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Higher blood pressure after thrombectomy links with bad stroke outcomes
HONOLULU – Acute ischemic stroke patients who underwent endovascular thrombectomy and then had a peak systolic blood pressure of greater than 158 mm Hg during the next 24 hours had worse 90-day outcomes than did patients whose peak systolic pressure remained at or below 158 mm Hg in a prospective, multicenter, observational study with 485 patients.
The results hint that maintaining a lower systolic blood pressure after thrombectomy in acute ischemic stroke patients may improve outcomes, but because the current study was observational, the hypothesis that patients benefit when treatment keeps their systolic pressure at or below 158 mm Hg must undergo testing in a prospective, randomized trial, Eva A. Mistry, MBBS, said at the International Stroke Conference, sponsored by the American Heart Association.
The finding from this study that 158 mm Hg provided the best dichotomous division between systolic blood pressures linked with good or bad outcomes is a first step toward trying to devise a more systematic and evidence-based approach to blood pressure management in acute ischemic stroke patients following endovascular thrombectomy, said Dr. Mistry, a neurologist at Vanderbilt University in Nashville, Tenn.
Neither Vanderbilt nor any of the other 11 major U.S. stroke centers that participated in the current study currently have an established protocol for blood pressure management after thrombectomy, Dr. Mistry said in an interview.
“We usually treat to reduce blood pressure, but we don’t have a [broadly agreed on] threshold” to trigger treatment. “It depends on a collective decision” by the various medical specialists who care for an individual acute stroke patient. In addition, no consensus yet exists for the best treatment strategy for blood pressure lowering in acute ischemic stroke patients. Intravenous nicardipine is often the top choice because it is fast-acting and easy to administer and control as an intravenous agent. Those same properties make the beta blocker labetalol a frequently used second drug, she said.
The BEST (Blood Pressure After Endovascular Stroke Therapy) study ran at 12 U.S. centers and enrolled 485 patients who underwent endovascular thrombectomy to treat an acute ischemic stroke. The patients averaged 69 years old, and 48% also underwent thrombolytic treatment. The study’s primary outcome was the percentage of patients with a modified Rankin Scale score of 0-2 at 90 days after their stroke, an outcome reached by 39% of all patients in the study.
Statistical analysis of the collected data showed that a peak systolic blood pressure of 158 mm Hg reached during the 24 hours following thrombectomy best divided patients with good 90-day outcomes from those with worse outcomes. Patients with a postthrombectomy peak systolic pressure above 158 mm Hg had a 2.2-fold increased rate of having a modified Rankin Scale score of 3 or higher after 90 days, a statistically significant relationship, Dr. Mistry reported. However, in an analysis that also adjusted for age, baseline stroke severity, glucose level, time to reperfusion, ASPECTS score, history of hypertension, and recanalization status, the elevated risk for a bad outcome linked with higher systolic pressure dropped to 39% greater than that for patients with systolic pressures that did not rise above 158 mm Hg, a difference that was not statistically significant. This suggests that these adjustments were unable to account for all confounders and further highlighted the need for a prospective, randomized trial to test the value of controlling blood pressure following thrombectomy, Dr. Mistry said. The unadjusted results confirmed a prior report from Dr. Mistry and her associates that found a link between higher blood pressure after stroke thrombectomy and worse outcomes (J Am Heart Assoc. 2017 May 18. doi: 10.1161/JAHA.117.006167).
The analysis also showed that patients who were successfully recanalized by thrombectomy, achieving a thrombolysis in cerebral infarction (TICI) score of 2b or 3, had lower peak systolic blood pressures than did patients who failed to get this level of restored cerebral blood flow from thrombectomy.
BEST received no commercial funding. Dr. Mistry had no disclosures.
SOURCE: Mistry EA et al. Stroke. 2019 Feb;50(Suppl_1): Abstract 94.
HONOLULU – Acute ischemic stroke patients who underwent endovascular thrombectomy and then had a peak systolic blood pressure of greater than 158 mm Hg during the next 24 hours had worse 90-day outcomes than did patients whose peak systolic pressure remained at or below 158 mm Hg in a prospective, multicenter, observational study with 485 patients.
The results hint that maintaining a lower systolic blood pressure after thrombectomy in acute ischemic stroke patients may improve outcomes, but because the current study was observational, the hypothesis that patients benefit when treatment keeps their systolic pressure at or below 158 mm Hg must undergo testing in a prospective, randomized trial, Eva A. Mistry, MBBS, said at the International Stroke Conference, sponsored by the American Heart Association.
The finding from this study that 158 mm Hg provided the best dichotomous division between systolic blood pressures linked with good or bad outcomes is a first step toward trying to devise a more systematic and evidence-based approach to blood pressure management in acute ischemic stroke patients following endovascular thrombectomy, said Dr. Mistry, a neurologist at Vanderbilt University in Nashville, Tenn.
Neither Vanderbilt nor any of the other 11 major U.S. stroke centers that participated in the current study currently have an established protocol for blood pressure management after thrombectomy, Dr. Mistry said in an interview.
“We usually treat to reduce blood pressure, but we don’t have a [broadly agreed on] threshold” to trigger treatment. “It depends on a collective decision” by the various medical specialists who care for an individual acute stroke patient. In addition, no consensus yet exists for the best treatment strategy for blood pressure lowering in acute ischemic stroke patients. Intravenous nicardipine is often the top choice because it is fast-acting and easy to administer and control as an intravenous agent. Those same properties make the beta blocker labetalol a frequently used second drug, she said.
The BEST (Blood Pressure After Endovascular Stroke Therapy) study ran at 12 U.S. centers and enrolled 485 patients who underwent endovascular thrombectomy to treat an acute ischemic stroke. The patients averaged 69 years old, and 48% also underwent thrombolytic treatment. The study’s primary outcome was the percentage of patients with a modified Rankin Scale score of 0-2 at 90 days after their stroke, an outcome reached by 39% of all patients in the study.
Statistical analysis of the collected data showed that a peak systolic blood pressure of 158 mm Hg reached during the 24 hours following thrombectomy best divided patients with good 90-day outcomes from those with worse outcomes. Patients with a postthrombectomy peak systolic pressure above 158 mm Hg had a 2.2-fold increased rate of having a modified Rankin Scale score of 3 or higher after 90 days, a statistically significant relationship, Dr. Mistry reported. However, in an analysis that also adjusted for age, baseline stroke severity, glucose level, time to reperfusion, ASPECTS score, history of hypertension, and recanalization status, the elevated risk for a bad outcome linked with higher systolic pressure dropped to 39% greater than that for patients with systolic pressures that did not rise above 158 mm Hg, a difference that was not statistically significant. This suggests that these adjustments were unable to account for all confounders and further highlighted the need for a prospective, randomized trial to test the value of controlling blood pressure following thrombectomy, Dr. Mistry said. The unadjusted results confirmed a prior report from Dr. Mistry and her associates that found a link between higher blood pressure after stroke thrombectomy and worse outcomes (J Am Heart Assoc. 2017 May 18. doi: 10.1161/JAHA.117.006167).
The analysis also showed that patients who were successfully recanalized by thrombectomy, achieving a thrombolysis in cerebral infarction (TICI) score of 2b or 3, had lower peak systolic blood pressures than did patients who failed to get this level of restored cerebral blood flow from thrombectomy.
BEST received no commercial funding. Dr. Mistry had no disclosures.
SOURCE: Mistry EA et al. Stroke. 2019 Feb;50(Suppl_1): Abstract 94.
HONOLULU – Acute ischemic stroke patients who underwent endovascular thrombectomy and then had a peak systolic blood pressure of greater than 158 mm Hg during the next 24 hours had worse 90-day outcomes than did patients whose peak systolic pressure remained at or below 158 mm Hg in a prospective, multicenter, observational study with 485 patients.
