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Anticoagulation Hub contains news and clinical review articles for physicians seeking the most up-to-date information on the rapidly evolving treatment options for preventing stroke, acute coronary events, deep vein thrombosis, and pulmonary embolism in at-risk patients. The Anticoagulation Hub is powered by Frontline Medical Communications.
Mesh cylinder effective for small to medium wide-necked aneurysms
HOUSTON – An expandable mesh cylinder that is approved to treat large, wide-necked carotid aneurysms has now proved successful in treating small lesions of the internal carotid or vertebral artery up to 12 mm in diameter.
The Pipeline Embolization Device (PED, Medtronic) completely occluded 84% of such lesions without significant stenosis or retreatment within 1 year in the PREMIER trial, Ricardo Hanel, MD, PhD, said at the International Stroke Conference sponsored by the American Heart Association.
Overall morbidity and mortality in the year-long trial was very low (2.2%). However, within the first year, three patients had a major stroke in brain regions supplied by the treated artery; one of these was related to device deployment and was fatal, said Dr. Hanel, director of the Baptist Neurological Institute, Jacksonville, Fla.
Counseling patients with these lesions is not easy, Dr. Hanel said. Treatment decisions must take into account not only the patient’s current clinical status and comorbidities, but family history and personal preference. In fact, patient preference was the largest driver of treatment (63%) in the PREMIER study.
In an interview, Dr. Hanel illustrated the importance of individualized decision making. A middle-aged female had been monitored for a small aneurysm for 7 years. When the patient was 6 years old, her mother died during an open operation to treat an aneurysm.
“We had tried to treat this patient with coiling [when the lesion was first detected], but it was unsuccessful,” Dr. Hanel said. “And since her mother had died during surgery, she did not want to go for an open approach. Now, 6 years later, we have the technology to cure her with a single device, and the odds of [recurrence over 10 years] are virtually zero. It is a very personal decision, and we take a lot of factors under consideration before we decide to expose the patient to the risks of this treatment.”
The PED is a flexible 75% cobalt-chromium/25% platinum-tungsten mesh with a braided configuration. It is advanced slightly beyond the aneurysm neck and then deployed. As it opens, it partially occludes the lesion, immediately decreasing the amount of blood entering the sac. Within a month, vascular remodeling is well underway; as endothelium grows throughout the mesh, blood flow into the aneurysm is gradually cut off. Eventually the aneurysmal sac recedes, and the normal vascular architecture is restored.
“Within 4 weeks you can’t see the metal at all,” Dr. Hanel said. “It’s covered by a thin layer of endothelial cells. This device allows the patient’s body to heal and close the aneurysm, and we don’t have to deal with the reoccurrence problem we have with stent coils. The pipeline treats the entire circumference of the vessel.”
The PED is used in combination with dual-antiplatelet therapy (DAP, aspirin/clopidogrel). Dr. Hanel initiates DAP 7 days before the procedure and continues it for 3 months. At that time, clopidogrel may be discontinued. “I advise my patients to then take a baby aspirin every day for the rest of their lives,” and they are regularly monitored, he said. “Aspirin seems to protect against the formation and rupture of aneurysms.”
PREMIER followed 141 patients with unruptured, wide-necked small aneurysms of the internal carotid (up to the terminus) or the vertebral artery segment up to and including the posterior inferior cerebellar artery. The primary efficacy endpoint was complete aneurysm occlusion and absence of significant parent artery stenosis at 1 year. The secondary endpoint was successful device deployment.
The primary safety endpoint was major stroke in the territory supplied by the treated artery or neurologic death at 1 year. There were two secondary safety endpoints: major stroke or neurologic death within 30 days, attributable to procedural complications, and intracerebral hemorrhage more than 30 days later.
The patients were largely female (88%) with a mean age of 55 years. They were asymptomatic with a mean modified Rankin Scale score of 0.2 and National Institutes of Health Stroke Scale score of 0.1. Nearly half of the patients had hypertension, and 38% had hyperlipidemia. About 28% were current smokers, and another 16% had a history of smoking.
The patients’ mean maximal aneurysm diameter was 4.6 mm, with a mean neck width of 3.7 mm. The majority of lesions (84%) were less than 7 mm in diameter, but they ranged up to 12 mm.
Internal carotid artery aneurysms comprised 95% of all in the study; 5% were in the vertebral artery. Most involved the side wall (84%), while the remainder involved a side branch (12%) or were fusiform (4%).
There was only one unsuccessful initial deployment, resulting in a 99.3% deployment success rate. The mean procedure time was 78 minutes. While most patients received just one PED, 10 received multiple devices. The PED completely covered the entire neck of the lesion in 97%. There were no intraoperative aneurysm ruptures and no intraoperative deaths.
At 1 year after implantation, 84% of the aneurysms were completely occluded, with the aneurysmal sac eliminated in 92%. A residual aneurysm remained in 11 patients (8%), and a residual neck in 8 patients (6%). Two patients (1.4%) had arterial stenosis of more than 50%. Three patients (2.2%) required retreatment.
There were three major strokes in the region supplied by the target artery in three patients.
The fatal stroke occurred in a patient who had an aneurysm on the right ophthalmic carotid segment. The first device failed to deploy correctly and was removed. A second device was implanted. The next day the patient developed a facial droop, slurred speech, and a headache. She experienced a distal intraparenchymal hemorrhage and underwent hemicraniotomy, but did not survive.
The second stroke occurred in a patient who needed two devices to occlude a lesion in the left ophthalmic segment of the carotid. The patient developed an intraparenchymal hemorrhage on postoperative day 15. The stroke resolved with sequelae and the clopidogrel dose was increased.
The third stroke was associated with treatment of a right communicating segment aneurysm. The patient stopped taking the recommended DAP and experienced an acute ischemic stroke 169 days after the procedure. This stroke also resolved with sequelae.
Based on the results of PREMIER, Medtronic will pursue Food and Drug Administration approval of the PED for small to medium wide-necked aneurysms, Dr. Hanel noted.
Medtronic sponsored the study. Dr. Hanel is an adviser to the company and has received research funds from it.
[email protected]
On Twitter @alz_gal
HOUSTON – An expandable mesh cylinder that is approved to treat large, wide-necked carotid aneurysms has now proved successful in treating small lesions of the internal carotid or vertebral artery up to 12 mm in diameter.
The Pipeline Embolization Device (PED, Medtronic) completely occluded 84% of such lesions without significant stenosis or retreatment within 1 year in the PREMIER trial, Ricardo Hanel, MD, PhD, said at the International Stroke Conference sponsored by the American Heart Association.
Overall morbidity and mortality in the year-long trial was very low (2.2%). However, within the first year, three patients had a major stroke in brain regions supplied by the treated artery; one of these was related to device deployment and was fatal, said Dr. Hanel, director of the Baptist Neurological Institute, Jacksonville, Fla.
Counseling patients with these lesions is not easy, Dr. Hanel said. Treatment decisions must take into account not only the patient’s current clinical status and comorbidities, but family history and personal preference. In fact, patient preference was the largest driver of treatment (63%) in the PREMIER study.
In an interview, Dr. Hanel illustrated the importance of individualized decision making. A middle-aged female had been monitored for a small aneurysm for 7 years. When the patient was 6 years old, her mother died during an open operation to treat an aneurysm.
“We had tried to treat this patient with coiling [when the lesion was first detected], but it was unsuccessful,” Dr. Hanel said. “And since her mother had died during surgery, she did not want to go for an open approach. Now, 6 years later, we have the technology to cure her with a single device, and the odds of [recurrence over 10 years] are virtually zero. It is a very personal decision, and we take a lot of factors under consideration before we decide to expose the patient to the risks of this treatment.”
The PED is a flexible 75% cobalt-chromium/25% platinum-tungsten mesh with a braided configuration. It is advanced slightly beyond the aneurysm neck and then deployed. As it opens, it partially occludes the lesion, immediately decreasing the amount of blood entering the sac. Within a month, vascular remodeling is well underway; as endothelium grows throughout the mesh, blood flow into the aneurysm is gradually cut off. Eventually the aneurysmal sac recedes, and the normal vascular architecture is restored.
“Within 4 weeks you can’t see the metal at all,” Dr. Hanel said. “It’s covered by a thin layer of endothelial cells. This device allows the patient’s body to heal and close the aneurysm, and we don’t have to deal with the reoccurrence problem we have with stent coils. The pipeline treats the entire circumference of the vessel.”
The PED is used in combination with dual-antiplatelet therapy (DAP, aspirin/clopidogrel). Dr. Hanel initiates DAP 7 days before the procedure and continues it for 3 months. At that time, clopidogrel may be discontinued. “I advise my patients to then take a baby aspirin every day for the rest of their lives,” and they are regularly monitored, he said. “Aspirin seems to protect against the formation and rupture of aneurysms.”
PREMIER followed 141 patients with unruptured, wide-necked small aneurysms of the internal carotid (up to the terminus) or the vertebral artery segment up to and including the posterior inferior cerebellar artery. The primary efficacy endpoint was complete aneurysm occlusion and absence of significant parent artery stenosis at 1 year. The secondary endpoint was successful device deployment.
The primary safety endpoint was major stroke in the territory supplied by the treated artery or neurologic death at 1 year. There were two secondary safety endpoints: major stroke or neurologic death within 30 days, attributable to procedural complications, and intracerebral hemorrhage more than 30 days later.
The patients were largely female (88%) with a mean age of 55 years. They were asymptomatic with a mean modified Rankin Scale score of 0.2 and National Institutes of Health Stroke Scale score of 0.1. Nearly half of the patients had hypertension, and 38% had hyperlipidemia. About 28% were current smokers, and another 16% had a history of smoking.
The patients’ mean maximal aneurysm diameter was 4.6 mm, with a mean neck width of 3.7 mm. The majority of lesions (84%) were less than 7 mm in diameter, but they ranged up to 12 mm.
Internal carotid artery aneurysms comprised 95% of all in the study; 5% were in the vertebral artery. Most involved the side wall (84%), while the remainder involved a side branch (12%) or were fusiform (4%).
There was only one unsuccessful initial deployment, resulting in a 99.3% deployment success rate. The mean procedure time was 78 minutes. While most patients received just one PED, 10 received multiple devices. The PED completely covered the entire neck of the lesion in 97%. There were no intraoperative aneurysm ruptures and no intraoperative deaths.
At 1 year after implantation, 84% of the aneurysms were completely occluded, with the aneurysmal sac eliminated in 92%. A residual aneurysm remained in 11 patients (8%), and a residual neck in 8 patients (6%). Two patients (1.4%) had arterial stenosis of more than 50%. Three patients (2.2%) required retreatment.
There were three major strokes in the region supplied by the target artery in three patients.
The fatal stroke occurred in a patient who had an aneurysm on the right ophthalmic carotid segment. The first device failed to deploy correctly and was removed. A second device was implanted. The next day the patient developed a facial droop, slurred speech, and a headache. She experienced a distal intraparenchymal hemorrhage and underwent hemicraniotomy, but did not survive.
The second stroke occurred in a patient who needed two devices to occlude a lesion in the left ophthalmic segment of the carotid. The patient developed an intraparenchymal hemorrhage on postoperative day 15. The stroke resolved with sequelae and the clopidogrel dose was increased.
The third stroke was associated with treatment of a right communicating segment aneurysm. The patient stopped taking the recommended DAP and experienced an acute ischemic stroke 169 days after the procedure. This stroke also resolved with sequelae.
Based on the results of PREMIER, Medtronic will pursue Food and Drug Administration approval of the PED for small to medium wide-necked aneurysms, Dr. Hanel noted.
Medtronic sponsored the study. Dr. Hanel is an adviser to the company and has received research funds from it.
[email protected]
On Twitter @alz_gal
HOUSTON – An expandable mesh cylinder that is approved to treat large, wide-necked carotid aneurysms has now proved successful in treating small lesions of the internal carotid or vertebral artery up to 12 mm in diameter.
The Pipeline Embolization Device (PED, Medtronic) completely occluded 84% of such lesions without significant stenosis or retreatment within 1 year in the PREMIER trial, Ricardo Hanel, MD, PhD, said at the International Stroke Conference sponsored by the American Heart Association.
Overall morbidity and mortality in the year-long trial was very low (2.2%). However, within the first year, three patients had a major stroke in brain regions supplied by the treated artery; one of these was related to device deployment and was fatal, said Dr. Hanel, director of the Baptist Neurological Institute, Jacksonville, Fla.
Counseling patients with these lesions is not easy, Dr. Hanel said. Treatment decisions must take into account not only the patient’s current clinical status and comorbidities, but family history and personal preference. In fact, patient preference was the largest driver of treatment (63%) in the PREMIER study.
In an interview, Dr. Hanel illustrated the importance of individualized decision making. A middle-aged female had been monitored for a small aneurysm for 7 years. When the patient was 6 years old, her mother died during an open operation to treat an aneurysm.
“We had tried to treat this patient with coiling [when the lesion was first detected], but it was unsuccessful,” Dr. Hanel said. “And since her mother had died during surgery, she did not want to go for an open approach. Now, 6 years later, we have the technology to cure her with a single device, and the odds of [recurrence over 10 years] are virtually zero. It is a very personal decision, and we take a lot of factors under consideration before we decide to expose the patient to the risks of this treatment.”
The PED is a flexible 75% cobalt-chromium/25% platinum-tungsten mesh with a braided configuration. It is advanced slightly beyond the aneurysm neck and then deployed. As it opens, it partially occludes the lesion, immediately decreasing the amount of blood entering the sac. Within a month, vascular remodeling is well underway; as endothelium grows throughout the mesh, blood flow into the aneurysm is gradually cut off. Eventually the aneurysmal sac recedes, and the normal vascular architecture is restored.
“Within 4 weeks you can’t see the metal at all,” Dr. Hanel said. “It’s covered by a thin layer of endothelial cells. This device allows the patient’s body to heal and close the aneurysm, and we don’t have to deal with the reoccurrence problem we have with stent coils. The pipeline treats the entire circumference of the vessel.”
The PED is used in combination with dual-antiplatelet therapy (DAP, aspirin/clopidogrel). Dr. Hanel initiates DAP 7 days before the procedure and continues it for 3 months. At that time, clopidogrel may be discontinued. “I advise my patients to then take a baby aspirin every day for the rest of their lives,” and they are regularly monitored, he said. “Aspirin seems to protect against the formation and rupture of aneurysms.”
PREMIER followed 141 patients with unruptured, wide-necked small aneurysms of the internal carotid (up to the terminus) or the vertebral artery segment up to and including the posterior inferior cerebellar artery. The primary efficacy endpoint was complete aneurysm occlusion and absence of significant parent artery stenosis at 1 year. The secondary endpoint was successful device deployment.
The primary safety endpoint was major stroke in the territory supplied by the treated artery or neurologic death at 1 year. There were two secondary safety endpoints: major stroke or neurologic death within 30 days, attributable to procedural complications, and intracerebral hemorrhage more than 30 days later.
The patients were largely female (88%) with a mean age of 55 years. They were asymptomatic with a mean modified Rankin Scale score of 0.2 and National Institutes of Health Stroke Scale score of 0.1. Nearly half of the patients had hypertension, and 38% had hyperlipidemia. About 28% were current smokers, and another 16% had a history of smoking.
The patients’ mean maximal aneurysm diameter was 4.6 mm, with a mean neck width of 3.7 mm. The majority of lesions (84%) were less than 7 mm in diameter, but they ranged up to 12 mm.
Internal carotid artery aneurysms comprised 95% of all in the study; 5% were in the vertebral artery. Most involved the side wall (84%), while the remainder involved a side branch (12%) or were fusiform (4%).
There was only one unsuccessful initial deployment, resulting in a 99.3% deployment success rate. The mean procedure time was 78 minutes. While most patients received just one PED, 10 received multiple devices. The PED completely covered the entire neck of the lesion in 97%. There were no intraoperative aneurysm ruptures and no intraoperative deaths.
At 1 year after implantation, 84% of the aneurysms were completely occluded, with the aneurysmal sac eliminated in 92%. A residual aneurysm remained in 11 patients (8%), and a residual neck in 8 patients (6%). Two patients (1.4%) had arterial stenosis of more than 50%. Three patients (2.2%) required retreatment.
There were three major strokes in the region supplied by the target artery in three patients.
