survival with good neurologic outcome in the two study arms. Plus, bag-mask ventilation had a significantly higher complication rate.
“So, at this time, we will not yet change our technique,” according to coinvestigator Eric Vicaut, MD, of Fernand Widal Hospital in Paris.
This major prospective randomized trial included 2,043 patients with out-of-hospital cardiac arrest at 20 centers in France and Belgium. The primary endpoint – day-28 survival with good neurologic status as defined by a Glasgow-Pittsburgh Cerebral Performance Scale score of 2 or less – occurred in 4.2% of the bag-mask ventilation group and 4.1% of the endotracheal intubation group.
However, the rate of aspiration or regurgitation of gastric contents was significantly higher in the bag-mask ventilation group by a margin of 14.9% to 7.7%. Moreover, the bag-mask ventilation technique failed in 6.3% of patients, compared with a 2.5% endotracheal intubation failure rate.
Discussant Susanna Price, MD, praised the study as a high-quality, well-conducted randomized trial, adding that it’s just the sort of study that the field of resuscitation science had needed for a long time. Indeed, most guidelines in the field are based on faint supporting evidence. That may be one reason why good outcomes of out-of-hospital cardiac arrest are so disappointingly low: The worldwide average is roughly 7%, with huge differences between countries.
“It is really very depressing sometimes when one looks at the percentage of patients who actually return to normal life and normal functional neurologic status and, indeed, whose relatives get back to work,” commented Dr. Price, a cardiologist and intensivist at Royal Brompton Hospital in London.
“This is a huge study for resuscitation science,” she continued. “Prehospital airway management is currently a very hot topic. Bear in mind that in the United States, roughly 88% of cardiac arrests happen in the home.”
“This trial does challenge the current feeling that bag-mask ventilation is definitely superior to advanced airway interventions,” Dr. Price added.
For her, the study contained three surprises, she continued. One was the high bag-mask failure rate in the hands of very experienced operators. Another was the high complication rate associated with the device, again even in expert hands. Also, contrary to numerous published reports, the chest compression rate in this RCT was not better with bag mask ventilation.
“The study did not demonstrate that endotracheal intubation interrupts chest compressions. In fact, chest compression pauses were actually significantly more frequent in the bag-mask ventilation group than with endotracheal intubation,” she observed.
It’s worth noting that in the French EMS system, a physician experienced in cardiopulmonary resuscitation is typically on board for ambulance runs. This creates an element of uncertainty as to the generalizability of the study findings to EMS systems where paramedics who may be less proficient in endotracheal intubation are the first responders. Indeed, whether endotracheal intubation will stack up as favorably as it did against bag-mask ventilation in this randomized trial when tested in other settings where airway management is left in the hands of paramedics is an open question that’s the topic of ongoing studies, Dr. Price noted.
Dr. Adnet and Dr. Vicaut reported having no financial conflicts regarding their study, which was funded by the French Ministry of Health.
[email protected]
BARCELONA – Bag-mask ventilation for airway management during resuscitation of patients with out-of-hospital cardiac arrest was considerably less safe and yet no more effective than endotracheal intubation in a large randomized trial, Frederic Adnet, MD, reported at the annual congress of the European Society of Cardiology.
This was an unexpected result.
Several large, well-respected observational registry studies had strongly suggested that bag-mask ventilation is associated with a superior survival rate with good neurologic outcome. As a result, many in the resuscitation science field have been moving closer to replacing endotracheal intubation as the standard of care in favor of bag-mask ventilation. But this first-of-its-kind, large, randomized trial to formally address the issue showed virtually identical rates of day-28 survival with good neurologic outcome in the two study arms. Plus, bag-mask ventilation had a significantly higher complication rate.
“So, at this time, we will not yet change our technique,” according to coinvestigator Eric Vicaut, MD, of Fernand Widal Hospital in Paris.
This major prospective randomized trial included 2,043 patients with out-of-hospital cardiac arrest at 20 centers in France and Belgium. The primary endpoint – day-28 survival with good neurologic status as defined by a Glasgow-Pittsburgh Cerebral Performance Scale score of 2 or less – occurred in 4.2% of the bag-mask ventilation group and 4.1% of the endotracheal intubation group.
However, the rate of aspiration or regurgitation of gastric contents was significantly higher in the bag-mask ventilation group by a margin of 14.9% to 7.7%. Moreover, the bag-mask ventilation technique failed in 6.3% of patients, compared with a 2.5% endotracheal intubation failure rate.
Discussant Susanna Price, MD, praised the study as a high-quality, well-conducted randomized trial, adding that it’s just the sort of study that the field of resuscitation science had needed for a long time. Indeed, most guidelines in the field are based on faint supporting evidence. That may be one reason why good outcomes of out-of-hospital cardiac arrest are so disappointingly low: The worldwide average is roughly 7%, with huge differences between countries.
“It is really very depressing sometimes when one looks at the percentage of patients who actually return to normal life and normal functional neurologic status and, indeed, whose relatives get back to work,” commented Dr. Price, a cardiologist and intensivist at Royal Brompton Hospital in London.
“This is a huge study for resuscitation science,” she continued. “Prehospital airway management is currently a very hot topic. Bear in mind that in the United States, roughly 88% of cardiac arrests happen in the home.”
“This trial does challenge the current feeling that bag-mask ventilation is definitely superior to advanced airway interventions,” Dr. Price added.
For her, the study contained three surprises, she continued. One was the high bag-mask failure rate in the hands of very experienced operators. Another was the high complication rate associated with the device, again even in expert hands. Also, contrary to numerous published reports, the chest compression rate in this RCT was not better with bag mask ventilation.
“The study did not demonstrate that endotracheal intubation interrupts chest compressions. In fact, chest compression pauses were actually significantly more frequent in the bag-mask ventilation group than with endotracheal intubation,” she observed.
It’s worth noting that in the French EMS system, a physician experienced in cardiopulmonary resuscitation is typically on board for ambulance runs. This creates an element of uncertainty as to the generalizability of the study findings to EMS systems where paramedics who may be less proficient in endotracheal intubation are the first responders. Indeed, whether endotracheal intubation will stack up as favorably as it did against bag-mask ventilation in this randomized trial when tested in other settings where airway management is left in the hands of paramedics is an open question that’s the topic of ongoing studies, Dr. Price noted.
Dr. Adnet and Dr. Vicaut reported having no financial conflicts regarding their study, which was funded by the French Ministry of Health.
[email protected]
BARCELONA – Bag-mask ventilation for airway management during resuscitation of patients with out-of-hospital cardiac arrest was considerably less safe and yet no more effective than endotracheal intubation in a large randomized trial, Frederic Adnet, MD, reported at the annual congress of the European Society of Cardiology.
This was an unexpected result.
Several large, well-respected observational registry studies had strongly suggested that bag-mask ventilation is associated with a superior survival rate with good neurologic outcome. As a result, many in the resuscitation science field have been moving closer to replacing endotracheal intubation as the standard of care in favor of bag-mask ventilation. But this first-of-its-kind, large, randomized trial to formally address the issue showed virtually identical rates of day-28 survival with good neurologic outcome in the two study arms. Plus, bag-mask ventilation had a significantly higher complication rate.
“So, at this time, we will not yet change our technique,” according to coinvestigator Eric Vicaut, MD, of Fernand Widal Hospital in Paris.
This major prospective randomized trial included 2,043 patients with out-of-hospital cardiac arrest at 20 centers in France and Belgium. The primary endpoint – day-28 survival with good neurologic status as defined by a Glasgow-Pittsburgh Cerebral Performance Scale score of 2 or less – occurred in 4.2% of the bag-mask ventilation group and 4.1% of the endotracheal intubation group.
However, the rate of aspiration or regurgitation of gastric contents was significantly higher in the bag-mask ventilation group by a margin of 14.9% to 7.7%. Moreover, the bag-mask ventilation technique failed in 6.3% of patients, compared with a 2.5% endotracheal intubation failure rate.
Discussant Susanna Price, MD, praised the study as a high-quality, well-conducted randomized trial, adding that it’s just the sort of study that the field of resuscitation science had needed for a long time. Indeed, most guidelines in the field are based on faint supporting evidence. That may be one reason why good outcomes of out-of-hospital cardiac arrest are so disappointingly low: The worldwide average is roughly 7%, with huge differences between countries.
“It is really very depressing sometimes when one looks at the percentage of patients who actually return to normal life and normal functional neurologic status and, indeed, whose relatives get back to work,” commented Dr. Price, a cardiologist and intensivist at Royal Brompton Hospital in London.
“This is a huge study for resuscitation science,” she continued. “Prehospital airway management is currently a very hot topic. Bear in mind that in the United States, roughly 88% of cardiac arrests happen in the home.”
“This trial does challenge the current feeling that bag-mask ventilation is definitely superior to advanced airway interventions,” Dr. Price added.
For her, the study contained three surprises, she continued. One was the high bag-mask failure rate in the hands of very experienced operators. Another was the high complication rate associated with the device, again even in expert hands. Also, contrary to numerous published reports, the chest compression rate in this RCT was not better with bag mask ventilation.
“The study did not demonstrate that endotracheal intubation interrupts chest compressions. In fact, chest compression pauses were actually significantly more frequent in the bag-mask ventilation group than with endotracheal intubation,” she observed.
It’s worth noting that in the French EMS system, a physician experienced in cardiopulmonary resuscitation is typically on board for ambulance runs. This creates an element of uncertainty as to the generalizability of the study findings to EMS systems where paramedics who may be less proficient in endotracheal intubation are the first responders. Indeed, whether endotracheal intubation will stack up as favorably as it did against bag-mask ventilation in this randomized trial when tested in other settings where airway management is left in the hands of paramedics is an open question that’s the topic of ongoing studies, Dr. Price noted.
Dr. Adnet and Dr. Vicaut reported having no financial conflicts regarding their study, which was funded by the French Ministry of Health.
[email protected]
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: Rates of survival with good neurologic outcome 28 days after out-of-hospital cardiac arrest were similarly low whether airway management during CPR relied upon endotracheal intubation or bag-mask ventilation, but the latter strategy had a significantly higher complication rate.
Data source: This prospective randomized trial included 2,043 patients with out-of-hospital cardiac arrest at 20 centers in France and Belgium.
Disclosures: The study was funded by the French Ministry of Health. The presenter reported having no financial conflicts.
AF patients without oral anticoagulation face higher dementia risk
BARCELONA – The risk of developing dementia was reduced by 48% in patients with atrial fibrillation who were adherent to oral anticoagulation compared with those who were not, according to a Swedish propensity-matched registry study involving nearly 162,000 patients with the arrhythmia.
The study also addressed whether patients with atrial fibrillation (AF) are better off in terms of reducing their dementia risk if they’re on warfarin versus one of the novel oral anticoagulants. The answer is that it makes absolutely no difference, Leif Friberg, MD, reported at the annual congress of the European Society of Cardiology.
“We found no difference whatsoever in any of the subgroups. It appears that it is more important that you have some kind of oral treatment than exactly what kind to have,” said Dr. Friberg, a cardiologist at the Karolinska Institute in Stockholm.
It’s well established that AF is associated with increased risk of dementia, presumably because the arrhythmia kicks out microemboli that get distributed throughout the brain. But it has been unclear whether oral anticoagulation (OAC) prescribed for stroke prevention has the side benefit of reducing the elevated dementia risk.
“A randomized, controlled trial would be ideal to look at this, but it would be impractical and unethical. Second best [would be] a registry study with propensity matching,” according to Dr. Friberg.