The results hint that maintaining a lower systolic blood pressure after thrombectomy in acute ischemic stroke patients may improve outcomes, but because the current study was observational, the hypothesis that patients benefit when treatment keeps their systolic pressure at or below 158 mm Hg must undergo testing in a prospective, randomized trial, Eva A. Mistry, MBBS, said at the International Stroke Conference, sponsored by the American Heart Association.
The finding from this study that 158 mm Hg provided the best dichotomous division between systolic blood pressures linked with good or bad outcomes is a first step toward trying to devise a more systematic and evidence-based approach to blood pressure management in acute ischemic stroke patients following endovascular thrombectomy, said Dr. Mistry, a neurologist at Vanderbilt University in Nashville, Tenn.
Neither Vanderbilt nor any of the other 11 major U.S. stroke centers that participated in the current study currently have an established protocol for blood pressure management after thrombectomy, Dr. Mistry said in an interview.
“We usually treat to reduce blood pressure, but we don’t have a [broadly agreed on] threshold” to trigger treatment. “It depends on a collective decision” by the various medical specialists who care for an individual acute stroke patient. In addition, no consensus yet exists for the best treatment strategy for blood pressure lowering in acute ischemic stroke patients. Intravenous nicardipine is often the top choice because it is fast-acting and easy to administer and control as an intravenous agent. Those same properties make the beta blocker labetalol a frequently used second drug, she said.
The BEST (Blood Pressure After Endovascular Stroke Therapy) study ran at 12 U.S. centers and enrolled 485 patients who underwent endovascular thrombectomy to treat an acute ischemic stroke. The patients averaged 69 years old, and 48% also underwent thrombolytic treatment. The study’s primary outcome was the percentage of patients with a modified Rankin Scale score of 0-2 at 90 days after their stroke, an outcome reached by 39% of all patients in the study.
Statistical analysis of the collected data showed that a peak systolic blood pressure of 158 mm Hg reached during the 24 hours following thrombectomy best divided patients with good 90-day outcomes from those with worse outcomes. Patients with a postthrombectomy peak systolic pressure above 158 mm Hg had a 2.2-fold increased rate of having a modified Rankin Scale score of 3 or higher after 90 days, a statistically significant relationship, Dr. Mistry reported. However, in an analysis that also adjusted for age, baseline stroke severity, glucose level, time to reperfusion, ASPECTS score, history of hypertension, and recanalization status, the elevated risk for a bad outcome linked with higher systolic pressure dropped to 39% greater than that for patients with systolic pressures that did not rise above 158 mm Hg, a difference that was not statistically significant. This suggests that these adjustments were unable to account for all confounders and further highlighted the need for a prospective, randomized trial to test the value of controlling blood pressure following thrombectomy, Dr. Mistry said. The unadjusted results confirmed a prior report from Dr. Mistry and her associates that found a link between higher blood pressure after stroke thrombectomy and worse outcomes (J Am Heart Assoc. 2017 May 18. doi: 10.1161/JAHA.117.006167).
The analysis also showed that patients who were successfully recanalized by thrombectomy, achieving a thrombolysis in cerebral infarction (TICI) score of 2b or 3, had lower peak systolic blood pressures than did patients who failed to get this level of restored cerebral blood flow from thrombectomy.
BEST received no commercial funding. Dr. Mistry had no disclosures.
SOURCE: Mistry EA et al. Stroke. 2019 Feb;50(Suppl_1): Abstract 94.
REPORTING FROM ISC 2019
Eisenmenger syndrome is a minefield for unwary physicians
SNOWMASS, COLO. – Interventions that are simple and straightforward for other patients – such as therapeutic phlebotomy, bronchoscopy, anticoagulation, administration of IV antibiotics – can quickly have catastrophic results in patients with Eisenmenger syndrome, Carole A. Warnes, MD, cautioned at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
This is why the 2018 ACC/American Heart Association guidelines on the management of patients with adult congenital heart disease recommend as a Class I indication that most patients with ACHD, including all those with Eisenmenger syndrome, be managed in collaboration with a cardiologist at a specialized ACHD center (Circulation. 2018 Aug 16. doi: 10.1161/CIR.0000000000000603), noted Dr. Warnes, professor of medicine at the Mayo Clinic in Rochester, Minn., and director of the Snowmass conference.
“There are lots of mistakes in diagnosis and management because so many physicians are unfamiliar with the kinds of problems these patients face,” the cardiologist said.
She cited as a real-world example a patient with Eisenmenger syndrome admitted for pneumonia. Twenty minutes after being placed on intravenous antibiotics she had a stroke. Why?
“She didn’t have an air filter on her IV line. Any air going into a cyanotic’s blood stream will go to the head and give them a stroke. Something that is simple – routine for other patients – may kill a patient with cyanotic heart disease,” Dr. Warnes said.
Another illustrative case: a patient with Eisenmenger syndrome presents with hemoptysis, an infiltrate in her right lung, a hemoglobin of 19.8 g/dL, and anemia. Should she undergo therapeutic phlebotomy? How about urgent bronchoscopy?
No and no, Dr. Warnes emphasized.
“You do not phlebotomize cyanotic patients unless they have symptoms of hyperviscosity, meaning terrible headache or poor concentration, along with a hemoglobin greater than 20 g/dL. They need that high hemoglobin. They may be blue, and you need those red cells to carry the oxygen around. Otherwise you may make them worse. And if you give them iron for their anemia, you will increase their risk of stroke,” she explained.
Hemoptysis in patients with Eisenmenger syndrome is a life-threatening warning sign. By the time Eisenmenger syndrome patients reach age 40 years, nearly all of them have experienced episodes of hemoptysis. And more and more patients with the syndrome are moving well beyond that milestone and surviving into their 60s and beyond.
“Many Eisenmenger syndrome patients are not dying when they’re 20 or 30. We can get them to a good old age,” according to Dr. Warnes, who founded the ACHD center at the Mayo Clinic.
Most of the time the cause of hemoptysis in patients with Eisenmenger syndrome is an intrapulmonary hemorrhage. Anticoagulation can turn that hemorrhage catastrophic. So can bronchoscopy. Indeed, the cause of death in roughly 30% of patients with this form of congenital heart disease is catastrophic hemoptysis.
“You bar the door from your friendly pulmonologist who wants to bronchoscope these patients. Bronchoscopy never does any good unless the patient is so hypoxic that you need to suck the blood out of their lungs,” Dr. Warnes emphasized.
Anticoagulation is ordinarily to be avoided in patients with Eisenmenger syndrome because of their bleeding risk, even when pulmonary thrombosis is suspected, she added.
So, to summarize: These patients basically need stabilizing, with no anticoagulation, no bronchoscopy, and no phlebotomy, she said.
Another danger zone for patients with Eisenmenger syndrome is pregnancy. The condition is associated with a 30% maternal mortality rate.
Dr. Warnes noted that, even at the Mayo Clinic, which has had a pioneering ACHD center for decades, awareness of key elements of management of affected patients is low among nonspecialists.
“As I’ve done my hospital services in the last couple of months, I sort of felt I was on patrol, snatching these patients from problems,” she recalled.
Dr. Warnes reported having no financial conflicts regarding her presentation.
SNOWMASS, COLO. – Interventions that are simple and straightforward for other patients – such as therapeutic phlebotomy, bronchoscopy, anticoagulation, administration of IV antibiotics – can quickly have catastrophic results in patients with Eisenmenger syndrome, Carole A. Warnes, MD, cautioned at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
This is why the 2018 ACC/American Heart Association guidelines on the management of patients with adult congenital heart disease recommend as a Class I indication that most patients with ACHD, including all those with Eisenmenger syndrome, be managed in collaboration with a cardiologist at a specialized ACHD center (Circulation. 2018 Aug 16. doi: 10.1161/CIR.0000000000000603), noted Dr. Warnes, professor of medicine at the Mayo Clinic in Rochester, Minn., and director of the Snowmass conference.