The fatal stroke occurred in a patient who had an aneurysm on the right ophthalmic carotid segment. The first device failed to deploy correctly and was removed. A second device was implanted. The next day the patient developed a facial droop, slurred speech, and a headache. She experienced a distal intraparenchymal hemorrhage and underwent hemicraniotomy, but did not survive.
The second stroke occurred in a patient who needed two devices to occlude a lesion in the left ophthalmic segment of the carotid. The patient developed an intraparenchymal hemorrhage on postoperative day 15. The stroke resolved with sequelae and the clopidogrel dose was increased.
The third stroke was associated with treatment of a right communicating segment aneurysm. The patient stopped taking the recommended DAP and experienced an acute ischemic stroke 169 days after the procedure. This stroke also resolved with sequelae.
Based on the results of PREMIER, Medtronic will pursue Food and Drug Administration approval of the PED for small to medium wide-necked aneurysms, Dr. Hanel noted.
Medtronic sponsored the study. Dr. Hanel is an adviser to the company and has received research funds from it.
[email protected]
On Twitter @alz_gal
AT THE INTERNATIONAL STROKE CONFERENCE
Key clinical point:
Major finding: The PED completely occluded 84% of aneurysms of the internal carotid or vertebral artery up to 12 mm in diameter at 1 year.
Data source: PREMIER investigators prospectively evaluated the PED in 141 patients.
Disclosures: Medtronic sponsored the study. Dr. Hanel is an adviser to the company and has received research funds from it.
New ACC guidance on periprocedural management of anticoagulation in A-fib falls short
SNOWMASS, COLO. – The 2017 American College of Cardiology Expert Consensus Decision Pathway for Periprocedural Management of Anticoagulation in Patients with Nonvalvular Atrial Fibrillation is a dense, 28-page document filled with multicolored flow charts and six separate management algorithms. But this complex scheme is no substitute for practical clinical judgment and individualized decision making, N.A. Mark Estes, MD, said at the Annual Cardiovascular Conference at Snowmass.
The decision pathway attempts to guide physicians in making decisions about whether and how to interrupt anticoagulation or bridge with a parenteral agent such as low-molecular-weight heparin, and how to restart oral anticoagulation post-procedure (J Am Coll Cardiol. 2017 Jan 5; doi: 10.1016/j.jacc.2016.11.024).
The document defies concise summary. Dr. Estes chose instead to describe the approach he uses in clinical decision-making regarding anticoagulation in patients with atrial fibrillation undergoing invasive procedures. He relies upon three elements: stroke risk as assessed by CHA2DS2-VASc score; bleeding risk using the HAS-BLED score; and the inherent bleeding risk of the procedure itself.
“An important thing to remember is, any procedure done along the spinal cord or intracranially carries an extremely high risk of bleeding,” the cardiologist noted by way of example.
If a patient with atrial fibrillation has a CHA2DS2-VASc score of 2 or less, he doesn’t offer bridging regardless of the HAS-BLED score. If the stroke risk is high as defined by a CHA2DS2-VASc score of 7 or more, and the patient’s bleeding risk isn’t high, meaning the HAS-BLED score is less than 3, he seriously considers bridging, provided that the patient’s oral anticoagulant is warfarin.
“I don’t think at this point we should be bridging with the DOACs [the direct oral anticoagulants dabigatran, rivaroxaban, apixaban, and edoxaban]. All the available data on bridging with the DOACs indicates that it results in a high risk of bleeding with no reduction in risk of stroke,” Dr. Estes said.
The “vast majority” of patients with atrial fibrillation facing surgery have a CHA2DS2-VASc score of 3-7 and thus fall into a category where individualized consideration of the risks and benefits of bridging rules. The large, randomized, double-blind BRIDGE trial speaks to this population. In this study of atrial fibrillation patients on warfarin prior to their procedure, bridging with low-molecular-weight heparin resulted in an increased risk of major bleeding with no reduction in stroke risk compared with a temporary halt of warfarin with no bridging (N Engl J Med. 2015 Aug 27;373[9]:823-33).
“This is a no-brainer,” Dr. Estes said. “When you bridge, your patients bleed more, and you don’t reduce strokes.”
The real challenge is the type of patient who falls into what he called “the dilemma zone,” with a CHA2DS2-VASc score of 7 or more and a HAS-BLED score of 3 or higher, meaning they are at very high risk for both stroke and bleeding.
“I have a discussion with those patients. I usually do not bridge. I’m biased because of having done a lot more harm than good in bridging,” the cardiologist said.
Dr. Estes reported serving as a consultant to Boston Scientific, Medtronic, and St. Jude Medical.
In reviewing Dr. Estes’ comments on a consensus statement regarding anticoagulation bridging for patients with atrial fibrillation, the most important point is that there are minimal good data to support decision making; therefore, treatments need to be individualized to the patient. He provides a reasonable paradigm for his own decision making in these complex patients. Ultimately, until there is better evidence, the decision on whether to bridge or not to bridge patients’ anticoagulation will continue to be an individual choice based upon bleeding risk with the planned surgical procedure, potential for significant adverse outcomes if bleeding occurs, and the risk of stroke or other embolic phenomenon with cessation of anticoagulation.
Dr. Linda Harris is the division chief, vascular surgery, at the State University of New York at Buffalo and an associate editor of Vascular Specialist.
In reviewing Dr. Estes’ comments on a consensus statement regarding anticoagulation bridging for patients with atrial fibrillation, the most important point is that there are minimal good data to support decision making; therefore, treatments need to be individualized to the patient. He provides a reasonable paradigm for his own decision making in these complex patients. Ultimately, until there is better evidence, the decision on whether to bridge or not to bridge patients’ anticoagulation will continue to be an individual choice based upon bleeding risk with the planned surgical procedure, potential for significant adverse outcomes if bleeding occurs, and the risk of stroke or other embolic phenomenon with cessation of anticoagulation.
Dr. Linda Harris is the division chief, vascular surgery, at the State University of New York at Buffalo and an associate editor of Vascular Specialist.
In reviewing Dr. Estes’ comments on a consensus statement regarding anticoagulation bridging for patients with atrial fibrillation, the most important point is that there are minimal good data to support decision making; therefore, treatments need to be individualized to the patient. He provides a reasonable paradigm for his own decision making in these complex patients. Ultimately, until there is better evidence, the decision on whether to bridge or not to bridge patients’ anticoagulation will continue to be an individual choice based upon bleeding risk with the planned surgical procedure, potential for significant adverse outcomes if bleeding occurs, and the risk of stroke or other embolic phenomenon with cessation of anticoagulation.
Dr. Linda Harris is the division chief, vascular surgery, at the State University of New York at Buffalo and an associate editor of Vascular Specialist.
SNOWMASS, COLO. – The 2017 American College of Cardiology Expert Consensus Decision Pathway for Periprocedural Management of Anticoagulation in Patients with Nonvalvular Atrial Fibrillation is a dense, 28-page document filled with multicolored flow charts and six separate management algorithms. But this complex scheme is no substitute for practical clinical judgment and individualized decision making, N.A. Mark Estes, MD, said at the Annual Cardiovascular Conference at Snowmass.
The decision pathway attempts to guide physicians in making decisions about whether and how to interrupt anticoagulation or bridge with a parenteral agent such as low-molecular-weight heparin, and how to restart oral anticoagulation post-procedure (J Am Coll Cardiol. 2017 Jan 5; doi: 10.1016/j.jacc.2016.11.024).
The document defies concise summary. Dr. Estes chose instead to describe the approach he uses in clinical decision-making regarding anticoagulation in patients with atrial fibrillation undergoing invasive procedures. He relies upon three elements: stroke risk as assessed by CHA2DS2-VASc score; bleeding risk using the HAS-BLED score; and the inherent bleeding risk of the procedure itself.
“An important thing to remember is, any procedure done along the spinal cord or intracranially carries an extremely high risk of bleeding,” the cardiologist noted by way of example.
If a patient with atrial fibrillation has a CHA2DS2-VASc score of 2 or less, he doesn’t offer bridging regardless of the HAS-BLED score. If the stroke risk is high as defined by a CHA2DS2-VASc score of 7 or more, and the patient’s bleeding risk isn’t high, meaning the HAS-BLED score is less than 3, he seriously considers bridging, provided that the patient’s oral anticoagulant is warfarin.
“I don’t think at this point we should be bridging with the DOACs [the direct oral anticoagulants dabigatran, rivaroxaban, apixaban, and edoxaban]. All the available data on bridging with the DOACs indicates that it results in a high risk of bleeding with no reduction in risk of stroke,” Dr. Estes said.
The “vast majority” of patients with atrial fibrillation facing surgery have a CHA2DS2-VASc score of 3-7 and thus fall into a category where individualized consideration of the risks and benefits of bridging rules. The large, randomized, double-blind BRIDGE trial speaks to this population. In this study of atrial fibrillation patients on warfarin prior to their procedure, bridging with low-molecular-weight heparin resulted in an increased risk of major bleeding with no reduction in stroke risk compared with a temporary halt of warfarin with no bridging (N Engl J Med. 2015 Aug 27;373[9]:823-33).
“This is a no-brainer,” Dr. Estes said. “When you bridge, your patients bleed more, and you don’t reduce strokes.”
The real challenge is the type of patient who falls into what he called “the dilemma zone,” with a CHA2DS2-VASc score of 7 or more and a HAS-BLED score of 3 or higher, meaning they are at very high risk for both stroke and bleeding.
“I have a discussion with those patients. I usually do not bridge. I’m biased because of having done a lot more harm than good in bridging,” the cardiologist said.
Dr. Estes reported serving as a consultant to Boston Scientific, Medtronic, and St. Jude Medical.
SNOWMASS, COLO. – The 2017 American College of Cardiology Expert Consensus Decision Pathway for Periprocedural Management of Anticoagulation in Patients with Nonvalvular Atrial Fibrillation is a dense, 28-page document filled with multicolored flow charts and six separate management algorithms. But this complex scheme is no substitute for practical clinical judgment and individualized decision making, N.A. Mark Estes, MD, said at the Annual Cardiovascular Conference at Snowmass.
The decision pathway attempts to guide physicians in making decisions about whether and how to interrupt anticoagulation or bridge with a parenteral agent such as low-molecular-weight heparin, and how to restart oral anticoagulation post-procedure (J Am Coll Cardiol. 2017 Jan 5; doi: 10.1016/j.jacc.2016.11.024).
The document defies concise summary. Dr. Estes chose instead to describe the approach he uses in clinical decision-making regarding anticoagulation in patients with atrial fibrillation undergoing invasive procedures. He relies upon three elements: stroke risk as assessed by CHA2DS2-VASc score; bleeding risk using the HAS-BLED score; and the inherent bleeding risk of the procedure itself.
“An important thing to remember is, any procedure done along the spinal cord or intracranially carries an extremely high risk of bleeding,” the cardiologist noted by way of example.
If a patient with atrial fibrillation has a CHA2DS2-VASc score of 2 or less, he doesn’t offer bridging regardless of the HAS-BLED score. If the stroke risk is high as defined by a CHA2DS2-VASc score of 7 or more, and the patient’s bleeding risk isn’t high, meaning the HAS-BLED score is less than 3, he seriously considers bridging, provided that the patient’s oral anticoagulant is warfarin.
“I don’t think at this point we should be bridging with the DOACs [the direct oral anticoagulants dabigatran, rivaroxaban, apixaban, and edoxaban]. All the available data on bridging with the DOACs indicates that it results in a high risk of bleeding with no reduction in risk of stroke,” Dr. Estes said.
The “vast majority” of patients with atrial fibrillation facing surgery have a CHA2DS2-VASc score of 3-7 and thus fall into a category where individualized consideration of the risks and benefits of bridging rules. The large, randomized, double-blind BRIDGE trial speaks to this population. In this study of atrial fibrillation patients on warfarin prior to their procedure, bridging with low-molecular-weight heparin resulted in an increased risk of major bleeding with no reduction in stroke risk compared with a temporary halt of warfarin with no bridging (N Engl J Med. 2015 Aug 27;373[9]:823-33).
“This is a no-brainer,” Dr. Estes said. “When you bridge, your patients bleed more, and you don’t reduce strokes.”
The real challenge is the type of patient who falls into what he called “the dilemma zone,” with a CHA2DS2-VASc score of 7 or more and a HAS-BLED score of 3 or higher, meaning they are at very high risk for both stroke and bleeding.
“I have a discussion with those patients. I usually do not bridge. I’m biased because of having done a lot more harm than good in bridging,” the cardiologist said.
Dr. Estes reported serving as a consultant to Boston Scientific, Medtronic, and St. Jude Medical.
EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS
Atherosclerosis severity in diabetes can be predicted by select biomarkers
in patient with type 2 diabetes, results from a long-term analysis of VA patients suggest.
Advanced glycation end products (AGEs) and oxidation products (OxPs) “can damage vascular cells by different mechanisms,” wrote researchers led by corresponding authors Aramesh Saremi, MD, and Peter D. Reaven, MD, and colleagues. The report appeared online Feb. 1 in Diabetes Care.
“One frequently reported pathway is AGE binding to their purported (and relatively promiscuous) receptors on cells, such as macrophages, vascular endothelial cells, and vascular smooth muscle cells, although this has not been consistent for all AGEs. Other mechanisms include, among others, binding to and altering the function of intracellular proteins, the activation of vascular NADPH [nicotinamide adenine dinucleotide phosphate] oxidase, and the uncoupling of endothelial nitric oxide synthase.”
Noting that data in the current medical literature are lacking with respect to long-term longitudinal associations between plasma levels of AGEs and OxPs on the extent of subclinical atherosclerosis in T2D patients, the researchers set out to determine whether baseline plasma levels of AGEs and OxPs are associated with the extent of carotid intima-media thickness (CIMT), coronary artery calcification (CAC), and abdominal aortic artery calcification (AAC) over an average of 10 years of follow-up in the VA Diabetes Trial (VADT). They also examined whether this relationship was altered by intervening improved glucose control (Diabetes Care 2017 Feb. 1. doi: 10.2337/dc16-1875]).
At baseline of the VADT, 411 study participants underwent plasma measurements of methylglyoxal hydroimidazolone, N epsilon–carboxymethyl lysine (CML), N epsilon–carboxyethyl lysine (CEL), 3-deoxyglucosone hydroimidazolone and glyoxal hydroimidazolone (G-H1), 2-aminoadipic acid (2-AAA), and methionine sulfoxide. The mean age of the study subjects was 58 years, 64% were non-Hispanic white, 96% were male, 69% had a history of hypertension, and they had diabetes for a mean of 11 years.
After a mean follow-up of 10 years, the 411 patients underwent ultrasound assessment of CIMT, and computed tomography scanning of CAC and AAC.
In risk factor–adjusted multivariable regression models, G-H1was associated with the extent of CIMT as well as with the extent of CAC (P = .01 for both associations). In addition, 2-AAA was strongly associated with the extent of CAC (P = .03 for continuous variables and P less than .01 for dichotomous variables), and CEL was strongly associated with the extent of AAC (P less than .01).
“These findings suggest that the effect of hyperglycemia and subsequent increased levels of AGEs and OxPs in patients with long-standing T2D may have long-lasting adverse effects on the development of macrovascular complications,” the researchers concluded. They acknowledged certain limitations of the analysis, including the fact that it was conducted in an older, primarily male population. Therefore, “extrapolation of the study findings to other populations must be done with caution,” they wrote. “This study also does not allow us to make a definite claim of causation between AGEs and OxPs with the extent of atherosclerosis.”
The Veterans Affairs Cooperative Studies Program of the U.S. Department of Veterans Affairs Office of Research and Development funded the study. Additional support was received from National Institutes of Health, the American Diabetes Association, and the National Institute of Diabetes and Digestive and Kidney Diseases. Two study authors, Scott Howell, MS, and Paul J. Beisswenger, MD, disclosed that they are affiliated with PreventAGE Healthcare. The other researchers reported having no financial disclosures.
[email protected]
For a long time the question about how glucose control relates to macrovascular disease has not been easy to answer. There are reports suggesting that glucose control correlates with macrovascular disease later in life, and others that do not make the association so convincing. This paper provides an important link between glucose control and the subsequent development of macrovascular disease. The link is by way of advanced glycation end products as well as oxidative byproducts and how they set the stage for macrovascular disease later on in life. It’s something that clinicians have postulated as being important, but to my knowledge this is one of the only studies to actually show the association.