And that’s just what he and his coinvestigators carried out. The study included 80,948 AF patients with no baseline diagnosis of dementia who were prescribed an OAC and an equal number of propensity-matched, dementia-free AF patients not on OAC therapy. During up to 8 years of follow-up, the unadjusted risk of a new diagnosis of dementia was 29% lower in the group on an OAC at baseline.
But the Swedish registries also enabled investigators to zero in on the impact of OAC in patients who were actually medication adherent over time. Dr. Friberg and his coworkers identified a subgroup of 50,406 AF patients who regularly filled their OAC prescriptions and took the medication at least 80% of the time, as well as 48,947 propensity-matched controls who never used OACs. In this on-treatment analysis, the OAC users had a robust 48% relative risk reduction in new diagnosis of dementia. The dementia curves diverged almost immediately and the gap between the two curves continued to widen throughout follow-up. All examined subgroups benefited, regardless of age, gender, AF duration, CHA2DS2-VASc score, or the presence or absence of diabetes, renal failure, or frequent falling.
“This is an important issue,” Dr. Friberg declared. “You may say, ‘What do we care about these findings? These patients are all supposed to be on an oral anticoagulant anyway.’ But you know, patients stop taking their oral anticoagulant. We’re pretty good at initiating treatment when we meet patients for the first time, if they have stroke risk factors, but annually, 10%-15% of patients drop out of treatment. And if patients aren’t concerned enough about their risk of stroke, they might be more concerned about the risk of becoming demented. So these data provide an additional argument for the need to persevere with oral anticoagulation therapy.”
Session cochair Gabriel Tatu-Chitoiu, MD, was skeptical.
“I’ve been working in the atrial fibrillation field for 40 years, and I have to say I haven’t seen a strong dementia possibility in my patients,” said Dr. Tatu-Chitoiu, a cardiologist in Bucharest, Romania, and immediate past president of the Romanian Cardiology Society.
Dr. Friberg replied that AF patients are elderly, and many of them may stop going to their cardiologist when they develop dementia.
“I don’t think you can make extensions from personal experience on this. You have to trust in statistical evidence,” he observed.
Dr. Friberg reported receiving research funding from Bayer, Bristol-Myers Squibb, Pfizer, and Sanofi. However, the registry study was carried out without commercial support.
BARCELONA – The risk of developing dementia was reduced by 48% in patients with atrial fibrillation who were adherent to oral anticoagulation compared with those who were not, according to a Swedish propensity-matched registry study involving nearly 162,000 patients with the arrhythmia.
The study also addressed whether patients with atrial fibrillation (AF) are better off in terms of reducing their dementia risk if they’re on warfarin versus one of the novel oral anticoagulants. The answer is that it makes absolutely no difference, Leif Friberg, MD, reported at the annual congress of the European Society of Cardiology.
“We found no difference whatsoever in any of the subgroups. It appears that it is more important that you have some kind of oral treatment than exactly what kind to have,” said Dr. Friberg, a cardiologist at the Karolinska Institute in Stockholm.
It’s well established that AF is associated with increased risk of dementia, presumably because the arrhythmia kicks out microemboli that get distributed throughout the brain. But it has been unclear whether oral anticoagulation (OAC) prescribed for stroke prevention has the side benefit of reducing the elevated dementia risk.
“A randomized, controlled trial would be ideal to look at this, but it would be impractical and unethical. Second best [would be] a registry study with propensity matching,” according to Dr. Friberg.
And that’s just what he and his coinvestigators carried out. The study included 80,948 AF patients with no baseline diagnosis of dementia who were prescribed an OAC and an equal number of propensity-matched, dementia-free AF patients not on OAC therapy. During up to 8 years of follow-up, the unadjusted risk of a new diagnosis of dementia was 29% lower in the group on an OAC at baseline.
But the Swedish registries also enabled investigators to zero in on the impact of OAC in patients who were actually medication adherent over time. Dr. Friberg and his coworkers identified a subgroup of 50,406 AF patients who regularly filled their OAC prescriptions and took the medication at least 80% of the time, as well as 48,947 propensity-matched controls who never used OACs. In this on-treatment analysis, the OAC users had a robust 48% relative risk reduction in new diagnosis of dementia. The dementia curves diverged almost immediately and the gap between the two curves continued to widen throughout follow-up. All examined subgroups benefited, regardless of age, gender, AF duration, CHA2DS2-VASc score, or the presence or absence of diabetes, renal failure, or frequent falling.
“This is an important issue,” Dr. Friberg declared. “You may say, ‘What do we care about these findings? These patients are all supposed to be on an oral anticoagulant anyway.’ But you know, patients stop taking their oral anticoagulant. We’re pretty good at initiating treatment when we meet patients for the first time, if they have stroke risk factors, but annually, 10%-15% of patients drop out of treatment. And if patients aren’t concerned enough about their risk of stroke, they might be more concerned about the risk of becoming demented. So these data provide an additional argument for the need to persevere with oral anticoagulation therapy.”
Session cochair Gabriel Tatu-Chitoiu, MD, was skeptical.
“I’ve been working in the atrial fibrillation field for 40 years, and I have to say I haven’t seen a strong dementia possibility in my patients,” said Dr. Tatu-Chitoiu, a cardiologist in Bucharest, Romania, and immediate past president of the Romanian Cardiology Society.
Dr. Friberg replied that AF patients are elderly, and many of them may stop going to their cardiologist when they develop dementia.
“I don’t think you can make extensions from personal experience on this. You have to trust in statistical evidence,” he observed.
Dr. Friberg reported receiving research funding from Bayer, Bristol-Myers Squibb, Pfizer, and Sanofi. However, the registry study was carried out without commercial support.
BARCELONA – The risk of developing dementia was reduced by 48% in patients with atrial fibrillation who were adherent to oral anticoagulation compared with those who were not, according to a Swedish propensity-matched registry study involving nearly 162,000 patients with the arrhythmia.
The study also addressed whether patients with atrial fibrillation (AF) are better off in terms of reducing their dementia risk if they’re on warfarin versus one of the novel oral anticoagulants. The answer is that it makes absolutely no difference, Leif Friberg, MD, reported at the annual congress of the European Society of Cardiology.
“We found no difference whatsoever in any of the subgroups. It appears that it is more important that you have some kind of oral treatment than exactly what kind to have,” said Dr. Friberg, a cardiologist at the Karolinska Institute in Stockholm.
It’s well established that AF is associated with increased risk of dementia, presumably because the arrhythmia kicks out microemboli that get distributed throughout the brain. But it has been unclear whether oral anticoagulation (OAC) prescribed for stroke prevention has the side benefit of reducing the elevated dementia risk.
“A randomized, controlled trial would be ideal to look at this, but it would be impractical and unethical. Second best [would be] a registry study with propensity matching,” according to Dr. Friberg.
And that’s just what he and his coinvestigators carried out. The study included 80,948 AF patients with no baseline diagnosis of dementia who were prescribed an OAC and an equal number of propensity-matched, dementia-free AF patients not on OAC therapy. During up to 8 years of follow-up, the unadjusted risk of a new diagnosis of dementia was 29% lower in the group on an OAC at baseline.
But the Swedish registries also enabled investigators to zero in on the impact of OAC in patients who were actually medication adherent over time. Dr. Friberg and his coworkers identified a subgroup of 50,406 AF patients who regularly filled their OAC prescriptions and took the medication at least 80% of the time, as well as 48,947 propensity-matched controls who never used OACs. In this on-treatment analysis, the OAC users had a robust 48% relative risk reduction in new diagnosis of dementia. The dementia curves diverged almost immediately and the gap between the two curves continued to widen throughout follow-up. All examined subgroups benefited, regardless of age, gender, AF duration, CHA2DS2-VASc score, or the presence or absence of diabetes, renal failure, or frequent falling.
“This is an important issue,” Dr. Friberg declared. “You may say, ‘What do we care about these findings? These patients are all supposed to be on an oral anticoagulant anyway.’ But you know, patients stop taking their oral anticoagulant. We’re pretty good at initiating treatment when we meet patients for the first time, if they have stroke risk factors, but annually, 10%-15% of patients drop out of treatment. And if patients aren’t concerned enough about their risk of stroke, they might be more concerned about the risk of becoming demented. So these data provide an additional argument for the need to persevere with oral anticoagulation therapy.”
Session cochair Gabriel Tatu-Chitoiu, MD, was skeptical.
“I’ve been working in the atrial fibrillation field for 40 years, and I have to say I haven’t seen a strong dementia possibility in my patients,” said Dr. Tatu-Chitoiu, a cardiologist in Bucharest, Romania, and immediate past president of the Romanian Cardiology Society.
Dr. Friberg replied that AF patients are elderly, and many of them may stop going to their cardiologist when they develop dementia.
“I don’t think you can make extensions from personal experience on this. You have to trust in statistical evidence,” he observed.
Dr. Friberg reported receiving research funding from Bayer, Bristol-Myers Squibb, Pfizer, and Sanofi. However, the registry study was carried out without commercial support.
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: The risk of new diagnosis of dementia during up to 8 years of follow-up was 48% lower in AF patients on an oral anticoagulant at least 80% of the time, compared with those not on the medication.
Data source: This was a Swedish registry study including nearly 162,000 propensity-matched patients with atrial fibrillation free of baseline dementia.
Disclosures: The study was conducted without commercial support.
PCI advances produce CABG-like 1-year outcomes
BARCELONA – Improvements in percutaneous coronary intervention over the past decade have made a difference. Coronary stenting to treat triple-vessel disease produced roughly the same 1-year results as coronary artery bypass surgery, based on results from 454 patients in an uncontrolled, prospective trial.
With state-of-the-art percutaneous coronary intervention (PCI), the 1-year incidence of major cardiac and cerebrovascular events was 11% in the Synergy Between PCI with Taxus and Cardiac Surgery (SYNTAX) II trial, a PCI outcome substantially better than the 18% rate with PCI seen in the original SYNTAX trial, run during 2005-2007. That incidence was similar to the 11% 1-year major adverse event rate seen in patients who underwent coronary artery bypass grafting (CABG) in the first SYNTAX trial (N Engl J Med. 2009 Mar 5;360[10]:961-72), said Javier Escaned, MD, who reported the results at the annual congress of the European Society of Cardiology.
- Initial assessment of patients using both clinical and anatomic criteria with the SYNTAX score II (Lancet. 2013 Feb 23;381[9867]:639-50), an improvement over the original SYNTAX score that only used anatomic data.
- Assessment of each coronary stenosis for its physiologic impact using a pressure wire to measure the instantaneous wave-free ratio and fractional flow reserve of each suspicious lesion.
- Performing PCI with a second-generation everolimus-eluting stent with a bioabsorbable polymer stent (Synergy) instead of the paclitaxel-eluting first-generation stent (Taxus) used in the first SYNTAX trial.
- Optimization of stent placement with intravascular ultrasound.
- Application of contemporary methods for treating total chronic occlusions that produce higher success rates than a decade ago.
- Prescription of current guideline-directed medical therapy to each patient following PCI.
“To get the best results you need to do all of this; none of these steps takes full credit by itself,” said Dr. Escaned, an interventional cardiologist at the Hospital Clinic San Carlos in Madrid. “The message from SYNTAX II is that if you put all of these steps together, this is the result,” he said in an interview.