“There are lots of mistakes in diagnosis and management because so many physicians are unfamiliar with the kinds of problems these patients face,” the cardiologist said.
She cited as a real-world example a patient with Eisenmenger syndrome admitted for pneumonia. Twenty minutes after being placed on intravenous antibiotics she had a stroke. Why?
“She didn’t have an air filter on her IV line. Any air going into a cyanotic’s blood stream will go to the head and give them a stroke. Something that is simple – routine for other patients – may kill a patient with cyanotic heart disease,” Dr. Warnes said.
Another illustrative case: a patient with Eisenmenger syndrome presents with hemoptysis, an infiltrate in her right lung, a hemoglobin of 19.8 g/dL, and anemia. Should she undergo therapeutic phlebotomy? How about urgent bronchoscopy?
No and no, Dr. Warnes emphasized.
“You do not phlebotomize cyanotic patients unless they have symptoms of hyperviscosity, meaning terrible headache or poor concentration, along with a hemoglobin greater than 20 g/dL. They need that high hemoglobin. They may be blue, and you need those red cells to carry the oxygen around. Otherwise you may make them worse. And if you give them iron for their anemia, you will increase their risk of stroke,” she explained.
Hemoptysis in patients with Eisenmenger syndrome is a life-threatening warning sign. By the time Eisenmenger syndrome patients reach age 40 years, nearly all of them have experienced episodes of hemoptysis. And more and more patients with the syndrome are moving well beyond that milestone and surviving into their 60s and beyond.
“Many Eisenmenger syndrome patients are not dying when they’re 20 or 30. We can get them to a good old age,” according to Dr. Warnes, who founded the ACHD center at the Mayo Clinic.
Most of the time the cause of hemoptysis in patients with Eisenmenger syndrome is an intrapulmonary hemorrhage. Anticoagulation can turn that hemorrhage catastrophic. So can bronchoscopy. Indeed, the cause of death in roughly 30% of patients with this form of congenital heart disease is catastrophic hemoptysis.
“You bar the door from your friendly pulmonologist who wants to bronchoscope these patients. Bronchoscopy never does any good unless the patient is so hypoxic that you need to suck the blood out of their lungs,” Dr. Warnes emphasized.
Anticoagulation is ordinarily to be avoided in patients with Eisenmenger syndrome because of their bleeding risk, even when pulmonary thrombosis is suspected, she added.
So, to summarize: These patients basically need stabilizing, with no anticoagulation, no bronchoscopy, and no phlebotomy, she said.
Another danger zone for patients with Eisenmenger syndrome is pregnancy. The condition is associated with a 30% maternal mortality rate.
Dr. Warnes noted that, even at the Mayo Clinic, which has had a pioneering ACHD center for decades, awareness of key elements of management of affected patients is low among nonspecialists.
“As I’ve done my hospital services in the last couple of months, I sort of felt I was on patrol, snatching these patients from problems,” she recalled.
Dr. Warnes reported having no financial conflicts regarding her presentation.
SNOWMASS, COLO. – Interventions that are simple and straightforward for other patients – such as therapeutic phlebotomy, bronchoscopy, anticoagulation, administration of IV antibiotics – can quickly have catastrophic results in patients with Eisenmenger syndrome, Carole A. Warnes, MD, cautioned at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
This is why the 2018 ACC/American Heart Association guidelines on the management of patients with adult congenital heart disease recommend as a Class I indication that most patients with ACHD, including all those with Eisenmenger syndrome, be managed in collaboration with a cardiologist at a specialized ACHD center (Circulation. 2018 Aug 16. doi: 10.1161/CIR.0000000000000603), noted Dr. Warnes, professor of medicine at the Mayo Clinic in Rochester, Minn., and director of the Snowmass conference.
“There are lots of mistakes in diagnosis and management because so many physicians are unfamiliar with the kinds of problems these patients face,” the cardiologist said.
She cited as a real-world example a patient with Eisenmenger syndrome admitted for pneumonia. Twenty minutes after being placed on intravenous antibiotics she had a stroke. Why?
“She didn’t have an air filter on her IV line. Any air going into a cyanotic’s blood stream will go to the head and give them a stroke. Something that is simple – routine for other patients – may kill a patient with cyanotic heart disease,” Dr. Warnes said.
Another illustrative case: a patient with Eisenmenger syndrome presents with hemoptysis, an infiltrate in her right lung, a hemoglobin of 19.8 g/dL, and anemia. Should she undergo therapeutic phlebotomy? How about urgent bronchoscopy?
No and no, Dr. Warnes emphasized.
“You do not phlebotomize cyanotic patients unless they have symptoms of hyperviscosity, meaning terrible headache or poor concentration, along with a hemoglobin greater than 20 g/dL. They need that high hemoglobin. They may be blue, and you need those red cells to carry the oxygen around. Otherwise you may make them worse. And if you give them iron for their anemia, you will increase their risk of stroke,” she explained.
Hemoptysis in patients with Eisenmenger syndrome is a life-threatening warning sign. By the time Eisenmenger syndrome patients reach age 40 years, nearly all of them have experienced episodes of hemoptysis. And more and more patients with the syndrome are moving well beyond that milestone and surviving into their 60s and beyond.
“Many Eisenmenger syndrome patients are not dying when they’re 20 or 30. We can get them to a good old age,” according to Dr. Warnes, who founded the ACHD center at the Mayo Clinic.
Most of the time the cause of hemoptysis in patients with Eisenmenger syndrome is an intrapulmonary hemorrhage. Anticoagulation can turn that hemorrhage catastrophic. So can bronchoscopy. Indeed, the cause of death in roughly 30% of patients with this form of congenital heart disease is catastrophic hemoptysis.
“You bar the door from your friendly pulmonologist who wants to bronchoscope these patients. Bronchoscopy never does any good unless the patient is so hypoxic that you need to suck the blood out of their lungs,” Dr. Warnes emphasized.
Anticoagulation is ordinarily to be avoided in patients with Eisenmenger syndrome because of their bleeding risk, even when pulmonary thrombosis is suspected, she added.
So, to summarize: These patients basically need stabilizing, with no anticoagulation, no bronchoscopy, and no phlebotomy, she said.
Another danger zone for patients with Eisenmenger syndrome is pregnancy. The condition is associated with a 30% maternal mortality rate.
Dr. Warnes noted that, even at the Mayo Clinic, which has had a pioneering ACHD center for decades, awareness of key elements of management of affected patients is low among nonspecialists.
“As I’ve done my hospital services in the last couple of months, I sort of felt I was on patrol, snatching these patients from problems,” she recalled.
Dr. Warnes reported having no financial conflicts regarding her presentation.
REPORTING FROM ACC SNOWMASS 2019
Glyceryl trinitrate does not improve outcomes of ischemic stroke
HONOLULU – , according to data presented at the International Stroke Conference sponsored by the American Heart Association. Results suggest that GTN causes adverse effects in patients with intracerebral hemorrhage (ICH), but this observation is not definitive, according to the researchers. Study results were published online ahead of print Feb. 6 in the Lancet.
Nitric oxide is a regulatory molecule that has vasoactive effects and promotes blood pressure reduction. Vascular levels of nitric oxide are low in stroke, which suggests that the molecule may be a target for stroke treatment. GTN, a nitric oxide donor, lowered blood pressure and improved functional outcome among patients with acute stroke in the phase 2 Rapid Intervention with GTN in Hypertensive Stroke Trial (RIGHT).
