Anticoagulation Hub

New guidelines decrease the minimum duration of dual-antiplatelet therapy (DAPT) to as little as 3 months after drug-eluting stent placement in certain lower-risk patients with coronary artery disease.

The updated recommendations harmonize and replace six other guidelines, and apply to everolimus and zotarolimus stents, not Cypher or Taxus stents, said Dr. Eric R. Bates, who helped author the American College of Cardiology/American Heart Association Focused Update. “The emphasis is on balancing ischemic risk versus bleeding risk. The recommendations give clinicians guideline coverage to make personalized DAPT recommendations,” he said in an interview.

The guidance reflects recent evidence that shorter duration (3-6 months) of DAPT, compared with the standard 12 months of therapy does not increase the risk of stent thrombosis and potentially lessens bleeding risk in select patients. Other studies of an additional 18 or 36 months of DAPT found a decrease in the risk of MI and stent thrombosis, at the cost of greater risk of bleeding. Thus, the updated guidelines call for “a thoughtful assessment of the benefit-risk ratio, integration of study data, and consideration of patient preference” when selecting duration of DAPT. “In general, shorter-duration DAPT can be considered for patients at lower ischemic risk with high bleeding risk, whereas longer-duration DAPT may be reasonable for patients at higher ischemic risk with lower bleeding risk,” the authors wrote, led by Dr. Glenn N. Levineof Baylor College of Medicine, Houston (J Am Coll Cardiol. 2016 Mar 29. doi: 10.1016/j.jacc.2016.03.512).

The recommendations define DAPT as combination therapy with aspirin and a P2Y12 receptor inhibitor – that is, clopidogrel, prasugrel, or ticagrelor. “When indicated, ticagrelor and prasugrel have a Class IIa preference over clopidogrel,” Dr. Bates said. The recommended daily dose of aspirin is 81 mg (range, 75-100 mg), which is usually continued indefinitely, regardless of how long patients receive dual therapy.

The shortened durations of dual-antiplatelet therapy include several scenarios. For elective percutaneous coronary intervention, the former Class I recommendation for 12 months of DAPT has been reduced to 6 months, with a Class IIb recommendation for either longer treatment or shorter (3-month) treatment, Dr. Bates, professor of medicine at the University of Michigan Health System in Ann Arbor, said. For patients with acute coronary syndrome, the guidelines retain the Class I recommendation for 12 months of DAPT, but also add a Class IIb recommendation for longer or shorter (6 months) DAPT.

The guidelines also include a new Class IIb recommendation for 12 months of DAPT started early after coronary artery bypass graft in patients with stable ischemic heart disease. This strategy “may be reasonable to improve vein graft patency” in these patients, the recommendations state.

The guidance clarifies previous recommendations on the timing of elective noncardiac surgery, and assigns Class IIb support for consideration of such surgeries starting 3 months after implantation of drug-eluting stents, if the risks of delaying surgery outweigh the expected risk of stent thrombosis when it is necessary to stop P2Y12 inhibitor therapy.

©Svisio/Thinkstock

The recommendations now distinguish between B and C levels of evidence to increase granularity, according to Dr. Bates. The document updates recommendations on duration of DAPT across six previously published guidelines – the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention (PCI); the 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery; the 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease; the 2013ACC/AHA Guideline for the Management of ST-Elevation Myocardial Infarction; the 2014 ACC/AHA Guideline for Non-ST-Elevation Acute Coronary Syndromes, and the 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery.

The extensive evidence review that informed guideline development was simultaneously reported by Dr. John Bittl at Munroe Regional Medical Center in Ocala, Fla., and his colleagues. The investigators synthesized evidence from 11 randomized controlled trials of more than 33,000 patients who received mainly newer generation stents. They also reviewed a randomized controlled trial of more than 21,000 patients with stable ischemic heart disease who were more than 1 year post-MI, and a post hoc analysis of a trial of more than 15,000 such patients.

These reviews uncovered “moderately strong evidence” that prolonged DAPT after implantation of newer generation drug-eluting stents “entails a trade-off between reductions in stent thrombosis and MI and increases in major hemorrhage,” Dr. Bittl and his colleagues wrote. Likewise, they found moderately strong evidence that prolonged DAPT helps prevent cardiovascular events at the cost of increased bleeding in patients whose coronary thrombotic risk stemmed from prior MI, not stent implantation. They found weak evidence of increased mortality in stent patients who received prolonged DAPT.

Dr. Bates reported consulting relationships with Merck and AstraZeneca. Eight other coauthors disclosed financial relationships with a number of pharmaceutical or device companies. Dr. Glenn Levine and seven coauthors disclosed no relationships with industry.

New guidelines decrease the minimum duration of dual-antiplatelet therapy (DAPT) to as little as 3 months after drug-eluting stent placement in certain lower-risk patients with coronary artery disease.

The updated recommendations harmonize and replace six other guidelines, and apply to everolimus and zotarolimus stents, not Cypher or Taxus stents, said Dr. Eric R. Bates, who helped author the American College of Cardiology/American Heart Association Focused Update. “The emphasis is on balancing ischemic risk versus bleeding risk. The recommendations give clinicians guideline coverage to make personalized DAPT recommendations,” he said in an interview.

The guidance reflects recent evidence that shorter duration (3-6 months) of DAPT, compared with the standard 12 months of therapy does not increase the risk of stent thrombosis and potentially lessens bleeding risk in select patients. Other studies of an additional 18 or 36 months of DAPT found a decrease in the risk of MI and stent thrombosis, at the cost of greater risk of bleeding. Thus, the updated guidelines call for “a thoughtful assessment of the benefit-risk ratio, integration of study data, and consideration of patient preference” when selecting duration of DAPT. “In general, shorter-duration DAPT can be considered for patients at lower ischemic risk with high bleeding risk, whereas longer-duration DAPT may be reasonable for patients at higher ischemic risk with lower bleeding risk,” the authors wrote, led by Dr. Glenn N. Levineof Baylor College of Medicine, Houston (J Am Coll Cardiol. 2016 Mar 29. doi: 10.1016/j.jacc.2016.03.512).

The recommendations define DAPT as combination therapy with aspirin and a P2Y12 receptor inhibitor – that is, clopidogrel, prasugrel, or ticagrelor. “When indicated, ticagrelor and prasugrel have a Class IIa preference over clopidogrel,” Dr. Bates said. The recommended daily dose of aspirin is 81 mg (range, 75-100 mg), which is usually continued indefinitely, regardless of how long patients receive dual therapy.

The shortened durations of dual-antiplatelet therapy include several scenarios. For elective percutaneous coronary intervention, the former Class I recommendation for 12 months of DAPT has been reduced to 6 months, with a Class IIb recommendation for either longer treatment or shorter (3-month) treatment, Dr. Bates, professor of medicine at the University of Michigan Health System in Ann Arbor, said. For patients with acute coronary syndrome, the guidelines retain the Class I recommendation for 12 months of DAPT, but also add a Class IIb recommendation for longer or shorter (6 months) DAPT.

The guidelines also include a new Class IIb recommendation for 12 months of DAPT started early after coronary artery bypass graft in patients with stable ischemic heart disease. This strategy “may be reasonable to improve vein graft patency” in these patients, the recommendations state.

The guidance clarifies previous recommendations on the timing of elective noncardiac surgery, and assigns Class IIb support for consideration of such surgeries starting 3 months after implantation of drug-eluting stents, if the risks of delaying surgery outweigh the expected risk of stent thrombosis when it is necessary to stop P2Y12 inhibitor therapy.

©Svisio/Thinkstock

The recommendations now distinguish between B and C levels of evidence to increase granularity, according to Dr. Bates. The document updates recommendations on duration of DAPT across six previously published guidelines – the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention (PCI); the 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery; the 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease; the 2013ACC/AHA Guideline for the Management of ST-Elevation Myocardial Infarction; the 2014 ACC/AHA Guideline for Non-ST-Elevation Acute Coronary Syndromes, and the 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery.

The extensive evidence review that informed guideline development was simultaneously reported by Dr. John Bittl at Munroe Regional Medical Center in Ocala, Fla., and his colleagues. The investigators synthesized evidence from 11 randomized controlled trials of more than 33,000 patients who received mainly newer generation stents. They also reviewed a randomized controlled trial of more than 21,000 patients with stable ischemic heart disease who were more than 1 year post-MI, and a post hoc analysis of a trial of more than 15,000 such patients.

These reviews uncovered “moderately strong evidence” that prolonged DAPT after implantation of newer generation drug-eluting stents “entails a trade-off between reductions in stent thrombosis and MI and increases in major hemorrhage,” Dr. Bittl and his colleagues wrote. Likewise, they found moderately strong evidence that prolonged DAPT helps prevent cardiovascular events at the cost of increased bleeding in patients whose coronary thrombotic risk stemmed from prior MI, not stent implantation. They found weak evidence of increased mortality in stent patients who received prolonged DAPT.

Dr. Bates reported consulting relationships with Merck and AstraZeneca. Eight other coauthors disclosed financial relationships with a number of pharmaceutical or device companies. Dr. Glenn Levine and seven coauthors disclosed no relationships with industry.

New guidelines decrease the minimum duration of dual-antiplatelet therapy (DAPT) to as little as 3 months after drug-eluting stent placement in certain lower-risk patients with coronary artery disease.

The updated recommendations harmonize and replace six other guidelines, and apply to everolimus and zotarolimus stents, not Cypher or Taxus stents, said Dr. Eric R. Bates, who helped author the American College of Cardiology/American Heart Association Focused Update. “The emphasis is on balancing ischemic risk versus bleeding risk. The recommendations give clinicians guideline coverage to make personalized DAPT recommendations,” he said in an interview.

The guidance reflects recent evidence that shorter duration (3-6 months) of DAPT, compared with the standard 12 months of therapy does not increase the risk of stent thrombosis and potentially lessens bleeding risk in select patients. Other studies of an additional 18 or 36 months of DAPT found a decrease in the risk of MI and stent thrombosis, at the cost of greater risk of bleeding. Thus, the updated guidelines call for “a thoughtful assessment of the benefit-risk ratio, integration of study data, and consideration of patient preference” when selecting duration of DAPT. “In general, shorter-duration DAPT can be considered for patients at lower ischemic risk with high bleeding risk, whereas longer-duration DAPT may be reasonable for patients at higher ischemic risk with lower bleeding risk,” the authors wrote, led by Dr. Glenn N. Levineof Baylor College of Medicine, Houston (J Am Coll Cardiol. 2016 Mar 29. doi: 10.1016/j.jacc.2016.03.512).

The recommendations define DAPT as combination therapy with aspirin and a P2Y12 receptor inhibitor – that is, clopidogrel, prasugrel, or ticagrelor. “When indicated, ticagrelor and prasugrel have a Class IIa preference over clopidogrel,” Dr. Bates said. The recommended daily dose of aspirin is 81 mg (range, 75-100 mg), which is usually continued indefinitely, regardless of how long patients receive dual therapy.

The shortened durations of dual-antiplatelet therapy include several scenarios. For elective percutaneous coronary intervention, the former Class I recommendation for 12 months of DAPT has been reduced to 6 months, with a Class IIb recommendation for either longer treatment or shorter (3-month) treatment, Dr. Bates, professor of medicine at the University of Michigan Health System in Ann Arbor, said. For patients with acute coronary syndrome, the guidelines retain the Class I recommendation for 12 months of DAPT, but also add a Class IIb recommendation for longer or shorter (6 months) DAPT.

The guidelines also include a new Class IIb recommendation for 12 months of DAPT started early after coronary artery bypass graft in patients with stable ischemic heart disease. This strategy “may be reasonable to improve vein graft patency” in these patients, the recommendations state.

The guidance clarifies previous recommendations on the timing of elective noncardiac surgery, and assigns Class IIb support for consideration of such surgeries starting 3 months after implantation of drug-eluting stents, if the risks of delaying surgery outweigh the expected risk of stent thrombosis when it is necessary to stop P2Y12 inhibitor therapy.

©Svisio/Thinkstock

The recommendations now distinguish between B and C levels of evidence to increase granularity, according to Dr. Bates. The document updates recommendations on duration of DAPT across six previously published guidelines – the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention (PCI); the 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery; the 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease; the 2013ACC/AHA Guideline for the Management of ST-Elevation Myocardial Infarction; the 2014 ACC/AHA Guideline for Non-ST-Elevation Acute Coronary Syndromes, and the 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery.

The extensive evidence review that informed guideline development was simultaneously reported by Dr. John Bittl at Munroe Regional Medical Center in Ocala, Fla., and his colleagues. The investigators synthesized evidence from 11 randomized controlled trials of more than 33,000 patients who received mainly newer generation stents. They also reviewed a randomized controlled trial of more than 21,000 patients with stable ischemic heart disease who were more than 1 year post-MI, and a post hoc analysis of a trial of more than 15,000 such patients.

These reviews uncovered “moderately strong evidence” that prolonged DAPT after implantation of newer generation drug-eluting stents “entails a trade-off between reductions in stent thrombosis and MI and increases in major hemorrhage,” Dr. Bittl and his colleagues wrote. Likewise, they found moderately strong evidence that prolonged DAPT helps prevent cardiovascular events at the cost of increased bleeding in patients whose coronary thrombotic risk stemmed from prior MI, not stent implantation. They found weak evidence of increased mortality in stent patients who received prolonged DAPT.

Dr. Bates reported consulting relationships with Merck and AstraZeneca. Eight other coauthors disclosed financial relationships with a number of pharmaceutical or device companies. Dr. Glenn Levine and seven coauthors disclosed no relationships with industry.

Stress seems to be a strong driver of cardiovascular events, including heart attack, stroke, and even death.

For the first time, brain imaging has confirmed a link that has long been suspected: Activation of one of the brain’s prime emotional centers, the amygdala, directly correlates with the risk of cardiovascular events.

“This study illustrates a clear relationship between the activity of the amygdala and heart disease,” Dr. Ahmed A. Tawakol said at a press teleconference leading up to the annual meeting of the American College of Cardiology.

“Stress is known to be associated with an increase in the risk of cardiovascular events, and the risk is on par with that exerted by smoking, hypertension, and diabetes, but we don’t address it,” said Dr. Tawakol, codirector of the Cardiac MRI PET CT Program at Massachusetts General Hospital, Boston.