An underlying assumption of the single-arm design of SYNTAX II and its “exploratory” comparison to a 334-patient subset of the 897 patients who underwent CABG in the original SYNTAX trial who retrospectively met the SYNTAX score II enrollment criteria used in the current trial was that “CABG has not changed much” since the first SYNTAX trial, Dr. Escaned said. Although he acknowledged that some progress also occurred with CABG in the subsequent 10 years, “it has not been as big a change” as going to second-generation drug-eluting stents, using a pressure wire assessment to target physiologically important stenoses, and improved techniques for treating chronic total occlusions that have nearly doubled success rates in patients with these lesions.
The SYNTAX II trial enrolled 454 patients with de novo triple-vessel coronary disease without left main stem involvement at 22 centers in four European countries during 2014 and 2015. The improvement in the primary 1-year endpoint in the current patients compared with PCI patients from the first SYNTAX trial was driven primarily by reductions in MI and in repeat revascularizations. The SYNTAX II patients also had a 0.7% rate of definite stent thrombosis events, compared with a 2.4% rate in the original SYNTAX PCI patients, a statistically significant difference. Concurrently with Dr. Escaned’s report at the meeting an article with the results appeared online (Eur Heart J. 2017 Aug 26;doi: 10.1093/eurheartj/ehx512).
Dr. Escaned cautioned that longer-term follow-up is needed to more fully compare the PCI results with CABG.
SYNTAX II received unrestricted grant support from Philips/Volcano and Boston Scientific, the companies that market the pressure wires and stents used in the study. Dr. Escaned reported ties to Abbott, AstraZeneca, Biosensors, Boston Scientific, Medtronic, OrbusNeich, Philips/Volcano, and Boston Scientific.
[email protected]
On Twitter @mitchelzoler
BARCELONA – Improvements in percutaneous coronary intervention over the past decade have made a difference. Coronary stenting to treat triple-vessel disease produced roughly the same 1-year results as coronary artery bypass surgery, based on results from 454 patients in an uncontrolled, prospective trial.
With state-of-the-art percutaneous coronary intervention (PCI), the 1-year incidence of major cardiac and cerebrovascular events was 11% in the Synergy Between PCI with Taxus and Cardiac Surgery (SYNTAX) II trial, a PCI outcome substantially better than the 18% rate with PCI seen in the original SYNTAX trial, run during 2005-2007. That incidence was similar to the 11% 1-year major adverse event rate seen in patients who underwent coronary artery bypass grafting (CABG) in the first SYNTAX trial (N Engl J Med. 2009 Mar 5;360[10]:961-72), said Javier Escaned, MD, who reported the results at the annual congress of the European Society of Cardiology.
- Initial assessment of patients using both clinical and anatomic criteria with the SYNTAX score II (Lancet. 2013 Feb 23;381[9867]:639-50), an improvement over the original SYNTAX score that only used anatomic data.
- Assessment of each coronary stenosis for its physiologic impact using a pressure wire to measure the instantaneous wave-free ratio and fractional flow reserve of each suspicious lesion.
- Performing PCI with a second-generation everolimus-eluting stent with a bioabsorbable polymer stent (Synergy) instead of the paclitaxel-eluting first-generation stent (Taxus) used in the first SYNTAX trial.
- Optimization of stent placement with intravascular ultrasound.
- Application of contemporary methods for treating total chronic occlusions that produce higher success rates than a decade ago.
- Prescription of current guideline-directed medical therapy to each patient following PCI.
“To get the best results you need to do all of this; none of these steps takes full credit by itself,” said Dr. Escaned, an interventional cardiologist at the Hospital Clinic San Carlos in Madrid. “The message from SYNTAX II is that if you put all of these steps together, this is the result,” he said in an interview.
An underlying assumption of the single-arm design of SYNTAX II and its “exploratory” comparison to a 334-patient subset of the 897 patients who underwent CABG in the original SYNTAX trial who retrospectively met the SYNTAX score II enrollment criteria used in the current trial was that “CABG has not changed much” since the first SYNTAX trial, Dr. Escaned said. Although he acknowledged that some progress also occurred with CABG in the subsequent 10 years, “it has not been as big a change” as going to second-generation drug-eluting stents, using a pressure wire assessment to target physiologically important stenoses, and improved techniques for treating chronic total occlusions that have nearly doubled success rates in patients with these lesions.
The SYNTAX II trial enrolled 454 patients with de novo triple-vessel coronary disease without left main stem involvement at 22 centers in four European countries during 2014 and 2015. The improvement in the primary 1-year endpoint in the current patients compared with PCI patients from the first SYNTAX trial was driven primarily by reductions in MI and in repeat revascularizations. The SYNTAX II patients also had a 0.7% rate of definite stent thrombosis events, compared with a 2.4% rate in the original SYNTAX PCI patients, a statistically significant difference. Concurrently with Dr. Escaned’s report at the meeting an article with the results appeared online (Eur Heart J. 2017 Aug 26;doi: 10.1093/eurheartj/ehx512).
Dr. Escaned cautioned that longer-term follow-up is needed to more fully compare the PCI results with CABG.
SYNTAX II received unrestricted grant support from Philips/Volcano and Boston Scientific, the companies that market the pressure wires and stents used in the study. Dr. Escaned reported ties to Abbott, AstraZeneca, Biosensors, Boston Scientific, Medtronic, OrbusNeich, Philips/Volcano, and Boston Scientific.
[email protected]
On Twitter @mitchelzoler
BARCELONA – Improvements in percutaneous coronary intervention over the past decade have made a difference. Coronary stenting to treat triple-vessel disease produced roughly the same 1-year results as coronary artery bypass surgery, based on results from 454 patients in an uncontrolled, prospective trial.
With state-of-the-art percutaneous coronary intervention (PCI), the 1-year incidence of major cardiac and cerebrovascular events was 11% in the Synergy Between PCI with Taxus and Cardiac Surgery (SYNTAX) II trial, a PCI outcome substantially better than the 18% rate with PCI seen in the original SYNTAX trial, run during 2005-2007. That incidence was similar to the 11% 1-year major adverse event rate seen in patients who underwent coronary artery bypass grafting (CABG) in the first SYNTAX trial (N Engl J Med. 2009 Mar 5;360[10]:961-72), said Javier Escaned, MD, who reported the results at the annual congress of the European Society of Cardiology.
- Initial assessment of patients using both clinical and anatomic criteria with the SYNTAX score II (Lancet. 2013 Feb 23;381[9867]:639-50), an improvement over the original SYNTAX score that only used anatomic data.
- Assessment of each coronary stenosis for its physiologic impact using a pressure wire to measure the instantaneous wave-free ratio and fractional flow reserve of each suspicious lesion.
- Performing PCI with a second-generation everolimus-eluting stent with a bioabsorbable polymer stent (Synergy) instead of the paclitaxel-eluting first-generation stent (Taxus) used in the first SYNTAX trial.
- Optimization of stent placement with intravascular ultrasound.
- Application of contemporary methods for treating total chronic occlusions that produce higher success rates than a decade ago.
- Prescription of current guideline-directed medical therapy to each patient following PCI.
“To get the best results you need to do all of this; none of these steps takes full credit by itself,” said Dr. Escaned, an interventional cardiologist at the Hospital Clinic San Carlos in Madrid. “The message from SYNTAX II is that if you put all of these steps together, this is the result,” he said in an interview.
An underlying assumption of the single-arm design of SYNTAX II and its “exploratory” comparison to a 334-patient subset of the 897 patients who underwent CABG in the original SYNTAX trial who retrospectively met the SYNTAX score II enrollment criteria used in the current trial was that “CABG has not changed much” since the first SYNTAX trial, Dr. Escaned said. Although he acknowledged that some progress also occurred with CABG in the subsequent 10 years, “it has not been as big a change” as going to second-generation drug-eluting stents, using a pressure wire assessment to target physiologically important stenoses, and improved techniques for treating chronic total occlusions that have nearly doubled success rates in patients with these lesions.
The SYNTAX II trial enrolled 454 patients with de novo triple-vessel coronary disease without left main stem involvement at 22 centers in four European countries during 2014 and 2015. The improvement in the primary 1-year endpoint in the current patients compared with PCI patients from the first SYNTAX trial was driven primarily by reductions in MI and in repeat revascularizations. The SYNTAX II patients also had a 0.7% rate of definite stent thrombosis events, compared with a 2.4% rate in the original SYNTAX PCI patients, a statistically significant difference. Concurrently with Dr. Escaned’s report at the meeting an article with the results appeared online (Eur Heart J. 2017 Aug 26;doi: 10.1093/eurheartj/ehx512).
Dr. Escaned cautioned that longer-term follow-up is needed to more fully compare the PCI results with CABG.
SYNTAX II received unrestricted grant support from Philips/Volcano and Boston Scientific, the companies that market the pressure wires and stents used in the study. Dr. Escaned reported ties to Abbott, AstraZeneca, Biosensors, Boston Scientific, Medtronic, OrbusNeich, Philips/Volcano, and Boston Scientific.
[email protected]
On Twitter @mitchelzoler
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: At 1 year, the combined major adverse event rate was 11%, similar to the CABG rate in the original SYNTAX trial.
Data source: SYNTAX II, a prospective, multicenter, single-arm study with 454 patients.
Disclosures: SYNTAX II received unrestricted grant support from Philips/Volcano and Boston Scientific, the companies that market the pressure wires and stents used in the study. Dr. Escaned reported ties to Abbott, AstraZeneca, Biosensors, Boston Scientific, Medtronic, OrbusNeich, Philips/Volcano, and Boston Scientific.
Abnormal potassium plus suspected ACS spell trouble
BARCELONA – A serum potassium level of at least 5.0 mmol/L or 3.5 mmol/L or less at admission for suspected acute coronary syndrome is a red flag for increased risk of in-hospital mortality and cardiac arrest, according to a Swedish study of nearly 33,000 consecutive patients.
That’s true even if, as so often ultimately proves to be the case, the patient turns out not to have ACS, Jonas Faxén, MD, of the Karolinska Institute, Stockholm, reported at the annual congress of the European Society of Cardiology.
“This study highlights that, if you have a patient in the emergency department with a possible ACS and potassium imbalance, you should really be cautious,” Dr. Faxén said.
He reported on 32,955 consecutive patients admitted to Stockholm County hospitals for suspected ACS during 2006-2011 and thereby enrolled in the SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry.
Overall in-hospital mortality was 2.7%. In-hospital cardiac arrest occurred in 1.5% of patients. New-onset atrial fibrillation occurred in 2.4% of patients. These key outcomes were compared between the reference group – defined as patients with an admission serum potassium of 3.5 to less than 4.0 mmol/L – and patients with an admission serum potassium above or below those cutoffs.
In a multivariate logistic regression analysis adjusted for 24 potential confounders, including demographics, presentation characteristics, main diagnosis, comorbid conditions, medications on admission, and estimated glomerular filtration rate, patients with a serum potassium of 5.0 to less than 5.5 mmol/L were at 1.8-fold increased risk of in-hospital mortality. Those with a potassium of 5.5 mmol/L or greater were at 2.3-fold increased risk.
In contrast, a low rather than a high serum potassium was an independent risk factor cardiac arrest. An admission potassium of 3.0 to less than 3.5 mmol/L carried a 1.8-fold increased risk of in-hospital cardiac arrest, while a potassium of less than 3.0 was associated with a 2.7-fold increased risk.
A serum potassium below 3.0 mmol/L at admission also was associated with a 1.7-fold increased risk of new-onset atrial fibrillation.
These elevated risks of bad outcomes didn’t differ significantly between patients with ST-elevation MI, non-STEMI ACS, and those whose final diagnosis was not ACS, Dr. Faxén noted.