Philip Bath, MD, Stroke Association Professor of Stroke Medicine at the University of Nottingham (England), and colleagues conducted the RIGHT-2 study to evaluate the safety and efficacy of GTN when administered early after onset of suspected stroke. Paramedics randomized patients in equal groups to a GTN patch or a sham patch in the ambulance. Three more patches were administered in the hospital on the following days. Active and sham patches looked similar and had no writing on them, thus ensuring effective blinding upon administration. Investigators followed up patients by telephone at 90 days to assess the modified Rankin Scale score and markers of disability, mood, cognition, and quality of life.
Eligible participants were adults who had dialed emergency services, independently or with assistance, because of a possible stroke. They had a Face, Arm, Speech, Time (FAST) score of 2 or 3, were within 4 hours of onset, and had a systolic blood pressure greater than 120 mm Hg. Patients from nursing homes, those with hypoglycemia, those who were unconscious, and those with a witnessed seizure were excluded.
Dr. Bath and colleagues planned to enroll 850 patients from five ambulance services in 30 hospitals across the United Kingdom. Data were to be examined through an intention-to-treat analysis. During the trial, however, the investigators observed that the rate of stroke mimics was 26%, rather than the 12% that they had anticipated. To ensure the proper power for the study, the investigators increased the sample size to 1,149 patients. They also changed the planned data analysis from intention-to-treat to hierarchical analysis. Specifically, the researchers planned to perform the primary analysis in patients with stroke or TIA. If the results were positive, then they would perform a standard intention-to-treat analysis.
More than 99% of patients received the first patch. Approximately 57% of the population received the first two patches. One reason for this decrease in adherence was that many patients were discharged from the hospital with a TIA or a stroke mimic. Participants’ average age was 72. The median time from onset to randomization was 71 minutes, and the median time to treatment was 73 minutes. Participants’ mean systolic blood pressure was 162 mm Hg. Approximately 60% of the patients had a FAST score of 3. About 50% of participants had ischemic stroke, 13% had ICH, 10% had TIA, and 26% had stroke mimics.
At 1 hour after treatment initiation, systolic blood pressure decreased by 6.2 mm Hg and diastolic blood pressure decreased by 2.7 mm Hg among patients who received GTN, compared with controls. At one day, the differences were 5.2 mm Hg and 2.5 mm Hg, respectively, in treated patients, compared with controls. Blood pressure became similar between groups thereafter, “in part because of the tachyphylaxis that we know happens with GTN,” said Dr. Bath.
The researchers found no evidence of an effect of GTN on functional outcome at 90 days in participants with stroke or transient ischemic attack. The adjusted common odds ratio of poor outcome was 1.25 in the GTN group, compared with the control group (95 % confidence interval, 0.97-1.60; P = .083). “We were close to getting a negative trial,” said Dr. Bath.
Subgroup analyses revealed differences in outcome according to the time to randomization. GTN had a negative effect in patients treated within 1 hour of onset. Results were neutral, but tended to be negative, in patients treated between 1 and 2 hours of onset. Results were neutral, but tended to be positive, among patients treated at more than 2 hours after onset. There was no difference between groups in the rate of mortality.
One of the study’s limitations was its single-blind design. In addition, the trial was conducted in a single country, and the investigators changed the protocol after it was initiated. “We had a higher-than-expected [stroke] mimic rate, although I’m reassured by most experts that ... this is probably about right,” said Dr. Bath.
A potential reason for the neutral results is the negative effect that GTN had among patients with ICH, said Dr. Bath. “In that very early first hour, we are of course breaking a law that we learned in medical school, which is that the first part of hemostasis is spasm. We gave an antispasmodic: a vasodilator,” he added. “That is speculation.”
The trial was funded by the British Heart Foundation. Dr. Bath declared a modest ownership interest in Platelet Solutions and consultant or advisory board positions with Moleac, DiaMedica, Phagenesis, Nestle, and ReNeuron. The other investigators declared no conflicts of interest.
The RIGHT-2 trial shows the limitations of a prehospital enrollment model, wrote Karen C. Johnston, MD, professor of neurology at the University of Virginia in Charlottesville, and Valerie L. Durkalski-Mauldin, PhD, professor of medicine at Medical University of South Carolina in Charleston, in an editorial accompanying the RIGHT-2 trial results. The rate of nonstroke diagnoses was so high that it would have reduced the study’s power to assess the efficacy of glyceryl trinitrate (GTN), had the investigators not increased the sample size and changed the statistical analysis plan.
“Future prehospital trials need to consider the implications of enrolling, yet excluding, stroke mimics in the primary analysis,” said Dr. Johnston and Dr. Durkalski-Mauldin. Using telemedicine in the ambulance to facilitate direct contact between the stroke provider and the patient and emergency medical services provider could reduce the enrollment of patients with stroke mimics in clinical trials, they added. “Improved tools to exclude stroke mimics in the field have been difficult to develop and validate. The absence of imaging in most ambulances will continue to limit field personnel from definitively determining ischemic stroke from intracerebral hemorrhage, which will limit hyperacute trials to interventions presumed safe in both populations.”
In addition, the blood pressure reduction that GTN provided might not be clinically relevant, said Dr. Johnston and Dr. Durkalski-Mauldin. “The RIGHT-2 investigators report no difference in blood pressure at day 3 or day 4 of treatment, which might have been related to the very low adherence to study protocol by day 4.
“Regardless of these limitations, RIGHT-2 has provided high-level evidence that GTN given within 4 hours of onset does not significantly improve outcome in hyperacute patients presenting with possible stroke,” the authors concluded (Lancet. 2019 Feb 6. doi: 10.1016/
S0140-6736(19)30276-4). Dr. Johnston and Dr. Durkalski-Mauldin declared no conflicts of interest.
The RIGHT-2 trial shows the limitations of a prehospital enrollment model, wrote Karen C. Johnston, MD, professor of neurology at the University of Virginia in Charlottesville, and Valerie L. Durkalski-Mauldin, PhD, professor of medicine at Medical University of South Carolina in Charleston, in an editorial accompanying the RIGHT-2 trial results. The rate of nonstroke diagnoses was so high that it would have reduced the study’s power to assess the efficacy of glyceryl trinitrate (GTN), had the investigators not increased the sample size and changed the statistical analysis plan.
“Future prehospital trials need to consider the implications of enrolling, yet excluding, stroke mimics in the primary analysis,” said Dr. Johnston and Dr. Durkalski-Mauldin. Using telemedicine in the ambulance to facilitate direct contact between the stroke provider and the patient and emergency medical services provider could reduce the enrollment of patients with stroke mimics in clinical trials, they added. “Improved tools to exclude stroke mimics in the field have been difficult to develop and validate. The absence of imaging in most ambulances will continue to limit field personnel from definitively determining ischemic stroke from intracerebral hemorrhage, which will limit hyperacute trials to interventions presumed safe in both populations.”
In addition, the blood pressure reduction that GTN provided might not be clinically relevant, said Dr. Johnston and Dr. Durkalski-Mauldin. “The RIGHT-2 investigators report no difference in blood pressure at day 3 or day 4 of treatment, which might have been related to the very low adherence to study protocol by day 4.
“Regardless of these limitations, RIGHT-2 has provided high-level evidence that GTN given within 4 hours of onset does not significantly improve outcome in hyperacute patients presenting with possible stroke,” the authors concluded (Lancet. 2019 Feb 6. doi: 10.1016/
S0140-6736(19)30276-4). Dr. Johnston and Dr. Durkalski-Mauldin declared no conflicts of interest.