The findings also highlight a possible pathway for this relationship, suggesting that stress-related noradrenalin stimulates extramedullary hematopoiesis, a key driver of inflammation. This can contribute to atherosclerotic inflammation, which increases the likelihood of a heart attack or stroke, said Dr. Tawakol.

His study comprised 293 subjects who had undergone a PET or CT scan for cancer evaluation, but were determined to be cancer free. All scans contained brain and bone imaging data. Dr. Tawakol assessed amygdala and bone marrow activation, and evaluated inflammatory response in arteries.

These findings were then correlated with any cardiovascular events occurring in the next 5 years; the median follow-up was 3.8 years. Events were significantly more common among those with high levels of amygdala activation, occurring in 35% of this group, but in just 5% of those with low activation.

After adjusting for risk factors in the Framingham model, Dr. Tawakol found that high amygdala activation conferred a 14-fold increase in the risk of a cardiovascular event. These were likely to be precipitous as well, he said: The higher the level of activation, the more likely the event was to happen within the first year of follow-up.

He had no financial disclosures.

msullivan@frontlinemedcom.com

Stress seems to be a strong driver of cardiovascular events, including heart attack, stroke, and even death.

For the first time, brain imaging has confirmed a link that has long been suspected: Activation of one of the brain’s prime emotional centers, the amygdala, directly correlates with the risk of cardiovascular events.

“This study illustrates a clear relationship between the activity of the amygdala and heart disease,” Dr. Ahmed A. Tawakol said at a press teleconference leading up to the annual meeting of the American College of Cardiology.

“Stress is known to be associated with an increase in the risk of cardiovascular events, and the risk is on par with that exerted by smoking, hypertension, and diabetes, but we don’t address it,” said Dr. Tawakol, codirector of the Cardiac MRI PET CT Program at Massachusetts General Hospital, Boston.

The findings also highlight a possible pathway for this relationship, suggesting that stress-related noradrenalin stimulates extramedullary hematopoiesis, a key driver of inflammation. This can contribute to atherosclerotic inflammation, which increases the likelihood of a heart attack or stroke, said Dr. Tawakol.

His study comprised 293 subjects who had undergone a PET or CT scan for cancer evaluation, but were determined to be cancer free. All scans contained brain and bone imaging data. Dr. Tawakol assessed amygdala and bone marrow activation, and evaluated inflammatory response in arteries.

These findings were then correlated with any cardiovascular events occurring in the next 5 years; the median follow-up was 3.8 years. Events were significantly more common among those with high levels of amygdala activation, occurring in 35% of this group, but in just 5% of those with low activation.

After adjusting for risk factors in the Framingham model, Dr. Tawakol found that high amygdala activation conferred a 14-fold increase in the risk of a cardiovascular event. These were likely to be precipitous as well, he said: The higher the level of activation, the more likely the event was to happen within the first year of follow-up.

He had no financial disclosures.

msullivan@frontlinemedcom.com

Stress seems to be a strong driver of cardiovascular events, including heart attack, stroke, and even death.

For the first time, brain imaging has confirmed a link that has long been suspected: Activation of one of the brain’s prime emotional centers, the amygdala, directly correlates with the risk of cardiovascular events.

“This study illustrates a clear relationship between the activity of the amygdala and heart disease,” Dr. Ahmed A. Tawakol said at a press teleconference leading up to the annual meeting of the American College of Cardiology.

“Stress is known to be associated with an increase in the risk of cardiovascular events, and the risk is on par with that exerted by smoking, hypertension, and diabetes, but we don’t address it,” said Dr. Tawakol, codirector of the Cardiac MRI PET CT Program at Massachusetts General Hospital, Boston.

The findings also highlight a possible pathway for this relationship, suggesting that stress-related noradrenalin stimulates extramedullary hematopoiesis, a key driver of inflammation. This can contribute to atherosclerotic inflammation, which increases the likelihood of a heart attack or stroke, said Dr. Tawakol.

His study comprised 293 subjects who had undergone a PET or CT scan for cancer evaluation, but were determined to be cancer free. All scans contained brain and bone imaging data. Dr. Tawakol assessed amygdala and bone marrow activation, and evaluated inflammatory response in arteries.

These findings were then correlated with any cardiovascular events occurring in the next 5 years; the median follow-up was 3.8 years. Events were significantly more common among those with high levels of amygdala activation, occurring in 35% of this group, but in just 5% of those with low activation.

After adjusting for risk factors in the Framingham model, Dr. Tawakol found that high amygdala activation conferred a 14-fold increase in the risk of a cardiovascular event. These were likely to be precipitous as well, he said: The higher the level of activation, the more likely the event was to happen within the first year of follow-up.

He had no financial disclosures.

msullivan@frontlinemedcom.com

LOS ANGELES – It only took a few minutes for idarucizumab to normalize blood-clotting parameters in 18 patients with dabigatran-associated intracranial hemorrhages, according to interim results from an ongoing phase III trial presented at the International Stroke Conference.

“When I put patients on [dabigatran], they always ask me what happens if they bleed or need surgery. … Until now, I haven’t been able to tell them with any confidence that I have a way of reversing it. Now I think I can. ... It makes a big difference” in their comfort, said lead investigator Dr. Richard Bernstein, a Northwestern University neurology professor and director of the stroke program at Northwestern Memorial Hospital, in Chicago.

“We would love to know if hematoma expansion was limited [and outcomes improved] by giving this reversal agent,” but the study so far is too small. “We hope to have a larger cohort of brain hemorrhage patients to answer these questions,” he said.

Approved in October 2015, idarucizumab (Praxbind) was fast tracked by the Food and Drug Administration to reverse the blockbuster atrial fibrillation anticoagulant dabigatran (Pradaxa); the labeling for idarucizumab doesn’t mention intracranial hemorrhage patients specifically. Boehringer Ingelheim makes both drugs, and funded Dr. Bernstein’s work.

Eleven of the 18 patients were men, and the average age in the study was about 80 years. The patients had either subdural hematomas or bleeding into the brain itself. They were culled from the 90 subjects analyzed so far in the idarucizumab trial, dubbed RE-VERSE AD (Reversal Effects of Idarucizumab in Patients on Active Dabigatran).

The team followed label dosing: 5 g total given as two separate 2.5-g infusions. Blood samples were taken in between to check how well idarucizumab worked. The whole process took no more than 15 minutes.

The first 2.5 g completely reversed dabigatran in all 18 patients, based on their dilute thrombin or ecarin clotting times. Patients “remained reversed out to 12 hours, and all but one out to 24 hours,” Dr. Bernstein said at the conference, sponsored by the American Heart Association.

Idarucizumab is a monoclonal antibody fragment that binds dabigatran more powerfully than dabigatran binds thrombin. In vitro studies have found no prothrombotic effects. “It has no endogenous target, so the drug has no effect on any other clotting factors that we can tell. We did have, I think, five thrombotic events in our cohort, most of them many days after the dabigatran was reversed. It may have just been a reversion to [patient] clotting risks,” he said.

When – or if – to restart dabigatran “is a clinical question.” If bleeding is controlled or patients are stable after surgery, you can go back on the next day,” he said.

Idarucizumab’s labeling notes that 5% or more of patients developed hypokalemia, delirium, constipation, pyrexia, and pneumonia. It wasn’t clear these events were drug related. Patients had dabigatran reversed either for serious bleeding or emergency surgery.

Dr. Bernstein is a speaker and adviser for Boehringer Ingelheim, and reported honoraria from the company.

aotto@frontlinemedcom.com

LOS ANGELES – It only took a few minutes for idarucizumab to normalize blood-clotting parameters in 18 patients with dabigatran-associated intracranial hemorrhages, according to interim results from an ongoing phase III trial presented at the International Stroke Conference.

“When I put patients on [dabigatran], they always ask me what happens if they bleed or need surgery. … Until now, I haven’t been able to tell them with any confidence that I have a way of reversing it. Now I think I can. ... It makes a big difference” in their comfort, said lead investigator Dr. Richard Bernstein, a Northwestern University neurology professor and director of the stroke program at Northwestern Memorial Hospital, in Chicago.

“We would love to know if hematoma expansion was limited [and outcomes improved] by giving this reversal agent,” but the study so far is too small. “We hope to have a larger cohort of brain hemorrhage patients to answer these questions,” he said.

Approved in October 2015, idarucizumab (Praxbind) was fast tracked by the Food and Drug Administration to reverse the blockbuster atrial fibrillation anticoagulant dabigatran (Pradaxa); the labeling for idarucizumab doesn’t mention intracranial hemorrhage patients specifically. Boehringer Ingelheim makes both drugs, and funded Dr. Bernstein’s work.

Eleven of the 18 patients were men, and the average age in the study was about 80 years. The patients had either subdural hematomas or bleeding into the brain itself. They were culled from the 90 subjects analyzed so far in the idarucizumab trial, dubbed RE-VERSE AD (Reversal Effects of Idarucizumab in Patients on Active Dabigatran).

The team followed label dosing: 5 g total given as two separate 2.5-g infusions. Blood samples were taken in between to check how well idarucizumab worked. The whole process took no more than 15 minutes.

The first 2.5 g completely reversed dabigatran in all 18 patients, based on their dilute thrombin or ecarin clotting times. Patients “remained reversed out to 12 hours, and all but one out to 24 hours,” Dr. Bernstein said at the conference, sponsored by the American Heart Association.

Idarucizumab is a monoclonal antibody fragment that binds dabigatran more powerfully than dabigatran binds thrombin. In vitro studies have found no prothrombotic effects. “It has no endogenous target, so the drug has no effect on any other clotting factors that we can tell. We did have, I think, five thrombotic events in our cohort, most of them many days after the dabigatran was reversed. It may have just been a reversion to [patient] clotting risks,” he said.

When – or if – to restart dabigatran “is a clinical question.” If bleeding is controlled or patients are stable after surgery, you can go back on the next day,” he said.

Idarucizumab’s labeling notes that 5% or more of patients developed hypokalemia, delirium, constipation, pyrexia, and pneumonia. It wasn’t clear these events were drug related. Patients had dabigatran reversed either for serious bleeding or emergency surgery.

Dr. Bernstein is a speaker and adviser for Boehringer Ingelheim, and reported honoraria from the company.

aotto@frontlinemedcom.com

LOS ANGELES – It only took a few minutes for idarucizumab to normalize blood-clotting parameters in 18 patients with dabigatran-associated intracranial hemorrhages, according to interim results from an ongoing phase III trial presented at the International Stroke Conference.

“When I put patients on [dabigatran], they always ask me what happens if they bleed or need surgery. … Until now, I haven’t been able to tell them with any confidence that I have a way of reversing it. Now I think I can. ... It makes a big difference” in their comfort, said lead investigator Dr. Richard Bernstein, a Northwestern University neurology professor and director of the stroke program at Northwestern Memorial Hospital, in Chicago.

“We would love to know if hematoma expansion was limited [and outcomes improved] by giving this reversal agent,” but the study so far is too small. “We hope to have a larger cohort of brain hemorrhage patients to answer these questions,” he said.

Approved in October 2015, idarucizumab (Praxbind) was fast tracked by the Food and Drug Administration to reverse the blockbuster atrial fibrillation anticoagulant dabigatran (Pradaxa); the labeling for idarucizumab doesn’t mention intracranial hemorrhage patients specifically. Boehringer Ingelheim makes both drugs, and funded Dr. Bernstein’s work.

Eleven of the 18 patients were men, and the average age in the study was about 80 years. The patients had either subdural hematomas or bleeding into the brain itself. They were culled from the 90 subjects analyzed so far in the idarucizumab trial, dubbed RE-VERSE AD (Reversal Effects of Idarucizumab in Patients on Active Dabigatran).

The team followed label dosing: 5 g total given as two separate 2.5-g infusions. Blood samples were taken in between to check how well idarucizumab worked. The whole process took no more than 15 minutes.

The first 2.5 g completely reversed dabigatran in all 18 patients, based on their dilute thrombin or ecarin clotting times. Patients “remained reversed out to 12 hours, and all but one out to 24 hours,” Dr. Bernstein said at the conference, sponsored by the American Heart Association.

Idarucizumab is a monoclonal antibody fragment that binds dabigatran more powerfully than dabigatran binds thrombin. In vitro studies have found no prothrombotic effects. “It has no endogenous target, so the drug has no effect on any other clotting factors that we can tell. We did have, I think, five thrombotic events in our cohort, most of them many days after the dabigatran was reversed. It may have just been a reversion to [patient] clotting risks,” he said.

When – or if – to restart dabigatran “is a clinical question.” If bleeding is controlled or patients are stable after surgery, you can go back on the next day,” he said.

Idarucizumab’s labeling notes that 5% or more of patients developed hypokalemia, delirium, constipation, pyrexia, and pneumonia. It wasn’t clear these events were drug related. Patients had dabigatran reversed either for serious bleeding or emergency surgery.

Dr. Bernstein is a speaker and adviser for Boehringer Ingelheim, and reported honoraria from the company.

aotto@frontlinemedcom.com

Pediatric patients with systemic lupus erythematosus may have greater odds for developing thrombosis if they have a history of vasculitis, antiphospholipid antibody positivity (aPL), and/or avascular necrosis (AVN), according to Dr. Kyla Driest and her associates.

Among 974 pediatric systemic lupus erythematosus (pSLE) patients in the CARRA (Childhood Arthritis & Rheumatology Research Alliance) registry cohort who had available data on thrombosis history, 24 (2.5%) had a history of arterial thrombosis and 35 (3.6%) had a history of venous thrombosis. The researchers conducted a multivariable analysis that found statistically higher odds of thrombosis (P less than .10) among patients with histories of AVN (odds ratio, 4.24; 95% confidence interval, 1.53-11.74), aPL (OR, 2.95; 95% CI, 1.38-6.28), and vasculitis (OR, 2.19; 95% CI, 1.03-4.77), whereas significantly lower odds occurred in patients with a history of renal disease (OR, 0.47; 95% CI, 0.24-0.92). Gender and body-mass index were not statistically significant.

“This study adds to our understanding of which pSLE patients are at the most risk for thrombosis,” the researchers concluded. “These results may prompt discussion concerning potential measures to prevent thrombosis in high-risk patients.”