Session cochair David W. Walker, MD, medical director of the East Sussex (England) Healthcare NHS Trust, observed, “When I was a junior doctor I was always taught that when patients came onto coronary care we had to get their potassium to 4.5-5.0 mmol/L. I think you might want to change that advice now.”
“The implication would be that, if you intervene quickly in a patient with an abnormal potassium level, you might make a difference. Clearly, a potassium that’s too high is much worse than too low, since patients with in-hospital cardiac arrest can often be resuscitated,” Dr. Walker commented.
Dr. Faxén reported having no financial conflicts regarding his study, which was funded by the Swedish Heart and Lung Foundation and the Stockholm County Council.
BARCELONA – A serum potassium level of at least 5.0 mmol/L or 3.5 mmol/L or less at admission for suspected acute coronary syndrome is a red flag for increased risk of in-hospital mortality and cardiac arrest, according to a Swedish study of nearly 33,000 consecutive patients.
That’s true even if, as so often ultimately proves to be the case, the patient turns out not to have ACS, Jonas Faxén, MD, of the Karolinska Institute, Stockholm, reported at the annual congress of the European Society of Cardiology.
“This study highlights that, if you have a patient in the emergency department with a possible ACS and potassium imbalance, you should really be cautious,” Dr. Faxén said.
He reported on 32,955 consecutive patients admitted to Stockholm County hospitals for suspected ACS during 2006-2011 and thereby enrolled in the SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry.
Overall in-hospital mortality was 2.7%. In-hospital cardiac arrest occurred in 1.5% of patients. New-onset atrial fibrillation occurred in 2.4% of patients. These key outcomes were compared between the reference group – defined as patients with an admission serum potassium of 3.5 to less than 4.0 mmol/L – and patients with an admission serum potassium above or below those cutoffs.
In a multivariate logistic regression analysis adjusted for 24 potential confounders, including demographics, presentation characteristics, main diagnosis, comorbid conditions, medications on admission, and estimated glomerular filtration rate, patients with a serum potassium of 5.0 to less than 5.5 mmol/L were at 1.8-fold increased risk of in-hospital mortality. Those with a potassium of 5.5 mmol/L or greater were at 2.3-fold increased risk.
In contrast, a low rather than a high serum potassium was an independent risk factor cardiac arrest. An admission potassium of 3.0 to less than 3.5 mmol/L carried a 1.8-fold increased risk of in-hospital cardiac arrest, while a potassium of less than 3.0 was associated with a 2.7-fold increased risk.
A serum potassium below 3.0 mmol/L at admission also was associated with a 1.7-fold increased risk of new-onset atrial fibrillation.
These elevated risks of bad outcomes didn’t differ significantly between patients with ST-elevation MI, non-STEMI ACS, and those whose final diagnosis was not ACS, Dr. Faxén noted.
Session cochair David W. Walker, MD, medical director of the East Sussex (England) Healthcare NHS Trust, observed, “When I was a junior doctor I was always taught that when patients came onto coronary care we had to get their potassium to 4.5-5.0 mmol/L. I think you might want to change that advice now.”
“The implication would be that, if you intervene quickly in a patient with an abnormal potassium level, you might make a difference. Clearly, a potassium that’s too high is much worse than too low, since patients with in-hospital cardiac arrest can often be resuscitated,” Dr. Walker commented.
Dr. Faxén reported having no financial conflicts regarding his study, which was funded by the Swedish Heart and Lung Foundation and the Stockholm County Council.
BARCELONA – A serum potassium level of at least 5.0 mmol/L or 3.5 mmol/L or less at admission for suspected acute coronary syndrome is a red flag for increased risk of in-hospital mortality and cardiac arrest, according to a Swedish study of nearly 33,000 consecutive patients.
That’s true even if, as so often ultimately proves to be the case, the patient turns out not to have ACS, Jonas Faxén, MD, of the Karolinska Institute, Stockholm, reported at the annual congress of the European Society of Cardiology.
“This study highlights that, if you have a patient in the emergency department with a possible ACS and potassium imbalance, you should really be cautious,” Dr. Faxén said.
He reported on 32,955 consecutive patients admitted to Stockholm County hospitals for suspected ACS during 2006-2011 and thereby enrolled in the SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry.
Overall in-hospital mortality was 2.7%. In-hospital cardiac arrest occurred in 1.5% of patients. New-onset atrial fibrillation occurred in 2.4% of patients. These key outcomes were compared between the reference group – defined as patients with an admission serum potassium of 3.5 to less than 4.0 mmol/L – and patients with an admission serum potassium above or below those cutoffs.
In a multivariate logistic regression analysis adjusted for 24 potential confounders, including demographics, presentation characteristics, main diagnosis, comorbid conditions, medications on admission, and estimated glomerular filtration rate, patients with a serum potassium of 5.0 to less than 5.5 mmol/L were at 1.8-fold increased risk of in-hospital mortality. Those with a potassium of 5.5 mmol/L or greater were at 2.3-fold increased risk.
In contrast, a low rather than a high serum potassium was an independent risk factor cardiac arrest. An admission potassium of 3.0 to less than 3.5 mmol/L carried a 1.8-fold increased risk of in-hospital cardiac arrest, while a potassium of less than 3.0 was associated with a 2.7-fold increased risk.
A serum potassium below 3.0 mmol/L at admission also was associated with a 1.7-fold increased risk of new-onset atrial fibrillation.
These elevated risks of bad outcomes didn’t differ significantly between patients with ST-elevation MI, non-STEMI ACS, and those whose final diagnosis was not ACS, Dr. Faxén noted.
Session cochair David W. Walker, MD, medical director of the East Sussex (England) Healthcare NHS Trust, observed, “When I was a junior doctor I was always taught that when patients came onto coronary care we had to get their potassium to 4.5-5.0 mmol/L. I think you might want to change that advice now.”
“The implication would be that, if you intervene quickly in a patient with an abnormal potassium level, you might make a difference. Clearly, a potassium that’s too high is much worse than too low, since patients with in-hospital cardiac arrest can often be resuscitated,” Dr. Walker commented.
Dr. Faxén reported having no financial conflicts regarding his study, which was funded by the Swedish Heart and Lung Foundation and the Stockholm County Council.
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: Hyperkalemia of 5.0 to less than 5.5 mmol/L at admission for suspected ACS was associated with close to a twofold increased risk of in-hospital mortality.
Data source: The SWEDEHEART study is an ongoing prospective registry of patients with cardiovascular disease admitted to Stockholm County hospitals.
Disclosures: The presenter reported having no financial conflicts regarding his study, which was funded by the Swedish Heart and Lung Foundation and the Stockholm County Council.
Fentanyl in the cath lab questioned
BARCELONA – The current routine use of intravenous fentanyl in the cardiac catheterization lab for patient comfort during coronary angiography has been called into question by the results of a double-blind randomized trial presented at the annual congress of the European Society of Cardiology.
The trial, known as PACIFY, showed that IV fentanyl delayed absorption of the oral P2Y12 inhibitor ticagrelor (Brilinta) by up to 4 hours. That’s a disturbing finding that could account for the relatively high risk of stent thrombosis in the first hours after percutaneous coronary intervention, according to lead investigator John W. McEvoy, MD, a cardiologist at Johns Hopkins University in Baltimore.
“These data challenge the routine and nonselective use of fentanyl for cardiac catheterization and PCI, particularly when rapid platelet inhibition is desirable,” he said, adding, “This would represent a significant change in U.S. cath lab practice.”
PACIFY (Platelet Aggregation After Ticagrelor Inhibition and Fentanyl) was a single-center trial in which 212 patients undergoing PCI were randomized in double-blind fashion to fentanyl or no fentanyl on top of a local anesthetic and IV midazolam (Versed). In addition, the 70 subjects undergoing PCI with stent placement received a 180-mg loading dose of ticagrelor intraprocedurally.
The primary endpoint was ticagrelor plasma concentration during the first 24 hours after the drug’s administration. Secondary endpoints were patients’ self-reported maximum pain during the procedure and platelet inhibition at 2 hours.
The plasma concentration time area under the curve over the course of 24 hours was superior in the no-fentanyl group by a margin of 3,441 ng/mL–1 per hour to 2,016 ng/mL–1 per hour. Moreover, 37% of fentanyl recipients displayed high platelet reactivity at 2 hours as measured by light transmission platelet aggregometry, compared with none of the no-fentanyl controls.
Pain was similarly well controlled in both treatment arms, casting doubt on the widespread belief among U.S. interventionalists that routine administration of fentanyl in the cath lab is necessary for patient comfort. Patients in the control arm could receive bailout fentanyl upon request; only two did so.
Dr. McEvoy reported having no financial conflicts regarding this study, which was conducted free of commercial support.
BARCELONA – The current routine use of intravenous fentanyl in the cardiac catheterization lab for patient comfort during coronary angiography has been called into question by the results of a double-blind randomized trial presented at the annual congress of the European Society of Cardiology.
The trial, known as PACIFY, showed that IV fentanyl delayed absorption of the oral P2Y12 inhibitor ticagrelor (Brilinta) by up to 4 hours. That’s a disturbing finding that could account for the relatively high risk of stent thrombosis in the first hours after percutaneous coronary intervention, according to lead investigator John W. McEvoy, MD, a cardiologist at Johns Hopkins University in Baltimore.
“These data challenge the routine and nonselective use of fentanyl for cardiac catheterization and PCI, particularly when rapid platelet inhibition is desirable,” he said, adding, “This would represent a significant change in U.S. cath lab practice.”
PACIFY (Platelet Aggregation After Ticagrelor Inhibition and Fentanyl) was a single-center trial in which 212 patients undergoing PCI were randomized in double-blind fashion to fentanyl or no fentanyl on top of a local anesthetic and IV midazolam (Versed). In addition, the 70 subjects undergoing PCI with stent placement received a 180-mg loading dose of ticagrelor intraprocedurally.
The primary endpoint was ticagrelor plasma concentration during the first 24 hours after the drug’s administration. Secondary endpoints were patients’ self-reported maximum pain during the procedure and platelet inhibition at 2 hours.
The plasma concentration time area under the curve over the course of 24 hours was superior in the no-fentanyl group by a margin of 3,441 ng/mL–1 per hour to 2,016 ng/mL–1 per hour. Moreover, 37% of fentanyl recipients displayed high platelet reactivity at 2 hours as measured by light transmission platelet aggregometry, compared with none of the no-fentanyl controls.
Pain was similarly well controlled in both treatment arms, casting doubt on the widespread belief among U.S. interventionalists that routine administration of fentanyl in the cath lab is necessary for patient comfort. Patients in the control arm could receive bailout fentanyl upon request; only two did so.
Dr. McEvoy reported having no financial conflicts regarding this study, which was conducted free of commercial support.
BARCELONA – The current routine use of intravenous fentanyl in the cardiac catheterization lab for patient comfort during coronary angiography has been called into question by the results of a double-blind randomized trial presented at the annual congress of the European Society of Cardiology.
The trial, known as PACIFY, showed that IV fentanyl delayed absorption of the oral P2Y12 inhibitor ticagrelor (Brilinta) by up to 4 hours. That’s a disturbing finding that could account for the relatively high risk of stent thrombosis in the first hours after percutaneous coronary intervention, according to lead investigator John W. McEvoy, MD, a cardiologist at Johns Hopkins University in Baltimore.
“These data challenge the routine and nonselective use of fentanyl for cardiac catheterization and PCI, particularly when rapid platelet inhibition is desirable,” he said, adding, “This would represent a significant change in U.S. cath lab practice.”