The investigators used important endpoints like coronary artery calcification and carotid intima-media thickness. I was surprised at how well the relationship between glycosylated end products and oxidative products correlated, but there’s biologic plausibility; it makes sense. Glucose not only glycosates hemoglobin, but glycosates proteins throughout. This provides a logical, stepwise pathway for how the initial glycosylated protein will result years later in macrovascular disease as evidenced by the parameters that were used.
It was interesting to learn from this study that glycosylated end products and oxidative products interact with each other. That’s important, because as blood sugars rise acutely, both oxidative products and glycosylated products are produced. As a result of the oxidative stress that’s created by the sharp rise in blood sugar, endothelial function is affected and more glycosylated proteins are being formed.
Clinically, this study shows the importance of early, aggressive control of diabetes to not allow accumulation of both glycosylated end products and oxidative end products. It demonstrates that accumulation of these byproducts years later seems to relate strongly to macrovascular disease.
The study should be reproduced in younger, less sick patients. That may or may not further clarify the findings, but these findings need to be demonstrated in patients at a much earlier stage as well. We’ve been saying for a long time that early control of diabetes is so important because years later it makes a difference. This is a link to that rationale.
Paul S. Jellinger, MD, MACE, is professor of clinical medicine at the University of Miami Miller School of Medicine, Ft. Lauderdale. He is past president of the American Association of Clinical Endocrinologists (AACE) and past president of the American College of Endocrinology. Dr. Jellinger provided these comments in an interview.
For a long time the question about how glucose control relates to macrovascular disease has not been easy to answer. There are reports suggesting that glucose control correlates with macrovascular disease later in life, and others that do not make the association so convincing. This paper provides an important link between glucose control and the subsequent development of macrovascular disease. The link is by way of advanced glycation end products as well as oxidative byproducts and how they set the stage for macrovascular disease later on in life. It’s something that clinicians have postulated as being important, but to my knowledge this is one of the only studies to actually show the association.
The investigators used important endpoints like coronary artery calcification and carotid intima-media thickness. I was surprised at how well the relationship between glycosylated end products and oxidative products correlated, but there’s biologic plausibility; it makes sense. Glucose not only glycosates hemoglobin, but glycosates proteins throughout. This provides a logical, stepwise pathway for how the initial glycosylated protein will result years later in macrovascular disease as evidenced by the parameters that were used.
It was interesting to learn from this study that glycosylated end products and oxidative products interact with each other. That’s important, because as blood sugars rise acutely, both oxidative products and glycosylated products are produced. As a result of the oxidative stress that’s created by the sharp rise in blood sugar, endothelial function is affected and more glycosylated proteins are being formed.
Clinically, this study shows the importance of early, aggressive control of diabetes to not allow accumulation of both glycosylated end products and oxidative end products. It demonstrates that accumulation of these byproducts years later seems to relate strongly to macrovascular disease.
The study should be reproduced in younger, less sick patients. That may or may not further clarify the findings, but these findings need to be demonstrated in patients at a much earlier stage as well. We’ve been saying for a long time that early control of diabetes is so important because years later it makes a difference. This is a link to that rationale.
Paul S. Jellinger, MD, MACE, is professor of clinical medicine at the University of Miami Miller School of Medicine, Ft. Lauderdale. He is past president of the American Association of Clinical Endocrinologists (AACE) and past president of the American College of Endocrinology. Dr. Jellinger provided these comments in an interview.
For a long time the question about how glucose control relates to macrovascular disease has not been easy to answer. There are reports suggesting that glucose control correlates with macrovascular disease later in life, and others that do not make the association so convincing. This paper provides an important link between glucose control and the subsequent development of macrovascular disease. The link is by way of advanced glycation end products as well as oxidative byproducts and how they set the stage for macrovascular disease later on in life. It’s something that clinicians have postulated as being important, but to my knowledge this is one of the only studies to actually show the association.
The investigators used important endpoints like coronary artery calcification and carotid intima-media thickness. I was surprised at how well the relationship between glycosylated end products and oxidative products correlated, but there’s biologic plausibility; it makes sense. Glucose not only glycosates hemoglobin, but glycosates proteins throughout. This provides a logical, stepwise pathway for how the initial glycosylated protein will result years later in macrovascular disease as evidenced by the parameters that were used.
It was interesting to learn from this study that glycosylated end products and oxidative products interact with each other. That’s important, because as blood sugars rise acutely, both oxidative products and glycosylated products are produced. As a result of the oxidative stress that’s created by the sharp rise in blood sugar, endothelial function is affected and more glycosylated proteins are being formed.
Clinically, this study shows the importance of early, aggressive control of diabetes to not allow accumulation of both glycosylated end products and oxidative end products. It demonstrates that accumulation of these byproducts years later seems to relate strongly to macrovascular disease.
The study should be reproduced in younger, less sick patients. That may or may not further clarify the findings, but these findings need to be demonstrated in patients at a much earlier stage as well. We’ve been saying for a long time that early control of diabetes is so important because years later it makes a difference. This is a link to that rationale.
Paul S. Jellinger, MD, MACE, is professor of clinical medicine at the University of Miami Miller School of Medicine, Ft. Lauderdale. He is past president of the American Association of Clinical Endocrinologists (AACE) and past president of the American College of Endocrinology. Dr. Jellinger provided these comments in an interview.
in patient with type 2 diabetes, results from a long-term analysis of VA patients suggest.
Advanced glycation end products (AGEs) and oxidation products (OxPs) “can damage vascular cells by different mechanisms,” wrote researchers led by corresponding authors Aramesh Saremi, MD, and Peter D. Reaven, MD, and colleagues. The report appeared online Feb. 1 in Diabetes Care.
“One frequently reported pathway is AGE binding to their purported (and relatively promiscuous) receptors on cells, such as macrophages, vascular endothelial cells, and vascular smooth muscle cells, although this has not been consistent for all AGEs. Other mechanisms include, among others, binding to and altering the function of intracellular proteins, the activation of vascular NADPH [nicotinamide adenine dinucleotide phosphate] oxidase, and the uncoupling of endothelial nitric oxide synthase.”
Noting that data in the current medical literature are lacking with respect to long-term longitudinal associations between plasma levels of AGEs and OxPs on the extent of subclinical atherosclerosis in T2D patients, the researchers set out to determine whether baseline plasma levels of AGEs and OxPs are associated with the extent of carotid intima-media thickness (CIMT), coronary artery calcification (CAC), and abdominal aortic artery calcification (AAC) over an average of 10 years of follow-up in the VA Diabetes Trial (VADT). They also examined whether this relationship was altered by intervening improved glucose control (Diabetes Care 2017 Feb. 1. doi: 10.2337/dc16-1875]).
At baseline of the VADT, 411 study participants underwent plasma measurements of methylglyoxal hydroimidazolone, N epsilon–carboxymethyl lysine (CML), N epsilon–carboxyethyl lysine (CEL), 3-deoxyglucosone hydroimidazolone and glyoxal hydroimidazolone (G-H1), 2-aminoadipic acid (2-AAA), and methionine sulfoxide. The mean age of the study subjects was 58 years, 64% were non-Hispanic white, 96% were male, 69% had a history of hypertension, and they had diabetes for a mean of 11 years.
After a mean follow-up of 10 years, the 411 patients underwent ultrasound assessment of CIMT, and computed tomography scanning of CAC and AAC.
In risk factor–adjusted multivariable regression models, G-H1was associated with the extent of CIMT as well as with the extent of CAC (P = .01 for both associations). In addition, 2-AAA was strongly associated with the extent of CAC (P = .03 for continuous variables and P less than .01 for dichotomous variables), and CEL was strongly associated with the extent of AAC (P less than .01).
“These findings suggest that the effect of hyperglycemia and subsequent increased levels of AGEs and OxPs in patients with long-standing T2D may have long-lasting adverse effects on the development of macrovascular complications,” the researchers concluded. They acknowledged certain limitations of the analysis, including the fact that it was conducted in an older, primarily male population. Therefore, “extrapolation of the study findings to other populations must be done with caution,” they wrote. “This study also does not allow us to make a definite claim of causation between AGEs and OxPs with the extent of atherosclerosis.”
The Veterans Affairs Cooperative Studies Program of the U.S. Department of Veterans Affairs Office of Research and Development funded the study. Additional support was received from National Institutes of Health, the American Diabetes Association, and the National Institute of Diabetes and Digestive and Kidney Diseases. Two study authors, Scott Howell, MS, and Paul J. Beisswenger, MD, disclosed that they are affiliated with PreventAGE Healthcare. The other researchers reported having no financial disclosures.
[email protected]
in patient with type 2 diabetes, results from a long-term analysis of VA patients suggest.
Advanced glycation end products (AGEs) and oxidation products (OxPs) “can damage vascular cells by different mechanisms,” wrote researchers led by corresponding authors Aramesh Saremi, MD, and Peter D. Reaven, MD, and colleagues. The report appeared online Feb. 1 in Diabetes Care.
“One frequently reported pathway is AGE binding to their purported (and relatively promiscuous) receptors on cells, such as macrophages, vascular endothelial cells, and vascular smooth muscle cells, although this has not been consistent for all AGEs. Other mechanisms include, among others, binding to and altering the function of intracellular proteins, the activation of vascular NADPH [nicotinamide adenine dinucleotide phosphate] oxidase, and the uncoupling of endothelial nitric oxide synthase.”
Noting that data in the current medical literature are lacking with respect to long-term longitudinal associations between plasma levels of AGEs and OxPs on the extent of subclinical atherosclerosis in T2D patients, the researchers set out to determine whether baseline plasma levels of AGEs and OxPs are associated with the extent of carotid intima-media thickness (CIMT), coronary artery calcification (CAC), and abdominal aortic artery calcification (AAC) over an average of 10 years of follow-up in the VA Diabetes Trial (VADT). They also examined whether this relationship was altered by intervening improved glucose control (Diabetes Care 2017 Feb. 1. doi: 10.2337/dc16-1875]).
At baseline of the VADT, 411 study participants underwent plasma measurements of methylglyoxal hydroimidazolone, N epsilon–carboxymethyl lysine (CML), N epsilon–carboxyethyl lysine (CEL), 3-deoxyglucosone hydroimidazolone and glyoxal hydroimidazolone (G-H1), 2-aminoadipic acid (2-AAA), and methionine sulfoxide. The mean age of the study subjects was 58 years, 64% were non-Hispanic white, 96% were male, 69% had a history of hypertension, and they had diabetes for a mean of 11 years.
After a mean follow-up of 10 years, the 411 patients underwent ultrasound assessment of CIMT, and computed tomography scanning of CAC and AAC.
In risk factor–adjusted multivariable regression models, G-H1was associated with the extent of CIMT as well as with the extent of CAC (P = .01 for both associations). In addition, 2-AAA was strongly associated with the extent of CAC (P = .03 for continuous variables and P less than .01 for dichotomous variables), and CEL was strongly associated with the extent of AAC (P less than .01).
“These findings suggest that the effect of hyperglycemia and subsequent increased levels of AGEs and OxPs in patients with long-standing T2D may have long-lasting adverse effects on the development of macrovascular complications,” the researchers concluded. They acknowledged certain limitations of the analysis, including the fact that it was conducted in an older, primarily male population. Therefore, “extrapolation of the study findings to other populations must be done with caution,” they wrote. “This study also does not allow us to make a definite claim of causation between AGEs and OxPs with the extent of atherosclerosis.”
The Veterans Affairs Cooperative Studies Program of the U.S. Department of Veterans Affairs Office of Research and Development funded the study. Additional support was received from National Institutes of Health, the American Diabetes Association, and the National Institute of Diabetes and Digestive and Kidney Diseases. Two study authors, Scott Howell, MS, and Paul J. Beisswenger, MD, disclosed that they are affiliated with PreventAGE Healthcare. The other researchers reported having no financial disclosures.
[email protected]
Key clinical point:
Major finding: Glyoxal hydroimidazolone was associated with the extent of carotid intima-media thickness as well as with the extent of coronary artery calcification.
Data source: An analysis of 411 patients the VA Diabetes Trial.
Disclosures: The Veterans Affairs Cooperative Studies Program of the U.S. Department of Veterans Affairs Office of Research and Development funded the study. Additional support was received from National Institutes of Health, the American Diabetes Association, and the National Institute of Diabetes and Digestive and Kidney Diseases. Two study authors, Scott Howell, MS, and Paul J. Beisswenger, MD, disclosed that they are affiliated with PreventAGE Healthcare. The other researchers reported having no financial disclosures.
Heart disease risk soars in young adults with coronary calcium
Younger adults who have any calcium deposited in their coronary arteries, even a small amount, are at increased risk for adverse coronary heart disease (CHD) outcomes and death, finds an analysis of the Coronary Artery Risk Development in Young Adults (CARDIA) Study.
There’s no evidence, however, that treating such patients would make a difference in outcomes, John Jeffrey Carr, MD, reported in JAMA Cardiology on Feb. 8.
In the prospective, community-based, cohort study, 5,115 black and white adults underwent coronary computed tomographic (CT) imaging between the ages of 32 and 46 years, and had a mean follow-up of 12.5 years.
Compared with counterparts not having any coronary artery calcium (CAC), those having at least some had a 5.0-fold increased risk of CHD events and a 1.6-fold increased risk of death (JAMA Cardiol. 2017 Feb 8; doi: 10.1001/jamacardio.2016.5493).
Estimates suggested that identification of individuals at elevated risk for developing CAC could inform a selective CT screening strategy whereby the number of younger adults screened could be reduced by half, and the number needing to be imaged to find one person with CAC could be reduced from 3.5 to 2.2.
“The finding that CAC present by ages 32-46 years is associated with increased risk of premature CHD and death emphasizes the need for reduction of risk factors and primordial prevention beginning in early life,” wrote Dr. Carr, professor radiology at Vanderbilt University in Nashville, Tenn.
“Whether any kind of general screening for CAC is warranted needs further study, although we suggest that a strategy in which all individuals aged 32 to 46 years are screened is not indicated. Rather, a more targeted approach based on measuring risk factors in early adult life to predict individuals at high risk for developing CAC in whom the CT scan would have the greatest value can be considered,” they propose.
Study details
Participants were recruited to CARDIA when aged 18-30 years, and they underwent CAC measurement at 15, 20, and 25 years after recruitment. Incident events were ascertained starting from the time of the year-15 scan.
At that year-15 scan, 10.2% of participants were found to have CAC. The geometric mean Agatston score was 21.6.
In adjusted analyses, participants with any CAC had sharply higher risks of CHD events (hazard ratio, 5.0), as well as cardiovascular disease events (HR, 3.0). The risk of CHD events increased with CAC score, with hazard ratios of 2.6, 5.8, and 9.8 for individuals with scores of 1-19, 20-99, and 100 or more, respectively.
In addition, participants with any CAC had an elevated adjusted risk of all-cause mortality (HR, 1.6). This risk similarly rose with score but was significant for those having a score of 100 or greater only (hazard ratio, 3.7); the large majority of deaths in this group were deemed to be from CHD events.
The model that the investigators developed predicted the probability of CAC by ages 32-56 years based on risk factors assessed 7 years apart, between the ages of 18 and 38 years.
When stratified by this model, 4.2% of study participants falling into the lowest-risk decile had CAC, compared with 67.8% of those falling into the highest-risk decile.
Analyses suggested that if screening were restricted to those participants having an above-median risk score, fully 77.3% of all those with coronary calcium and 95.5% of all those with CHD events would be identified. Moreover, these yields would be obtained while reducing the number of individuals recommended to be screened by 50.0%.
Several challenges will need to be addressed before computed tomographic (CT) screening of younger adults for coronary artery calcium is ready for prime time.
First, such screenings must be efficient, and the investigator’s new model seems to be a step in this direction.
The model should be further validated in other populations as well as across younger populations (i.e., during the first CAC test, when the age of the cohort was aged 32-46 years) to help substantiate whether testing of younger individuals is efficient or if waiting to screen those who are older than 40-45 years may be preferable.
Second, even if coronary calcium is detected in young adults, individuals’ risk may not be sufficiently elevated to justify long-term statin therapy.
Finally, there are no data in this context to show that intervening with statins improves cardiovascular outcomes. The absence of such data, and consequently the fact that treatment is often not started until later in life, is owing to the economic and ethical considerations of performing a trial that would take decades to conduct.
In the meantime, the study’s findings have implications for care in younger adults who are found to have coronary calcium incidentally and underscore the importance of primordial prevention.