Find the full study in Lupus (doi: 10.1177/0961203316638164).

llaubach@frontlinemedcom.com

Pediatric patients with systemic lupus erythematosus may have greater odds for developing thrombosis if they have a history of vasculitis, antiphospholipid antibody positivity (aPL), and/or avascular necrosis (AVN), according to Dr. Kyla Driest and her associates.

Among 974 pediatric systemic lupus erythematosus (pSLE) patients in the CARRA (Childhood Arthritis & Rheumatology Research Alliance) registry cohort who had available data on thrombosis history, 24 (2.5%) had a history of arterial thrombosis and 35 (3.6%) had a history of venous thrombosis. The researchers conducted a multivariable analysis that found statistically higher odds of thrombosis (P less than .10) among patients with histories of AVN (odds ratio, 4.24; 95% confidence interval, 1.53-11.74), aPL (OR, 2.95; 95% CI, 1.38-6.28), and vasculitis (OR, 2.19; 95% CI, 1.03-4.77), whereas significantly lower odds occurred in patients with a history of renal disease (OR, 0.47; 95% CI, 0.24-0.92). Gender and body-mass index were not statistically significant.

“This study adds to our understanding of which pSLE patients are at the most risk for thrombosis,” the researchers concluded. “These results may prompt discussion concerning potential measures to prevent thrombosis in high-risk patients.”

Find the full study in Lupus (doi: 10.1177/0961203316638164).

llaubach@frontlinemedcom.com

Pediatric patients with systemic lupus erythematosus may have greater odds for developing thrombosis if they have a history of vasculitis, antiphospholipid antibody positivity (aPL), and/or avascular necrosis (AVN), according to Dr. Kyla Driest and her associates.

Among 974 pediatric systemic lupus erythematosus (pSLE) patients in the CARRA (Childhood Arthritis & Rheumatology Research Alliance) registry cohort who had available data on thrombosis history, 24 (2.5%) had a history of arterial thrombosis and 35 (3.6%) had a history of venous thrombosis. The researchers conducted a multivariable analysis that found statistically higher odds of thrombosis (P less than .10) among patients with histories of AVN (odds ratio, 4.24; 95% confidence interval, 1.53-11.74), aPL (OR, 2.95; 95% CI, 1.38-6.28), and vasculitis (OR, 2.19; 95% CI, 1.03-4.77), whereas significantly lower odds occurred in patients with a history of renal disease (OR, 0.47; 95% CI, 0.24-0.92). Gender and body-mass index were not statistically significant.

“This study adds to our understanding of which pSLE patients are at the most risk for thrombosis,” the researchers concluded. “These results may prompt discussion concerning potential measures to prevent thrombosis in high-risk patients.”

Find the full study in Lupus (doi: 10.1177/0961203316638164).

llaubach@frontlinemedcom.com

MAUI, HAWAII – One of the major happenings in the field of osteoarthritis in the past year was a disturbing report of dramatically increased risk of acute MI for at least 6 months after total knee replacement, panelists agreed at the 2016 Rheumatology Winter Clinical Symposium.

“What they found borders on frightening,” according to Dr. Martin J. Bergman of Drexel University, Philadelphia, and chief of rheumatology at Taylor Hospital in Ridley Park, Pa.

Bruce Jancin/Frontline Medical News

Dr. Bergman and copanelist Dr. Orrin M. Troum of the University of Southern California in Los Angeles highlighted key developments in osteoarthritis during the past year, including two major studies on total knee replacement, the Food and Drug Administration’s updated stronger warning on the cardiac and stroke risks of NSAIDs, a randomized trial which effectively takes hydroxychloroquine (Plaquenil) off the treatment menu for hand osteoarthritis, and a reassuring report on the safety of repeated intra-articular corticosteroid injections in patients with synovitic knee osteoarthritis.

Acute MI risk after total knee replacement

British investigators utilizing the U.K. National Health Service database retrospectively identified 13,849 patients who underwent total knee replacement (TKR) and an equal number of nonsurgical controls propensity-matched for cardiovascular risk factors. These two very large groups were followed for 5 years.

During the first month after TKR, the acute MI risk was 8.75-fold greater than in the matched controls. The elevated risk gradually declined thereafter, but it remained significantly higher than in controls until 1 year after surgery. At 3 months post surgery the TKR group was at fourfold increased risk of MI, compared with controls, and at 6 months their risk was still nearly double that of controls (Arthritis Rheumatol. 2015 Oct;67[10]:2771-9).

The British investigators also found a prolonged postsurgical elevated risk of MI in a large group of patients who underwent total hip replacement, although the magnitude of the increased risk, compared with matched controls, wasn’t as large as that seen after TKR.

Dr. Troum commented that the increased risk of MI during the first year after TKR identified in this study is something physicians now need to bring up in the risk/benefit discussion with patients considering TKR.

“Also, this study underscores that it may behoove us to make sure that these presurgical patients are really well worked up by a cardiologist or their primary care physician to mitigate that coronary risk as much as possible,” he added.

Another key finding in the U.K. study was that unlike the acute MI risk, the risk of venous thromboembolism following TKR remained elevated throughout the full 5 years of follow-up.

“Once you’ve had that surgery, you are at increased risk for venous thromboembolism. I think that’s something we have to keep in mind when a patient comes in with a history of total knee replacement and a complaint of calf pain or swelling – at that point, you have to think about deep venous thrombosis,” Dr. Bergman said.

TKR – Why wait?

In a Danish trial of 100 knee osteoarthritis patients deemed eligible for TKR, participants were randomized to prompt TKR followed by a 3-month regimen of exercise, dietary weight loss, physical therapy, and pain medication or to the nonsurgical regimen alone. At 12 months of follow-up, the prompt TKR group showed significantly greater improvement in a standardized score encompassing pain, symptoms, quality of life, and activities of daily living, even though one-quarter of patients in the nonsurgical treatment group bailed and underwent TKR before 12 months was up (N Engl J Med. 2015 Oct 22;373[17]:1597-606).

“My conclusion is that once you’ve determined that a patient needs and wants a total knee replacement, the patient should probably get it. Delaying – trying other modalities in an effort to lose weight and improve function – is really not going to buy you much in the way of time,” Dr. Bergman observed.

Hydroxychloroquine for hand osteoarthritis

At the 2015 European League Against Rheumatism (EULAR) meeting in Rome, Dutch investigators presented a randomized, double-blind trial in which 196 patients with symptomatic hand osteoarthritis received 6 months of hydroxychloroquine at 400 mg/day or placebo. Unlike in mild rheumatoid arthritis or lupus, hydroxychloroquine had no beneficial effect on hand osteoarthritis pain, disability, or quality of life measures.

“Plaquenil [Hydroxychloroquine] is not a good choice for patients with osteoarthritis of the hand. I think it’s a dead therapy,” Dr. Troum declared.

FDA expands warning on NSAIDs’ cardiovascular risk

On July 9, 2015, the FDA announced updated labels for NSAIDs. The new warning states that MI and stroke risk can increase as early as in the first week of NSAID use and appear to be dose- and duration-related. The agency also warned that patients who take an NSAID after a first MI are more likely to die within 1 year.

“This really brought a lot of folks to my office,” Dr. Troum recalled.

“Absolutely, this was big stuff,” Dr. Bergman agreed. “This became a nightmare for many of us because all of a sudden patients were scared to death about taking their NSAIDs.”

Intra-articular corticosteroids for knee osteoarthritis don’t accelerate cartilage deterioration

At last fall’s American College of Rheumatology meeting in San Francisco, Jeffrey B. Driban, Ph.D., of Tufts Medical Center, Boston, presented a double-blind, randomized trial of intra-articular injections of triamcinolone hexacetonide 40 mg versus saline quarterly for 2 years in 140 patients with symptomatic knee osteoarthritis with ultrasound evidence of synovitis. Participants underwent annual evaluation of periarticular bone and cartilage changes via MRI and dual-energy x-ray absorptiometry.

After 2 years, there was no difference between the two groups in terms of pain scores, walk time, or other functional measures. The injections – eight in total over 2 years – were safe, with new-onset hypertension and hyperglycemia rates of 3% in this obese population. And most important of all, there were no major differences between the two groups in terms of quantitative or semiquantitative structural endpoints; in other words, the injections didn’t increase the rate of structural disease progression. The intra-articular steroid group showed a modestly greater rate of loss of cartilage thickness, which the investigators deemed of uncertain clinical significance.

“The structural changes were minimal,” Dr. Troum noted. “This is only a 2-year study, but I can say that I now feel more comfortable giving these injections in patients who for whatever reason can’t get surgery.”

Dr. Bergman said that many orthopedic surgeons talk up the potential risk that intra-articular steroid injections will accelerate cartilage damage. They place an arbitrary limit on the number of injections a patient can receive.

“I think this study really helps us push back and say, ‘No, I think you’re fine in getting this procedure,’” the rheumatologist commented.

Dr. Bergman and Dr. Troum reported having no financial conflicts regarding their presentation.

bjancin@frontlinemedcom.com

MAUI, HAWAII – One of the major happenings in the field of osteoarthritis in the past year was a disturbing report of dramatically increased risk of acute MI for at least 6 months after total knee replacement, panelists agreed at the 2016 Rheumatology Winter Clinical Symposium.

“What they found borders on frightening,” according to Dr. Martin J. Bergman of Drexel University, Philadelphia, and chief of rheumatology at Taylor Hospital in Ridley Park, Pa.

Bruce Jancin/Frontline Medical News

Dr. Bergman and copanelist Dr. Orrin M. Troum of the University of Southern California in Los Angeles highlighted key developments in osteoarthritis during the past year, including two major studies on total knee replacement, the Food and Drug Administration’s updated stronger warning on the cardiac and stroke risks of NSAIDs, a randomized trial which effectively takes hydroxychloroquine (Plaquenil) off the treatment menu for hand osteoarthritis, and a reassuring report on the safety of repeated intra-articular corticosteroid injections in patients with synovitic knee osteoarthritis.

Acute MI risk after total knee replacement

British investigators utilizing the U.K. National Health Service database retrospectively identified 13,849 patients who underwent total knee replacement (TKR) and an equal number of nonsurgical controls propensity-matched for cardiovascular risk factors. These two very large groups were followed for 5 years.

During the first month after TKR, the acute MI risk was 8.75-fold greater than in the matched controls. The elevated risk gradually declined thereafter, but it remained significantly higher than in controls until 1 year after surgery. At 3 months post surgery the TKR group was at fourfold increased risk of MI, compared with controls, and at 6 months their risk was still nearly double that of controls (Arthritis Rheumatol. 2015 Oct;67[10]:2771-9).

The British investigators also found a prolonged postsurgical elevated risk of MI in a large group of patients who underwent total hip replacement, although the magnitude of the increased risk, compared with matched controls, wasn’t as large as that seen after TKR.

Dr. Troum commented that the increased risk of MI during the first year after TKR identified in this study is something physicians now need to bring up in the risk/benefit discussion with patients considering TKR.

“Also, this study underscores that it may behoove us to make sure that these presurgical patients are really well worked up by a cardiologist or their primary care physician to mitigate that coronary risk as much as possible,” he added.

Another key finding in the U.K. study was that unlike the acute MI risk, the risk of venous thromboembolism following TKR remained elevated throughout the full 5 years of follow-up.

“Once you’ve had that surgery, you are at increased risk for venous thromboembolism. I think that’s something we have to keep in mind when a patient comes in with a history of total knee replacement and a complaint of calf pain or swelling – at that point, you have to think about deep venous thrombosis,” Dr. Bergman said.

TKR – Why wait?

In a Danish trial of 100 knee osteoarthritis patients deemed eligible for TKR, participants were randomized to prompt TKR followed by a 3-month regimen of exercise, dietary weight loss, physical therapy, and pain medication or to the nonsurgical regimen alone. At 12 months of follow-up, the prompt TKR group showed significantly greater improvement in a standardized score encompassing pain, symptoms, quality of life, and activities of daily living, even though one-quarter of patients in the nonsurgical treatment group bailed and underwent TKR before 12 months was up (N Engl J Med. 2015 Oct 22;373[17]:1597-606).

“My conclusion is that once you’ve determined that a patient needs and wants a total knee replacement, the patient should probably get it. Delaying – trying other modalities in an effort to lose weight and improve function – is really not going to buy you much in the way of time,” Dr. Bergman observed.

Hydroxychloroquine for hand osteoarthritis

At the 2015 European League Against Rheumatism (EULAR) meeting in Rome, Dutch investigators presented a randomized, double-blind trial in which 196 patients with symptomatic hand osteoarthritis received 6 months of hydroxychloroquine at 400 mg/day or placebo. Unlike in mild rheumatoid arthritis or lupus, hydroxychloroquine had no beneficial effect on hand osteoarthritis pain, disability, or quality of life measures.

“Plaquenil [Hydroxychloroquine] is not a good choice for patients with osteoarthritis of the hand. I think it’s a dead therapy,” Dr. Troum declared.

FDA expands warning on NSAIDs’ cardiovascular risk

On July 9, 2015, the FDA announced updated labels for NSAIDs. The new warning states that MI and stroke risk can increase as early as in the first week of NSAID use and appear to be dose- and duration-related. The agency also warned that patients who take an NSAID after a first MI are more likely to die within 1 year.

“This really brought a lot of folks to my office,” Dr. Troum recalled.

“Absolutely, this was big stuff,” Dr. Bergman agreed. “This became a nightmare for many of us because all of a sudden patients were scared to death about taking their NSAIDs.”

Intra-articular corticosteroids for knee osteoarthritis don’t accelerate cartilage deterioration

At last fall’s American College of Rheumatology meeting in San Francisco, Jeffrey B. Driban, Ph.D., of Tufts Medical Center, Boston, presented a double-blind, randomized trial of intra-articular injections of triamcinolone hexacetonide 40 mg versus saline quarterly for 2 years in 140 patients with symptomatic knee osteoarthritis with ultrasound evidence of synovitis. Participants underwent annual evaluation of periarticular bone and cartilage changes via MRI and dual-energy x-ray absorptiometry.

After 2 years, there was no difference between the two groups in terms of pain scores, walk time, or other functional measures. The injections – eight in total over 2 years – were safe, with new-onset hypertension and hyperglycemia rates of 3% in this obese population. And most important of all, there were no major differences between the two groups in terms of quantitative or semiquantitative structural endpoints; in other words, the injections didn’t increase the rate of structural disease progression. The intra-articular steroid group showed a modestly greater rate of loss of cartilage thickness, which the investigators deemed of uncertain clinical significance.