PACIFY (Platelet Aggregation After Ticagrelor Inhibition and Fentanyl) was a single-center trial in which 212 patients undergoing PCI were randomized in double-blind fashion to fentanyl or no fentanyl on top of a local anesthetic and IV midazolam (Versed). In addition, the 70 subjects undergoing PCI with stent placement received a 180-mg loading dose of ticagrelor intraprocedurally.
The primary endpoint was ticagrelor plasma concentration during the first 24 hours after the drug’s administration. Secondary endpoints were patients’ self-reported maximum pain during the procedure and platelet inhibition at 2 hours.
The plasma concentration time area under the curve over the course of 24 hours was superior in the no-fentanyl group by a margin of 3,441 ng/mL–1 per hour to 2,016 ng/mL–1 per hour. Moreover, 37% of fentanyl recipients displayed high platelet reactivity at 2 hours as measured by light transmission platelet aggregometry, compared with none of the no-fentanyl controls.
Pain was similarly well controlled in both treatment arms, casting doubt on the widespread belief among U.S. interventionalists that routine administration of fentanyl in the cath lab is necessary for patient comfort. Patients in the control arm could receive bailout fentanyl upon request; only two did so.
Dr. McEvoy reported having no financial conflicts regarding this study, which was conducted free of commercial support.
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: High platelet reactivity at 2 hours was present in 37% of patients who underwent coronary angiography with IV fentanyl and in none randomized to going without the opiate.
Data source: PACIFY, a single-center, double-blind, randomized trial included 212 patients undergoing coronary angiography.
Disclosures: The presenter reported having no financial conflicts regarding this study, which was conducted free of commercial support.
Hyperlipidemia diagnosis protects against breast cancer
BARCELONA – Women diagnosed with hyperlipidemia had a strikingly reduced risk of subsequently developing breast cancer in a big-data, case-control study, Paul R. Carter, MD, reported at the annual congress of the European Society of Cardiology.
Moreover, those baseline hyperlipidemic women who later got breast cancer had a 40% lower risk of all-cause mortality than did matched nonhyperlipidemic controls diagnosed with the malignancy during follow-up, according to Dr. Carter, a cardiology fellow at Cambridge (England) University.
The inference isn’t that hyperlipidemia somehow protects against the most common type of cancer in women. Indeed, preclinical evidence indicates high cholesterol drives several key steps in carcinogenesis. Rather, the strong implication is that the explanation for the observed preventive effect lies in the pleotropic effects of the statin therapy routinely prescribed in accordance with guidelines once women received the diagnosis of hyperlipidemia, he continued.
“The results of this study provide the strongest justification to date for a clinical trial evaluating the protective effect of statins in patients with breast cancer, and this is what we intend to do,” according to Dr. Carter.
He presented a retrospective longitudinal study of the Algorithm for Comorbidities, Associations, Length of Stay and Mortality database, comprising more than 1.2 million patients admitted for various reasons to selected hospitals in northern England during 2000-2014. This big-data study entailed recruitment of 16,043 women aged 40 years and older who were diagnosed with hyperlipidemia during their hospital stay along with an equal number of age-matched women with normal lipid levels. None of the participants had a breast cancer diagnosis at baseline.
The all-cause mortality rate in baseline hyperlipidemic women who later developed breast cancer was 27.4%, significantly lower than the 37.4% rate in normolipidemic women with breast cancer. This translated into an adjusted 40% relative risk reduction.
All-cause mortality occurred during follow-up in 13.7% of breast cancer–free women with baseline hyperlipidemia, compared with 23.6% of nonhyperlipidemic controls without breast cancer.
In an analysis adjusted for age, ethnicity, and the top-10 causes of death in the U.K., women with baseline hyperlipidemia were 40% less likely to die during follow-up than were women without high cholesterol.
Dr. Carter reported having no financial conflicts of interest regarding his study, which was conducted free of commercial support.
BARCELONA – Women diagnosed with hyperlipidemia had a strikingly reduced risk of subsequently developing breast cancer in a big-data, case-control study, Paul R. Carter, MD, reported at the annual congress of the European Society of Cardiology.
Moreover, those baseline hyperlipidemic women who later got breast cancer had a 40% lower risk of all-cause mortality than did matched nonhyperlipidemic controls diagnosed with the malignancy during follow-up, according to Dr. Carter, a cardiology fellow at Cambridge (England) University.
The inference isn’t that hyperlipidemia somehow protects against the most common type of cancer in women. Indeed, preclinical evidence indicates high cholesterol drives several key steps in carcinogenesis. Rather, the strong implication is that the explanation for the observed preventive effect lies in the pleotropic effects of the statin therapy routinely prescribed in accordance with guidelines once women received the diagnosis of hyperlipidemia, he continued.
“The results of this study provide the strongest justification to date for a clinical trial evaluating the protective effect of statins in patients with breast cancer, and this is what we intend to do,” according to Dr. Carter.
He presented a retrospective longitudinal study of the Algorithm for Comorbidities, Associations, Length of Stay and Mortality database, comprising more than 1.2 million patients admitted for various reasons to selected hospitals in northern England during 2000-2014. This big-data study entailed recruitment of 16,043 women aged 40 years and older who were diagnosed with hyperlipidemia during their hospital stay along with an equal number of age-matched women with normal lipid levels. None of the participants had a breast cancer diagnosis at baseline.
The all-cause mortality rate in baseline hyperlipidemic women who later developed breast cancer was 27.4%, significantly lower than the 37.4% rate in normolipidemic women with breast cancer. This translated into an adjusted 40% relative risk reduction.
All-cause mortality occurred during follow-up in 13.7% of breast cancer–free women with baseline hyperlipidemia, compared with 23.6% of nonhyperlipidemic controls without breast cancer.
In an analysis adjusted for age, ethnicity, and the top-10 causes of death in the U.K., women with baseline hyperlipidemia were 40% less likely to die during follow-up than were women without high cholesterol.
Dr. Carter reported having no financial conflicts of interest regarding his study, which was conducted free of commercial support.
BARCELONA – Women diagnosed with hyperlipidemia had a strikingly reduced risk of subsequently developing breast cancer in a big-data, case-control study, Paul R. Carter, MD, reported at the annual congress of the European Society of Cardiology.
Moreover, those baseline hyperlipidemic women who later got breast cancer had a 40% lower risk of all-cause mortality than did matched nonhyperlipidemic controls diagnosed with the malignancy during follow-up, according to Dr. Carter, a cardiology fellow at Cambridge (England) University.
The inference isn’t that hyperlipidemia somehow protects against the most common type of cancer in women. Indeed, preclinical evidence indicates high cholesterol drives several key steps in carcinogenesis. Rather, the strong implication is that the explanation for the observed preventive effect lies in the pleotropic effects of the statin therapy routinely prescribed in accordance with guidelines once women received the diagnosis of hyperlipidemia, he continued.
“The results of this study provide the strongest justification to date for a clinical trial evaluating the protective effect of statins in patients with breast cancer, and this is what we intend to do,” according to Dr. Carter.
He presented a retrospective longitudinal study of the Algorithm for Comorbidities, Associations, Length of Stay and Mortality database, comprising more than 1.2 million patients admitted for various reasons to selected hospitals in northern England during 2000-2014. This big-data study entailed recruitment of 16,043 women aged 40 years and older who were diagnosed with hyperlipidemia during their hospital stay along with an equal number of age-matched women with normal lipid levels. None of the participants had a breast cancer diagnosis at baseline.
The all-cause mortality rate in baseline hyperlipidemic women who later developed breast cancer was 27.4%, significantly lower than the 37.4% rate in normolipidemic women with breast cancer. This translated into an adjusted 40% relative risk reduction.
All-cause mortality occurred during follow-up in 13.7% of breast cancer–free women with baseline hyperlipidemia, compared with 23.6% of nonhyperlipidemic controls without breast cancer.
In an analysis adjusted for age, ethnicity, and the top-10 causes of death in the U.K., women with baseline hyperlipidemia were 40% less likely to die during follow-up than were women without high cholesterol.
Dr. Carter reported having no financial conflicts of interest regarding his study, which was conducted free of commercial support.
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: The risk of subsequent development of breast cancer was one-third lower in women diagnosed with hyperlipidemia than in controls with normal lipid levels.
Data source: A retrospective longitudinal case-control study of 16,043 U.K. women aged 40 years or older when diagnosed with hyperlipidemia and an equal number of age-matched women with normal lipids.
Disclosures: The presenter reported having no financial conflicts of interest regarding his study, which was conducted free of commercial support.
Avoid sildenafil for pulmonary hypertension after corrected valvular disease
BARCELONA – Off-label use of the phosphodiesterase-5 inhibitor sildenafil to treat residual pulmonary hypertension after successful correction of valvular heart disease is not merely ineffective, it’s counterproductive, according to the results of the randomized, placebo-controlled SIOVAC study.
“We believe based upon our results that off-label use of sildenafil in patients with left heart disease-pulmonary hypertension due to valvular disease should be discouraged,” Javier Bermejo, MD, declared at the annual congress of the European Society of Cardiology. 
Sildenafil is approved with a solid, evidence-based indication for treating some other types of pulmonary hypertension. Many cardiologists also prescribe the drug off label for residual pulmonary hypertension in patients with corrected valve disease, hoping that it will be of benefit, since there is currently no approved treatment for this common and serious condition associated with increased mortality. But because the anecdotal literature on sildenafil for this specific type of pulmonary hypertension is mixed, Dr. Bermejo and his coinvestigators in the Spanish Network Center for Cardiovascular Research decided to conduct a multicenter randomized trial.
SIOVAC (Sildenafil for Improving Clinical Outcomes After Valvular Correction) comprised 200 patients with residual pulmonary hypertension after corrected valvular heart disease at 17 Spanish general hospitals. The patients were randomized to receive sildenafil at 40 mg t.i.d. or placebo for 6 months in this double-blind trial.
The primary endpoint was a standardized composite clinical score widely used in heart failure trials. It consists of all-cause mortality, hospital admission for heart failure, worsening exercise tolerance, and deterioration in a global self-assessment rating.
The shocker for the investigators – who had expected a positive study – was that 33% of patients in the sildenafil group worsened significantly on the composite clinical score at 6 months, compared with 14% of placebo-treated controls, said Dr. Bermejo, a cardiologist at Gregorio Marañón University Hospital in Madrid.
Moreover, only 27% of the sildenafil group improved, compared with 44% of controls. About one-third of patients in both groups remained unchanged over the course of the 6-month trial.
Dr. Bermejo noted that valvular disease is considered the next cardiac epidemic because of its strong association with advancing age and the rapid aging of the population worldwide. Pulmonary hypertension occurs is virtually all patients with severe mitral disease and in up to two-thirds of those with asymptomatic aortic stenosis. Regression of the pulmonary hypertension is often incomplete after successful surgical or transcatheter correction of the valvular lesion.
Discussant Irene M. Lang, MD, called SIOVAC “a very clear study.” It convincingly establishes that sildenafil – a vasodilator – is ineffective for the treatment of what the current ESC/European Respiratory Society guidelines on pulmonary hypertension call isolated post-capillary pulmonary hypertension, a condition defined hemodynamically by a diastolic pulmonary vascular pressure gradient of less than 7 mm Hg and/or a pulmonary vascular resistance below 3 Wood units (Eur Heart J. 2016 Jan 1;37[1]:67-119.)