Future studies will be needed to refine our approaches to better select appropriate candidates for CAC testing, even more so in younger than in older individuals.
Ron Blankstein, MD, of Harvard University, Boston, and Philip Greenland, MD, of Northwestern University, Chicago, made these comments in an accompanying editorial (JAMA Cardiol. 2017 Feb 8; doi: 10.1001/jamacardio.2016.5552). They reported having no relevant financial disclosures.
Several challenges will need to be addressed before computed tomographic (CT) screening of younger adults for coronary artery calcium is ready for prime time.
First, such screenings must be efficient, and the investigator’s new model seems to be a step in this direction.
The model should be further validated in other populations as well as across younger populations (i.e., during the first CAC test, when the age of the cohort was aged 32-46 years) to help substantiate whether testing of younger individuals is efficient or if waiting to screen those who are older than 40-45 years may be preferable.
Second, even if coronary calcium is detected in young adults, individuals’ risk may not be sufficiently elevated to justify long-term statin therapy.
Finally, there are no data in this context to show that intervening with statins improves cardiovascular outcomes. The absence of such data, and consequently the fact that treatment is often not started until later in life, is owing to the economic and ethical considerations of performing a trial that would take decades to conduct.
In the meantime, the study’s findings have implications for care in younger adults who are found to have coronary calcium incidentally and underscore the importance of primordial prevention.
Future studies will be needed to refine our approaches to better select appropriate candidates for CAC testing, even more so in younger than in older individuals.
Ron Blankstein, MD, of Harvard University, Boston, and Philip Greenland, MD, of Northwestern University, Chicago, made these comments in an accompanying editorial (JAMA Cardiol. 2017 Feb 8; doi: 10.1001/jamacardio.2016.5552). They reported having no relevant financial disclosures.
Several challenges will need to be addressed before computed tomographic (CT) screening of younger adults for coronary artery calcium is ready for prime time.
First, such screenings must be efficient, and the investigator’s new model seems to be a step in this direction.
The model should be further validated in other populations as well as across younger populations (i.e., during the first CAC test, when the age of the cohort was aged 32-46 years) to help substantiate whether testing of younger individuals is efficient or if waiting to screen those who are older than 40-45 years may be preferable.
Second, even if coronary calcium is detected in young adults, individuals’ risk may not be sufficiently elevated to justify long-term statin therapy.
Finally, there are no data in this context to show that intervening with statins improves cardiovascular outcomes. The absence of such data, and consequently the fact that treatment is often not started until later in life, is owing to the economic and ethical considerations of performing a trial that would take decades to conduct.
In the meantime, the study’s findings have implications for care in younger adults who are found to have coronary calcium incidentally and underscore the importance of primordial prevention.
Future studies will be needed to refine our approaches to better select appropriate candidates for CAC testing, even more so in younger than in older individuals.
Ron Blankstein, MD, of Harvard University, Boston, and Philip Greenland, MD, of Northwestern University, Chicago, made these comments in an accompanying editorial (JAMA Cardiol. 2017 Feb 8; doi: 10.1001/jamacardio.2016.5552). They reported having no relevant financial disclosures.
Younger adults who have any calcium deposited in their coronary arteries, even a small amount, are at increased risk for adverse coronary heart disease (CHD) outcomes and death, finds an analysis of the Coronary Artery Risk Development in Young Adults (CARDIA) Study.
There’s no evidence, however, that treating such patients would make a difference in outcomes, John Jeffrey Carr, MD, reported in JAMA Cardiology on Feb. 8.
In the prospective, community-based, cohort study, 5,115 black and white adults underwent coronary computed tomographic (CT) imaging between the ages of 32 and 46 years, and had a mean follow-up of 12.5 years.
Compared with counterparts not having any coronary artery calcium (CAC), those having at least some had a 5.0-fold increased risk of CHD events and a 1.6-fold increased risk of death (JAMA Cardiol. 2017 Feb 8; doi: 10.1001/jamacardio.2016.5493).
Estimates suggested that identification of individuals at elevated risk for developing CAC could inform a selective CT screening strategy whereby the number of younger adults screened could be reduced by half, and the number needing to be imaged to find one person with CAC could be reduced from 3.5 to 2.2.
“The finding that CAC present by ages 32-46 years is associated with increased risk of premature CHD and death emphasizes the need for reduction of risk factors and primordial prevention beginning in early life,” wrote Dr. Carr, professor radiology at Vanderbilt University in Nashville, Tenn.
“Whether any kind of general screening for CAC is warranted needs further study, although we suggest that a strategy in which all individuals aged 32 to 46 years are screened is not indicated. Rather, a more targeted approach based on measuring risk factors in early adult life to predict individuals at high risk for developing CAC in whom the CT scan would have the greatest value can be considered,” they propose.
Study details
Participants were recruited to CARDIA when aged 18-30 years, and they underwent CAC measurement at 15, 20, and 25 years after recruitment. Incident events were ascertained starting from the time of the year-15 scan.
At that year-15 scan, 10.2% of participants were found to have CAC. The geometric mean Agatston score was 21.6.
In adjusted analyses, participants with any CAC had sharply higher risks of CHD events (hazard ratio, 5.0), as well as cardiovascular disease events (HR, 3.0). The risk of CHD events increased with CAC score, with hazard ratios of 2.6, 5.8, and 9.8 for individuals with scores of 1-19, 20-99, and 100 or more, respectively.
In addition, participants with any CAC had an elevated adjusted risk of all-cause mortality (HR, 1.6). This risk similarly rose with score but was significant for those having a score of 100 or greater only (hazard ratio, 3.7); the large majority of deaths in this group were deemed to be from CHD events.
The model that the investigators developed predicted the probability of CAC by ages 32-56 years based on risk factors assessed 7 years apart, between the ages of 18 and 38 years.
When stratified by this model, 4.2% of study participants falling into the lowest-risk decile had CAC, compared with 67.8% of those falling into the highest-risk decile.
Analyses suggested that if screening were restricted to those participants having an above-median risk score, fully 77.3% of all those with coronary calcium and 95.5% of all those with CHD events would be identified. Moreover, these yields would be obtained while reducing the number of individuals recommended to be screened by 50.0%.
Younger adults who have any calcium deposited in their coronary arteries, even a small amount, are at increased risk for adverse coronary heart disease (CHD) outcomes and death, finds an analysis of the Coronary Artery Risk Development in Young Adults (CARDIA) Study.
There’s no evidence, however, that treating such patients would make a difference in outcomes, John Jeffrey Carr, MD, reported in JAMA Cardiology on Feb. 8.
In the prospective, community-based, cohort study, 5,115 black and white adults underwent coronary computed tomographic (CT) imaging between the ages of 32 and 46 years, and had a mean follow-up of 12.5 years.
Compared with counterparts not having any coronary artery calcium (CAC), those having at least some had a 5.0-fold increased risk of CHD events and a 1.6-fold increased risk of death (JAMA Cardiol. 2017 Feb 8; doi: 10.1001/jamacardio.2016.5493).
Estimates suggested that identification of individuals at elevated risk for developing CAC could inform a selective CT screening strategy whereby the number of younger adults screened could be reduced by half, and the number needing to be imaged to find one person with CAC could be reduced from 3.5 to 2.2.
“The finding that CAC present by ages 32-46 years is associated with increased risk of premature CHD and death emphasizes the need for reduction of risk factors and primordial prevention beginning in early life,” wrote Dr. Carr, professor radiology at Vanderbilt University in Nashville, Tenn.
“Whether any kind of general screening for CAC is warranted needs further study, although we suggest that a strategy in which all individuals aged 32 to 46 years are screened is not indicated. Rather, a more targeted approach based on measuring risk factors in early adult life to predict individuals at high risk for developing CAC in whom the CT scan would have the greatest value can be considered,” they propose.
Study details
Participants were recruited to CARDIA when aged 18-30 years, and they underwent CAC measurement at 15, 20, and 25 years after recruitment. Incident events were ascertained starting from the time of the year-15 scan.
At that year-15 scan, 10.2% of participants were found to have CAC. The geometric mean Agatston score was 21.6.
In adjusted analyses, participants with any CAC had sharply higher risks of CHD events (hazard ratio, 5.0), as well as cardiovascular disease events (HR, 3.0). The risk of CHD events increased with CAC score, with hazard ratios of 2.6, 5.8, and 9.8 for individuals with scores of 1-19, 20-99, and 100 or more, respectively.
In addition, participants with any CAC had an elevated adjusted risk of all-cause mortality (HR, 1.6). This risk similarly rose with score but was significant for those having a score of 100 or greater only (hazard ratio, 3.7); the large majority of deaths in this group were deemed to be from CHD events.
The model that the investigators developed predicted the probability of CAC by ages 32-56 years based on risk factors assessed 7 years apart, between the ages of 18 and 38 years.
When stratified by this model, 4.2% of study participants falling into the lowest-risk decile had CAC, compared with 67.8% of those falling into the highest-risk decile.
Analyses suggested that if screening were restricted to those participants having an above-median risk score, fully 77.3% of all those with coronary calcium and 95.5% of all those with CHD events would be identified. Moreover, these yields would be obtained while reducing the number of individuals recommended to be screened by 50.0%.
FROM JAMA CARDIOLOGY
Key clinical point:
Major finding: Individuals having any versus no coronary artery calcium when aged 32-46 years had elevated risks of CHD events (HR, 5.0) and death (HR, 1.6) by the age of 58 years.
Data source: A prospective community-based cohort study of 5,115 black and white adults (CARDIA Study).
Disclosures: Dr. Carr disclosed that he had no relevant conflicts of interest.
Hypertensive disease of pregnancy linked to earlier mortality
LAS VEGAS – Women who develop any form of hypertensive disease during pregnancy have a significantly increased mortality rate until they reach age 50, compared with women without the condition.
The findings, presented at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine, are based on a review of more than 2 million mothers who delivered babies in Utah during 1939-2012.
The relatively increased mortality rate linked with hypertensive disease of pregnancy (HDP) reached its peak during the first decade immediately following the index delivery and was dramatically higher in women for whom the index HDP was preceded by at least one earlier HDP. Increased mortality was especially elevated for certain types of deaths including stroke, diabetes, circulatory disease, and ischemic heart disease, said Lauren Theilen, MD, a maternal-fetal medicine researcher at the University of Utah in Salt Lake City.
She calculated that during the decade following an index case of HDP, life expectancy among mothers who had two or more HDP-affected pregnancies was about 49 years, life expectancy among women with a history of one HDP was 52 years, and postpartum women without HDP had a life expectancy of 55 years.
The data came from 2,083,331 singleton pregnancies delivered in Utah during 1939-2012 where the mother remained in Utah for at least 1 year following delivery. From this group, Dr. Theilen and her associates identified 67,384 women (3%) with HDP, including 49,598 women without a prior history of HDP and 7,786 with at least one prior HDP pregnancy. They included four different diagnoses as HDP: gestational hypertension, preeclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count), or eclampsia.
The analysis excluded women with chronic hypertension, antiphospholipid syndrome, pregestational diabetes, or chronic kidney disease. It also excluded women who died within a year of the index delivery. For each of the included 67,384 cases with HDP, the researchers selected two controls with a delivery unaffected by HDP and matched them to a case by age, year of childbirth, and parity.
The women in the study were 26 years old on average. Gestational age at delivery among the HDP cases averaged 1 week less than among the controls, 37.8 weeks compared with 38.9 weeks, a statistically significant difference. Average birth weight also differed by a significant amount, 3,079 grams in the HDP neonates and 3,319 grams in the control newborns. During follow-up, 8% of the HDP women died, compared with 6% of the control women.
Analysis showed that relative mortality rates in HDP women were especially elevated for certain types of death: endocrine and metabolic, circulatory, genitourinary, infectious disease, and digestive. In most types of death, the increased risk linked with HDP was markedly higher in the women with recurrent HDP.
Dr. Theilen reported the relative risks of death for certain specific mortality causes (Am J Obstet Gynecol. 2017 Jan;216[1][suppl]:S32-3). In women with a single index case of HDP, the mortality rate compared to women with no HDP was threefold higher for diabetes, twofold higher for ischemic heart disease, and 85% higher for stroke. In women with recurrent HDP, the relative mortality risks were fourfold higher for diabetes, threefold higher for ischemic heart disease, and fivefold higher for stroke.
For all causes of death except stroke, the increased relative risk from HDP existed only for women younger than 51 years. Once HDP women passed the age of 50, their excess mortality risk was substantially muted, even in women with recurrent HDP. But for stroke mortality, the added risk persisted among older women with a history of at least two HDPs. In this subgroup, stroke deaths were nearly fourfold higher than in the matched controls.
Dr. Theilen reported having no financial disclosures.
[email protected]
On Twitter @mitchelzoler
The findings Dr. Theilen and her associates made in this study confirm results reported several decades ago that first established a link between hypertensive disease of pregnancy (HDP) and significantly reduced life expectancy. We have known for some time that HDP identifies women with a long-term mortality risk. The real question is: Can we ameliorate the risk linked with HDP?
We know that HDP requires acute management, but we are not sure how to best manage these women once they have delivered. To address that, we need prospective studies.
Not all women who experience HDP receive appropriate follow-up after delivery. We need to ensure a better handoff of women who developed HDP from the physicians who cared for these women during pregnancy to the physicians who care for these women postpartum and during the balance of their life. Ideally, a primary care physician should closely follow and manage blood pressure and other risk factors of HDP women once they are no longer pregnant.
Mary E. D’Alton, MD , is professor and chair of ob.gyn. at Columbia University Medical Center in New York City. She is on the advisory board of Merck for Mothers. She made these comments in an interview.
The findings Dr. Theilen and her associates made in this study confirm results reported several decades ago that first established a link between hypertensive disease of pregnancy (HDP) and significantly reduced life expectancy. We have known for some time that HDP identifies women with a long-term mortality risk. The real question is: Can we ameliorate the risk linked with HDP?
We know that HDP requires acute management, but we are not sure how to best manage these women once they have delivered. To address that, we need prospective studies.
Not all women who experience HDP receive appropriate follow-up after delivery. We need to ensure a better handoff of women who developed HDP from the physicians who cared for these women during pregnancy to the physicians who care for these women postpartum and during the balance of their life. Ideally, a primary care physician should closely follow and manage blood pressure and other risk factors of HDP women once they are no longer pregnant.
Mary E. D’Alton, MD , is professor and chair of ob.gyn. at Columbia University Medical Center in New York City. She is on the advisory board of Merck for Mothers. She made these comments in an interview.
The findings Dr. Theilen and her associates made in this study confirm results reported several decades ago that first established a link between hypertensive disease of pregnancy (HDP) and significantly reduced life expectancy. We have known for some time that HDP identifies women with a long-term mortality risk. The real question is: Can we ameliorate the risk linked with HDP?
We know that HDP requires acute management, but we are not sure how to best manage these women once they have delivered. To address that, we need prospective studies.
Not all women who experience HDP receive appropriate follow-up after delivery. We need to ensure a better handoff of women who developed HDP from the physicians who cared for these women during pregnancy to the physicians who care for these women postpartum and during the balance of their life. Ideally, a primary care physician should closely follow and manage blood pressure and other risk factors of HDP women once they are no longer pregnant.
Mary E. D’Alton, MD , is professor and chair of ob.gyn. at Columbia University Medical Center in New York City. She is on the advisory board of Merck for Mothers. She made these comments in an interview.
LAS VEGAS – Women who develop any form of hypertensive disease during pregnancy have a significantly increased mortality rate until they reach age 50, compared with women without the condition.
The findings, presented at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine, are based on a review of more than 2 million mothers who delivered babies in Utah during 1939-2012.
The relatively increased mortality rate linked with hypertensive disease of pregnancy (HDP) reached its peak during the first decade immediately following the index delivery and was dramatically higher in women for whom the index HDP was preceded by at least one earlier HDP. Increased mortality was especially elevated for certain types of deaths including stroke, diabetes, circulatory disease, and ischemic heart disease, said Lauren Theilen, MD, a maternal-fetal medicine researcher at the University of Utah in Salt Lake City.
She calculated that during the decade following an index case of HDP, life expectancy among mothers who had two or more HDP-affected pregnancies was about 49 years, life expectancy among women with a history of one HDP was 52 years, and postpartum women without HDP had a life expectancy of 55 years.