The RIGHT-2 trial shows the limitations of a prehospital enrollment model, wrote Karen C. Johnston, MD, professor of neurology at the University of Virginia in Charlottesville, and Valerie L. Durkalski-Mauldin, PhD, professor of medicine at Medical University of South Carolina in Charleston, in an editorial accompanying the RIGHT-2 trial results. The rate of nonstroke diagnoses was so high that it would have reduced the study’s power to assess the efficacy of glyceryl trinitrate (GTN), had the investigators not increased the sample size and changed the statistical analysis plan.
“Future prehospital trials need to consider the implications of enrolling, yet excluding, stroke mimics in the primary analysis,” said Dr. Johnston and Dr. Durkalski-Mauldin. Using telemedicine in the ambulance to facilitate direct contact between the stroke provider and the patient and emergency medical services provider could reduce the enrollment of patients with stroke mimics in clinical trials, they added. “Improved tools to exclude stroke mimics in the field have been difficult to develop and validate. The absence of imaging in most ambulances will continue to limit field personnel from definitively determining ischemic stroke from intracerebral hemorrhage, which will limit hyperacute trials to interventions presumed safe in both populations.”
In addition, the blood pressure reduction that GTN provided might not be clinically relevant, said Dr. Johnston and Dr. Durkalski-Mauldin. “The RIGHT-2 investigators report no difference in blood pressure at day 3 or day 4 of treatment, which might have been related to the very low adherence to study protocol by day 4.
“Regardless of these limitations, RIGHT-2 has provided high-level evidence that GTN given within 4 hours of onset does not significantly improve outcome in hyperacute patients presenting with possible stroke,” the authors concluded (Lancet. 2019 Feb 6. doi: 10.1016/
S0140-6736(19)30276-4). Dr. Johnston and Dr. Durkalski-Mauldin declared no conflicts of interest.
HONOLULU – , according to data presented at the International Stroke Conference sponsored by the American Heart Association. Results suggest that GTN causes adverse effects in patients with intracerebral hemorrhage (ICH), but this observation is not definitive, according to the researchers. Study results were published online ahead of print Feb. 6 in the Lancet.
Nitric oxide is a regulatory molecule that has vasoactive effects and promotes blood pressure reduction. Vascular levels of nitric oxide are low in stroke, which suggests that the molecule may be a target for stroke treatment. GTN, a nitric oxide donor, lowered blood pressure and improved functional outcome among patients with acute stroke in the phase 2 Rapid Intervention with GTN in Hypertensive Stroke Trial (RIGHT).
Philip Bath, MD, Stroke Association Professor of Stroke Medicine at the University of Nottingham (England), and colleagues conducted the RIGHT-2 study to evaluate the safety and efficacy of GTN when administered early after onset of suspected stroke. Paramedics randomized patients in equal groups to a GTN patch or a sham patch in the ambulance. Three more patches were administered in the hospital on the following days. Active and sham patches looked similar and had no writing on them, thus ensuring effective blinding upon administration. Investigators followed up patients by telephone at 90 days to assess the modified Rankin Scale score and markers of disability, mood, cognition, and quality of life.
Eligible participants were adults who had dialed emergency services, independently or with assistance, because of a possible stroke. They had a Face, Arm, Speech, Time (FAST) score of 2 or 3, were within 4 hours of onset, and had a systolic blood pressure greater than 120 mm Hg. Patients from nursing homes, those with hypoglycemia, those who were unconscious, and those with a witnessed seizure were excluded.
Dr. Bath and colleagues planned to enroll 850 patients from five ambulance services in 30 hospitals across the United Kingdom. Data were to be examined through an intention-to-treat analysis. During the trial, however, the investigators observed that the rate of stroke mimics was 26%, rather than the 12% that they had anticipated. To ensure the proper power for the study, the investigators increased the sample size to 1,149 patients. They also changed the planned data analysis from intention-to-treat to hierarchical analysis. Specifically, the researchers planned to perform the primary analysis in patients with stroke or TIA. If the results were positive, then they would perform a standard intention-to-treat analysis.
More than 99% of patients received the first patch. Approximately 57% of the population received the first two patches. One reason for this decrease in adherence was that many patients were discharged from the hospital with a TIA or a stroke mimic. Participants’ average age was 72. The median time from onset to randomization was 71 minutes, and the median time to treatment was 73 minutes. Participants’ mean systolic blood pressure was 162 mm Hg. Approximately 60% of the patients had a FAST score of 3. About 50% of participants had ischemic stroke, 13% had ICH, 10% had TIA, and 26% had stroke mimics.
At 1 hour after treatment initiation, systolic blood pressure decreased by 6.2 mm Hg and diastolic blood pressure decreased by 2.7 mm Hg among patients who received GTN, compared with controls. At one day, the differences were 5.2 mm Hg and 2.5 mm Hg, respectively, in treated patients, compared with controls. Blood pressure became similar between groups thereafter, “in part because of the tachyphylaxis that we know happens with GTN,” said Dr. Bath.
The researchers found no evidence of an effect of GTN on functional outcome at 90 days in participants with stroke or transient ischemic attack. The adjusted common odds ratio of poor outcome was 1.25 in the GTN group, compared with the control group (95 % confidence interval, 0.97-1.60; P = .083). “We were close to getting a negative trial,” said Dr. Bath.
Subgroup analyses revealed differences in outcome according to the time to randomization. GTN had a negative effect in patients treated within 1 hour of onset. Results were neutral, but tended to be negative, in patients treated between 1 and 2 hours of onset. Results were neutral, but tended to be positive, among patients treated at more than 2 hours after onset. There was no difference between groups in the rate of mortality.
One of the study’s limitations was its single-blind design. In addition, the trial was conducted in a single country, and the investigators changed the protocol after it was initiated. “We had a higher-than-expected [stroke] mimic rate, although I’m reassured by most experts that ... this is probably about right,” said Dr. Bath.
A potential reason for the neutral results is the negative effect that GTN had among patients with ICH, said Dr. Bath. “In that very early first hour, we are of course breaking a law that we learned in medical school, which is that the first part of hemostasis is spasm. We gave an antispasmodic: a vasodilator,” he added. “That is speculation.”
The trial was funded by the British Heart Foundation. Dr. Bath declared a modest ownership interest in Platelet Solutions and consultant or advisory board positions with Moleac, DiaMedica, Phagenesis, Nestle, and ReNeuron. The other investigators declared no conflicts of interest.
HONOLULU – , according to data presented at the International Stroke Conference sponsored by the American Heart Association. Results suggest that GTN causes adverse effects in patients with intracerebral hemorrhage (ICH), but this observation is not definitive, according to the researchers. Study results were published online ahead of print Feb. 6 in the Lancet.
Nitric oxide is a regulatory molecule that has vasoactive effects and promotes blood pressure reduction. Vascular levels of nitric oxide are low in stroke, which suggests that the molecule may be a target for stroke treatment. GTN, a nitric oxide donor, lowered blood pressure and improved functional outcome among patients with acute stroke in the phase 2 Rapid Intervention with GTN in Hypertensive Stroke Trial (RIGHT).
Philip Bath, MD, Stroke Association Professor of Stroke Medicine at the University of Nottingham (England), and colleagues conducted the RIGHT-2 study to evaluate the safety and efficacy of GTN when administered early after onset of suspected stroke. Paramedics randomized patients in equal groups to a GTN patch or a sham patch in the ambulance. Three more patches were administered in the hospital on the following days. Active and sham patches looked similar and had no writing on them, thus ensuring effective blinding upon administration. Investigators followed up patients by telephone at 90 days to assess the modified Rankin Scale score and markers of disability, mood, cognition, and quality of life.