The SIOVAC findings underscore the strong IIIC recommendation in the European guidelines that the use of approved therapies for pulmonary arterial hypertension is not recommended in patients with left heart disease-pulmonary hypertension, added Dr. Lang, a coauthor of the guidelines and professor of vascular biology at the Medical University of Vienna.
The Spanish government funded SIOVAC. Dr. Bermejo reported having no financial conflicts of interest.
BARCELONA – Off-label use of the phosphodiesterase-5 inhibitor sildenafil to treat residual pulmonary hypertension after successful correction of valvular heart disease is not merely ineffective, it’s counterproductive, according to the results of the randomized, placebo-controlled SIOVAC study.
“We believe based upon our results that off-label use of sildenafil in patients with left heart disease-pulmonary hypertension due to valvular disease should be discouraged,” Javier Bermejo, MD, declared at the annual congress of the European Society of Cardiology.
Sildenafil is approved with a solid, evidence-based indication for treating some other types of pulmonary hypertension. Many cardiologists also prescribe the drug off label for residual pulmonary hypertension in patients with corrected valve disease, hoping that it will be of benefit, since there is currently no approved treatment for this common and serious condition associated with increased mortality. But because the anecdotal literature on sildenafil for this specific type of pulmonary hypertension is mixed, Dr. Bermejo and his coinvestigators in the Spanish Network Center for Cardiovascular Research decided to conduct a multicenter randomized trial.
SIOVAC (Sildenafil for Improving Clinical Outcomes After Valvular Correction) comprised 200 patients with residual pulmonary hypertension after corrected valvular heart disease at 17 Spanish general hospitals. The patients were randomized to receive sildenafil at 40 mg t.i.d. or placebo for 6 months in this double-blind trial.
The primary endpoint was a standardized composite clinical score widely used in heart failure trials. It consists of all-cause mortality, hospital admission for heart failure, worsening exercise tolerance, and deterioration in a global self-assessment rating.
The shocker for the investigators – who had expected a positive study – was that 33% of patients in the sildenafil group worsened significantly on the composite clinical score at 6 months, compared with 14% of placebo-treated controls, said Dr. Bermejo, a cardiologist at Gregorio Marañón University Hospital in Madrid.
Moreover, only 27% of the sildenafil group improved, compared with 44% of controls. About one-third of patients in both groups remained unchanged over the course of the 6-month trial.
Dr. Bermejo noted that valvular disease is considered the next cardiac epidemic because of its strong association with advancing age and the rapid aging of the population worldwide. Pulmonary hypertension occurs is virtually all patients with severe mitral disease and in up to two-thirds of those with asymptomatic aortic stenosis. Regression of the pulmonary hypertension is often incomplete after successful surgical or transcatheter correction of the valvular lesion.
Discussant Irene M. Lang, MD, called SIOVAC “a very clear study.” It convincingly establishes that sildenafil – a vasodilator – is ineffective for the treatment of what the current ESC/European Respiratory Society guidelines on pulmonary hypertension call isolated post-capillary pulmonary hypertension, a condition defined hemodynamically by a diastolic pulmonary vascular pressure gradient of less than 7 mm Hg and/or a pulmonary vascular resistance below 3 Wood units (Eur Heart J. 2016 Jan 1;37[1]:67-119.)
The SIOVAC findings underscore the strong IIIC recommendation in the European guidelines that the use of approved therapies for pulmonary arterial hypertension is not recommended in patients with left heart disease-pulmonary hypertension, added Dr. Lang, a coauthor of the guidelines and professor of vascular biology at the Medical University of Vienna.
The Spanish government funded SIOVAC. Dr. Bermejo reported having no financial conflicts of interest.
BARCELONA – Off-label use of the phosphodiesterase-5 inhibitor sildenafil to treat residual pulmonary hypertension after successful correction of valvular heart disease is not merely ineffective, it’s counterproductive, according to the results of the randomized, placebo-controlled SIOVAC study.
“We believe based upon our results that off-label use of sildenafil in patients with left heart disease-pulmonary hypertension due to valvular disease should be discouraged,” Javier Bermejo, MD, declared at the annual congress of the European Society of Cardiology.
Sildenafil is approved with a solid, evidence-based indication for treating some other types of pulmonary hypertension. Many cardiologists also prescribe the drug off label for residual pulmonary hypertension in patients with corrected valve disease, hoping that it will be of benefit, since there is currently no approved treatment for this common and serious condition associated with increased mortality. But because the anecdotal literature on sildenafil for this specific type of pulmonary hypertension is mixed, Dr. Bermejo and his coinvestigators in the Spanish Network Center for Cardiovascular Research decided to conduct a multicenter randomized trial.
SIOVAC (Sildenafil for Improving Clinical Outcomes After Valvular Correction) comprised 200 patients with residual pulmonary hypertension after corrected valvular heart disease at 17 Spanish general hospitals. The patients were randomized to receive sildenafil at 40 mg t.i.d. or placebo for 6 months in this double-blind trial.
The primary endpoint was a standardized composite clinical score widely used in heart failure trials. It consists of all-cause mortality, hospital admission for heart failure, worsening exercise tolerance, and deterioration in a global self-assessment rating.
The shocker for the investigators – who had expected a positive study – was that 33% of patients in the sildenafil group worsened significantly on the composite clinical score at 6 months, compared with 14% of placebo-treated controls, said Dr. Bermejo, a cardiologist at Gregorio Marañón University Hospital in Madrid.
Moreover, only 27% of the sildenafil group improved, compared with 44% of controls. About one-third of patients in both groups remained unchanged over the course of the 6-month trial.
Dr. Bermejo noted that valvular disease is considered the next cardiac epidemic because of its strong association with advancing age and the rapid aging of the population worldwide. Pulmonary hypertension occurs is virtually all patients with severe mitral disease and in up to two-thirds of those with asymptomatic aortic stenosis. Regression of the pulmonary hypertension is often incomplete after successful surgical or transcatheter correction of the valvular lesion.
Discussant Irene M. Lang, MD, called SIOVAC “a very clear study.” It convincingly establishes that sildenafil – a vasodilator – is ineffective for the treatment of what the current ESC/European Respiratory Society guidelines on pulmonary hypertension call isolated post-capillary pulmonary hypertension, a condition defined hemodynamically by a diastolic pulmonary vascular pressure gradient of less than 7 mm Hg and/or a pulmonary vascular resistance below 3 Wood units (Eur Heart J. 2016 Jan 1;37[1]:67-119.)
The SIOVAC findings underscore the strong IIIC recommendation in the European guidelines that the use of approved therapies for pulmonary arterial hypertension is not recommended in patients with left heart disease-pulmonary hypertension, added Dr. Lang, a coauthor of the guidelines and professor of vascular biology at the Medical University of Vienna.
The Spanish government funded SIOVAC. Dr. Bermejo reported having no financial conflicts of interest.
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: One-third of patients with residual pulmonary hypertension after successful correction of valvular heart disease experienced significant clinical worsening during 6 months of sildenafil therapy, compared with 14% on placebo.
Data source: SIOVAC, a 6-month, double-blind, placebo-controlled study of 200 patients with residual pulmonary hypertension after correction for valvular heart disease.
Disclosures: The Spanish government funded SIOVAC. The presenter reported having no financial conflicts of interest.
HOPE-3 wades into fray regarding optimal blood pressure targets
BARCELONA – How low to go in treating hypertension is a topic of considerable recent controversy. Now the HOPE-3 trial investigators have weighed in, reporting that optimal outcomes in their landmark randomized trial were seen with an achieved, on-treatment systolic blood pressure of 130-140 mm Hg and a diastolic blood pressure of 75-80 mm Hg, Eva M. Lonn, MD, reported at the annual congress of the European Society of Cardiology.
Those results stand in glaring contrast to the findings of the much-discussed SPRINT trial, in which hypertensive patients fared best with an on-treatment SBP driven below 120 mm Hg (N Engl J Med. 2015 Nov 26; 373:2103-16).
“Please note that lower blood pressures, both systolic and diastolic, weren’t associated with lower risk, whereas higher blood pressures considerably increased the risk for major vascular events,” she added.
HOPE-3 (the Third Heart Outcomes Prevention Evaluation) included 12,705 patients in 21 countries who did not have cardiovascular disease and were at intermediate risk, with an average age of 65 years at enrollment and a Framinhgam Risk Score of about 10%. They were randomized double-blind in a 2x2 factorial design to rosuvastatin at 10 mg per day or placebo and/or candesartan at 16 mg plus hydrochlorothiazide at 12.5 mg per day or placebo and prospectively followed for a median of 5.6 years.
The primary outcomes of HOPE-3 have been published (N Engl J Med. 2016 May 26;374[21]:2009-20 and 2021-31). This was a practice-changing trial that opened the door to broader use of statin therapy for primary prevention.
At the ESC congress in Barcelona, Dr. Lonn presented a secondary post-hoc analysis that focused on the impact of antihypertensive therapy in HOPE-3. The results shed new light on the optimal blood pressure levels for triggering initation of antihypertensive therapy, as well as defining the achieved blood pressures that resulted in the greatest reductions in major vascular events.
As this was essentially an all-comers trial of intermediate-risk patients, participants presented with a range of blood pressures at baseline. But more than 4,700 subjects had a baseline SBP of 140-159.9 mm Hg, and 833 had an SBP of 160 mm Hg or more.
The candesartan/hydrochlorothiazide regimen resulted in what Dr. Lonn termed a “moderate” net placebo-subtracted blood pressure reduction of 6/3 mm Hg. The higher the baseline blood pressure, the bigger the reduction.
In the one-third of subjects with a baseline SBP greater than 143.5 mm Hg, antihypertensive therapy resulted in a significant 27% reduction in the composite endpoint of cardiovascular death, MI, or stroke compared with placebo. Those with a baseline SBP of 150 mm Hg or more showed even greater benefit from antihypertensive therapy, with a composite event rate of 4.8% compared with 7.2% for placebo, representing a 34% relative risk reduction in which the event curves began separating at about 2 years.
In contrast, antihypertensive therapy brought no significant reduction in events in patients in the lower two tertiles of baseline SBP. And there was no association at all between baseline DBP and major cardiovascular events across the range of DBP values evaluated in HOPE-3.
But wait: Things get more interesting, according to the cardiac electrophysiologist.
“I find the association between mean in-trial blood pressure as recorded in many measurements and vascular outcomes to be the most interesting analysis. This may be a better look at the association between blood pressure and outcomes than a measurement obtained just once or twice at baseline,” she explained.
Of note, among the 6,356 subjects on candesartan/hydrochlorothiazide, those with a mean on-treatment SBP of 160 mm Hg or more had a 2.61% per year rate of the composite of cardiovascular death, MI, stroke, rescue from cardiac arrest, heart failure, or revascularization. This was more than three-fold higher than the 0.75% per year rate in patients with an on-treatment SBP of 120-139.9 mm Hg. The composite event rate was also significantly higher in those with a mean on-treatment SBP of 140-159.9 mm Hg, at 1.4% per year. The event rate in patients with an on-treatment SBP below 120 mm Hg was identical to that of patients with a value of 120-139.9 mm Hg.
Only among patients with an on-treatment DBP of 90 mm Hg or more was the composite event rate significantly greater than in those with a DBP of 70-79.9 mm Hg, who had the lowest event rate by a margin of 1.89% versus 0.75% per year.
An Australian cardiologist in the audience who has been involved in revamping hypertension treatment guidelines Down Under expressed frustration. He only recently succeeded in wrangling his fellow panelists into incorporating the SPRINT results into the draft guidelines; now HOPE-3 is sending a very different message. What gives? Could the disparate findings simply be due to play of chance? he asked.