The data came from 2,083,331 singleton pregnancies delivered in Utah during 1939-2012 where the mother remained in Utah for at least 1 year following delivery. From this group, Dr. Theilen and her associates identified 67,384 women (3%) with HDP, including 49,598 women without a prior history of HDP and 7,786 with at least one prior HDP pregnancy. They included four different diagnoses as HDP: gestational hypertension, preeclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count), or eclampsia.
The analysis excluded women with chronic hypertension, antiphospholipid syndrome, pregestational diabetes, or chronic kidney disease. It also excluded women who died within a year of the index delivery. For each of the included 67,384 cases with HDP, the researchers selected two controls with a delivery unaffected by HDP and matched them to a case by age, year of childbirth, and parity.
The women in the study were 26 years old on average. Gestational age at delivery among the HDP cases averaged 1 week less than among the controls, 37.8 weeks compared with 38.9 weeks, a statistically significant difference. Average birth weight also differed by a significant amount, 3,079 grams in the HDP neonates and 3,319 grams in the control newborns. During follow-up, 8% of the HDP women died, compared with 6% of the control women.
Analysis showed that relative mortality rates in HDP women were especially elevated for certain types of death: endocrine and metabolic, circulatory, genitourinary, infectious disease, and digestive. In most types of death, the increased risk linked with HDP was markedly higher in the women with recurrent HDP.
Dr. Theilen reported the relative risks of death for certain specific mortality causes (Am J Obstet Gynecol. 2017 Jan;216[1][suppl]:S32-3). In women with a single index case of HDP, the mortality rate compared to women with no HDP was threefold higher for diabetes, twofold higher for ischemic heart disease, and 85% higher for stroke. In women with recurrent HDP, the relative mortality risks were fourfold higher for diabetes, threefold higher for ischemic heart disease, and fivefold higher for stroke.
For all causes of death except stroke, the increased relative risk from HDP existed only for women younger than 51 years. Once HDP women passed the age of 50, their excess mortality risk was substantially muted, even in women with recurrent HDP. But for stroke mortality, the added risk persisted among older women with a history of at least two HDPs. In this subgroup, stroke deaths were nearly fourfold higher than in the matched controls.
Dr. Theilen reported having no financial disclosures.
[email protected]
On Twitter @mitchelzoler
LAS VEGAS – Women who develop any form of hypertensive disease during pregnancy have a significantly increased mortality rate until they reach age 50, compared with women without the condition.
The findings, presented at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine, are based on a review of more than 2 million mothers who delivered babies in Utah during 1939-2012.
The relatively increased mortality rate linked with hypertensive disease of pregnancy (HDP) reached its peak during the first decade immediately following the index delivery and was dramatically higher in women for whom the index HDP was preceded by at least one earlier HDP. Increased mortality was especially elevated for certain types of deaths including stroke, diabetes, circulatory disease, and ischemic heart disease, said Lauren Theilen, MD, a maternal-fetal medicine researcher at the University of Utah in Salt Lake City.
She calculated that during the decade following an index case of HDP, life expectancy among mothers who had two or more HDP-affected pregnancies was about 49 years, life expectancy among women with a history of one HDP was 52 years, and postpartum women without HDP had a life expectancy of 55 years.
The data came from 2,083,331 singleton pregnancies delivered in Utah during 1939-2012 where the mother remained in Utah for at least 1 year following delivery. From this group, Dr. Theilen and her associates identified 67,384 women (3%) with HDP, including 49,598 women without a prior history of HDP and 7,786 with at least one prior HDP pregnancy. They included four different diagnoses as HDP: gestational hypertension, preeclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count), or eclampsia.
The analysis excluded women with chronic hypertension, antiphospholipid syndrome, pregestational diabetes, or chronic kidney disease. It also excluded women who died within a year of the index delivery. For each of the included 67,384 cases with HDP, the researchers selected two controls with a delivery unaffected by HDP and matched them to a case by age, year of childbirth, and parity.
The women in the study were 26 years old on average. Gestational age at delivery among the HDP cases averaged 1 week less than among the controls, 37.8 weeks compared with 38.9 weeks, a statistically significant difference. Average birth weight also differed by a significant amount, 3,079 grams in the HDP neonates and 3,319 grams in the control newborns. During follow-up, 8% of the HDP women died, compared with 6% of the control women.
Analysis showed that relative mortality rates in HDP women were especially elevated for certain types of death: endocrine and metabolic, circulatory, genitourinary, infectious disease, and digestive. In most types of death, the increased risk linked with HDP was markedly higher in the women with recurrent HDP.
Dr. Theilen reported the relative risks of death for certain specific mortality causes (Am J Obstet Gynecol. 2017 Jan;216[1][suppl]:S32-3). In women with a single index case of HDP, the mortality rate compared to women with no HDP was threefold higher for diabetes, twofold higher for ischemic heart disease, and 85% higher for stroke. In women with recurrent HDP, the relative mortality risks were fourfold higher for diabetes, threefold higher for ischemic heart disease, and fivefold higher for stroke.
For all causes of death except stroke, the increased relative risk from HDP existed only for women younger than 51 years. Once HDP women passed the age of 50, their excess mortality risk was substantially muted, even in women with recurrent HDP. But for stroke mortality, the added risk persisted among older women with a history of at least two HDPs. In this subgroup, stroke deaths were nearly fourfold higher than in the matched controls.
Dr. Theilen reported having no financial disclosures.
[email protected]
On Twitter @mitchelzoler
AT THE PREGNANCY MEETING
Key clinical point:
Major finding: Postpartum life expectancy was 49 years in women with two or more hypertensive pregnancies and 55 years in women without hypertension.
Data source: Retrospective, case-control study of 2,083,331 singleton pregnancies delivered in Utah during 1939-2012.
Disclosures: Dr. Theilen reported having no financial disclosures.
Stroke rates high when catheter ablation of AF fails
ORLANDO – In patients with atrial fibrillation (AF) who fail to achieve rhythm control after catheter ablation, the risk of ischemic stroke may approach 30% over 5 or more years of follow-up, despite optimized anticoagulation therapy, according to data from 1,002 consecutive patients presented at the annual International AF Symposium.
“The risk of stroke is high among patients after unsuccessful catheter ablation,” confirmed Mihran Martirosyan, MD, Erasmus Medical Center, Rotterdam, the Netherlands. He asserted that this is the first study to investigate long-term clinical outcomes of AF patients with unsuccessful rhythm control following repeated catheter ablation.
The retrospective analysis was conducted in 1,002 patients who underwent catheter ablation after failing pharmacologic treatment of AF. Of these, 169 (17%) failed the ablation, but the focus of this study was on the subgroup of 67 catheter ablation treatment failures that have been followed for at least 5 years. All had been maintained on anticoagulation therapy.
Within this group, 18 (27%) had an ischemic stroke over the course of follow-up. The average time to stroke after the first ablation procedure was 3.9 years.
Prior to being declared catheter ablation failures, the average number of ablation procedures in this long-term follow-up group was 1.7. In 55.2% of patients, the first ablation was performed with a cryoballoon. The remaining first ablations were delivered with radiofrequency. For a second or third ablation, the same techniques were commonly repeated, but 25% received a cavotricuspid isthmus ablation, and 12% underwent a VATS-Maze procedure.
There were no deaths in this series, in which the average patient age was 66 years. The average duration of AF was 12 years, the mean left atrial size was 45 mm, and the average left ventricular ejection fraction was 55%.
In this study, catheter ablation failure was defined as inability to regain rhythm control despite repeated ablation procedures. However, many patients who initially achieve rhythm control after catheter ablation have recurrence of AF over time. It is unclear whether patients who initially achieve but then lose rhythm control face the same high risk for stroke as seen in the Dutch series if followed long-term.
One study suggests that they may not. In 631 consecutive patients who underwent a mean 1.5 catheter ablations before achieving rhythm control, 34% had an AF recurrence at 1 year (Europace 2014 Oct 21;17[3]:403-8). When followed for a mean 4.1 years of additional follow-up (5.1 years from the initial ablation), only 10% had a serious adverse event, such as heart failure or hemorrhage, and only 2% had a cerebrovascular event.
Numerous clinical studies have shown that catheter ablation is more effective than pharmacologic therapy for both regaining rhythm control in AF patients and reducing symptoms, according to Dr. Martirosyan, but these long-term follow-up data confirm that the risk of thromboembolic complications remains high in those who fail the initial catheter ablation. Of the 18 strokes, only 4 occurred in the first year of follow-up. The remaining strokes accrued slowly over time. Strokes were recorded up until 10 years after the ablation, the longest period that any patient was followed.
Dr. Martirosyan reports no relevant financial relationships.
ORLANDO – In patients with atrial fibrillation (AF) who fail to achieve rhythm control after catheter ablation, the risk of ischemic stroke may approach 30% over 5 or more years of follow-up, despite optimized anticoagulation therapy, according to data from 1,002 consecutive patients presented at the annual International AF Symposium.
“The risk of stroke is high among patients after unsuccessful catheter ablation,” confirmed Mihran Martirosyan, MD, Erasmus Medical Center, Rotterdam, the Netherlands. He asserted that this is the first study to investigate long-term clinical outcomes of AF patients with unsuccessful rhythm control following repeated catheter ablation.
The retrospective analysis was conducted in 1,002 patients who underwent catheter ablation after failing pharmacologic treatment of AF. Of these, 169 (17%) failed the ablation, but the focus of this study was on the subgroup of 67 catheter ablation treatment failures that have been followed for at least 5 years. All had been maintained on anticoagulation therapy.
Within this group, 18 (27%) had an ischemic stroke over the course of follow-up. The average time to stroke after the first ablation procedure was 3.9 years.
Prior to being declared catheter ablation failures, the average number of ablation procedures in this long-term follow-up group was 1.7. In 55.2% of patients, the first ablation was performed with a cryoballoon. The remaining first ablations were delivered with radiofrequency. For a second or third ablation, the same techniques were commonly repeated, but 25% received a cavotricuspid isthmus ablation, and 12% underwent a VATS-Maze procedure.
There were no deaths in this series, in which the average patient age was 66 years. The average duration of AF was 12 years, the mean left atrial size was 45 mm, and the average left ventricular ejection fraction was 55%.
In this study, catheter ablation failure was defined as inability to regain rhythm control despite repeated ablation procedures. However, many patients who initially achieve rhythm control after catheter ablation have recurrence of AF over time. It is unclear whether patients who initially achieve but then lose rhythm control face the same high risk for stroke as seen in the Dutch series if followed long-term.
One study suggests that they may not. In 631 consecutive patients who underwent a mean 1.5 catheter ablations before achieving rhythm control, 34% had an AF recurrence at 1 year (Europace 2014 Oct 21;17[3]:403-8). When followed for a mean 4.1 years of additional follow-up (5.1 years from the initial ablation), only 10% had a serious adverse event, such as heart failure or hemorrhage, and only 2% had a cerebrovascular event.
Numerous clinical studies have shown that catheter ablation is more effective than pharmacologic therapy for both regaining rhythm control in AF patients and reducing symptoms, according to Dr. Martirosyan, but these long-term follow-up data confirm that the risk of thromboembolic complications remains high in those who fail the initial catheter ablation. Of the 18 strokes, only 4 occurred in the first year of follow-up. The remaining strokes accrued slowly over time. Strokes were recorded up until 10 years after the ablation, the longest period that any patient was followed.
Dr. Martirosyan reports no relevant financial relationships.
ORLANDO – In patients with atrial fibrillation (AF) who fail to achieve rhythm control after catheter ablation, the risk of ischemic stroke may approach 30% over 5 or more years of follow-up, despite optimized anticoagulation therapy, according to data from 1,002 consecutive patients presented at the annual International AF Symposium.
“The risk of stroke is high among patients after unsuccessful catheter ablation,” confirmed Mihran Martirosyan, MD, Erasmus Medical Center, Rotterdam, the Netherlands. He asserted that this is the first study to investigate long-term clinical outcomes of AF patients with unsuccessful rhythm control following repeated catheter ablation.
The retrospective analysis was conducted in 1,002 patients who underwent catheter ablation after failing pharmacologic treatment of AF. Of these, 169 (17%) failed the ablation, but the focus of this study was on the subgroup of 67 catheter ablation treatment failures that have been followed for at least 5 years. All had been maintained on anticoagulation therapy.
Within this group, 18 (27%) had an ischemic stroke over the course of follow-up. The average time to stroke after the first ablation procedure was 3.9 years.
Prior to being declared catheter ablation failures, the average number of ablation procedures in this long-term follow-up group was 1.7. In 55.2% of patients, the first ablation was performed with a cryoballoon. The remaining first ablations were delivered with radiofrequency. For a second or third ablation, the same techniques were commonly repeated, but 25% received a cavotricuspid isthmus ablation, and 12% underwent a VATS-Maze procedure.
There were no deaths in this series, in which the average patient age was 66 years. The average duration of AF was 12 years, the mean left atrial size was 45 mm, and the average left ventricular ejection fraction was 55%.
In this study, catheter ablation failure was defined as inability to regain rhythm control despite repeated ablation procedures. However, many patients who initially achieve rhythm control after catheter ablation have recurrence of AF over time. It is unclear whether patients who initially achieve but then lose rhythm control face the same high risk for stroke as seen in the Dutch series if followed long-term.
One study suggests that they may not. In 631 consecutive patients who underwent a mean 1.5 catheter ablations before achieving rhythm control, 34% had an AF recurrence at 1 year (Europace 2014 Oct 21;17[3]:403-8). When followed for a mean 4.1 years of additional follow-up (5.1 years from the initial ablation), only 10% had a serious adverse event, such as heart failure or hemorrhage, and only 2% had a cerebrovascular event.
Numerous clinical studies have shown that catheter ablation is more effective than pharmacologic therapy for both regaining rhythm control in AF patients and reducing symptoms, according to Dr. Martirosyan, but these long-term follow-up data confirm that the risk of thromboembolic complications remains high in those who fail the initial catheter ablation. Of the 18 strokes, only 4 occurred in the first year of follow-up. The remaining strokes accrued slowly over time. Strokes were recorded up until 10 years after the ablation, the longest period that any patient was followed.
Dr. Martirosyan reports no relevant financial relationships.
AT THE AF SYMPOSIUM 2017
Key clinical point: If catheter ablation of atrial fibrillation fails, stroke rates are high despite optimized anticoagulation therapy.
Major finding: In a median follow-up of up to 5 years after ablation, 27% of patients had an ischemic stroke.
Data source: Retrospective analysis.
Disclosures: Dr. Martirosyan reports no relevant financial relationships.
Strokes cut by extended NOAC prophylaxis in hospitalized, medically ill patients
NEW ORLEANS – Thromboprophylaxis for 35-42 days with the new oral anticoagulant betrixaban led to a significant reduction in all-cause and ischemic strokes in medically ill patients who required hospitalization as compared with conventional prophylaxis for 10 days, based on a post-hoc analysis of data from a randomized trial with more than 7,500 patients.
But the trial’s unusual design left it unclear whether the incremental benefit seen from prolonged prophylaxis with a NOAC resulted primarily from a longer period of treatment, the drug used, or both.
The safety analysis showed that prolonged treatment with betrixaban roughly doubled the rate of major or clinically relevant nonmajor bleeding events during the period of treatment and for the first 7 days after treatment stopped. The incidence of these bleeds was 1.6% among control patients on 10 days of enoxaparin treatment and 3.1% among patients who received extended treatment with betrixaban, a statistically significant difference. The rates of fatal bleeds and intracranial hemorrhages in the two study groups did not significantly differ.
The data Dr. Gibson reported came from the Multicenter, Randomized, Active-Controlled Efficacy And Safety Study Comparing Extended Duration Betrixaban With Standard Of Care Enoxaparin For The Prevention Of Venous Thromboembolism In Acute Medically Ill Patients (APEX). The study’s primary aim was testing in 7,513 hospitalized medically ill patients the safety and efficacy of prolonged prophylaxis with the oral, factor Xa inhibitor betrixaban, compared with 10 days of prophylaxis with the low molecular weight heparin enoxaparin. The primary endpoint was the rate of venous thromboembolic events and deaths from venous thromboembolism (VTE) out to 47 days after the start of treatment.
APEX enrolled patients hospitalized for acute decompensated heart failure, chronic respiratory failure, acute infection without septic shock, acute rheumatic disorders or acute ischemic stroke. All enrolled patients had to be expected to be immobilized for at least 24 hours following randomization and to be hospitalized for at least 3 days. Patients also had to have an additional risk marker for high thrombotic risk: They had to be at least 75 years old, or 60-74 years old with a D-dimer level at least twice the upper limit of normal, or 40-59 years old with a D-dimer level at least twice the upper limit of normal and a history of either VTE or cancer.