Eligible participants were adults who had dialed emergency services, independently or with assistance, because of a possible stroke. They had a Face, Arm, Speech, Time (FAST) score of 2 or 3, were within 4 hours of onset, and had a systolic blood pressure greater than 120 mm Hg. Patients from nursing homes, those with hypoglycemia, those who were unconscious, and those with a witnessed seizure were excluded.
Dr. Bath and colleagues planned to enroll 850 patients from five ambulance services in 30 hospitals across the United Kingdom. Data were to be examined through an intention-to-treat analysis. During the trial, however, the investigators observed that the rate of stroke mimics was 26%, rather than the 12% that they had anticipated. To ensure the proper power for the study, the investigators increased the sample size to 1,149 patients. They also changed the planned data analysis from intention-to-treat to hierarchical analysis. Specifically, the researchers planned to perform the primary analysis in patients with stroke or TIA. If the results were positive, then they would perform a standard intention-to-treat analysis.
More than 99% of patients received the first patch. Approximately 57% of the population received the first two patches. One reason for this decrease in adherence was that many patients were discharged from the hospital with a TIA or a stroke mimic. Participants’ average age was 72. The median time from onset to randomization was 71 minutes, and the median time to treatment was 73 minutes. Participants’ mean systolic blood pressure was 162 mm Hg. Approximately 60% of the patients had a FAST score of 3. About 50% of participants had ischemic stroke, 13% had ICH, 10% had TIA, and 26% had stroke mimics.
At 1 hour after treatment initiation, systolic blood pressure decreased by 6.2 mm Hg and diastolic blood pressure decreased by 2.7 mm Hg among patients who received GTN, compared with controls. At one day, the differences were 5.2 mm Hg and 2.5 mm Hg, respectively, in treated patients, compared with controls. Blood pressure became similar between groups thereafter, “in part because of the tachyphylaxis that we know happens with GTN,” said Dr. Bath.
The researchers found no evidence of an effect of GTN on functional outcome at 90 days in participants with stroke or transient ischemic attack. The adjusted common odds ratio of poor outcome was 1.25 in the GTN group, compared with the control group (95 % confidence interval, 0.97-1.60; P = .083). “We were close to getting a negative trial,” said Dr. Bath.
Subgroup analyses revealed differences in outcome according to the time to randomization. GTN had a negative effect in patients treated within 1 hour of onset. Results were neutral, but tended to be negative, in patients treated between 1 and 2 hours of onset. Results were neutral, but tended to be positive, among patients treated at more than 2 hours after onset. There was no difference between groups in the rate of mortality.
One of the study’s limitations was its single-blind design. In addition, the trial was conducted in a single country, and the investigators changed the protocol after it was initiated. “We had a higher-than-expected [stroke] mimic rate, although I’m reassured by most experts that ... this is probably about right,” said Dr. Bath.
A potential reason for the neutral results is the negative effect that GTN had among patients with ICH, said Dr. Bath. “In that very early first hour, we are of course breaking a law that we learned in medical school, which is that the first part of hemostasis is spasm. We gave an antispasmodic: a vasodilator,” he added. “That is speculation.”
The trial was funded by the British Heart Foundation. Dr. Bath declared a modest ownership interest in Platelet Solutions and consultant or advisory board positions with Moleac, DiaMedica, Phagenesis, Nestle, and ReNeuron. The other investigators declared no conflicts of interest.
REPORTING FROM ISC 2019
Stroke thrombolysis looks safe 31+ days after prior stroke
HONOLULU – , based on a review of more than 40,000 U.S. stroke patients.
Current U.S. stroke management guidelines say that thrombolytic therapy with tissue plasminogen activator (tPA; alteplase; Activase) is contraindicated for index stroke patients who had a prior stroke within the previous 3 months (Stroke. 2018 Mar;49[3]:e46-99). But analysis of 293 U.S. patients who received thrombolytic treatment for an index acute ischemic stroke despite having had a recent, prior stroke showed no increased risk for adverse outcomes when the prior stroke occurred more than 30 days before, Shreyansh Shah, MD, said at the International Stroke Conference sponsored by the American Heart Association.
“The risk of symptomatic intracranial hemorrhage [ICH] after thrombolysis was highest among those with a history of prior ischemic stroke within the past 14 days,” said Dr. Shah, a neurologist at Duke University in Durham, N.C.
“Even after many adjustments we still saw a high risk of symptomatic ICH within the first 2 weeks, suggesting that these patients are at especially high risk” from treatment with tissue plasminogen activator for the index stroke. These findings “are very important because I don’t see a randomized trial happening to test the hypothesis,” Dr. Shah said in an interview.
He also suggested that prior treatment with tPA was not an important factor, just the occurrence of a recent, prior ischemic stoke that left blood vessels in the affected brain region “friable and at high risk for hemorrhage,” he said.
His study used data from 40,396 patients with an acute ischemic stroke who presented at and received treatment with tPA at any of 1,522 hospitals that participated in the Get With the Guidelines-Stroke program during 2009-2015. The analysis focused on 30,655 of these patients with no prior stroke history who served as the controls, and 293 who had a prior ischemic stroke within the preceding 90 days. These 293 patients further broke into 43 who received thrombolysis within 14 days of their prior stroke, 47 who had the treatment 15-30 days after their prior stroke, and 203 who underwent thrombolysis 31-90 days after their prior stroke. Patients ages’ in both the no-stroke history and recent-stroke subgroups each averaged 80 years.
A comparison between all 293 patients who had a prior stroke within 90 days and the controls showed no statistically significant difference in the rate of symptomatic ICH: 5% among those with no stroke history and 8% in those with a recent stroke. There was also no significant difference in the rate of in-hospital mortality, occurring in 9% of those without a prior stroke, compared with 13% of those with a recent prior stroke. But the patients with no stroke history fared better by other measures, with a significantly lower rate of in-hospital death or discharge to a hospice, and also a significantly higher rate of 0-1 scores on the modified Rankin Scale, compared with patients with a history of prior stroke.
A more granular analysis of the timing of the prior stroke showed that most of risk from thrombolysis clustered in patients with a very recent prior stroke. The 43 patients with a prior stroke within the preceding 14 days had a symptomatic ICH rate of 16% after thrombolysis, 3.7-fold higher than the control patients in an adjusted analysis. Once the patients with a prior stroke within the past 14 days were pulled out, the remaining patients with prior strokes 15-30 days before as well as those with a prior stroke 31-90 days previously had symptomatic ICH rates that were not significantly different from the controls, Dr. Shah reported.
The results also showed an increased rate of in-hospital mortality or discharge to a hospice clustered in patients treated either within 14 days or during 15-30 days after a prior stroke. In both subgroups, the rate of this outcome was about triple the control rate. In the subgroup treated with thrombolysis 31-90 days after a prior stroke, the rate of in-hospital mortality or discharge to a hospice was about the same as the controls.
“It appears that some patients could benefit from tPA; there is a potential safety signal. It allows for some discretion when using thrombolytic treatment” in patients with a recent, prior stroke, Dr. Shah suggested. “This is by far the largest analysis ever reported” for thrombolytic treatment of patients following a recent, prior stroke, noted Ying Xian, MD, PhD, a Duke neurologist and study coauthor.
But Gregg C. Fonarow, MD, another coauthor, cautioned against immediately applying this finding to practice. “The findings of Dr. Shah’s study suggest that selected patients with prior stroke within a 14- to 90-day window may be considered for tPA treatment. However, further study is warranted given the relatively small number of patients,” said Dr. Fonarow, professor of medicine and cochief of cardiology at the University of California, Los Angeles.
Dr. Shah and Dr. Xian had no disclosures. Dr. Fonarow had no relevant disclosures.
SOURCE: Shah S et al. Stroke. 2019 Feb;50(Suppl_1): Abstract 35.
HONOLULU – , based on a review of more than 40,000 U.S. stroke patients.