“The structural changes were minimal,” Dr. Troum noted. “This is only a 2-year study, but I can say that I now feel more comfortable giving these injections in patients who for whatever reason can’t get surgery.”

Dr. Bergman said that many orthopedic surgeons talk up the potential risk that intra-articular steroid injections will accelerate cartilage damage. They place an arbitrary limit on the number of injections a patient can receive.

“I think this study really helps us push back and say, ‘No, I think you’re fine in getting this procedure,’” the rheumatologist commented.

Dr. Bergman and Dr. Troum reported having no financial conflicts regarding their presentation.

bjancin@frontlinemedcom.com

MAUI, HAWAII – One of the major happenings in the field of osteoarthritis in the past year was a disturbing report of dramatically increased risk of acute MI for at least 6 months after total knee replacement, panelists agreed at the 2016 Rheumatology Winter Clinical Symposium.

“What they found borders on frightening,” according to Dr. Martin J. Bergman of Drexel University, Philadelphia, and chief of rheumatology at Taylor Hospital in Ridley Park, Pa.

Bruce Jancin/Frontline Medical News

Dr. Bergman and copanelist Dr. Orrin M. Troum of the University of Southern California in Los Angeles highlighted key developments in osteoarthritis during the past year, including two major studies on total knee replacement, the Food and Drug Administration’s updated stronger warning on the cardiac and stroke risks of NSAIDs, a randomized trial which effectively takes hydroxychloroquine (Plaquenil) off the treatment menu for hand osteoarthritis, and a reassuring report on the safety of repeated intra-articular corticosteroid injections in patients with synovitic knee osteoarthritis.

Acute MI risk after total knee replacement

British investigators utilizing the U.K. National Health Service database retrospectively identified 13,849 patients who underwent total knee replacement (TKR) and an equal number of nonsurgical controls propensity-matched for cardiovascular risk factors. These two very large groups were followed for 5 years.

During the first month after TKR, the acute MI risk was 8.75-fold greater than in the matched controls. The elevated risk gradually declined thereafter, but it remained significantly higher than in controls until 1 year after surgery. At 3 months post surgery the TKR group was at fourfold increased risk of MI, compared with controls, and at 6 months their risk was still nearly double that of controls (Arthritis Rheumatol. 2015 Oct;67[10]:2771-9).

The British investigators also found a prolonged postsurgical elevated risk of MI in a large group of patients who underwent total hip replacement, although the magnitude of the increased risk, compared with matched controls, wasn’t as large as that seen after TKR.

Dr. Troum commented that the increased risk of MI during the first year after TKR identified in this study is something physicians now need to bring up in the risk/benefit discussion with patients considering TKR.

“Also, this study underscores that it may behoove us to make sure that these presurgical patients are really well worked up by a cardiologist or their primary care physician to mitigate that coronary risk as much as possible,” he added.

Another key finding in the U.K. study was that unlike the acute MI risk, the risk of venous thromboembolism following TKR remained elevated throughout the full 5 years of follow-up.

“Once you’ve had that surgery, you are at increased risk for venous thromboembolism. I think that’s something we have to keep in mind when a patient comes in with a history of total knee replacement and a complaint of calf pain or swelling – at that point, you have to think about deep venous thrombosis,” Dr. Bergman said.

TKR – Why wait?

In a Danish trial of 100 knee osteoarthritis patients deemed eligible for TKR, participants were randomized to prompt TKR followed by a 3-month regimen of exercise, dietary weight loss, physical therapy, and pain medication or to the nonsurgical regimen alone. At 12 months of follow-up, the prompt TKR group showed significantly greater improvement in a standardized score encompassing pain, symptoms, quality of life, and activities of daily living, even though one-quarter of patients in the nonsurgical treatment group bailed and underwent TKR before 12 months was up (N Engl J Med. 2015 Oct 22;373[17]:1597-606).

“My conclusion is that once you’ve determined that a patient needs and wants a total knee replacement, the patient should probably get it. Delaying – trying other modalities in an effort to lose weight and improve function – is really not going to buy you much in the way of time,” Dr. Bergman observed.

Hydroxychloroquine for hand osteoarthritis

At the 2015 European League Against Rheumatism (EULAR) meeting in Rome, Dutch investigators presented a randomized, double-blind trial in which 196 patients with symptomatic hand osteoarthritis received 6 months of hydroxychloroquine at 400 mg/day or placebo. Unlike in mild rheumatoid arthritis or lupus, hydroxychloroquine had no beneficial effect on hand osteoarthritis pain, disability, or quality of life measures.

“Plaquenil [Hydroxychloroquine] is not a good choice for patients with osteoarthritis of the hand. I think it’s a dead therapy,” Dr. Troum declared.

FDA expands warning on NSAIDs’ cardiovascular risk

On July 9, 2015, the FDA announced updated labels for NSAIDs. The new warning states that MI and stroke risk can increase as early as in the first week of NSAID use and appear to be dose- and duration-related. The agency also warned that patients who take an NSAID after a first MI are more likely to die within 1 year.

“This really brought a lot of folks to my office,” Dr. Troum recalled.

“Absolutely, this was big stuff,” Dr. Bergman agreed. “This became a nightmare for many of us because all of a sudden patients were scared to death about taking their NSAIDs.”

Intra-articular corticosteroids for knee osteoarthritis don’t accelerate cartilage deterioration

At last fall’s American College of Rheumatology meeting in San Francisco, Jeffrey B. Driban, Ph.D., of Tufts Medical Center, Boston, presented a double-blind, randomized trial of intra-articular injections of triamcinolone hexacetonide 40 mg versus saline quarterly for 2 years in 140 patients with symptomatic knee osteoarthritis with ultrasound evidence of synovitis. Participants underwent annual evaluation of periarticular bone and cartilage changes via MRI and dual-energy x-ray absorptiometry.

After 2 years, there was no difference between the two groups in terms of pain scores, walk time, or other functional measures. The injections – eight in total over 2 years – were safe, with new-onset hypertension and hyperglycemia rates of 3% in this obese population. And most important of all, there were no major differences between the two groups in terms of quantitative or semiquantitative structural endpoints; in other words, the injections didn’t increase the rate of structural disease progression. The intra-articular steroid group showed a modestly greater rate of loss of cartilage thickness, which the investigators deemed of uncertain clinical significance.

“The structural changes were minimal,” Dr. Troum noted. “This is only a 2-year study, but I can say that I now feel more comfortable giving these injections in patients who for whatever reason can’t get surgery.”

Dr. Bergman said that many orthopedic surgeons talk up the potential risk that intra-articular steroid injections will accelerate cartilage damage. They place an arbitrary limit on the number of injections a patient can receive.

“I think this study really helps us push back and say, ‘No, I think you’re fine in getting this procedure,’” the rheumatologist commented.

Dr. Bergman and Dr. Troum reported having no financial conflicts regarding their presentation.

bjancin@frontlinemedcom.com

Obese women taking oral contraceptives had a 30-fold increased odds for cerebral venous thrombosis (CVT), compared with normal-weight women, in an unmatched case-control study of 186 CVT cases and 6,134 controls.

The association between a body-mass index of 30 kg/m² or higher and increased odds of CVT “appears to be fully attributable to a strongly increased risk in women who use oral contraceptives [OCs],” said Dr. Susanna M. Zuurbier of the Academic Medical Centre in Amsterdam, and her colleagues.

©Tina Sbrigato/iStockphoto.com

“Although the relative risks are increased substantially, the absolute risks of CVT are still small,” the researchers said. “Moreover, withholding oral contraceptives may lead to an increase in unintended pregnancies and thus the number of pregnancy-related thrombosis cases.”

After controlling for multiple variables, CVT was 2.63 times more likely to occur in obese individuals, compared with those of normal weight. When the findings were stratified by sex, a BMI greater than 30 kg/m² had no significant impact on CVT in men, but the odds rose 3.5-fold in women, the investigators reported online March 14 in JAMA Neurology (JAMA Neurol. 2016 Mar 14. doi: 10.1001/jamaneurol.2016.000100).

On further analysis, overweight and obesity had a dose-dependent impact on the odds of CVT among women who used OCs. Adjusted odds ratios were 11.87 for those with BMIs ranging from 25 kg/m² to 29 kg/m², and 29.26 for those with BMIs of 30 kg/m² or higher when compared against normal-weight women who did not use OCs. No association was found between obesity and CVT risk in women who did not use OCs, the researchers noted.

Patients with CVT were recruited in 2006-2014 from two medical centers, one in the Netherlands and the other in Switzerland. The controls were part of the Dutch Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis (MEGA) study. Overall, patients with CVT were more likely to be younger than controls (median age 40 years vs. 48 years). They also were more likely than controls to be female (72% vs. 53%), users of oral contraceptives (73% vs. 24%) and have a history of cancer (9% vs. 4%).

The study was limited by several factors, including the small number of CVT cases, the lack of complete BMI data for the study population, and time difference in recruitment of cases and controls, the researchers noted, but they advised clinicians to keep the risk in mind when counseling obese women about OC use.

“Alternative methods of contraception that are not associated with thrombosis, such as an intrauterine device, might be offered to these women,” they wrote.

The study was funded by grants from the Netherlands Organisation for Scientific Research, the Dutch Thrombosis Society, the Remmert Adriaan Laan Foundation, and the Swiss Heart Foundation. Study coauthor Dr. Marcel Arnold disclosed receiving honoraria for giving lectures and serving on advisory boards for Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, and Covidien.

Obese women taking oral contraceptives had a 30-fold increased odds for cerebral venous thrombosis (CVT), compared with normal-weight women, in an unmatched case-control study of 186 CVT cases and 6,134 controls.

The association between a body-mass index of 30 kg/m² or higher and increased odds of CVT “appears to be fully attributable to a strongly increased risk in women who use oral contraceptives [OCs],” said Dr. Susanna M. Zuurbier of the Academic Medical Centre in Amsterdam, and her colleagues.

©Tina Sbrigato/iStockphoto.com

“Although the relative risks are increased substantially, the absolute risks of CVT are still small,” the researchers said. “Moreover, withholding oral contraceptives may lead to an increase in unintended pregnancies and thus the number of pregnancy-related thrombosis cases.”

After controlling for multiple variables, CVT was 2.63 times more likely to occur in obese individuals, compared with those of normal weight. When the findings were stratified by sex, a BMI greater than 30 kg/m² had no significant impact on CVT in men, but the odds rose 3.5-fold in women, the investigators reported online March 14 in JAMA Neurology (JAMA Neurol. 2016 Mar 14. doi: 10.1001/jamaneurol.2016.000100).

On further analysis, overweight and obesity had a dose-dependent impact on the odds of CVT among women who used OCs. Adjusted odds ratios were 11.87 for those with BMIs ranging from 25 kg/m² to 29 kg/m², and 29.26 for those with BMIs of 30 kg/m² or higher when compared against normal-weight women who did not use OCs. No association was found between obesity and CVT risk in women who did not use OCs, the researchers noted.

Patients with CVT were recruited in 2006-2014 from two medical centers, one in the Netherlands and the other in Switzerland. The controls were part of the Dutch Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis (MEGA) study. Overall, patients with CVT were more likely to be younger than controls (median age 40 years vs. 48 years). They also were more likely than controls to be female (72% vs. 53%), users of oral contraceptives (73% vs. 24%) and have a history of cancer (9% vs. 4%).

The study was limited by several factors, including the small number of CVT cases, the lack of complete BMI data for the study population, and time difference in recruitment of cases and controls, the researchers noted, but they advised clinicians to keep the risk in mind when counseling obese women about OC use.

“Alternative methods of contraception that are not associated with thrombosis, such as an intrauterine device, might be offered to these women,” they wrote.

The study was funded by grants from the Netherlands Organisation for Scientific Research, the Dutch Thrombosis Society, the Remmert Adriaan Laan Foundation, and the Swiss Heart Foundation. Study coauthor Dr. Marcel Arnold disclosed receiving honoraria for giving lectures and serving on advisory boards for Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, and Covidien.

Obese women taking oral contraceptives had a 30-fold increased odds for cerebral venous thrombosis (CVT), compared with normal-weight women, in an unmatched case-control study of 186 CVT cases and 6,134 controls.

The association between a body-mass index of 30 kg/m² or higher and increased odds of CVT “appears to be fully attributable to a strongly increased risk in women who use oral contraceptives [OCs],” said Dr. Susanna M. Zuurbier of the Academic Medical Centre in Amsterdam, and her colleagues.

©Tina Sbrigato/iStockphoto.com

“Although the relative risks are increased substantially, the absolute risks of CVT are still small,” the researchers said. “Moreover, withholding oral contraceptives may lead to an increase in unintended pregnancies and thus the number of pregnancy-related thrombosis cases.”

After controlling for multiple variables, CVT was 2.63 times more likely to occur in obese individuals, compared with those of normal weight. When the findings were stratified by sex, a BMI greater than 30 kg/m² had no significant impact on CVT in men, but the odds rose 3.5-fold in women, the investigators reported online March 14 in JAMA Neurology (JAMA Neurol. 2016 Mar 14. doi: 10.1001/jamaneurol.2016.000100).

On further analysis, overweight and obesity had a dose-dependent impact on the odds of CVT among women who used OCs. Adjusted odds ratios were 11.87 for those with BMIs ranging from 25 kg/m² to 29 kg/m², and 29.26 for those with BMIs of 30 kg/m² or higher when compared against normal-weight women who did not use OCs. No association was found between obesity and CVT risk in women who did not use OCs, the researchers noted.

Patients with CVT were recruited in 2006-2014 from two medical centers, one in the Netherlands and the other in Switzerland. The controls were part of the Dutch Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis (MEGA) study. Overall, patients with CVT were more likely to be younger than controls (median age 40 years vs. 48 years). They also were more likely than controls to be female (72% vs. 53%), users of oral contraceptives (73% vs. 24%) and have a history of cancer (9% vs. 4%).

The study was limited by several factors, including the small number of CVT cases, the lack of complete BMI data for the study population, and time difference in recruitment of cases and controls, the researchers noted, but they advised clinicians to keep the risk in mind when counseling obese women about OC use.