Results for the primary endpoint, reported in 2016, showed that prolonged betrixaban prophylaxis linked with an absolute 1.6% reduction in the combined endpoint, which resulted in a 19% relative risk reduction that fell just short of the trial’s prespecified definition of statistical significance. The study’s primary safety endpoint was the occurrence of major bleeding events through 7 days after the stop of treatment, which occurred in 0.7% of the betrixaban patients and in 0.6% of those on enoxaparin (N Engl J Med. 2016 Aug 11;375[6]:534-44).
Even thought the primary results from this pivotal trial failed to meet the prespecified threshold for statistical significance, the company developing betrixaban, Portola, submitted an application to the Food and Drug Administration to approve marketing of extended-duration betrixaban for VTE prophylaxis in acute medically-ill patients with VTE risk factors. In December 2016, Portola announced that the FDA had given the application priority status for a decision.
The post-hoc analysis that Dr. Gibson presented at the meeting looked at the impact of betrixaban compared with enoxaparin on the incidence of all-cause and ischemic stroke during 77 days of follow-up after the start of treatment in the 7,432 patients who received at least one dose of their assigned drug, two endpoints that weren’t even secondary outcomes in APEX’s original design.
Among the 3,716 treated with betrixaban, the all-cause stroke incidence was 0.54%; among the 3,716 patients treated with enoxaparin, the all-cause stroke incidence was 0.97%. The 56% relative risk reduction was statistically significant. The incidence of ischemic strokes was 0.48% with betrixaban and 0.91% with enoxaparin, a 53% relative risk reduction that was also statistically significant.
The post-hoc analysis also looked specifically at the comparison between betrixaban and enoxaparin for stroke prevention in a subgroup of patients who had the highest stroke rate, the patients who were hospitalized because of an index stroke or an index heart failure episode. In this high-risk subgroup, prophylaxis with betrixaban cut the all-cause stroke rate compared with enoxaparin by 49% and the ischemic stroke rate by 45%, both statistically significant effects. When the high-risk subgroup also included patients hospitalized for an index episode of atrial fibrillation, betrixaban cut the rate of all-cause strokes by a relative 48% and ischemic strokes by a relative 44%.
Concurrently with Dr. Gibson’s report at the meeting, the results also appeared online (Circulation. 2016 Nov 14. doi: 10.1161/CIRCULATIONAHA.116.025427).
APEX was sponsored by Portola, the company developing betrixaban. Dr. Gibson has been a consultant to Eli Lilly, Gilead, The Medicines Company, Novo Nordisk, Pfizer, and St. Jude. He has received research support from Portola and several other companies.
[email protected]
On Twitter @mitchelzoler
The APEX study identified a group of patients hospitalized for medical reasons who were at high risk for both venous thromboembolism and for stroke. We are comfortable with the concept of thromboprophylaxis for hospitalized patients who are at high risk for venous thromboembolism, but we have generally not paid attention to prophylaxis against stroke during and immediately after hospitalization.
The results suggest that extending thromboprophylaxis beyond the standard period of 10 days may be a good idea. Because patients in the two treatment arms of the study differed in both the drugs they received and in the duration of prophylaxis, the results cannot distinguish which of these two variables was more important. Treating patients with enoxaparin for 35-42 days may provide a similar benefit to what was seen with extended-duration betrixaban. 
The findings are a wake-up call to the high thromboembolic risk faced by the types of patients enrolled in APEX, and they point to a new way to manage these patients. Guidelines already call for putting high-risk patients, such as those with heart failure, on anticoagulant prophylaxis if they have no contraindications. These new data suggest that thromboprophylaxis in appropriate patients should extend beyond 10 days and beyond acute hospitalization.
Steven R. Lentz, MD, is a professor of medicine and a hematologist oncologist at the University of Iowa in Iowa City. He has been a consultant to Novo Nordisk and Opko, has an ownership interest in Celgene, and has received research grants from Novo Nordisk. He made these comments in an interview.
The APEX study identified a group of patients hospitalized for medical reasons who were at high risk for both venous thromboembolism and for stroke. We are comfortable with the concept of thromboprophylaxis for hospitalized patients who are at high risk for venous thromboembolism, but we have generally not paid attention to prophylaxis against stroke during and immediately after hospitalization.
The results suggest that extending thromboprophylaxis beyond the standard period of 10 days may be a good idea. Because patients in the two treatment arms of the study differed in both the drugs they received and in the duration of prophylaxis, the results cannot distinguish which of these two variables was more important. Treating patients with enoxaparin for 35-42 days may provide a similar benefit to what was seen with extended-duration betrixaban.
The findings are a wake-up call to the high thromboembolic risk faced by the types of patients enrolled in APEX, and they point to a new way to manage these patients. Guidelines already call for putting high-risk patients, such as those with heart failure, on anticoagulant prophylaxis if they have no contraindications. These new data suggest that thromboprophylaxis in appropriate patients should extend beyond 10 days and beyond acute hospitalization.
Steven R. Lentz, MD, is a professor of medicine and a hematologist oncologist at the University of Iowa in Iowa City. He has been a consultant to Novo Nordisk and Opko, has an ownership interest in Celgene, and has received research grants from Novo Nordisk. He made these comments in an interview.
The APEX study identified a group of patients hospitalized for medical reasons who were at high risk for both venous thromboembolism and for stroke. We are comfortable with the concept of thromboprophylaxis for hospitalized patients who are at high risk for venous thromboembolism, but we have generally not paid attention to prophylaxis against stroke during and immediately after hospitalization.
The results suggest that extending thromboprophylaxis beyond the standard period of 10 days may be a good idea. Because patients in the two treatment arms of the study differed in both the drugs they received and in the duration of prophylaxis, the results cannot distinguish which of these two variables was more important. Treating patients with enoxaparin for 35-42 days may provide a similar benefit to what was seen with extended-duration betrixaban.
The findings are a wake-up call to the high thromboembolic risk faced by the types of patients enrolled in APEX, and they point to a new way to manage these patients. Guidelines already call for putting high-risk patients, such as those with heart failure, on anticoagulant prophylaxis if they have no contraindications. These new data suggest that thromboprophylaxis in appropriate patients should extend beyond 10 days and beyond acute hospitalization.
Steven R. Lentz, MD, is a professor of medicine and a hematologist oncologist at the University of Iowa in Iowa City. He has been a consultant to Novo Nordisk and Opko, has an ownership interest in Celgene, and has received research grants from Novo Nordisk. He made these comments in an interview.
NEW ORLEANS – Thromboprophylaxis for 35-42 days with the new oral anticoagulant betrixaban led to a significant reduction in all-cause and ischemic strokes in medically ill patients who required hospitalization as compared with conventional prophylaxis for 10 days, based on a post-hoc analysis of data from a randomized trial with more than 7,500 patients.
But the trial’s unusual design left it unclear whether the incremental benefit seen from prolonged prophylaxis with a NOAC resulted primarily from a longer period of treatment, the drug used, or both.
The safety analysis showed that prolonged treatment with betrixaban roughly doubled the rate of major or clinically relevant nonmajor bleeding events during the period of treatment and for the first 7 days after treatment stopped. The incidence of these bleeds was 1.6% among control patients on 10 days of enoxaparin treatment and 3.1% among patients who received extended treatment with betrixaban, a statistically significant difference. The rates of fatal bleeds and intracranial hemorrhages in the two study groups did not significantly differ.
The data Dr. Gibson reported came from the Multicenter, Randomized, Active-Controlled Efficacy And Safety Study Comparing Extended Duration Betrixaban With Standard Of Care Enoxaparin For The Prevention Of Venous Thromboembolism In Acute Medically Ill Patients (APEX). The study’s primary aim was testing in 7,513 hospitalized medically ill patients the safety and efficacy of prolonged prophylaxis with the oral, factor Xa inhibitor betrixaban, compared with 10 days of prophylaxis with the low molecular weight heparin enoxaparin. The primary endpoint was the rate of venous thromboembolic events and deaths from venous thromboembolism (VTE) out to 47 days after the start of treatment.
APEX enrolled patients hospitalized for acute decompensated heart failure, chronic respiratory failure, acute infection without septic shock, acute rheumatic disorders or acute ischemic stroke. All enrolled patients had to be expected to be immobilized for at least 24 hours following randomization and to be hospitalized for at least 3 days. Patients also had to have an additional risk marker for high thrombotic risk: They had to be at least 75 years old, or 60-74 years old with a D-dimer level at least twice the upper limit of normal, or 40-59 years old with a D-dimer level at least twice the upper limit of normal and a history of either VTE or cancer.
Results for the primary endpoint, reported in 2016, showed that prolonged betrixaban prophylaxis linked with an absolute 1.6% reduction in the combined endpoint, which resulted in a 19% relative risk reduction that fell just short of the trial’s prespecified definition of statistical significance. The study’s primary safety endpoint was the occurrence of major bleeding events through 7 days after the stop of treatment, which occurred in 0.7% of the betrixaban patients and in 0.6% of those on enoxaparin (N Engl J Med. 2016 Aug 11;375[6]:534-44).
Even thought the primary results from this pivotal trial failed to meet the prespecified threshold for statistical significance, the company developing betrixaban, Portola, submitted an application to the Food and Drug Administration to approve marketing of extended-duration betrixaban for VTE prophylaxis in acute medically-ill patients with VTE risk factors. In December 2016, Portola announced that the FDA had given the application priority status for a decision.
The post-hoc analysis that Dr. Gibson presented at the meeting looked at the impact of betrixaban compared with enoxaparin on the incidence of all-cause and ischemic stroke during 77 days of follow-up after the start of treatment in the 7,432 patients who received at least one dose of their assigned drug, two endpoints that weren’t even secondary outcomes in APEX’s original design.
Among the 3,716 treated with betrixaban, the all-cause stroke incidence was 0.54%; among the 3,716 patients treated with enoxaparin, the all-cause stroke incidence was 0.97%. The 56% relative risk reduction was statistically significant. The incidence of ischemic strokes was 0.48% with betrixaban and 0.91% with enoxaparin, a 53% relative risk reduction that was also statistically significant.
The post-hoc analysis also looked specifically at the comparison between betrixaban and enoxaparin for stroke prevention in a subgroup of patients who had the highest stroke rate, the patients who were hospitalized because of an index stroke or an index heart failure episode. In this high-risk subgroup, prophylaxis with betrixaban cut the all-cause stroke rate compared with enoxaparin by 49% and the ischemic stroke rate by 45%, both statistically significant effects. When the high-risk subgroup also included patients hospitalized for an index episode of atrial fibrillation, betrixaban cut the rate of all-cause strokes by a relative 48% and ischemic strokes by a relative 44%.
Concurrently with Dr. Gibson’s report at the meeting, the results also appeared online (Circulation. 2016 Nov 14. doi: 10.1161/CIRCULATIONAHA.116.025427).
APEX was sponsored by Portola, the company developing betrixaban. Dr. Gibson has been a consultant to Eli Lilly, Gilead, The Medicines Company, Novo Nordisk, Pfizer, and St. Jude. He has received research support from Portola and several other companies.
[email protected]
On Twitter @mitchelzoler
NEW ORLEANS – Thromboprophylaxis for 35-42 days with the new oral anticoagulant betrixaban led to a significant reduction in all-cause and ischemic strokes in medically ill patients who required hospitalization as compared with conventional prophylaxis for 10 days, based on a post-hoc analysis of data from a randomized trial with more than 7,500 patients.
But the trial’s unusual design left it unclear whether the incremental benefit seen from prolonged prophylaxis with a NOAC resulted primarily from a longer period of treatment, the drug used, or both.
The safety analysis showed that prolonged treatment with betrixaban roughly doubled the rate of major or clinically relevant nonmajor bleeding events during the period of treatment and for the first 7 days after treatment stopped. The incidence of these bleeds was 1.6% among control patients on 10 days of enoxaparin treatment and 3.1% among patients who received extended treatment with betrixaban, a statistically significant difference. The rates of fatal bleeds and intracranial hemorrhages in the two study groups did not significantly differ.
The data Dr. Gibson reported came from the Multicenter, Randomized, Active-Controlled Efficacy And Safety Study Comparing Extended Duration Betrixaban With Standard Of Care Enoxaparin For The Prevention Of Venous Thromboembolism In Acute Medically Ill Patients (APEX). The study’s primary aim was testing in 7,513 hospitalized medically ill patients the safety and efficacy of prolonged prophylaxis with the oral, factor Xa inhibitor betrixaban, compared with 10 days of prophylaxis with the low molecular weight heparin enoxaparin. The primary endpoint was the rate of venous thromboembolic events and deaths from venous thromboembolism (VTE) out to 47 days after the start of treatment.
APEX enrolled patients hospitalized for acute decompensated heart failure, chronic respiratory failure, acute infection without septic shock, acute rheumatic disorders or acute ischemic stroke. All enrolled patients had to be expected to be immobilized for at least 24 hours following randomization and to be hospitalized for at least 3 days. Patients also had to have an additional risk marker for high thrombotic risk: They had to be at least 75 years old, or 60-74 years old with a D-dimer level at least twice the upper limit of normal, or 40-59 years old with a D-dimer level at least twice the upper limit of normal and a history of either VTE or cancer.
Results for the primary endpoint, reported in 2016, showed that prolonged betrixaban prophylaxis linked with an absolute 1.6% reduction in the combined endpoint, which resulted in a 19% relative risk reduction that fell just short of the trial’s prespecified definition of statistical significance. The study’s primary safety endpoint was the occurrence of major bleeding events through 7 days after the stop of treatment, which occurred in 0.7% of the betrixaban patients and in 0.6% of those on enoxaparin (N Engl J Med. 2016 Aug 11;375[6]:534-44).
Even thought the primary results from this pivotal trial failed to meet the prespecified threshold for statistical significance, the company developing betrixaban, Portola, submitted an application to the Food and Drug Administration to approve marketing of extended-duration betrixaban for VTE prophylaxis in acute medically-ill patients with VTE risk factors. In December 2016, Portola announced that the FDA had given the application priority status for a decision.
The post-hoc analysis that Dr. Gibson presented at the meeting looked at the impact of betrixaban compared with enoxaparin on the incidence of all-cause and ischemic stroke during 77 days of follow-up after the start of treatment in the 7,432 patients who received at least one dose of their assigned drug, two endpoints that weren’t even secondary outcomes in APEX’s original design.
Among the 3,716 treated with betrixaban, the all-cause stroke incidence was 0.54%; among the 3,716 patients treated with enoxaparin, the all-cause stroke incidence was 0.97%. The 56% relative risk reduction was statistically significant. The incidence of ischemic strokes was 0.48% with betrixaban and 0.91% with enoxaparin, a 53% relative risk reduction that was also statistically significant.
The post-hoc analysis also looked specifically at the comparison between betrixaban and enoxaparin for stroke prevention in a subgroup of patients who had the highest stroke rate, the patients who were hospitalized because of an index stroke or an index heart failure episode. In this high-risk subgroup, prophylaxis with betrixaban cut the all-cause stroke rate compared with enoxaparin by 49% and the ischemic stroke rate by 45%, both statistically significant effects. When the high-risk subgroup also included patients hospitalized for an index episode of atrial fibrillation, betrixaban cut the rate of all-cause strokes by a relative 48% and ischemic strokes by a relative 44%.
Concurrently with Dr. Gibson’s report at the meeting, the results also appeared online (Circulation. 2016 Nov 14. doi: 10.1161/CIRCULATIONAHA.116.025427).
APEX was sponsored by Portola, the company developing betrixaban. Dr. Gibson has been a consultant to Eli Lilly, Gilead, The Medicines Company, Novo Nordisk, Pfizer, and St. Jude. He has received research support from Portola and several other companies.
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On Twitter @mitchelzoler
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: Strokes occurred in 0.54% of patients on extended-duration betrixaban prophylaxis and in 0.97% of patients on standard-duration enoxaparin.
Data source: APEX, a multicenter randomized trial with 7,513 patients.
Disclosures: APEX was sponsored by Portola, the company developing betrixaban. Dr. Gibson has been a consultant to Eli Lilly, Gilead, The Medicines Company, Novo Nordisk, Pfizer and St. Jude. He has received research support from Portola and several other companies.