Current U.S. stroke management guidelines say that thrombolytic therapy with tissue plasminogen activator (tPA; alteplase; Activase) is contraindicated for index stroke patients who had a prior stroke within the previous 3 months (Stroke. 2018 Mar;49[3]:e46-99). But analysis of 293 U.S. patients who received thrombolytic treatment for an index acute ischemic stroke despite having had a recent, prior stroke showed no increased risk for adverse outcomes when the prior stroke occurred more than 30 days before, Shreyansh Shah, MD, said at the International Stroke Conference sponsored by the American Heart Association.
“The risk of symptomatic intracranial hemorrhage [ICH] after thrombolysis was highest among those with a history of prior ischemic stroke within the past 14 days,” said Dr. Shah, a neurologist at Duke University in Durham, N.C.
“Even after many adjustments we still saw a high risk of symptomatic ICH within the first 2 weeks, suggesting that these patients are at especially high risk” from treatment with tissue plasminogen activator for the index stroke. These findings “are very important because I don’t see a randomized trial happening to test the hypothesis,” Dr. Shah said in an interview.
He also suggested that prior treatment with tPA was not an important factor, just the occurrence of a recent, prior ischemic stoke that left blood vessels in the affected brain region “friable and at high risk for hemorrhage,” he said.
His study used data from 40,396 patients with an acute ischemic stroke who presented at and received treatment with tPA at any of 1,522 hospitals that participated in the Get With the Guidelines-Stroke program during 2009-2015. The analysis focused on 30,655 of these patients with no prior stroke history who served as the controls, and 293 who had a prior ischemic stroke within the preceding 90 days. These 293 patients further broke into 43 who received thrombolysis within 14 days of their prior stroke, 47 who had the treatment 15-30 days after their prior stroke, and 203 who underwent thrombolysis 31-90 days after their prior stroke. Patients ages’ in both the no-stroke history and recent-stroke subgroups each averaged 80 years.
A comparison between all 293 patients who had a prior stroke within 90 days and the controls showed no statistically significant difference in the rate of symptomatic ICH: 5% among those with no stroke history and 8% in those with a recent stroke. There was also no significant difference in the rate of in-hospital mortality, occurring in 9% of those without a prior stroke, compared with 13% of those with a recent prior stroke. But the patients with no stroke history fared better by other measures, with a significantly lower rate of in-hospital death or discharge to a hospice, and also a significantly higher rate of 0-1 scores on the modified Rankin Scale, compared with patients with a history of prior stroke.
A more granular analysis of the timing of the prior stroke showed that most of risk from thrombolysis clustered in patients with a very recent prior stroke. The 43 patients with a prior stroke within the preceding 14 days had a symptomatic ICH rate of 16% after thrombolysis, 3.7-fold higher than the control patients in an adjusted analysis. Once the patients with a prior stroke within the past 14 days were pulled out, the remaining patients with prior strokes 15-30 days before as well as those with a prior stroke 31-90 days previously had symptomatic ICH rates that were not significantly different from the controls, Dr. Shah reported.
The results also showed an increased rate of in-hospital mortality or discharge to a hospice clustered in patients treated either within 14 days or during 15-30 days after a prior stroke. In both subgroups, the rate of this outcome was about triple the control rate. In the subgroup treated with thrombolysis 31-90 days after a prior stroke, the rate of in-hospital mortality or discharge to a hospice was about the same as the controls.
“It appears that some patients could benefit from tPA; there is a potential safety signal. It allows for some discretion when using thrombolytic treatment” in patients with a recent, prior stroke, Dr. Shah suggested. “This is by far the largest analysis ever reported” for thrombolytic treatment of patients following a recent, prior stroke, noted Ying Xian, MD, PhD, a Duke neurologist and study coauthor.
But Gregg C. Fonarow, MD, another coauthor, cautioned against immediately applying this finding to practice. “The findings of Dr. Shah’s study suggest that selected patients with prior stroke within a 14- to 90-day window may be considered for tPA treatment. However, further study is warranted given the relatively small number of patients,” said Dr. Fonarow, professor of medicine and cochief of cardiology at the University of California, Los Angeles.
Dr. Shah and Dr. Xian had no disclosures. Dr. Fonarow had no relevant disclosures.
SOURCE: Shah S et al. Stroke. 2019 Feb;50(Suppl_1): Abstract 35.
HONOLULU – , based on a review of more than 40,000 U.S. stroke patients.
Current U.S. stroke management guidelines say that thrombolytic therapy with tissue plasminogen activator (tPA; alteplase; Activase) is contraindicated for index stroke patients who had a prior stroke within the previous 3 months (Stroke. 2018 Mar;49[3]:e46-99). But analysis of 293 U.S. patients who received thrombolytic treatment for an index acute ischemic stroke despite having had a recent, prior stroke showed no increased risk for adverse outcomes when the prior stroke occurred more than 30 days before, Shreyansh Shah, MD, said at the International Stroke Conference sponsored by the American Heart Association.
“The risk of symptomatic intracranial hemorrhage [ICH] after thrombolysis was highest among those with a history of prior ischemic stroke within the past 14 days,” said Dr. Shah, a neurologist at Duke University in Durham, N.C.
“Even after many adjustments we still saw a high risk of symptomatic ICH within the first 2 weeks, suggesting that these patients are at especially high risk” from treatment with tissue plasminogen activator for the index stroke. These findings “are very important because I don’t see a randomized trial happening to test the hypothesis,” Dr. Shah said in an interview.
He also suggested that prior treatment with tPA was not an important factor, just the occurrence of a recent, prior ischemic stoke that left blood vessels in the affected brain region “friable and at high risk for hemorrhage,” he said.
His study used data from 40,396 patients with an acute ischemic stroke who presented at and received treatment with tPA at any of 1,522 hospitals that participated in the Get With the Guidelines-Stroke program during 2009-2015. The analysis focused on 30,655 of these patients with no prior stroke history who served as the controls, and 293 who had a prior ischemic stroke within the preceding 90 days. These 293 patients further broke into 43 who received thrombolysis within 14 days of their prior stroke, 47 who had the treatment 15-30 days after their prior stroke, and 203 who underwent thrombolysis 31-90 days after their prior stroke. Patients ages’ in both the no-stroke history and recent-stroke subgroups each averaged 80 years.
A comparison between all 293 patients who had a prior stroke within 90 days and the controls showed no statistically significant difference in the rate of symptomatic ICH: 5% among those with no stroke history and 8% in those with a recent stroke. There was also no significant difference in the rate of in-hospital mortality, occurring in 9% of those without a prior stroke, compared with 13% of those with a recent prior stroke. But the patients with no stroke history fared better by other measures, with a significantly lower rate of in-hospital death or discharge to a hospice, and also a significantly higher rate of 0-1 scores on the modified Rankin Scale, compared with patients with a history of prior stroke.
A more granular analysis of the timing of the prior stroke showed that most of risk from thrombolysis clustered in patients with a very recent prior stroke. The 43 patients with a prior stroke within the preceding 14 days had a symptomatic ICH rate of 16% after thrombolysis, 3.7-fold higher than the control patients in an adjusted analysis. Once the patients with a prior stroke within the past 14 days were pulled out, the remaining patients with prior strokes 15-30 days before as well as those with a prior stroke 31-90 days previously had symptomatic ICH rates that were not significantly different from the controls, Dr. Shah reported.
The results also showed an increased rate of in-hospital mortality or discharge to a hospice clustered in patients treated either within 14 days or during 15-30 days after a prior stroke. In both subgroups, the rate of this outcome was about triple the control rate. In the subgroup treated with thrombolysis 31-90 days after a prior stroke, the rate of in-hospital mortality or discharge to a hospice was about the same as the controls.