“Alternative methods of contraception that are not associated with thrombosis, such as an intrauterine device, might be offered to these women,” they wrote.

The study was funded by grants from the Netherlands Organisation for Scientific Research, the Dutch Thrombosis Society, the Remmert Adriaan Laan Foundation, and the Swiss Heart Foundation. Study coauthor Dr. Marcel Arnold disclosed receiving honoraria for giving lectures and serving on advisory boards for Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, and Covidien.

LOS ANGELES – Medtronic’s Reveal LINQ implantable loop recorders misidentified 84% of rhythm anomalies as atrial fibrillation in 52 stroke patients at Emory University in Atlanta, according to a presentation at the International Stroke Conference.

Two electrophysiologists reviewed a random sample of 166 rhythm strips from those patients that were identified by Reveal as atrial fibrillation (AF) over a 2-month period; 140 (84%) were false positives. Eighty (57%) of the false positives were premature atrial complexes, 31 (22%) were due to T wave over-sensing, 14 (10%) to noise, 7 (5%) to premature ventricular complexes, 4 (2.9%) to under-sensing, and 4 (2.9%) to sinus arrhythmias.

There wasn’t a mix-and-match of true and false positives in the same patient; false and true positives were consistent in patients over the study period.

The take-home message from the study is that the high sensitivity of Medtronic’s implantable loop recorders means that they are good at detecting possible AF, but their findings must be reviewed and confirmed before being acted upon.

“There are high rates of false positives, but the results can be easily adjudicated by electrophysiologists as evidenced by our observer agreement,” which was 100%. “These strips need to be adjudicated by somebody, and not taken at face value,” said investigator Dr. Spencer Maddox, an Emory resident.

The devices look mainly at RR intervals and the presence or absence of P waves. Runs of 2 minutes are required for AF. One of the issues in the study was that T waves were identified as QRS complexes, which changed the RR interval and trigged the device to report AF, he said.

Medtronic could reduce the false positive rate by, for instance, extending the run required for AF, but it would be a bad idea. “The goal here is to not miss atrial fibrillation,” Dr. Maddox said. “There are false positives, but as long as you go back and reread, I think that’s fine. I wouldn’t mess with the sensitivity of the device.”

The company said the same thing when asked for comment on the study.

“The AF detection algorithm ... is tuned to favor sensitivity because manual review can subsequently rule out any false positives. This is one reason it is important to have trained cardiologists or electrophysiologists involved in reviewing reports of irregular heart rhythms to determine a diagnosis of AF,” said Medtronic spokesman Ryan Mathre, who also noted that company data suggest a lower false positive rate (Cerebrovasc Dis. 2015;40:175-81).

Even so, confirmation doesn’t always happen, “and that’s the scary part. In practice almost all the time,” the report comes in “and it’s acted on,” said Dr. Robert Hart, a neurology professor at McMaster University in Hamilton, Ont., and comoderator of the study presentation.

The Emory patients were all recovering from ischemic strokes or TIAs. They were about 70 years old on average, about 60% were men, and almost all were white. A total of 38 had implantable loop recorders for cryptogenic strokes; the devices detected true AF in 4 (11%) after a mean of 92 days. Early Holter monitoring missed it.

Emory generally prescribes anticoagulants if AF is confirmed, but, as several audience members noted, the burden of AF that requires anticoagulation is unclear. “It’s an area with a lot of thought now, but no good answers,” Dr. Maddox said at the conference, sponsored by the American Heart Association.

The investigators had no disclosures, and there was no outside funding for the work.

aotto@frontlinemedcom.com

LOS ANGELES – Medtronic’s Reveal LINQ implantable loop recorders misidentified 84% of rhythm anomalies as atrial fibrillation in 52 stroke patients at Emory University in Atlanta, according to a presentation at the International Stroke Conference.

Two electrophysiologists reviewed a random sample of 166 rhythm strips from those patients that were identified by Reveal as atrial fibrillation (AF) over a 2-month period; 140 (84%) were false positives. Eighty (57%) of the false positives were premature atrial complexes, 31 (22%) were due to T wave over-sensing, 14 (10%) to noise, 7 (5%) to premature ventricular complexes, 4 (2.9%) to under-sensing, and 4 (2.9%) to sinus arrhythmias.

There wasn’t a mix-and-match of true and false positives in the same patient; false and true positives were consistent in patients over the study period.

The take-home message from the study is that the high sensitivity of Medtronic’s implantable loop recorders means that they are good at detecting possible AF, but their findings must be reviewed and confirmed before being acted upon.

“There are high rates of false positives, but the results can be easily adjudicated by electrophysiologists as evidenced by our observer agreement,” which was 100%. “These strips need to be adjudicated by somebody, and not taken at face value,” said investigator Dr. Spencer Maddox, an Emory resident.

The devices look mainly at RR intervals and the presence or absence of P waves. Runs of 2 minutes are required for AF. One of the issues in the study was that T waves were identified as QRS complexes, which changed the RR interval and trigged the device to report AF, he said.

Medtronic could reduce the false positive rate by, for instance, extending the run required for AF, but it would be a bad idea. “The goal here is to not miss atrial fibrillation,” Dr. Maddox said. “There are false positives, but as long as you go back and reread, I think that’s fine. I wouldn’t mess with the sensitivity of the device.”

The company said the same thing when asked for comment on the study.

“The AF detection algorithm ... is tuned to favor sensitivity because manual review can subsequently rule out any false positives. This is one reason it is important to have trained cardiologists or electrophysiologists involved in reviewing reports of irregular heart rhythms to determine a diagnosis of AF,” said Medtronic spokesman Ryan Mathre, who also noted that company data suggest a lower false positive rate (Cerebrovasc Dis. 2015;40:175-81).

Even so, confirmation doesn’t always happen, “and that’s the scary part. In practice almost all the time,” the report comes in “and it’s acted on,” said Dr. Robert Hart, a neurology professor at McMaster University in Hamilton, Ont., and comoderator of the study presentation.

The Emory patients were all recovering from ischemic strokes or TIAs. They were about 70 years old on average, about 60% were men, and almost all were white. A total of 38 had implantable loop recorders for cryptogenic strokes; the devices detected true AF in 4 (11%) after a mean of 92 days. Early Holter monitoring missed it.

Emory generally prescribes anticoagulants if AF is confirmed, but, as several audience members noted, the burden of AF that requires anticoagulation is unclear. “It’s an area with a lot of thought now, but no good answers,” Dr. Maddox said at the conference, sponsored by the American Heart Association.

The investigators had no disclosures, and there was no outside funding for the work.

aotto@frontlinemedcom.com

LOS ANGELES – Medtronic’s Reveal LINQ implantable loop recorders misidentified 84% of rhythm anomalies as atrial fibrillation in 52 stroke patients at Emory University in Atlanta, according to a presentation at the International Stroke Conference.

Two electrophysiologists reviewed a random sample of 166 rhythm strips from those patients that were identified by Reveal as atrial fibrillation (AF) over a 2-month period; 140 (84%) were false positives. Eighty (57%) of the false positives were premature atrial complexes, 31 (22%) were due to T wave over-sensing, 14 (10%) to noise, 7 (5%) to premature ventricular complexes, 4 (2.9%) to under-sensing, and 4 (2.9%) to sinus arrhythmias.

There wasn’t a mix-and-match of true and false positives in the same patient; false and true positives were consistent in patients over the study period.

The take-home message from the study is that the high sensitivity of Medtronic’s implantable loop recorders means that they are good at detecting possible AF, but their findings must be reviewed and confirmed before being acted upon.

“There are high rates of false positives, but the results can be easily adjudicated by electrophysiologists as evidenced by our observer agreement,” which was 100%. “These strips need to be adjudicated by somebody, and not taken at face value,” said investigator Dr. Spencer Maddox, an Emory resident.

The devices look mainly at RR intervals and the presence or absence of P waves. Runs of 2 minutes are required for AF. One of the issues in the study was that T waves were identified as QRS complexes, which changed the RR interval and trigged the device to report AF, he said.

Medtronic could reduce the false positive rate by, for instance, extending the run required for AF, but it would be a bad idea. “The goal here is to not miss atrial fibrillation,” Dr. Maddox said. “There are false positives, but as long as you go back and reread, I think that’s fine. I wouldn’t mess with the sensitivity of the device.”

The company said the same thing when asked for comment on the study.

“The AF detection algorithm ... is tuned to favor sensitivity because manual review can subsequently rule out any false positives. This is one reason it is important to have trained cardiologists or electrophysiologists involved in reviewing reports of irregular heart rhythms to determine a diagnosis of AF,” said Medtronic spokesman Ryan Mathre, who also noted that company data suggest a lower false positive rate (Cerebrovasc Dis. 2015;40:175-81).

Even so, confirmation doesn’t always happen, “and that’s the scary part. In practice almost all the time,” the report comes in “and it’s acted on,” said Dr. Robert Hart, a neurology professor at McMaster University in Hamilton, Ont., and comoderator of the study presentation.

The Emory patients were all recovering from ischemic strokes or TIAs. They were about 70 years old on average, about 60% were men, and almost all were white. A total of 38 had implantable loop recorders for cryptogenic strokes; the devices detected true AF in 4 (11%) after a mean of 92 days. Early Holter monitoring missed it.

Emory generally prescribes anticoagulants if AF is confirmed, but, as several audience members noted, the burden of AF that requires anticoagulation is unclear. “It’s an area with a lot of thought now, but no good answers,” Dr. Maddox said at the conference, sponsored by the American Heart Association.

The investigators had no disclosures, and there was no outside funding for the work.

aotto@frontlinemedcom.com

LOS ANGELES – Enlarge the field of CT angiography to include the heart in acute ischemic stroke patients; you’ll quickly identify sources of cardiogenic emboli and other problems that will otherwise be missed, according to investigators from the National University Hospital, Singapore.

It adds only a few seconds to the scan, with no extra contrast or meaningful increase in radiation. There’s no need to gate the heart with beta-blockers.

Among 20 acute ischemic stroke patients presenting within 4.5 hours of symptom onset, Dr. Leonard Yeo and his coinvestigators found one with a localized dissection in the ascending aorta, another with a ventricular thrombus, and a third with an atrial appendage blood clot. Both thrombus cases were confirmed by transesophageal echocardiography and started on anticoagulation the next day. The 2-phase, 64-slice nongated cardiac CT angiographies (CTA) were done in the same sitting as the brain CTA.

“Scans with 1-mm thick slices are best for screening for thrombus and structural abnormalities that cause embolism. Remarkably, [even without gating], the detail is excellent. There’s very little downside [to this, and] it maximizes your return on scans that are already a part of most acute stroke protocols,” said Dr. Yeo, a neurologist at the hospital.

“Since most of our patients get a CTA during acute stroke, it made sense to check the heart for embolic sources.” There isn’t any time to give a beta-blocker, so “these were nongated” scans, Dr. Yeo said during his presentation at the International Stroke Conference, sponsored by the American Heart Association.

If it’s confirmed that nongated heart CTAs provide useful information, “we will probably all be doing this in the future. Everybody does CTs for the head in acute stroke, so all you do is go down a little lower” without any more contrast. “Within an hour of somebody presenting, you know what they have,” said Dr. Robert Hart, a neurology professor at McMaster University in Hamilton, Ont., and co-moderator of Dr. Yeo’s presentation.

In most places, acute ischemic stroke patients only get an ECG. Transesophageal echocardiography (TEE) is also good for checking the heart, but it usually comes later. It “excels at detecting abnormalities with medium embolic risk,” such as patent foramen ovale and septal aneurysm. “However, for these medium-risk cardiac sources of embolism, the optimal choice of therapy is not clear. Unlike high-risk sources which require anticoagulation, TEE does not provide therapeutic gains in terms of clinical decision making,” Dr. Yeo said.

Nongated cardiac CTAs during acute stroke, he added, also check chamber, valve, pericardial, and great vessel morphology, as well as abnormal chambers-vessel communications and “left ventricular aneurysms that can rupture with [tissue plasminogen activator], with catastrophic consequences.”

The mean age in the study was 64 years old, and about 60% of the subjects were men. None of the patients were dead at 3 months, and by then eight (40%) had modified Rankin Scale scores of 0-1. Patients were excluded if they had contraindications to IV contrast, or were unable to provide informed consent. CTA images were read by the treating neurologist and radiologist.

The work was funded by the Singapore Ministry of Health’s National Medical Research Council. The investigators have no relevant disclosures.

aotto@frontlinemedcom.com

LOS ANGELES – Enlarge the field of CT angiography to include the heart in acute ischemic stroke patients; you’ll quickly identify sources of cardiogenic emboli and other problems that will otherwise be missed, according to investigators from the National University Hospital, Singapore.

It adds only a few seconds to the scan, with no extra contrast or meaningful increase in radiation. There’s no need to gate the heart with beta-blockers.

Among 20 acute ischemic stroke patients presenting within 4.5 hours of symptom onset, Dr. Leonard Yeo and his coinvestigators found one with a localized dissection in the ascending aorta, another with a ventricular thrombus, and a third with an atrial appendage blood clot. Both thrombus cases were confirmed by transesophageal echocardiography and started on anticoagulation the next day. The 2-phase, 64-slice nongated cardiac CT angiographies (CTA) were done in the same sitting as the brain CTA.

“Scans with 1-mm thick slices are best for screening for thrombus and structural abnormalities that cause embolism. Remarkably, [even without gating], the detail is excellent. There’s very little downside [to this, and] it maximizes your return on scans that are already a part of most acute stroke protocols,” said Dr. Yeo, a neurologist at the hospital.

“Since most of our patients get a CTA during acute stroke, it made sense to check the heart for embolic sources.” There isn’t any time to give a beta-blocker, so “these were nongated” scans, Dr. Yeo said during his presentation at the International Stroke Conference, sponsored by the American Heart Association.

If it’s confirmed that nongated heart CTAs provide useful information, “we will probably all be doing this in the future. Everybody does CTs for the head in acute stroke, so all you do is go down a little lower” without any more contrast. “Within an hour of somebody presenting, you know what they have,” said Dr. Robert Hart, a neurology professor at McMaster University in Hamilton, Ont., and co-moderator of Dr. Yeo’s presentation.