As-needed anticoagulation for intermittent Afib raises concerns
ORLANDO – A pilot study that suggested as-needed anticoagulation could be effective in preventing stroke in at least some patients after successful ablation of atrial fibrillation (AF) was received with caution at the annual International AF Symposium.
The positive findings, originally reported at the 2016 annual meeting of the Heart Rhythm Society (HRS), were updated at AF Symposium 2017 by Francis Marchlinski, MD, director of cardiac electrophysiology at the University of Pennsylvania. When delivering the data, he provided several caveats before other AF experts added their own.
The study was conducted in response to the substantial number of patients who request discontinuing anticoagulation therapy after a successful ablation for atrial fibrillation, according to Dr. Marchlinski. Current guidelines recommend anticoagulation in AF patients following ablation if they have risk factors for stroke even if their AF is controlled. However, according to Dr. Marchlinski, who cited five observational studies, the risk of stroke in patients with a negative electrocardiogram after ablation appears to be “in the neighborhood of 0.1%.”
“There are no randomized prospective trials that have assessed the safety of stopping anticoagulants, but the fact is that this is a pretty low event rate if the observational studies are accurate, and even if they are off by severalfold, it is likely that we would be unable to show the benefit of continuing anticoagulants in these patients,” Dr. Marchlinski observed.
A strategy of as-needed anticoagulants has been made practical by the introduction of novel oral anticoagulants (NOACs), which have a rapid onset of action relative to warfarin and would, therefore, be expected to provide rapid protection against AF-related stroke risk if initiated upon AF onset, according to Dr. Marchlinski. To test this approach, 105 “highly motivated” AF patients were selected for the pilot study.
In addition to 3 weeks of ECG monitoring to confirm the absence of AF, patients participating in the trial were required to demonstrate skill in pulse assessment, which they agreed to perform on a twice-daily basis. Use of a smartphone app that can detect AF was encouraged but not required. All patients were required to fill a prescription for a NOAC and told to initiate therapy for any AF episode of more than 1 hour.
Of the 105 patients, four were noncompliant with AF monitoring and removed from the study. Another two patients voluntarily requested to return to daily NOAC treatment. The remaining 99 were followed for 30 months. Of these, 18 had multiple episodes of AF and were transitioned back to daily NOAC therapy, 15 used NOAC on an as-needed basis at least once but remained off daily therapy, and the remaining 66 did not have an episode of AF that triggered a course of NOAC therapy.
In 263 patient years of follow-up, there was a single cerebrovascular accident (CVA). This occurred in an 81-year-old patient with a history of hypertrophic cardiomyopathy and an atherosclerotic aortic arch on imaging. The patient presented with neurologic symptoms but had a negative ECG. The CVA symptoms resolved with treatment.
In presenting these data, Dr. Marchlinski said, “PRN use of NOACs may be safe and effective to maintain a low risk of stroke when patients are adherent to diligent pulse monitoring.” However, he reiterated that the study group consisted of “a select group of motivated patients,” and he emphasized the patients must be followed closely.
In a discussion that followed this presentation, several experts expressed the usual caution about drawing conclusions from a single uncontrolled study, but Elaine M. Hylek, MD, professor of medicine, Boston University, added additional reservations to the “pill in a pocket” strategy. In particular, she noted an imperfect correlation between onset of AF and stroke risk. “I think this makes us [reluctant] to stop oral anticoagulation,” she said.
According to Daniel Singer, MD, chief of epidemiology, Harvard School of Public Health, Boston, the available data suggest that “once the AF is gone, the risk of stroke recedes,” but he indicated that all the variables of risk may not be fully understood. He said more “hard data” are needed to endorse a wider application of on-demand anticoagulation in patients like those entered into this study.
The fact that patients without AF following ablation remain at substantial risk of AF recurrences, including asymptomatic episodes, is a liability of as-needed anticoagulation, conceded Dr. Marchlinski. However, these initial results provide promise for the substantial proportion of patients without AF after ablation that wish to avoid anticoagulants and are willing to consider risks and benefits.
Dr. Marchlinski reports financial relationships with Abbott, Biosense Webster, Biotronik, Boston Scientific, St. Jude Medical, and Medtronic.
ORLANDO – A pilot study that suggested as-needed anticoagulation could be effective in preventing stroke in at least some patients after successful ablation of atrial fibrillation (AF) was received with caution at the annual International AF Symposium.
The positive findings, originally reported at the 2016 annual meeting of the Heart Rhythm Society (HRS), were updated at AF Symposium 2017 by Francis Marchlinski, MD, director of cardiac electrophysiology at the University of Pennsylvania. When delivering the data, he provided several caveats before other AF experts added their own.
The study was conducted in response to the substantial number of patients who request discontinuing anticoagulation therapy after a successful ablation for atrial fibrillation, according to Dr. Marchlinski. Current guidelines recommend anticoagulation in AF patients following ablation if they have risk factors for stroke even if their AF is controlled. However, according to Dr. Marchlinski, who cited five observational studies, the risk of stroke in patients with a negative electrocardiogram after ablation appears to be “in the neighborhood of 0.1%.”
“There are no randomized prospective trials that have assessed the safety of stopping anticoagulants, but the fact is that this is a pretty low event rate if the observational studies are accurate, and even if they are off by severalfold, it is likely that we would be unable to show the benefit of continuing anticoagulants in these patients,” Dr. Marchlinski observed.
A strategy of as-needed anticoagulants has been made practical by the introduction of novel oral anticoagulants (NOACs), which have a rapid onset of action relative to warfarin and would, therefore, be expected to provide rapid protection against AF-related stroke risk if initiated upon AF onset, according to Dr. Marchlinski. To test this approach, 105 “highly motivated” AF patients were selected for the pilot study.
In addition to 3 weeks of ECG monitoring to confirm the absence of AF, patients participating in the trial were required to demonstrate skill in pulse assessment, which they agreed to perform on a twice-daily basis. Use of a smartphone app that can detect AF was encouraged but not required. All patients were required to fill a prescription for a NOAC and told to initiate therapy for any AF episode of more than 1 hour.
Of the 105 patients, four were noncompliant with AF monitoring and removed from the study. Another two patients voluntarily requested to return to daily NOAC treatment. The remaining 99 were followed for 30 months. Of these, 18 had multiple episodes of AF and were transitioned back to daily NOAC therapy, 15 used NOAC on an as-needed basis at least once but remained off daily therapy, and the remaining 66 did not have an episode of AF that triggered a course of NOAC therapy.
In 263 patient years of follow-up, there was a single cerebrovascular accident (CVA). This occurred in an 81-year-old patient with a history of hypertrophic cardiomyopathy and an atherosclerotic aortic arch on imaging. The patient presented with neurologic symptoms but had a negative ECG. The CVA symptoms resolved with treatment.
In presenting these data, Dr. Marchlinski said, “PRN use of NOACs may be safe and effective to maintain a low risk of stroke when patients are adherent to diligent pulse monitoring.” However, he reiterated that the study group consisted of “a select group of motivated patients,” and he emphasized the patients must be followed closely.
In a discussion that followed this presentation, several experts expressed the usual caution about drawing conclusions from a single uncontrolled study, but Elaine M. Hylek, MD, professor of medicine, Boston University, added additional reservations to the “pill in a pocket” strategy. In particular, she noted an imperfect correlation between onset of AF and stroke risk. “I think this makes us [reluctant] to stop oral anticoagulation,” she said.
According to Daniel Singer, MD, chief of epidemiology, Harvard School of Public Health, Boston, the available data suggest that “once the AF is gone, the risk of stroke recedes,” but he indicated that all the variables of risk may not be fully understood. He said more “hard data” are needed to endorse a wider application of on-demand anticoagulation in patients like those entered into this study.
The fact that patients without AF following ablation remain at substantial risk of AF recurrences, including asymptomatic episodes, is a liability of as-needed anticoagulation, conceded Dr. Marchlinski. However, these initial results provide promise for the substantial proportion of patients without AF after ablation that wish to avoid anticoagulants and are willing to consider risks and benefits.
Dr. Marchlinski reports financial relationships with Abbott, Biosense Webster, Biotronik, Boston Scientific, St. Jude Medical, and Medtronic.
ORLANDO – A pilot study that suggested as-needed anticoagulation could be effective in preventing stroke in at least some patients after successful ablation of atrial fibrillation (AF) was received with caution at the annual International AF Symposium.
The positive findings, originally reported at the 2016 annual meeting of the Heart Rhythm Society (HRS), were updated at AF Symposium 2017 by Francis Marchlinski, MD, director of cardiac electrophysiology at the University of Pennsylvania. When delivering the data, he provided several caveats before other AF experts added their own.
The study was conducted in response to the substantial number of patients who request discontinuing anticoagulation therapy after a successful ablation for atrial fibrillation, according to Dr. Marchlinski. Current guidelines recommend anticoagulation in AF patients following ablation if they have risk factors for stroke even if their AF is controlled. However, according to Dr. Marchlinski, who cited five observational studies, the risk of stroke in patients with a negative electrocardiogram after ablation appears to be “in the neighborhood of 0.1%.”
“There are no randomized prospective trials that have assessed the safety of stopping anticoagulants, but the fact is that this is a pretty low event rate if the observational studies are accurate, and even if they are off by severalfold, it is likely that we would be unable to show the benefit of continuing anticoagulants in these patients,” Dr. Marchlinski observed.
A strategy of as-needed anticoagulants has been made practical by the introduction of novel oral anticoagulants (NOACs), which have a rapid onset of action relative to warfarin and would, therefore, be expected to provide rapid protection against AF-related stroke risk if initiated upon AF onset, according to Dr. Marchlinski. To test this approach, 105 “highly motivated” AF patients were selected for the pilot study.
In addition to 3 weeks of ECG monitoring to confirm the absence of AF, patients participating in the trial were required to demonstrate skill in pulse assessment, which they agreed to perform on a twice-daily basis. Use of a smartphone app that can detect AF was encouraged but not required. All patients were required to fill a prescription for a NOAC and told to initiate therapy for any AF episode of more than 1 hour.
Of the 105 patients, four were noncompliant with AF monitoring and removed from the study. Another two patients voluntarily requested to return to daily NOAC treatment. The remaining 99 were followed for 30 months. Of these, 18 had multiple episodes of AF and were transitioned back to daily NOAC therapy, 15 used NOAC on an as-needed basis at least once but remained off daily therapy, and the remaining 66 did not have an episode of AF that triggered a course of NOAC therapy.
In 263 patient years of follow-up, there was a single cerebrovascular accident (CVA). This occurred in an 81-year-old patient with a history of hypertrophic cardiomyopathy and an atherosclerotic aortic arch on imaging. The patient presented with neurologic symptoms but had a negative ECG. The CVA symptoms resolved with treatment.
In presenting these data, Dr. Marchlinski said, “PRN use of NOACs may be safe and effective to maintain a low risk of stroke when patients are adherent to diligent pulse monitoring.” However, he reiterated that the study group consisted of “a select group of motivated patients,” and he emphasized the patients must be followed closely.
In a discussion that followed this presentation, several experts expressed the usual caution about drawing conclusions from a single uncontrolled study, but Elaine M. Hylek, MD, professor of medicine, Boston University, added additional reservations to the “pill in a pocket” strategy. In particular, she noted an imperfect correlation between onset of AF and stroke risk. “I think this makes us [reluctant] to stop oral anticoagulation,” she said.
According to Daniel Singer, MD, chief of epidemiology, Harvard School of Public Health, Boston, the available data suggest that “once the AF is gone, the risk of stroke recedes,” but he indicated that all the variables of risk may not be fully understood. He said more “hard data” are needed to endorse a wider application of on-demand anticoagulation in patients like those entered into this study.
The fact that patients without AF following ablation remain at substantial risk of AF recurrences, including asymptomatic episodes, is a liability of as-needed anticoagulation, conceded Dr. Marchlinski. However, these initial results provide promise for the substantial proportion of patients without AF after ablation that wish to avoid anticoagulants and are willing to consider risks and benefits.
Dr. Marchlinski reports financial relationships with Abbott, Biosense Webster, Biotronik, Boston Scientific, St. Jude Medical, and Medtronic.
Key clinical point: Despite a positive pilot study, the efficacy of intermittent anticoagulation for stroke prevention after ablation for atrial fibrillation will be difficult to validate in a definitive fashion.
Major finding: Sixty-six percent of atrial fibrillation patients entirely avoided anticoagulation over 30 months of follow-up, but there are at least theoretical concerns.
Data source: A prospective, nonrandomized study.
Disclosures: Dr. Marchlinski reported financial relationships with Abbott, Biosense Webster, Biotronik, Boston Scientific, St. Jude Medical, and Medtronic.
Intracardiac echo safely guides LAA occluder placement
ORLANDO – Intracardiac echocardiography (ICE) can be safely substituted for transesophageal echocardiography (TEE) as a less invasive option in the placement of an investigational percutaneous device for left atrial appendage (LAA) occlusion, according to data presented at the annual International AF Symposium.
The relative safety and efficacy of ICE and TEE for placement of the device, called the Amplatzer Amulet, was evaluated as a subanalysis of a large, nonrandomized, observational study, according to Boris Schmidt, MD, of Cardiovascular Center Bethanien, Frankfurt, Germany.
The Amplatzer Amulet device, which is designed to prevent LAA-associated thromboembolism in patients with nonvalvular atrial fibrillation (AF), has been available in Europe for several years. It functions much like Boston Scientific’s Watchman implant. A registration trial in the United States was initiated in 2016.
In the study that provided the basis for this analysis, 1,088 AF patients were implanted. The average age was 75 years, and the population was relatively high risk for both stroke and bleeding. The CHA2DS2-VASc score was at least 4 in 65% of patients, with an average score of 4.2. Prior stroke (28%) and transient ischemic attack (11%) had occurred in more than one-third. Reflecting the fact that 72% had a history of a major bleed, the average HAS-BLED score was 3.3. More than 80% were hypertensive.
The decision to place the device with TEE, which Dr. Schmidt characterized as the standard, or ICE was left up to the discretion of the implanter. Ultimately, 958 (88.4%) of the devices were placed with TEE and 126 (11.6%) with ICE.
There were no significant differences in implant success or safety when the two methods for guiding implantation were compared. Specifically, success was achieved in 99.2% of the ICE group with 90.5% of cases requiring only one device. In the TEE group, the device was successfully implanted in 98.4%, and 94.4% needed only one device. The first device to be selected was ultimately implanted in 96.5% of the ICE group and 94.4% of the TEE group. The LAA closure rate, defined as gap of less than 3 mm, was 100% at implant and 3 months after transplant in the ICE group, when evaluated by an independent core laboratory. The closure rates in the TEE group at the time of implant and 3 months later were 99.8% and 98.6%, respectively. No difference between imaging methods approached statistical significance.
Adverse events, which were also adjudicated by independent investigators, occurred at low rates and also did not differ by imaging strategy. In the ICE and TEE groups, respectively, these included vascular complications in 0.9% and 1.6%, pericardial effusion in 1.0% and 0.8%, stroke in 0.3% and 0%, and embolization in 0.1% and 0%. With a median follow-up of 6.6 months, there have been four deaths. Two were considered to be device related by the adjudicators. One involved a perforation and another a cardiac arrest. Both were observed in the TEE group.
The Amplatzer Amulet device consists of a lobe that is designed to fit inside the LAA neck and a disk that provides a complete seal at the orifice. It was first introduced in Europe in 2008 but has undergone several modifications. In the United States, the Watchman, which opens like an umbrella in order to block passage of thromboemboli when deployed in the LAA, received FDA approval in 2015. Other LAA closure strategies are in development. There are no large randomized trials in which LAA closure devices have been compared.
Dr. Schmidt has financial relationships with Boston Scientific and St. Jude Medical.
ORLANDO – Intracardiac echocardiography (ICE) can be safely substituted for transesophageal echocardiography (TEE) as a less invasive option in the placement of an investigational percutaneous device for left atrial appendage (LAA) occlusion, according to data presented at the annual International AF Symposium.
The relative safety and efficacy of ICE and TEE for placement of the device, called the Amplatzer Amulet, was evaluated as a subanalysis of a large, nonrandomized, observational study, according to Boris Schmidt, MD, of Cardiovascular Center Bethanien, Frankfurt, Germany.