Highly unlikely, Dr. Lonn replied.
“There were substantial differences between our trials,” she explained. “First of all, the SPRINT population was at substantially higher risk. They either had to have established cardiovascular disease – we eliminated those people – or significant renal disease – we eliminated those people, too – or age greater than 75, or a Framingham Risk Score above 15%.”
Also, the SPRINT protocol controversially called for unattended blood pressure measurement.
“This is a very pure way ot eliminating white coat hypertension, but it is different from other studies, so it is very difficult to compare SPRINT to older studies or to HOPE-3. Some other investigators have suggested that the difference between attended and unattended blood pressure is close to 10 mm Hg. So our SBP of 130 mm Hg, which had the best outcomes in HOPE-3, may be the same as about 120 mm Hg in SPRINT,” according to Dr. Lonn.
HOPE-3 was funded by the Canadian Institutes of Health Research and AstraZeneca. Dr. Lonn reported serving as a consultant to and receiving research grants from AstraZeneca, Amgen, Bayer, and Novartis.
BARCELONA – How low to go in treating hypertension is a topic of considerable recent controversy. Now the HOPE-3 trial investigators have weighed in, reporting that optimal outcomes in their landmark randomized trial were seen with an achieved, on-treatment systolic blood pressure of 130-140 mm Hg and a diastolic blood pressure of 75-80 mm Hg, Eva M. Lonn, MD, reported at the annual congress of the European Society of Cardiology.
Those results stand in glaring contrast to the findings of the much-discussed SPRINT trial, in which hypertensive patients fared best with an on-treatment SBP driven below 120 mm Hg (N Engl J Med. 2015 Nov 26; 373:2103-16).
“Please note that lower blood pressures, both systolic and diastolic, weren’t associated with lower risk, whereas higher blood pressures considerably increased the risk for major vascular events,” she added.
HOPE-3 (the Third Heart Outcomes Prevention Evaluation) included 12,705 patients in 21 countries who did not have cardiovascular disease and were at intermediate risk, with an average age of 65 years at enrollment and a Framinhgam Risk Score of about 10%. They were randomized double-blind in a 2x2 factorial design to rosuvastatin at 10 mg per day or placebo and/or candesartan at 16 mg plus hydrochlorothiazide at 12.5 mg per day or placebo and prospectively followed for a median of 5.6 years.
The primary outcomes of HOPE-3 have been published (N Engl J Med. 2016 May 26;374[21]:2009-20 and 2021-31). This was a practice-changing trial that opened the door to broader use of statin therapy for primary prevention.
At the ESC congress in Barcelona, Dr. Lonn presented a secondary post-hoc analysis that focused on the impact of antihypertensive therapy in HOPE-3. The results shed new light on the optimal blood pressure levels for triggering initation of antihypertensive therapy, as well as defining the achieved blood pressures that resulted in the greatest reductions in major vascular events.
As this was essentially an all-comers trial of intermediate-risk patients, participants presented with a range of blood pressures at baseline. But more than 4,700 subjects had a baseline SBP of 140-159.9 mm Hg, and 833 had an SBP of 160 mm Hg or more.
The candesartan/hydrochlorothiazide regimen resulted in what Dr. Lonn termed a “moderate” net placebo-subtracted blood pressure reduction of 6/3 mm Hg. The higher the baseline blood pressure, the bigger the reduction.
In the one-third of subjects with a baseline SBP greater than 143.5 mm Hg, antihypertensive therapy resulted in a significant 27% reduction in the composite endpoint of cardiovascular death, MI, or stroke compared with placebo. Those with a baseline SBP of 150 mm Hg or more showed even greater benefit from antihypertensive therapy, with a composite event rate of 4.8% compared with 7.2% for placebo, representing a 34% relative risk reduction in which the event curves began separating at about 2 years.
In contrast, antihypertensive therapy brought no significant reduction in events in patients in the lower two tertiles of baseline SBP. And there was no association at all between baseline DBP and major cardiovascular events across the range of DBP values evaluated in HOPE-3.
But wait: Things get more interesting, according to the cardiac electrophysiologist.
“I find the association between mean in-trial blood pressure as recorded in many measurements and vascular outcomes to be the most interesting analysis. This may be a better look at the association between blood pressure and outcomes than a measurement obtained just once or twice at baseline,” she explained.
Of note, among the 6,356 subjects on candesartan/hydrochlorothiazide, those with a mean on-treatment SBP of 160 mm Hg or more had a 2.61% per year rate of the composite of cardiovascular death, MI, stroke, rescue from cardiac arrest, heart failure, or revascularization. This was more than three-fold higher than the 0.75% per year rate in patients with an on-treatment SBP of 120-139.9 mm Hg. The composite event rate was also significantly higher in those with a mean on-treatment SBP of 140-159.9 mm Hg, at 1.4% per year. The event rate in patients with an on-treatment SBP below 120 mm Hg was identical to that of patients with a value of 120-139.9 mm Hg.
Only among patients with an on-treatment DBP of 90 mm Hg or more was the composite event rate significantly greater than in those with a DBP of 70-79.9 mm Hg, who had the lowest event rate by a margin of 1.89% versus 0.75% per year.
An Australian cardiologist in the audience who has been involved in revamping hypertension treatment guidelines Down Under expressed frustration. He only recently succeeded in wrangling his fellow panelists into incorporating the SPRINT results into the draft guidelines; now HOPE-3 is sending a very different message. What gives? Could the disparate findings simply be due to play of chance? he asked.
Highly unlikely, Dr. Lonn replied.
“There were substantial differences between our trials,” she explained. “First of all, the SPRINT population was at substantially higher risk. They either had to have established cardiovascular disease – we eliminated those people – or significant renal disease – we eliminated those people, too – or age greater than 75, or a Framingham Risk Score above 15%.”
Also, the SPRINT protocol controversially called for unattended blood pressure measurement.
“This is a very pure way ot eliminating white coat hypertension, but it is different from other studies, so it is very difficult to compare SPRINT to older studies or to HOPE-3. Some other investigators have suggested that the difference between attended and unattended blood pressure is close to 10 mm Hg. So our SBP of 130 mm Hg, which had the best outcomes in HOPE-3, may be the same as about 120 mm Hg in SPRINT,” according to Dr. Lonn.
HOPE-3 was funded by the Canadian Institutes of Health Research and AstraZeneca. Dr. Lonn reported serving as a consultant to and receiving research grants from AstraZeneca, Amgen, Bayer, and Novartis.
BARCELONA – How low to go in treating hypertension is a topic of considerable recent controversy. Now the HOPE-3 trial investigators have weighed in, reporting that optimal outcomes in their landmark randomized trial were seen with an achieved, on-treatment systolic blood pressure of 130-140 mm Hg and a diastolic blood pressure of 75-80 mm Hg, Eva M. Lonn, MD, reported at the annual congress of the European Society of Cardiology.
Those results stand in glaring contrast to the findings of the much-discussed SPRINT trial, in which hypertensive patients fared best with an on-treatment SBP driven below 120 mm Hg (N Engl J Med. 2015 Nov 26; 373:2103-16).
“Please note that lower blood pressures, both systolic and diastolic, weren’t associated with lower risk, whereas higher blood pressures considerably increased the risk for major vascular events,” she added.
HOPE-3 (the Third Heart Outcomes Prevention Evaluation) included 12,705 patients in 21 countries who did not have cardiovascular disease and were at intermediate risk, with an average age of 65 years at enrollment and a Framinhgam Risk Score of about 10%. They were randomized double-blind in a 2x2 factorial design to rosuvastatin at 10 mg per day or placebo and/or candesartan at 16 mg plus hydrochlorothiazide at 12.5 mg per day or placebo and prospectively followed for a median of 5.6 years.
The primary outcomes of HOPE-3 have been published (N Engl J Med. 2016 May 26;374[21]:2009-20 and 2021-31). This was a practice-changing trial that opened the door to broader use of statin therapy for primary prevention.
At the ESC congress in Barcelona, Dr. Lonn presented a secondary post-hoc analysis that focused on the impact of antihypertensive therapy in HOPE-3. The results shed new light on the optimal blood pressure levels for triggering initation of antihypertensive therapy, as well as defining the achieved blood pressures that resulted in the greatest reductions in major vascular events.
As this was essentially an all-comers trial of intermediate-risk patients, participants presented with a range of blood pressures at baseline. But more than 4,700 subjects had a baseline SBP of 140-159.9 mm Hg, and 833 had an SBP of 160 mm Hg or more.
The candesartan/hydrochlorothiazide regimen resulted in what Dr. Lonn termed a “moderate” net placebo-subtracted blood pressure reduction of 6/3 mm Hg. The higher the baseline blood pressure, the bigger the reduction.
In the one-third of subjects with a baseline SBP greater than 143.5 mm Hg, antihypertensive therapy resulted in a significant 27% reduction in the composite endpoint of cardiovascular death, MI, or stroke compared with placebo. Those with a baseline SBP of 150 mm Hg or more showed even greater benefit from antihypertensive therapy, with a composite event rate of 4.8% compared with 7.2% for placebo, representing a 34% relative risk reduction in which the event curves began separating at about 2 years.
In contrast, antihypertensive therapy brought no significant reduction in events in patients in the lower two tertiles of baseline SBP. And there was no association at all between baseline DBP and major cardiovascular events across the range of DBP values evaluated in HOPE-3.
But wait: Things get more interesting, according to the cardiac electrophysiologist.
“I find the association between mean in-trial blood pressure as recorded in many measurements and vascular outcomes to be the most interesting analysis. This may be a better look at the association between blood pressure and outcomes than a measurement obtained just once or twice at baseline,” she explained.
Of note, among the 6,356 subjects on candesartan/hydrochlorothiazide, those with a mean on-treatment SBP of 160 mm Hg or more had a 2.61% per year rate of the composite of cardiovascular death, MI, stroke, rescue from cardiac arrest, heart failure, or revascularization. This was more than three-fold higher than the 0.75% per year rate in patients with an on-treatment SBP of 120-139.9 mm Hg. The composite event rate was also significantly higher in those with a mean on-treatment SBP of 140-159.9 mm Hg, at 1.4% per year. The event rate in patients with an on-treatment SBP below 120 mm Hg was identical to that of patients with a value of 120-139.9 mm Hg.
Only among patients with an on-treatment DBP of 90 mm Hg or more was the composite event rate significantly greater than in those with a DBP of 70-79.9 mm Hg, who had the lowest event rate by a margin of 1.89% versus 0.75% per year.
An Australian cardiologist in the audience who has been involved in revamping hypertension treatment guidelines Down Under expressed frustration. He only recently succeeded in wrangling his fellow panelists into incorporating the SPRINT results into the draft guidelines; now HOPE-3 is sending a very different message. What gives? Could the disparate findings simply be due to play of chance? he asked.
Highly unlikely, Dr. Lonn replied.
“There were substantial differences between our trials,” she explained. “First of all, the SPRINT population was at substantially higher risk. They either had to have established cardiovascular disease – we eliminated those people – or significant renal disease – we eliminated those people, too – or age greater than 75, or a Framingham Risk Score above 15%.”
Also, the SPRINT protocol controversially called for unattended blood pressure measurement.
“This is a very pure way ot eliminating white coat hypertension, but it is different from other studies, so it is very difficult to compare SPRINT to older studies or to HOPE-3. Some other investigators have suggested that the difference between attended and unattended blood pressure is close to 10 mm Hg. So our SBP of 130 mm Hg, which had the best outcomes in HOPE-3, may be the same as about 120 mm Hg in SPRINT,” according to Dr. Lonn.