In most places, acute ischemic stroke patients only get an ECG. Transesophageal echocardiography (TEE) is also good for checking the heart, but it usually comes later. It “excels at detecting abnormalities with medium embolic risk,” such as patent foramen ovale and septal aneurysm. “However, for these medium-risk cardiac sources of embolism, the optimal choice of therapy is not clear. Unlike high-risk sources which require anticoagulation, TEE does not provide therapeutic gains in terms of clinical decision making,” Dr. Yeo said.

Nongated cardiac CTAs during acute stroke, he added, also check chamber, valve, pericardial, and great vessel morphology, as well as abnormal chambers-vessel communications and “left ventricular aneurysms that can rupture with [tissue plasminogen activator], with catastrophic consequences.”

The mean age in the study was 64 years old, and about 60% of the subjects were men. None of the patients were dead at 3 months, and by then eight (40%) had modified Rankin Scale scores of 0-1. Patients were excluded if they had contraindications to IV contrast, or were unable to provide informed consent. CTA images were read by the treating neurologist and radiologist.

The work was funded by the Singapore Ministry of Health’s National Medical Research Council. The investigators have no relevant disclosures.

aotto@frontlinemedcom.com

LOS ANGELES – Enlarge the field of CT angiography to include the heart in acute ischemic stroke patients; you’ll quickly identify sources of cardiogenic emboli and other problems that will otherwise be missed, according to investigators from the National University Hospital, Singapore.

It adds only a few seconds to the scan, with no extra contrast or meaningful increase in radiation. There’s no need to gate the heart with beta-blockers.

Among 20 acute ischemic stroke patients presenting within 4.5 hours of symptom onset, Dr. Leonard Yeo and his coinvestigators found one with a localized dissection in the ascending aorta, another with a ventricular thrombus, and a third with an atrial appendage blood clot. Both thrombus cases were confirmed by transesophageal echocardiography and started on anticoagulation the next day. The 2-phase, 64-slice nongated cardiac CT angiographies (CTA) were done in the same sitting as the brain CTA.

“Scans with 1-mm thick slices are best for screening for thrombus and structural abnormalities that cause embolism. Remarkably, [even without gating], the detail is excellent. There’s very little downside [to this, and] it maximizes your return on scans that are already a part of most acute stroke protocols,” said Dr. Yeo, a neurologist at the hospital.

“Since most of our patients get a CTA during acute stroke, it made sense to check the heart for embolic sources.” There isn’t any time to give a beta-blocker, so “these were nongated” scans, Dr. Yeo said during his presentation at the International Stroke Conference, sponsored by the American Heart Association.

If it’s confirmed that nongated heart CTAs provide useful information, “we will probably all be doing this in the future. Everybody does CTs for the head in acute stroke, so all you do is go down a little lower” without any more contrast. “Within an hour of somebody presenting, you know what they have,” said Dr. Robert Hart, a neurology professor at McMaster University in Hamilton, Ont., and co-moderator of Dr. Yeo’s presentation.

In most places, acute ischemic stroke patients only get an ECG. Transesophageal echocardiography (TEE) is also good for checking the heart, but it usually comes later. It “excels at detecting abnormalities with medium embolic risk,” such as patent foramen ovale and septal aneurysm. “However, for these medium-risk cardiac sources of embolism, the optimal choice of therapy is not clear. Unlike high-risk sources which require anticoagulation, TEE does not provide therapeutic gains in terms of clinical decision making,” Dr. Yeo said.

Nongated cardiac CTAs during acute stroke, he added, also check chamber, valve, pericardial, and great vessel morphology, as well as abnormal chambers-vessel communications and “left ventricular aneurysms that can rupture with [tissue plasminogen activator], with catastrophic consequences.”

The mean age in the study was 64 years old, and about 60% of the subjects were men. None of the patients were dead at 3 months, and by then eight (40%) had modified Rankin Scale scores of 0-1. Patients were excluded if they had contraindications to IV contrast, or were unable to provide informed consent. CTA images were read by the treating neurologist and radiologist.

The work was funded by the Singapore Ministry of Health’s National Medical Research Council. The investigators have no relevant disclosures.

aotto@frontlinemedcom.com

LOS ANGELES – The use of endovascular thrombectomy in the United States to treat appropriate patients with acute ischemic stroke mushroomed during the past year, following several early-2015 reports that collectively documented the dramatic clinical benefit of the treatment.

As endovascular thrombectomy use grows, stroke centers are also refining and reshaping delivery of the treatment in concert with administration of intravenous tissue plasminogen activator (TPA; alteplase; Activase), which remains a key partner in producing best outcomes for acute ischemic-stroke patients with a proximal occlusion of a large cerebral artery. Collapsing delivery of the two treatments into a more seamless and streamlined process shaves critical minutes to treatment delivery, an approach called parallel processing. Recent findings have also emboldened stroke specialists to seriously consider simplifying the brain imaging that stroke patients receive prior to these treatments, a step that could further cut time to intervention while also making thrombectomy even more widely available.

Use of thrombectomy surges

The biggest endovascular thrombectomy news of the past year is how it has taken off for treating selected patients with acute ischemic stroke. “The rollout over the past year has been explosive. Everything pretty much shut down after the negative trial results in 2013, but now more hospitals are offering thrombectomy,” said Dr. Thomas A. Kent, professor of neurology and director of stroke research and education at Baylor College of Medicine in Houston, in an interview at the International Stroke Conference sponsored by the American Heart Association.

The best documentation of this surge came in a poster presented at the conference by researchers at the University of California, San Francisco. They analyzed data on treatment of 357,973 patients with acute ischemic stroke who were hospitalized at any one of 161 U.S. academic medical centers during October 2009-July 2015 and included in the University Healthsystem Consortium database. They tracked the percentage of patients treated endovascularly during each calendar quarter of the study period.

During 2009-2013, use of endovascular treatment rose steadily but gradually, from 1.5% of stroke patients in 2009 to 3.1% during the fourth quarter of 2012. Then, following three reports of no benefit from endovascular treatment presented at the International Stroke Conference in February 2013 – the IMS III, MR RESCUE, and SYNTHESIS trials – the endovascular rate dropped immediately and quickly bottomed out at a level of 2.6% that remained steady through the third quarter of 2014. But when the positive endovascular results from the MR CLEAN study became public in the final week of 2014, endovascular use began to quickly rise again, and then began to skyrocket during the first quarter of 2015 with three additional positive trial results reported during the Stroke Conference in February 2015. By the end of the second quarter of 2015, usage stood at 4.7%, representing a projected year-over-year increase of about 150% for all of 2015, compared with 2014, reported Dr. Anthony S. Kim, a vascular neurologist and medical director of the Stroke Center at the University of California, San Francisco, and his associates.

To put these percentages in perspective, experts estimate that roughly 10%-15% of all stroke patients qualify for thrombectomy intervention.

Their data also showed that the percentage of hospitals included in the database that performed endovascular therapies for stroke rose steadily from about 40% of centers in 2009 to nearly 60% by mid-2015.

“Endovascular therapy with newer-generation devices is increasingly part of standard treatment for acute ischemic stroke,” they said in their poster. In addition, they cited a “new urgency to evaluate regional access to embolectomy [another name for thrombectomy] nationally and to identify system-based solutions to improve access in underserved areas.”

Several stroke experts interviewed at the conference added their own anecdotal view of thrombectomy’s rapidly expanding use for appropriate acute ischemic stroke patients during 2015, and the need for continued effort to broaden its U.S. availability.

“The number of thrombectomies fell off after the negative 2013 trials and stayed flat until a year ago, but then jumped up. It has been very dramatic,” said Dr. Wade S. Smith, professor of neurology and director of the neurovascular service at the University of California, San Francisco.

“Thrombectomy use tremendously increased since February 2015,” said Dr. Mark J. Alberts, professor of neurology and medical director of the neurology service at the University of Texas Southwestern Medical Center in Dallas, in a video interview during the conference. But despite this growth, “the major challenge [today] is geography;” that is, reaching patients in suburban and rural areas who are not as close to the primarily urban medical centers that currently offer the procedure.

“We now have about 100 certified comprehensive stroke centers in the U.S.,” and by definition comprehensive stroke centers have the capability of treating patients with endovascular thrombectomy, noted Dr. Jeffrey Saver, professor of neurology and director of the stroke unit at the University of California, Los Angeles.

“Certification of these centers did not begin until about 2-3 years ago. But we probably need 300-400 of these centers” to provide thrombectomy to most U.S. stroke patients, he said. “A lot of additional hospitals are close to certification. I anticipate that over the next 1-2 years we will be in the neighborhood of having the number of centers we need,” Dr. Saver said in an interview.

Making thrombectomy better

In addition to expanding availability, the specifics of how endovascular thrombectomy gets delivered is evolving. A major trend is movement toward a “parallel processing” model, in which patients with an acute clinical presentation of a stroke amenable for endovascular treatment simultaneously undergo CT angiography to confirm and localize the large-artery clot causing their stroke, receive intravenous TPA, and undergo preparation for the endovascular access needed to remove the clot.

A pooled analysis of the recent, positive endovascular thrombectomy trials that was presented at the conference showed how quick you need to be to obtain a benefit from the procedures. “This gives us a starting point to further improve the target metrics for imaging and puncture times,” Dr. Saver said. “We want to shorten door-to-needle times for TPA and door-to-puncture times for thrombectomy, and the processes that need to be addressed for rapid delivery of both of these are very similar. We need for patients to only make a pit stop in the ED; we need to have the catheterization team ready to go in the thrombectomy suite within 30 minutes; and we need to emphasize speed in access to the target clot rather than time-consuming diagnostic angiography.”

“We now face the issue of how to best integrate TPA treatment and clot removal.” Dr. Kent said. “People are still trying to work that out. With parallel processing there is some overuse of resources: Some patients recover with TPA alone and don’t need thrombectomy. We are getting closer to the cardiology model of MI treatment. It’s now clear that there needs to be a simple, safe, effective way to do both TPA treatment and thrombectomy. We need to model ourselves on the cardiology experience.”

“If you can deal with the TPA decision in the same room without moving patients from room to room, from a scanner to a catheterization suite, you can really shorten the time to treatment,” Dr. Smith explained. “This is identical to the model that cardiologists have developed. We should now consider taking stroke patients directly to the angiography room in addition to administering TPA. We still need cross-sectional imaging, but the quality of the image from an angiography suite is probably sufficient to make a TPA decision. So you can start TPA while you are getting arterial access. The idea is simultaneous approaches to the patient instead of serial.”

“The whole system moves at the same time to eliminate wasted time,” Dr. Alberts summed up.

One of the big questions that has come up in this effort to speed up treatment and carve the quickest route to endovascular thrombectomy is whether TPA remains necessary. The skeptics’ position is, why waste time administering TPA if you’re also going to take out the offending clot?

The answer, at least for now, is that all signs indicate that giving TPA helps and is worth delivering.

“The 2015 thrombectomy trials had big differences among them in the dosage of TPA administered, and in the percentage of patients who received TPA. When 100% of patients received TPA they had the best outcomes,” Dr. Kent said. “There was a clear synergistic relationship between thrombectomy and TPA. There has been a trend to think about sending patients straight to thrombectomy and skipping TPA, but my colleagues and I think that we need to hold off on doing that. For now, if a patient is eligible to receive TPA they should get it and then quickly move to endovascular therapy. We are not yet ready to know it’s okay to go straight to endovascular treatment. In SWIFT-PRIME, it was pretty clear that the good outcomes were attributable to both [thrombectomy plus TPA]. Treating patients with TPA helps soften the clot to make it easier to remove, and improves flow through collateral arteries.”

“Our data in Memphis show that patients do better with thrombectomy plus intravenous TPA than on TPA alone,” agreed Dr. Lucas Elijovich, a neurologist at the University of Tennessee Health Science Center in Memphis, in an interview.

Simpler imaging also saves time

Although it’s not yet proven, another new wrinkle in working up acute ischemic-stroke patients for TPA and thrombectomy treatment is the idea that simpler and more widely available CT imaging, especially CT angiography of cerebral arteries, may suffice for confirming and localizing the culprit clot.

This concept received a significant boost at the International Stroke Conference in data reported from the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) trial, yet another study that compared treatment with TPA alone with TPA plus endovascular thrombectomy, this time in 65 randomized patients treated at any of 11 U.K. centers. PISTE had a low enrollment level because the trial stopped prematurely, in July 2015, following the news that several fully completed trials had collectively established the superiority of endovascular thrombectomy plus TPA, thereby making it unethical to continue yet another randomized study.

This premature stoppage prevented PISTE from itself producing a statistically significant difference for its primary efficacy endpoint in favor of the combined treatment, although the results did show a nominal advantage to using thrombectomy plus TPA over TPA alone that was fully consistent with the other studies, Dr. Keith W. Muir reported at the conference.

But what made the PISTE results especially notable was that the trial achieved this consistent outcome with a “simpler” imaging protocol for patients during their workup that used only CT angiography, avoiding the cerebral CT perfusion imaging or MRI used in several of the other TPA-plus-thrombectomy versus TPA-only trials, noted Dr. Muir, professor of neuroscience and head of the stroke imaging group at the University of Glasgow.

“PISTE raises the question of how much imaging is necessary,” Dr. Kent commented.

“The PISTE results are exciting. A lot of us believe that all we need to know is that there is a blockage in a target vessel,” Dr. Smith said. “If we have that information, then we can identify a population of patients who will benefit from [thrombectomy]. CT angiography is simple and can easily fit into work flows.”

“PISTE used a very simple imaging system that makes thrombectomy even more applicable and generalizable to less resourced health systems,” Dr. Saver said. “Although the results from PISTE were not internally statistically significant because the trial ended early, the results were consistent with the external studies of thrombectomy, so it provides further evidence for benefit from thrombectomy.” And because the consistent results were achieved with simpler imaging it suggests simpler imaging may be all that’s needed.

“That’s a major question to wrestle with,” Dr. Saver suggested. “We need addition trials with a head-to-head comparison of simpler and more sophisticated imaging so we can tailor treatment to patients who would benefit from simpler and faster imaging.”