The Amplatzer Amulet device, which is designed to prevent LAA-associated thromboembolism in patients with nonvalvular atrial fibrillation (AF), has been available in Europe for several years. It functions much like Boston Scientific’s Watchman implant. A registration trial in the United States was initiated in 2016.
In the study that provided the basis for this analysis, 1,088 AF patients were implanted. The average age was 75 years, and the population was relatively high risk for both stroke and bleeding. The CHA2DS2-VASc score was at least 4 in 65% of patients, with an average score of 4.2. Prior stroke (28%) and transient ischemic attack (11%) had occurred in more than one-third. Reflecting the fact that 72% had a history of a major bleed, the average HAS-BLED score was 3.3. More than 80% were hypertensive.
The decision to place the device with TEE, which Dr. Schmidt characterized as the standard, or ICE was left up to the discretion of the implanter. Ultimately, 958 (88.4%) of the devices were placed with TEE and 126 (11.6%) with ICE.
There were no significant differences in implant success or safety when the two methods for guiding implantation were compared. Specifically, success was achieved in 99.2% of the ICE group with 90.5% of cases requiring only one device. In the TEE group, the device was successfully implanted in 98.4%, and 94.4% needed only one device. The first device to be selected was ultimately implanted in 96.5% of the ICE group and 94.4% of the TEE group. The LAA closure rate, defined as gap of less than 3 mm, was 100% at implant and 3 months after transplant in the ICE group, when evaluated by an independent core laboratory. The closure rates in the TEE group at the time of implant and 3 months later were 99.8% and 98.6%, respectively. No difference between imaging methods approached statistical significance.
Adverse events, which were also adjudicated by independent investigators, occurred at low rates and also did not differ by imaging strategy. In the ICE and TEE groups, respectively, these included vascular complications in 0.9% and 1.6%, pericardial effusion in 1.0% and 0.8%, stroke in 0.3% and 0%, and embolization in 0.1% and 0%. With a median follow-up of 6.6 months, there have been four deaths. Two were considered to be device related by the adjudicators. One involved a perforation and another a cardiac arrest. Both were observed in the TEE group.
The Amplatzer Amulet device consists of a lobe that is designed to fit inside the LAA neck and a disk that provides a complete seal at the orifice. It was first introduced in Europe in 2008 but has undergone several modifications. In the United States, the Watchman, which opens like an umbrella in order to block passage of thromboemboli when deployed in the LAA, received FDA approval in 2015. Other LAA closure strategies are in development. There are no large randomized trials in which LAA closure devices have been compared.
Dr. Schmidt has financial relationships with Boston Scientific and St. Jude Medical.
ORLANDO – Intracardiac echocardiography (ICE) can be safely substituted for transesophageal echocardiography (TEE) as a less invasive option in the placement of an investigational percutaneous device for left atrial appendage (LAA) occlusion, according to data presented at the annual International AF Symposium.
The relative safety and efficacy of ICE and TEE for placement of the device, called the Amplatzer Amulet, was evaluated as a subanalysis of a large, nonrandomized, observational study, according to Boris Schmidt, MD, of Cardiovascular Center Bethanien, Frankfurt, Germany.
The Amplatzer Amulet device, which is designed to prevent LAA-associated thromboembolism in patients with nonvalvular atrial fibrillation (AF), has been available in Europe for several years. It functions much like Boston Scientific’s Watchman implant. A registration trial in the United States was initiated in 2016.
In the study that provided the basis for this analysis, 1,088 AF patients were implanted. The average age was 75 years, and the population was relatively high risk for both stroke and bleeding. The CHA2DS2-VASc score was at least 4 in 65% of patients, with an average score of 4.2. Prior stroke (28%) and transient ischemic attack (11%) had occurred in more than one-third. Reflecting the fact that 72% had a history of a major bleed, the average HAS-BLED score was 3.3. More than 80% were hypertensive.
The decision to place the device with TEE, which Dr. Schmidt characterized as the standard, or ICE was left up to the discretion of the implanter. Ultimately, 958 (88.4%) of the devices were placed with TEE and 126 (11.6%) with ICE.
There were no significant differences in implant success or safety when the two methods for guiding implantation were compared. Specifically, success was achieved in 99.2% of the ICE group with 90.5% of cases requiring only one device. In the TEE group, the device was successfully implanted in 98.4%, and 94.4% needed only one device. The first device to be selected was ultimately implanted in 96.5% of the ICE group and 94.4% of the TEE group. The LAA closure rate, defined as gap of less than 3 mm, was 100% at implant and 3 months after transplant in the ICE group, when evaluated by an independent core laboratory. The closure rates in the TEE group at the time of implant and 3 months later were 99.8% and 98.6%, respectively. No difference between imaging methods approached statistical significance.
Adverse events, which were also adjudicated by independent investigators, occurred at low rates and also did not differ by imaging strategy. In the ICE and TEE groups, respectively, these included vascular complications in 0.9% and 1.6%, pericardial effusion in 1.0% and 0.8%, stroke in 0.3% and 0%, and embolization in 0.1% and 0%. With a median follow-up of 6.6 months, there have been four deaths. Two were considered to be device related by the adjudicators. One involved a perforation and another a cardiac arrest. Both were observed in the TEE group.
The Amplatzer Amulet device consists of a lobe that is designed to fit inside the LAA neck and a disk that provides a complete seal at the orifice. It was first introduced in Europe in 2008 but has undergone several modifications. In the United States, the Watchman, which opens like an umbrella in order to block passage of thromboemboli when deployed in the LAA, received FDA approval in 2015. Other LAA closure strategies are in development. There are no large randomized trials in which LAA closure devices have been compared.
Dr. Schmidt has financial relationships with Boston Scientific and St. Jude Medical.
Key clinical point: Intracardiac echocardiography is a viable option for guiding placement of an experimental left atrial appendage thromboembolism blocker.
Major finding: LAA closure rates at 3 months were 100% with ICE and 98.6% with transesophageal echocardiograph.
Data source: Prospective, multicenter, observational study.
Disclosures: Dr. Schmidt has financial relationships with Boston Scientific and St. Jude Medical.
Subclinical AF found in 1/3 of asymptomatic elderly
NEW ORLEANS – About a third of elderly people at high cardiovascular risk but otherwise healthy and asymptomatic had subclinical atrial fibrillation in a multicenter study of 273 people.
This finding that subclinical atrial fibrillation (AF) is “extremely common” in elderly people with cardiovascular risk factors “weakens the case that detecting subclinical AF in patients following a stroke implies causality” of the stroke “because subclinical AF is so prevalent,” Jeff S. Healey, MD, said at the American Heart Association Scientific Sessions.
“I think that subclinical AF is a distinct subgroup of AF, with a risk for stroke that is quite low, about 1.5%-2% per year,” said Dr. Healey, a cardiologist at McMaster University in Hamilton, Canada. “Given that this was an elderly population [study participants averaged 74 years old] with bleeding risk, it’s reasonable to question” whether many people with subclinical AF need anticoagulation. The question of whether “45 seconds of AF seen 6 months after a stroke is worthy of treatment with an anticoagulant should give people pause,” he said.
The Prevalence of Sub-Clinical Atrial Fibrillation Using an Implantable Cardiac Monitor (ASSERT-II) study initially enrolled 273 people at 26 sites in Canada and The Netherlands. Researchers actually placed a loop recorder in 256, and complete follow-up of at least 9 months occurred for 252. Enrolled patients had to be at 65 years old, and have at least one of these risk factors for AF or stroke: a CHA2DS2-VASc score of 2 or greater; documented obstructive sleep apnea; or a body mass index greater than 30 kg/m2. In addition, enrollees also had to have one of these risk factors for AF: a left atrial volume of at least 58 ml; a left atrial diameter of at least 4.4 cm; or a serum NT-proBNP level of at least 290 pg/mL.
Dr. Healey and his associates prespecified subclinical AF as at least 5 minutes of AF seen in the loop recording during follow-up, which occurred in 34% of the participants during an average 16 months of follow-up, he reported. At least 30 minutes of AF occurred in 22% during follow-up, at least 6 hours in 7%, and at least 24 hours in 3%.
In a prespecified set of subgroup analyses, people with a large left atrium formed the only subgroup with a statistically significant association with outcome. People with a left atrial size at or above the study median of 73.5 ml had an 85% increased rate of subclinical AF compared with those with smaller left atria in the multivariate analysis. But increased left atrial size alone did not fully explain subclinical atrial fibrillation. Even among participants in the lowest quartile for left atrial diameter, less than 4.3 cm, the prevalence of subclinical AF was 27%, Dr. Healey noted.
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On Twitter @mitchelzoler
The results reported by Dr. Healey provide robust data that bridges a major gap we have had in our understanding of atrial fibrillation. The new finding of a high prevalence of subclinical atrial fibrillation in elderly people with cardiovascular risk factors, regardless of whether they had a prior stroke, substantially weakens the case that subclinical atrial fibrillation detected following a stroke has a causal relationship to the stroke. This implication is quite important.
Many questions remain about the meaning of subclinical atrial fibrillation. What relationship does it have with stroke, and what thresholds exist for atrial fibrillation to raise stroke risk? Also, what are the risks and benefits of anticoagulation in people with subclinical AF and is intermittent anticoagulation helpful?
N.A. Mark Estes III, MD , is professor of medicine and director of the New England Cardiac Arrhythmia Center at Tufts Medical Center in Boston. He has been a consultant to Boston Scientific, Medtronic and St. Jude. He made these comments as designated discussant for ASSERT-II.
The results reported by Dr. Healey provide robust data that bridges a major gap we have had in our understanding of atrial fibrillation. The new finding of a high prevalence of subclinical atrial fibrillation in elderly people with cardiovascular risk factors, regardless of whether they had a prior stroke, substantially weakens the case that subclinical atrial fibrillation detected following a stroke has a causal relationship to the stroke. This implication is quite important.
Many questions remain about the meaning of subclinical atrial fibrillation. What relationship does it have with stroke, and what thresholds exist for atrial fibrillation to raise stroke risk? Also, what are the risks and benefits of anticoagulation in people with subclinical AF and is intermittent anticoagulation helpful?
N.A. Mark Estes III, MD , is professor of medicine and director of the New England Cardiac Arrhythmia Center at Tufts Medical Center in Boston. He has been a consultant to Boston Scientific, Medtronic and St. Jude. He made these comments as designated discussant for ASSERT-II.
The results reported by Dr. Healey provide robust data that bridges a major gap we have had in our understanding of atrial fibrillation. The new finding of a high prevalence of subclinical atrial fibrillation in elderly people with cardiovascular risk factors, regardless of whether they had a prior stroke, substantially weakens the case that subclinical atrial fibrillation detected following a stroke has a causal relationship to the stroke. This implication is quite important.
Many questions remain about the meaning of subclinical atrial fibrillation. What relationship does it have with stroke, and what thresholds exist for atrial fibrillation to raise stroke risk? Also, what are the risks and benefits of anticoagulation in people with subclinical AF and is intermittent anticoagulation helpful?
N.A. Mark Estes III, MD , is professor of medicine and director of the New England Cardiac Arrhythmia Center at Tufts Medical Center in Boston. He has been a consultant to Boston Scientific, Medtronic and St. Jude. He made these comments as designated discussant for ASSERT-II.
NEW ORLEANS – About a third of elderly people at high cardiovascular risk but otherwise healthy and asymptomatic had subclinical atrial fibrillation in a multicenter study of 273 people.
This finding that subclinical atrial fibrillation (AF) is “extremely common” in elderly people with cardiovascular risk factors “weakens the case that detecting subclinical AF in patients following a stroke implies causality” of the stroke “because subclinical AF is so prevalent,” Jeff S. Healey, MD, said at the American Heart Association Scientific Sessions.
“I think that subclinical AF is a distinct subgroup of AF, with a risk for stroke that is quite low, about 1.5%-2% per year,” said Dr. Healey, a cardiologist at McMaster University in Hamilton, Canada. “Given that this was an elderly population [study participants averaged 74 years old] with bleeding risk, it’s reasonable to question” whether many people with subclinical AF need anticoagulation. The question of whether “45 seconds of AF seen 6 months after a stroke is worthy of treatment with an anticoagulant should give people pause,” he said.
The Prevalence of Sub-Clinical Atrial Fibrillation Using an Implantable Cardiac Monitor (ASSERT-II) study initially enrolled 273 people at 26 sites in Canada and The Netherlands. Researchers actually placed a loop recorder in 256, and complete follow-up of at least 9 months occurred for 252. Enrolled patients had to be at 65 years old, and have at least one of these risk factors for AF or stroke: a CHA2DS2-VASc score of 2 or greater; documented obstructive sleep apnea; or a body mass index greater than 30 kg/m2. In addition, enrollees also had to have one of these risk factors for AF: a left atrial volume of at least 58 ml; a left atrial diameter of at least 4.4 cm; or a serum NT-proBNP level of at least 290 pg/mL.
Dr. Healey and his associates prespecified subclinical AF as at least 5 minutes of AF seen in the loop recording during follow-up, which occurred in 34% of the participants during an average 16 months of follow-up, he reported. At least 30 minutes of AF occurred in 22% during follow-up, at least 6 hours in 7%, and at least 24 hours in 3%.
In a prespecified set of subgroup analyses, people with a large left atrium formed the only subgroup with a statistically significant association with outcome. People with a left atrial size at or above the study median of 73.5 ml had an 85% increased rate of subclinical AF compared with those with smaller left atria in the multivariate analysis. But increased left atrial size alone did not fully explain subclinical atrial fibrillation. Even among participants in the lowest quartile for left atrial diameter, less than 4.3 cm, the prevalence of subclinical AF was 27%, Dr. Healey noted.
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On Twitter @mitchelzoler
NEW ORLEANS – About a third of elderly people at high cardiovascular risk but otherwise healthy and asymptomatic had subclinical atrial fibrillation in a multicenter study of 273 people.
This finding that subclinical atrial fibrillation (AF) is “extremely common” in elderly people with cardiovascular risk factors “weakens the case that detecting subclinical AF in patients following a stroke implies causality” of the stroke “because subclinical AF is so prevalent,” Jeff S. Healey, MD, said at the American Heart Association Scientific Sessions.
“I think that subclinical AF is a distinct subgroup of AF, with a risk for stroke that is quite low, about 1.5%-2% per year,” said Dr. Healey, a cardiologist at McMaster University in Hamilton, Canada. “Given that this was an elderly population [study participants averaged 74 years old] with bleeding risk, it’s reasonable to question” whether many people with subclinical AF need anticoagulation. The question of whether “45 seconds of AF seen 6 months after a stroke is worthy of treatment with an anticoagulant should give people pause,” he said.
The Prevalence of Sub-Clinical Atrial Fibrillation Using an Implantable Cardiac Monitor (ASSERT-II) study initially enrolled 273 people at 26 sites in Canada and The Netherlands. Researchers actually placed a loop recorder in 256, and complete follow-up of at least 9 months occurred for 252. Enrolled patients had to be at 65 years old, and have at least one of these risk factors for AF or stroke: a CHA2DS2-VASc score of 2 or greater; documented obstructive sleep apnea; or a body mass index greater than 30 kg/m2. In addition, enrollees also had to have one of these risk factors for AF: a left atrial volume of at least 58 ml; a left atrial diameter of at least 4.4 cm; or a serum NT-proBNP level of at least 290 pg/mL.
Dr. Healey and his associates prespecified subclinical AF as at least 5 minutes of AF seen in the loop recording during follow-up, which occurred in 34% of the participants during an average 16 months of follow-up, he reported. At least 30 minutes of AF occurred in 22% during follow-up, at least 6 hours in 7%, and at least 24 hours in 3%.
In a prespecified set of subgroup analyses, people with a large left atrium formed the only subgroup with a statistically significant association with outcome. People with a left atrial size at or above the study median of 73.5 ml had an 85% increased rate of subclinical AF compared with those with smaller left atria in the multivariate analysis. But increased left atrial size alone did not fully explain subclinical atrial fibrillation. Even among participants in the lowest quartile for left atrial diameter, less than 4.3 cm, the prevalence of subclinical AF was 27%, Dr. Healey noted.
[email protected]
On Twitter @mitchelzoler
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: One-third of asymptomatic elderly people with cardiovascular risk factors had subclinical atrial fibrillation.
Data source: A multicenter study with 252 people followed for an average of 16 months.
Disclosures: Dr. Healey has been a consultant to or received honoraria from Bayer, Medtronic, Pfizer and Servier. He has received research support from Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Medtronic and St. Jude.