HOPE-3 was funded by the Canadian Institutes of Health Research and AstraZeneca. Dr. Lonn reported serving as a consultant to and receiving research grants from AstraZeneca, Amgen, Bayer, and Novartis.
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: The on-treatment systolic blood pressure target associated with the greatest reduction in vascular events in the HOPE-3 trial was 130-140 mm Hg.
Data source: The HOPE-3 trial was a randomized, double-blind, placebo-controlled study of 12,705 intermediate-cardiovascular-risk patients in 21 countries who were prospectively followed for a median 5.6 years.
Disclosures: HOPE-3 was funded by the Canadian Institutes of Health Research and AstraZeneca. The presenter reported serving as a consultant to and receiving research grants from AstraZeneca, Amgen, Bayer, and Novartis.
Obesity paradox slings its weight around in atrial fibrillation
BARCELONA – The obesity paradox is alive and well in the rapidly growing population with atrial fibrillation, Samuel Z. Goldhaber, MD, reported at the annual congress of the European Society of Cardiology.
In an analysis of 22,541 participants in the international registry known as GARFIELD-AF (Global Anticoagulation Registry in the Field-Atrial Fibrillation) – the largest ongoing prospective AF registry in the world – all-cause mortality during the first 2 years after diagnosis of the arrhythmia paradoxically decreased as body mass index increased all the way up to a ceiling of 40 kg/m2, according to Dr. Goldhaber, professor of medicine at Harvard Medical School and section head of vascular medicine and director of the thrombosis research group at Brigham and Women’s Hospital, Boston.
“It’s pretty impressive. This degree of mortality reduction with overweight and obesity is of about the same magnitude you might get with thrombolytic therapy for an acute MI, or with beta blocker therapy or statins post-MI,” the cardiologist said in an interview.
This newly described obesity paradox in AF is all the more baffling in light of the heavy cardiovascular risk factor burden that accompanied increased BMI. For example, the prevalence of type 2 diabetes rose from 14.1% among normal-weight individuals with AF, to 19.7% in the overweight, 27.5% in the obese, 34.6% in those with a BMI of 35 to less than 40 kg/m2, and 41.6% in patients with a BMI of 40 kg/m2 or more.
“It’s perplexing,” Dr. Goldhaber confessed. “I think there’s some hidden message here that we haven’t decoded yet.”
Patients with AF who were at the low extreme of the BMI spectrum -- the 3.3% who were underweight, with a BMI below 20 kg/m2 – fared particularly poorly. Their 2-year all-cause mortality rate of 8.71 per 100 person-years was by far the highest of any BMI class in the study. But that’s relatively straightforward to understand, as it’s likely that many underweight patients with AF were frail and/or had cancer. Indeed, only 49% of deaths in the underweight group were due to cardiovascular disease, in contrast to 64% of deaths in persons whose BMI was 40 kg/m2 or more.
Interestingly, only 5%-6% of all deaths in GARFIELD-AF were due to stroke; deaths from heart failure were far more common.
Overall, 71% of patients who presented with newly diagnosed AF in GARFIELD-AF were overweight or obese. The only contributory factor to the obesity paradox that Dr. Goldhaber could spot was that the heavier patients were younger at diagnosis of AF. But this age disparity seems unlikely to overcome their massive burden of multiple other cardiovascular risk factors. So he solicited theories from his audience. One physician argued that morbidly obese individuals are sedentary, so they don’t leave the house as much as leaner AF patients.
“You stay at home because you cannot move. You don’t get into fatal car accidents. You don’t get into conflicts and get murdered,” the physician postulated.
Dr. Goldhaber wasn’t convinced.
“When I go out to bars or dancing, I look around at people, and I estimate that a lot of them have a BMI of 35,” he commented.
Another proposed theory was that overweight and obese AF patients exercise less, so they inhale less of the airborne toxic fine particulates present in the urban environment. The adverse health impact of air pollution is a particularly hot topic of late among European cardiologists, but the notion that obese AF patients fare better because they don’t exercise runs contrary to a wealth of data supporting the health benefits of working out.
The GARFIELD-AF registry is funded by Bayer AG. Dr. Goldhaber reported receiving research grants and/or serving as a consultant to Bayer and numerous other entities, including the National Heart, Lung and Blood Institute.
BARCELONA – The obesity paradox is alive and well in the rapidly growing population with atrial fibrillation, Samuel Z. Goldhaber, MD, reported at the annual congress of the European Society of Cardiology.
In an analysis of 22,541 participants in the international registry known as GARFIELD-AF (Global Anticoagulation Registry in the Field-Atrial Fibrillation) – the largest ongoing prospective AF registry in the world – all-cause mortality during the first 2 years after diagnosis of the arrhythmia paradoxically decreased as body mass index increased all the way up to a ceiling of 40 kg/m2, according to Dr. Goldhaber, professor of medicine at Harvard Medical School and section head of vascular medicine and director of the thrombosis research group at Brigham and Women’s Hospital, Boston.
“It’s pretty impressive. This degree of mortality reduction with overweight and obesity is of about the same magnitude you might get with thrombolytic therapy for an acute MI, or with beta blocker therapy or statins post-MI,” the cardiologist said in an interview.
This newly described obesity paradox in AF is all the more baffling in light of the heavy cardiovascular risk factor burden that accompanied increased BMI. For example, the prevalence of type 2 diabetes rose from 14.1% among normal-weight individuals with AF, to 19.7% in the overweight, 27.5% in the obese, 34.6% in those with a BMI of 35 to less than 40 kg/m2, and 41.6% in patients with a BMI of 40 kg/m2 or more.
“It’s perplexing,” Dr. Goldhaber confessed. “I think there’s some hidden message here that we haven’t decoded yet.”
Patients with AF who were at the low extreme of the BMI spectrum -- the 3.3% who were underweight, with a BMI below 20 kg/m2 – fared particularly poorly. Their 2-year all-cause mortality rate of 8.71 per 100 person-years was by far the highest of any BMI class in the study. But that’s relatively straightforward to understand, as it’s likely that many underweight patients with AF were frail and/or had cancer. Indeed, only 49% of deaths in the underweight group were due to cardiovascular disease, in contrast to 64% of deaths in persons whose BMI was 40 kg/m2 or more.
Interestingly, only 5%-6% of all deaths in GARFIELD-AF were due to stroke; deaths from heart failure were far more common.
Overall, 71% of patients who presented with newly diagnosed AF in GARFIELD-AF were overweight or obese. The only contributory factor to the obesity paradox that Dr. Goldhaber could spot was that the heavier patients were younger at diagnosis of AF. But this age disparity seems unlikely to overcome their massive burden of multiple other cardiovascular risk factors. So he solicited theories from his audience. One physician argued that morbidly obese individuals are sedentary, so they don’t leave the house as much as leaner AF patients.
“You stay at home because you cannot move. You don’t get into fatal car accidents. You don’t get into conflicts and get murdered,” the physician postulated.
Dr. Goldhaber wasn’t convinced.
“When I go out to bars or dancing, I look around at people, and I estimate that a lot of them have a BMI of 35,” he commented.
Another proposed theory was that overweight and obese AF patients exercise less, so they inhale less of the airborne toxic fine particulates present in the urban environment. The adverse health impact of air pollution is a particularly hot topic of late among European cardiologists, but the notion that obese AF patients fare better because they don’t exercise runs contrary to a wealth of data supporting the health benefits of working out.
The GARFIELD-AF registry is funded by Bayer AG. Dr. Goldhaber reported receiving research grants and/or serving as a consultant to Bayer and numerous other entities, including the National Heart, Lung and Blood Institute.
BARCELONA – The obesity paradox is alive and well in the rapidly growing population with atrial fibrillation, Samuel Z. Goldhaber, MD, reported at the annual congress of the European Society of Cardiology.
In an analysis of 22,541 participants in the international registry known as GARFIELD-AF (Global Anticoagulation Registry in the Field-Atrial Fibrillation) – the largest ongoing prospective AF registry in the world – all-cause mortality during the first 2 years after diagnosis of the arrhythmia paradoxically decreased as body mass index increased all the way up to a ceiling of 40 kg/m2, according to Dr. Goldhaber, professor of medicine at Harvard Medical School and section head of vascular medicine and director of the thrombosis research group at Brigham and Women’s Hospital, Boston.
“It’s pretty impressive. This degree of mortality reduction with overweight and obesity is of about the same magnitude you might get with thrombolytic therapy for an acute MI, or with beta blocker therapy or statins post-MI,” the cardiologist said in an interview.
This newly described obesity paradox in AF is all the more baffling in light of the heavy cardiovascular risk factor burden that accompanied increased BMI. For example, the prevalence of type 2 diabetes rose from 14.1% among normal-weight individuals with AF, to 19.7% in the overweight, 27.5% in the obese, 34.6% in those with a BMI of 35 to less than 40 kg/m2, and 41.6% in patients with a BMI of 40 kg/m2 or more.
“It’s perplexing,” Dr. Goldhaber confessed. “I think there’s some hidden message here that we haven’t decoded yet.”
Patients with AF who were at the low extreme of the BMI spectrum -- the 3.3% who were underweight, with a BMI below 20 kg/m2 – fared particularly poorly. Their 2-year all-cause mortality rate of 8.71 per 100 person-years was by far the highest of any BMI class in the study. But that’s relatively straightforward to understand, as it’s likely that many underweight patients with AF were frail and/or had cancer. Indeed, only 49% of deaths in the underweight group were due to cardiovascular disease, in contrast to 64% of deaths in persons whose BMI was 40 kg/m2 or more.
Interestingly, only 5%-6% of all deaths in GARFIELD-AF were due to stroke; deaths from heart failure were far more common.
Overall, 71% of patients who presented with newly diagnosed AF in GARFIELD-AF were overweight or obese. The only contributory factor to the obesity paradox that Dr. Goldhaber could spot was that the heavier patients were younger at diagnosis of AF. But this age disparity seems unlikely to overcome their massive burden of multiple other cardiovascular risk factors. So he solicited theories from his audience. One physician argued that morbidly obese individuals are sedentary, so they don’t leave the house as much as leaner AF patients.
“You stay at home because you cannot move. You don’t get into fatal car accidents. You don’t get into conflicts and get murdered,” the physician postulated.
Dr. Goldhaber wasn’t convinced.
“When I go out to bars or dancing, I look around at people, and I estimate that a lot of them have a BMI of 35,” he commented.
Another proposed theory was that overweight and obese AF patients exercise less, so they inhale less of the airborne toxic fine particulates present in the urban environment. The adverse health impact of air pollution is a particularly hot topic of late among European cardiologists, but the notion that obese AF patients fare better because they don’t exercise runs contrary to a wealth of data supporting the health benefits of working out.
The GARFIELD-AF registry is funded by Bayer AG. Dr. Goldhaber reported receiving research grants and/or serving as a consultant to Bayer and numerous other entities, including the National Heart, Lung and Blood Institute.
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: Two-year all-cause mortality following diagnosis of atrial fibrillation fell substantially in stepwise fashion with increasing body mass index, for reasons unknown.
Data source: GARFIELD-AF is an ongoing enormous international prospective registry of patients newly diagnosed with atrial fibrillation.
Disclosures: The GARFIELD-AF registry is funded by Bayer AG. The presenter reported receiving research grants and/or consultant fees from that company and numerous others.