Dr. Kent had no disclosures. Dr. Kim has received research funding from SanBio and Biogen. Dr. Smith served on the data safety and monitoring board for a trial funded by Stryker. Dr. Alberts has been a consultant to Genentech. Dr. Saver has been a consultant to Stryker, Neuravi, Cognition Medical, Boehringer Ingelheim, and Medtronic. Dr. Elijovich has been a consultant to Stryker and Codman and received research support from Siemens. Dr. Muir has received research support from ReNeuron and unrestricted grants from Codman and Covidien.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

LOS ANGELES – The use of endovascular thrombectomy in the United States to treat appropriate patients with acute ischemic stroke mushroomed during the past year, following several early-2015 reports that collectively documented the dramatic clinical benefit of the treatment.

As endovascular thrombectomy use grows, stroke centers are also refining and reshaping delivery of the treatment in concert with administration of intravenous tissue plasminogen activator (TPA; alteplase; Activase), which remains a key partner in producing best outcomes for acute ischemic-stroke patients with a proximal occlusion of a large cerebral artery. Collapsing delivery of the two treatments into a more seamless and streamlined process shaves critical minutes to treatment delivery, an approach called parallel processing. Recent findings have also emboldened stroke specialists to seriously consider simplifying the brain imaging that stroke patients receive prior to these treatments, a step that could further cut time to intervention while also making thrombectomy even more widely available.

Use of thrombectomy surges

The biggest endovascular thrombectomy news of the past year is how it has taken off for treating selected patients with acute ischemic stroke. “The rollout over the past year has been explosive. Everything pretty much shut down after the negative trial results in 2013, but now more hospitals are offering thrombectomy,” said Dr. Thomas A. Kent, professor of neurology and director of stroke research and education at Baylor College of Medicine in Houston, in an interview at the International Stroke Conference sponsored by the American Heart Association.

The best documentation of this surge came in a poster presented at the conference by researchers at the University of California, San Francisco. They analyzed data on treatment of 357,973 patients with acute ischemic stroke who were hospitalized at any one of 161 U.S. academic medical centers during October 2009-July 2015 and included in the University Healthsystem Consortium database. They tracked the percentage of patients treated endovascularly during each calendar quarter of the study period.

During 2009-2013, use of endovascular treatment rose steadily but gradually, from 1.5% of stroke patients in 2009 to 3.1% during the fourth quarter of 2012. Then, following three reports of no benefit from endovascular treatment presented at the International Stroke Conference in February 2013 – the IMS III, MR RESCUE, and SYNTHESIS trials – the endovascular rate dropped immediately and quickly bottomed out at a level of 2.6% that remained steady through the third quarter of 2014. But when the positive endovascular results from the MR CLEAN study became public in the final week of 2014, endovascular use began to quickly rise again, and then began to skyrocket during the first quarter of 2015 with three additional positive trial results reported during the Stroke Conference in February 2015. By the end of the second quarter of 2015, usage stood at 4.7%, representing a projected year-over-year increase of about 150% for all of 2015, compared with 2014, reported Dr. Anthony S. Kim, a vascular neurologist and medical director of the Stroke Center at the University of California, San Francisco, and his associates.

To put these percentages in perspective, experts estimate that roughly 10%-15% of all stroke patients qualify for thrombectomy intervention.

Their data also showed that the percentage of hospitals included in the database that performed endovascular therapies for stroke rose steadily from about 40% of centers in 2009 to nearly 60% by mid-2015.

“Endovascular therapy with newer-generation devices is increasingly part of standard treatment for acute ischemic stroke,” they said in their poster. In addition, they cited a “new urgency to evaluate regional access to embolectomy [another name for thrombectomy] nationally and to identify system-based solutions to improve access in underserved areas.”

Several stroke experts interviewed at the conference added their own anecdotal view of thrombectomy’s rapidly expanding use for appropriate acute ischemic stroke patients during 2015, and the need for continued effort to broaden its U.S. availability.

“The number of thrombectomies fell off after the negative 2013 trials and stayed flat until a year ago, but then jumped up. It has been very dramatic,” said Dr. Wade S. Smith, professor of neurology and director of the neurovascular service at the University of California, San Francisco.

“Thrombectomy use tremendously increased since February 2015,” said Dr. Mark J. Alberts, professor of neurology and medical director of the neurology service at the University of Texas Southwestern Medical Center in Dallas, in a video interview during the conference. But despite this growth, “the major challenge [today] is geography;” that is, reaching patients in suburban and rural areas who are not as close to the primarily urban medical centers that currently offer the procedure.

“We now have about 100 certified comprehensive stroke centers in the U.S.,” and by definition comprehensive stroke centers have the capability of treating patients with endovascular thrombectomy, noted Dr. Jeffrey Saver, professor of neurology and director of the stroke unit at the University of California, Los Angeles.

“Certification of these centers did not begin until about 2-3 years ago. But we probably need 300-400 of these centers” to provide thrombectomy to most U.S. stroke patients, he said. “A lot of additional hospitals are close to certification. I anticipate that over the next 1-2 years we will be in the neighborhood of having the number of centers we need,” Dr. Saver said in an interview.

Making thrombectomy better

In addition to expanding availability, the specifics of how endovascular thrombectomy gets delivered is evolving. A major trend is movement toward a “parallel processing” model, in which patients with an acute clinical presentation of a stroke amenable for endovascular treatment simultaneously undergo CT angiography to confirm and localize the large-artery clot causing their stroke, receive intravenous TPA, and undergo preparation for the endovascular access needed to remove the clot.

A pooled analysis of the recent, positive endovascular thrombectomy trials that was presented at the conference showed how quick you need to be to obtain a benefit from the procedures. “This gives us a starting point to further improve the target metrics for imaging and puncture times,” Dr. Saver said. “We want to shorten door-to-needle times for TPA and door-to-puncture times for thrombectomy, and the processes that need to be addressed for rapid delivery of both of these are very similar. We need for patients to only make a pit stop in the ED; we need to have the catheterization team ready to go in the thrombectomy suite within 30 minutes; and we need to emphasize speed in access to the target clot rather than time-consuming diagnostic angiography.”

“We now face the issue of how to best integrate TPA treatment and clot removal.” Dr. Kent said. “People are still trying to work that out. With parallel processing there is some overuse of resources: Some patients recover with TPA alone and don’t need thrombectomy. We are getting closer to the cardiology model of MI treatment. It’s now clear that there needs to be a simple, safe, effective way to do both TPA treatment and thrombectomy. We need to model ourselves on the cardiology experience.”

“If you can deal with the TPA decision in the same room without moving patients from room to room, from a scanner to a catheterization suite, you can really shorten the time to treatment,” Dr. Smith explained. “This is identical to the model that cardiologists have developed. We should now consider taking stroke patients directly to the angiography room in addition to administering TPA. We still need cross-sectional imaging, but the quality of the image from an angiography suite is probably sufficient to make a TPA decision. So you can start TPA while you are getting arterial access. The idea is simultaneous approaches to the patient instead of serial.”

“The whole system moves at the same time to eliminate wasted time,” Dr. Alberts summed up.

One of the big questions that has come up in this effort to speed up treatment and carve the quickest route to endovascular thrombectomy is whether TPA remains necessary. The skeptics’ position is, why waste time administering TPA if you’re also going to take out the offending clot?

The answer, at least for now, is that all signs indicate that giving TPA helps and is worth delivering.

“The 2015 thrombectomy trials had big differences among them in the dosage of TPA administered, and in the percentage of patients who received TPA. When 100% of patients received TPA they had the best outcomes,” Dr. Kent said. “There was a clear synergistic relationship between thrombectomy and TPA. There has been a trend to think about sending patients straight to thrombectomy and skipping TPA, but my colleagues and I think that we need to hold off on doing that. For now, if a patient is eligible to receive TPA they should get it and then quickly move to endovascular therapy. We are not yet ready to know it’s okay to go straight to endovascular treatment. In SWIFT-PRIME, it was pretty clear that the good outcomes were attributable to both [thrombectomy plus TPA]. Treating patients with TPA helps soften the clot to make it easier to remove, and improves flow through collateral arteries.”

“Our data in Memphis show that patients do better with thrombectomy plus intravenous TPA than on TPA alone,” agreed Dr. Lucas Elijovich, a neurologist at the University of Tennessee Health Science Center in Memphis, in an interview.

Simpler imaging also saves time

Although it’s not yet proven, another new wrinkle in working up acute ischemic-stroke patients for TPA and thrombectomy treatment is the idea that simpler and more widely available CT imaging, especially CT angiography of cerebral arteries, may suffice for confirming and localizing the culprit clot.

This concept received a significant boost at the International Stroke Conference in data reported from the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) trial, yet another study that compared treatment with TPA alone with TPA plus endovascular thrombectomy, this time in 65 randomized patients treated at any of 11 U.K. centers. PISTE had a low enrollment level because the trial stopped prematurely, in July 2015, following the news that several fully completed trials had collectively established the superiority of endovascular thrombectomy plus TPA, thereby making it unethical to continue yet another randomized study.

This premature stoppage prevented PISTE from itself producing a statistically significant difference for its primary efficacy endpoint in favor of the combined treatment, although the results did show a nominal advantage to using thrombectomy plus TPA over TPA alone that was fully consistent with the other studies, Dr. Keith W. Muir reported at the conference.

But what made the PISTE results especially notable was that the trial achieved this consistent outcome with a “simpler” imaging protocol for patients during their workup that used only CT angiography, avoiding the cerebral CT perfusion imaging or MRI used in several of the other TPA-plus-thrombectomy versus TPA-only trials, noted Dr. Muir, professor of neuroscience and head of the stroke imaging group at the University of Glasgow.

“PISTE raises the question of how much imaging is necessary,” Dr. Kent commented.

“The PISTE results are exciting. A lot of us believe that all we need to know is that there is a blockage in a target vessel,” Dr. Smith said. “If we have that information, then we can identify a population of patients who will benefit from [thrombectomy]. CT angiography is simple and can easily fit into work flows.”

“PISTE used a very simple imaging system that makes thrombectomy even more applicable and generalizable to less resourced health systems,” Dr. Saver said. “Although the results from PISTE were not internally statistically significant because the trial ended early, the results were consistent with the external studies of thrombectomy, so it provides further evidence for benefit from thrombectomy.” And because the consistent results were achieved with simpler imaging it suggests simpler imaging may be all that’s needed.

“That’s a major question to wrestle with,” Dr. Saver suggested. “We need addition trials with a head-to-head comparison of simpler and more sophisticated imaging so we can tailor treatment to patients who would benefit from simpler and faster imaging.”

Dr. Kent had no disclosures. Dr. Kim has received research funding from SanBio and Biogen. Dr. Smith served on the data safety and monitoring board for a trial funded by Stryker. Dr. Alberts has been a consultant to Genentech. Dr. Saver has been a consultant to Stryker, Neuravi, Cognition Medical, Boehringer Ingelheim, and Medtronic. Dr. Elijovich has been a consultant to Stryker and Codman and received research support from Siemens. Dr. Muir has received research support from ReNeuron and unrestricted grants from Codman and Covidien.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

LOS ANGELES – The use of endovascular thrombectomy in the United States to treat appropriate patients with acute ischemic stroke mushroomed during the past year, following several early-2015 reports that collectively documented the dramatic clinical benefit of the treatment.

As endovascular thrombectomy use grows, stroke centers are also refining and reshaping delivery of the treatment in concert with administration of intravenous tissue plasminogen activator (TPA; alteplase; Activase), which remains a key partner in producing best outcomes for acute ischemic-stroke patients with a proximal occlusion of a large cerebral artery. Collapsing delivery of the two treatments into a more seamless and streamlined process shaves critical minutes to treatment delivery, an approach called parallel processing. Recent findings have also emboldened stroke specialists to seriously consider simplifying the brain imaging that stroke patients receive prior to these treatments, a step that could further cut time to intervention while also making thrombectomy even more widely available.

Use of thrombectomy surges

The biggest endovascular thrombectomy news of the past year is how it has taken off for treating selected patients with acute ischemic stroke. “The rollout over the past year has been explosive. Everything pretty much shut down after the negative trial results in 2013, but now more hospitals are offering thrombectomy,” said Dr. Thomas A. Kent, professor of neurology and director of stroke research and education at Baylor College of Medicine in Houston, in an interview at the International Stroke Conference sponsored by the American Heart Association.

The best documentation of this surge came in a poster presented at the conference by researchers at the University of California, San Francisco. They analyzed data on treatment of 357,973 patients with acute ischemic stroke who were hospitalized at any one of 161 U.S. academic medical centers during October 2009-July 2015 and included in the University Healthsystem Consortium database. They tracked the percentage of patients treated endovascularly during each calendar quarter of the study period.

During 2009-2013, use of endovascular treatment rose steadily but gradually, from 1.5% of stroke patients in 2009 to 3.1% during the fourth quarter of 2012. Then, following three reports of no benefit from endovascular treatment presented at the International Stroke Conference in February 2013 – the IMS III, MR RESCUE, and SYNTHESIS trials – the endovascular rate dropped immediately and quickly bottomed out at a level of 2.6% that remained steady through the third quarter of 2014. But when the positive endovascular results from the MR CLEAN study became public in the final week of 2014, endovascular use began to quickly rise again, and then began to skyrocket during the first quarter of 2015 with three additional positive trial results reported during the Stroke Conference in February 2015. By the end of the second quarter of 2015, usage stood at 4.7%, representing a projected year-over-year increase of about 150% for all of 2015, compared with 2014, reported Dr. Anthony S. Kim, a vascular neurologist and medical director of the Stroke Center at the University of California, San Francisco, and his associates.

To put these percentages in perspective, experts estimate that roughly 10%-15% of all stroke patients qualify for thrombectomy intervention.

Their data also showed that the percentage of hospitals included in the database that performed endovascular therapies for stroke rose steadily from about 40% of centers in 2009 to nearly 60% by mid-2015.

“Endovascular therapy with newer-generation devices is increasingly part of standard treatment for acute ischemic stroke,” they said in their poster. In addition, they cited a “new urgency to evaluate regional access to embolectomy [another name for thrombectomy] nationally and to identify system-based solutions to improve access in underserved areas.”

Several stroke experts interviewed at the conference added their own anecdotal view of thrombectomy’s rapidly expanding use for appropriate acute ischemic stroke patients during 2015, and the need for continued effort to broaden its U.S. availability.

“The number of thrombectomies fell off after the negative 2013 trials and stayed flat until a year ago, but then jumped up. It has been very dramatic,” said Dr. Wade S. Smith, professor of neurology and director of the neurovascular service at the University of California, San Francisco.

“Thrombectomy use tremendously increased since February 2015,” said Dr. Mark J. Alberts, professor of neurology and medical director of the neurology service at the University of Texas Southwestern Medical Center in Dallas, in a video interview during the conference. But despite this growth, “the major challenge [today] is geography;” that is, reaching patients in suburban and rural areas who are not as close to the primarily urban medical centers that currently offer the procedure.

“We now have about 100 certified comprehensive stroke centers in the U.S.,” and by definition comprehensive stroke centers have the capability of treating patients with endovascular thrombectomy, noted Dr. Jeffrey Saver, professor of neurology and director of the stroke unit at the University of California, Los Angeles.

“Certification of these centers did not begin until about 2-3 years ago. But we probably need 300-400 of these centers” to provide thrombectomy to most U.S. stroke patients, he said. “A lot of additional hospitals are close to certification. I anticipate that over the next 1-2 years we will be in the neighborhood of having the number of centers we need,” Dr. Saver said in an interview.

Making thrombectomy better

In addition to expanding availability, the specifics of how endovascular thrombectomy gets delivered is evolving. A major trend is movement toward a “parallel processing” model, in which patients with an acute clinical presentation of a stroke amenable for endovascular treatment simultaneously undergo CT angiography to confirm and localize the large-artery clot causing their stroke, receive intravenous TPA, and undergo preparation for the endovascular access needed to remove the clot.

A pooled analysis of the recent, positive endovascular thrombectomy trials that was presented at the conference showed how quick you need to be to obtain a benefit from the procedures. “This gives us a starting point to further improve the target metrics for imaging and puncture times,” Dr. Saver said. “We want to shorten door-to-needle times for TPA and door-to-puncture times for thrombectomy, and the processes that need to be addressed for rapid delivery of both of these are very similar. We need for patients to only make a pit stop in the ED; we need to have the catheterization team ready to go in the thrombectomy suite within 30 minutes; and we need to emphasize speed in access to the target clot rather than time-consuming diagnostic angiography.”

“We now face the issue of how to best integrate TPA treatment and clot removal.” Dr. Kent said. “People are still trying to work that out. With parallel processing there is some overuse of resources: Some patients recover with TPA alone and don’t need thrombectomy. We are getting closer to the cardiology model of MI treatment. It’s now clear that there needs to be a simple, safe, effective way to do both TPA treatment and thrombectomy. We need to model ourselves on the cardiology experience.”

“If you can deal with the TPA decision in the same room without moving patients from room to room, from a scanner to a catheterization suite, you can really shorten the time to treatment,” Dr. Smith explained. “This is identical to the model that cardiologists have developed. We should now consider taking stroke patients directly to the angiography room in addition to administering TPA. We still need cross-sectional imaging, but the quality of the image from an angiography suite is probably sufficient to make a TPA decision. So you can start TPA while you are getting arterial access. The idea is simultaneous approaches to the patient instead of serial.”

“The whole system moves at the same time to eliminate wasted time,” Dr. Alberts summed up.

One of the big questions that has come up in this effort to speed up treatment and carve the quickest route to endovascular thrombectomy is whether TPA remains necessary. The skeptics’ position is, why waste time administering TPA if you’re also going to take out the offending clot?

The answer, at least for now, is that all signs indicate that giving TPA helps and is worth delivering.

“The 2015 thrombectomy trials had big differences among them in the dosage of TPA administered, and in the percentage of patients who received TPA. When 100% of patients received TPA they had the best outcomes,” Dr. Kent said. “There was a clear synergistic relationship between thrombectomy and TPA. There has been a trend to think about sending patients straight to thrombectomy and skipping TPA, but my colleagues and I think that we need to hold off on doing that. For now, if a patient is eligible to receive TPA they should get it and then quickly move to endovascular therapy. We are not yet ready to know it’s okay to go straight to endovascular treatment. In SWIFT-PRIME, it was pretty clear that the good outcomes were attributable to both [thrombectomy plus TPA]. Treating patients with TPA helps soften the clot to make it easier to remove, and improves flow through collateral arteries.”

“Our data in Memphis show that patients do better with thrombectomy plus intravenous TPA than on TPA alone,” agreed Dr. Lucas Elijovich, a neurologist at the University of Tennessee Health Science Center in Memphis, in an interview.

Simpler imaging also saves time

Although it’s not yet proven, another new wrinkle in working up acute ischemic-stroke patients for TPA and thrombectomy treatment is the idea that simpler and more widely available CT imaging, especially CT angiography of cerebral arteries, may suffice for confirming and localizing the culprit clot.

This concept received a significant boost at the International Stroke Conference in data reported from the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) trial, yet another study that compared treatment with TPA alone with TPA plus endovascular thrombectomy, this time in 65 randomized patients treated at any of 11 U.K. centers. PISTE had a low enrollment level because the trial stopped prematurely, in July 2015, following the news that several fully completed trials had collectively established the superiority of endovascular thrombectomy plus TPA, thereby making it unethical to continue yet another randomized study.

This premature stoppage prevented PISTE from itself producing a statistically significant difference for its primary efficacy endpoint in favor of the combined treatment, although the results did show a nominal advantage to using thrombectomy plus TPA over TPA alone that was fully consistent with the other studies, Dr. Keith W. Muir reported at the conference.

But what made the PISTE results especially notable was that the trial achieved this consistent outcome with a “simpler” imaging protocol for patients during their workup that used only CT angiography, avoiding the cerebral CT perfusion imaging or MRI used in several of the other TPA-plus-thrombectomy versus TPA-only trials, noted Dr. Muir, professor of neuroscience and head of the stroke imaging group at the University of Glasgow.

“PISTE raises the question of how much imaging is necessary,” Dr. Kent commented.

“The PISTE results are exciting. A lot of us believe that all we need to know is that there is a blockage in a target vessel,” Dr. Smith said. “If we have that information, then we can identify a population of patients who will benefit from [thrombectomy]. CT angiography is simple and can easily fit into work flows.”

“PISTE used a very simple imaging system that makes thrombectomy even more applicable and generalizable to less resourced health systems,” Dr. Saver said. “Although the results from PISTE were not internally statistically significant because the trial ended early, the results were consistent with the external studies of thrombectomy, so it provides further evidence for benefit from thrombectomy.” And because the consistent results were achieved with simpler imaging it suggests simpler imaging may be all that’s needed.

“That’s a major question to wrestle with,” Dr. Saver suggested. “We need addition trials with a head-to-head comparison of simpler and more sophisticated imaging so we can tailor treatment to patients who would benefit from simpler and faster imaging.”

Dr. Kent had no disclosures. Dr. Kim has received research funding from SanBio and Biogen. Dr. Smith served on the data safety and monitoring board for a trial funded by Stryker. Dr. Alberts has been a consultant to Genentech. Dr. Saver has been a consultant to Stryker, Neuravi, Cognition Medical, Boehringer Ingelheim, and Medtronic. Dr. Elijovich has been a consultant to Stryker and Codman and received research support from Siemens. Dr. Muir has received research support from ReNeuron and unrestricted grants from Codman and Covidien.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

LOS ANGELES – Paroxysmal supraventricular tachycardia is associated with subsequent ischemic stroke in patients without documented atrial fibrillation, according to a claims analysis of 42,152 Medicare enrollees at least 66 years old.

Atrial fibrillation accounts for perhaps 30% of cryptogenic strokes, “so clearly there’s something more to the story than just atrial fibrillation in” the other 70%, said investigator Dr. Hooman Kamel, a neurologist at Weill Cornell Medical College, New York. “Most cryptogenic strokes seem like they are embolic. The question is what are the undiscovered sources of embolism?”

Dr. Kamel and his colleagues focused on paroxysmal supraventricular tachycardia (PSVT) even though it’s generally considered benign. But “PSVT is increasingly recognized as a marker for underlying atrial dysfunction, especially in older patients. In some cases, the abnormal atrial substrate could cause thromboembolism even before atrial fibrillation [AF] appears,” he said at the International Stroke Conference.

To ensure regular heart rhythm monitoring, the study was limited to patients with implanted pacemakers or defibrillators. Patients with AF or stroke before or at the time of device implantation were excluded.

After a median of 1.8 years of follow-up, 2,245 patients (5.3%) were diagnosed with PSVT, and 1,007 (2.4%) had an ischemic stroke. The incidence of stroke without PSVT diagnosis was 0.95% per year, but 2.17% per year with a preceding PSVT diagnosis (P less than .001). Adjusting for age, gender, income, hypertension, diabetes, heart failure, and other potential confounders, the team found that a diagnosis of PSVT was associated with a doubling of ischemic stroke risk (HR, 2.0; 95% CI, 1.3-3.0), and an almost quadrupling of the risk for embolic stroke (HR, 3.6; 95% CI, 1.1-11.8).

“A lot more work needs to be done to nail this down, but potentially we are broadening the pool of atrial markers for stroke risk. These results build on recent findings that disturbances of atrial rhythm and function other than AF may” lead to stroke, Dr. Kamel said.

It’s way too soon to consider atrial ablation for PSVT to reduce stroke risk, he said, but his team is interrogating its administrative data for clues of its utility. “The idea of ablation for stroke is really interesting. I think ablation should help reduce the risk of stroke. It’s a really important question, and we don’t know the answer yet. There’s a lot more to be learned, [but] there does seem to be a definite progression from PSVT to AF,” Dr. Kamel said.

The National Institutes of Health funded the work. Dr. Kamel is a speaker for Genentech.

aotto@frontlinemedcom.com

LOS ANGELES – Paroxysmal supraventricular tachycardia is associated with subsequent ischemic stroke in patients without documented atrial fibrillation, according to a claims analysis of 42,152 Medicare enrollees at least 66 years old.

Atrial fibrillation accounts for perhaps 30% of cryptogenic strokes, “so clearly there’s something more to the story than just atrial fibrillation in” the other 70%, said investigator Dr. Hooman Kamel, a neurologist at Weill Cornell Medical College, New York. “Most cryptogenic strokes seem like they are embolic. The question is what are the undiscovered sources of embolism?”

Dr. Kamel and his colleagues focused on paroxysmal supraventricular tachycardia (PSVT) even though it’s generally considered benign. But “PSVT is increasingly recognized as a marker for underlying atrial dysfunction, especially in older patients. In some cases, the abnormal atrial substrate could cause thromboembolism even before atrial fibrillation [AF] appears,” he said at the International Stroke Conference.

To ensure regular heart rhythm monitoring, the study was limited to patients with implanted pacemakers or defibrillators. Patients with AF or stroke before or at the time of device implantation were excluded.

After a median of 1.8 years of follow-up, 2,245 patients (5.3%) were diagnosed with PSVT, and 1,007 (2.4%) had an ischemic stroke. The incidence of stroke without PSVT diagnosis was 0.95% per year, but 2.17% per year with a preceding PSVT diagnosis (P less than .001). Adjusting for age, gender, income, hypertension, diabetes, heart failure, and other potential confounders, the team found that a diagnosis of PSVT was associated with a doubling of ischemic stroke risk (HR, 2.0; 95% CI, 1.3-3.0), and an almost quadrupling of the risk for embolic stroke (HR, 3.6; 95% CI, 1.1-11.8).

“A lot more work needs to be done to nail this down, but potentially we are broadening the pool of atrial markers for stroke risk. These results build on recent findings that disturbances of atrial rhythm and function other than AF may” lead to stroke, Dr. Kamel said.

It’s way too soon to consider atrial ablation for PSVT to reduce stroke risk, he said, but his team is interrogating its administrative data for clues of its utility. “The idea of ablation for stroke is really interesting. I think ablation should help reduce the risk of stroke. It’s a really important question, and we don’t know the answer yet. There’s a lot more to be learned, [but] there does seem to be a definite progression from PSVT to AF,” Dr. Kamel said.

The National Institutes of Health funded the work. Dr. Kamel is a speaker for Genentech.

aotto@frontlinemedcom.com

LOS ANGELES – Paroxysmal supraventricular tachycardia is associated with subsequent ischemic stroke in patients without documented atrial fibrillation, according to a claims analysis of 42,152 Medicare enrollees at least 66 years old.

Atrial fibrillation accounts for perhaps 30% of cryptogenic strokes, “so clearly there’s something more to the story than just atrial fibrillation in” the other 70%, said investigator Dr. Hooman Kamel, a neurologist at Weill Cornell Medical College, New York. “Most cryptogenic strokes seem like they are embolic. The question is what are the undiscovered sources of embolism?”

Dr. Kamel and his colleagues focused on paroxysmal supraventricular tachycardia (PSVT) even though it’s generally considered benign. But “PSVT is increasingly recognized as a marker for underlying atrial dysfunction, especially in older patients. In some cases, the abnormal atrial substrate could cause thromboembolism even before atrial fibrillation [AF] appears,” he said at the International Stroke Conference.

To ensure regular heart rhythm monitoring, the study was limited to patients with implanted pacemakers or defibrillators. Patients with AF or stroke before or at the time of device implantation were excluded.

After a median of 1.8 years of follow-up, 2,245 patients (5.3%) were diagnosed with PSVT, and 1,007 (2.4%) had an ischemic stroke. The incidence of stroke without PSVT diagnosis was 0.95% per year, but 2.17% per year with a preceding PSVT diagnosis (P less than .001). Adjusting for age, gender, income, hypertension, diabetes, heart failure, and other potential confounders, the team found that a diagnosis of PSVT was associated with a doubling of ischemic stroke risk (HR, 2.0; 95% CI, 1.3-3.0), and an almost quadrupling of the risk for embolic stroke (HR, 3.6; 95% CI, 1.1-11.8).

“A lot more work needs to be done to nail this down, but potentially we are broadening the pool of atrial markers for stroke risk. These results build on recent findings that disturbances of atrial rhythm and function other than AF may” lead to stroke, Dr. Kamel said.

It’s way too soon to consider atrial ablation for PSVT to reduce stroke risk, he said, but his team is interrogating its administrative data for clues of its utility. “The idea of ablation for stroke is really interesting. I think ablation should help reduce the risk of stroke. It’s a really important question, and we don’t know the answer yet. There’s a lot more to be learned, [but] there does seem to be a definite progression from PSVT to AF,” Dr. Kamel said.

The National Institutes of Health funded the work. Dr. Kamel is a speaker for Genentech.

aotto@frontlinemedcom.com