“It appears that some patients could benefit from tPA; there is a potential safety signal. It allows for some discretion when using thrombolytic treatment” in patients with a recent, prior stroke, Dr. Shah suggested. “This is by far the largest analysis ever reported” for thrombolytic treatment of patients following a recent, prior stroke, noted Ying Xian, MD, PhD, a Duke neurologist and study coauthor.
But Gregg C. Fonarow, MD, another coauthor, cautioned against immediately applying this finding to practice. “The findings of Dr. Shah’s study suggest that selected patients with prior stroke within a 14- to 90-day window may be considered for tPA treatment. However, further study is warranted given the relatively small number of patients,” said Dr. Fonarow, professor of medicine and cochief of cardiology at the University of California, Los Angeles.
Dr. Shah and Dr. Xian had no disclosures. Dr. Fonarow had no relevant disclosures.
SOURCE: Shah S et al. Stroke. 2019 Feb;50(Suppl_1): Abstract 35.
REPORTING FROM ISC 2019
Stroke endovascular therapy: The more you do, the better you do
HONOLULU – The well-documented link between higher procedure volumes and better procedure efficacy also applies to endovascular thrombectomy for acute ischemic stroke.
in analysis of data from two different U.S. sources: the National Inpatient Sample (NIS) and the state of Florida, Sunil A. Sheth, MD, said at the International Stroke Conference sponsored by the American Heart Association.
The finding raises questions about how to best triage patients with an acute ischemic stroke, suggesting that, in at least some situations, patients might be better served being taken to a higher-volume center even if it’s not the closest, noted Dr. Sheth, The results also suggest that the findings in the trials proving the value of EST run primarily at large, tertiary care, referral centers might not be generalizable to all centers that start an endovascular program.
The study looked at data collected during 2006-2016 in Florida and during 2012-2016 in the NIS, and found that in both databases the rate of EST procedures performed showed steadily increasing use over time, with a sharp increase in the number of centers performing EST in 2015. Each of the two data sets also showed that better discharge outcomes occurred in patients treated at centers with the highest procedural volumes.
In the nationwide NIS data, for every 10 additional patients a center treated with EST annually, the incidence of a “good” hospital-discharge outcome (defined as either discharge home or to an acute rehabilitation hospital) rose by 30%, compared with lower-volume centers in a multivariate regression analysis, a statistically significant relationship, said Dr. Sheth, a neurologist at the University of Texas, Houston. This volume-outcome relationship held fairly constant through volumes up to about 50 EST cases annually. “The more the better,” he observed.
“The data suggest that EST outcomes are not always the same,” but right now most emergency medical service systems do not take EST case volume into account when deciding where to take an acute stroke patient, Dr. Sheth said in an interview. But he cautioned against an oversimplified focus on just EST case volume.
A link between volume and better outcomes “is easy to understand and not surprising. We see this relationship for a variety of procedures. The data suggest we need to consider procedure volumes. But volume is only part of makes for good outcomes; it’s not the only factor,” he stressed.
Dr. Sheth and his associates used data collected by the Florida Agency for Health Care Administration on 3,890 acute ischemic stroke patients treated with EST at 56 Florida hospitals and on 42,505 such patients in the NIS database treated at 2,260 U.S. hospitals. During the 11-year period for Florida data collection, the number of centers performing EST in the state rose steadily at an average rate of about four new centers per year. Although the number of EST procedures done also rose sharply, in general over time a higher percentage of patients underwent treatment at lower-volume centers. Similar patterns existed in the national data. The Florida data showed a statistically significant 10% improvement in good discharge outcomes for every 10 additional EST patients a center treated a year, consistent with the NIS data.
Concurrently with Dr. Sheth’s report, the results also appeared in an article published online (Stroke. 2019 Feb 6. doi: 10.1161/STROKEAHA.118.023967).
Dr. Sheth reported no disclosures.
SOURCE: Sheth SA et al. ISC 2019, Abstract 002.
The idea that when centers perform more of a procedure, such as endovascular thrombectomy for acute ischemic stroke, they more often do it better is intuitively plausible, which helps makes these findings believable. It’s also a relationship we’ve already seen for other types of endovascular therapies. What this study did not address were other factors beyond case volume also might also make important contributions to outcome, such as the speed of treatment delivery.
Volume thresholds for endovascular stroke programs will come eventually, but for the time being our focus should be on insuring wide access to endovascular treatment.
Bruce Ovbiagele, MD, a neurologist and chief of staff for the San Francisco Veteran Affairs Health Care System, made these comments in an interview. He reported no disclosures.
The idea that when centers perform more of a procedure, such as endovascular thrombectomy for acute ischemic stroke, they more often do it better is intuitively plausible, which helps makes these findings believable. It’s also a relationship we’ve already seen for other types of endovascular therapies. What this study did not address were other factors beyond case volume also might also make important contributions to outcome, such as the speed of treatment delivery.
Volume thresholds for endovascular stroke programs will come eventually, but for the time being our focus should be on insuring wide access to endovascular treatment.
Bruce Ovbiagele, MD, a neurologist and chief of staff for the San Francisco Veteran Affairs Health Care System, made these comments in an interview. He reported no disclosures.
The idea that when centers perform more of a procedure, such as endovascular thrombectomy for acute ischemic stroke, they more often do it better is intuitively plausible, which helps makes these findings believable. It’s also a relationship we’ve already seen for other types of endovascular therapies. What this study did not address were other factors beyond case volume also might also make important contributions to outcome, such as the speed of treatment delivery.
Volume thresholds for endovascular stroke programs will come eventually, but for the time being our focus should be on insuring wide access to endovascular treatment.
Bruce Ovbiagele, MD, a neurologist and chief of staff for the San Francisco Veteran Affairs Health Care System, made these comments in an interview. He reported no disclosures.
HONOLULU – The well-documented link between higher procedure volumes and better procedure efficacy also applies to endovascular thrombectomy for acute ischemic stroke.
in analysis of data from two different U.S. sources: the National Inpatient Sample (NIS) and the state of Florida, Sunil A. Sheth, MD, said at the International Stroke Conference sponsored by the American Heart Association.
The finding raises questions about how to best triage patients with an acute ischemic stroke, suggesting that, in at least some situations, patients might be better served being taken to a higher-volume center even if it’s not the closest, noted Dr. Sheth, The results also suggest that the findings in the trials proving the value of EST run primarily at large, tertiary care, referral centers might not be generalizable to all centers that start an endovascular program.
The study looked at data collected during 2006-2016 in Florida and during 2012-2016 in the NIS, and found that in both databases the rate of EST procedures performed showed steadily increasing use over time, with a sharp increase in the number of centers performing EST in 2015. Each of the two data sets also showed that better discharge outcomes occurred in patients treated at centers with the highest procedural volumes.
In the nationwide NIS data, for every 10 additional patients a center treated with EST annually, the incidence of a “good” hospital-discharge outcome (defined as either discharge home or to an acute rehabilitation hospital) rose by 30%, compared with lower-volume centers in a multivariate regression analysis, a statistically significant relationship, said Dr. Sheth, a neurologist at the University of Texas, Houston. This volume-outcome relationship held fairly constant through volumes up to about 50 EST cases annually. “The more the better,” he observed.
“The data suggest that EST outcomes are not always the same,” but right now most emergency medical service systems do not take EST case volume into account when deciding where to take an acute stroke patient, Dr. Sheth said in an interview. But he cautioned against an oversimplified focus on just EST case volume.
A link between volume and better outcomes “is easy to understand and not surprising. We see this relationship for a variety of procedures. The data suggest we need to consider procedure volumes. But volume is only part of makes for good outcomes; it’s not the only factor,” he stressed.
Dr. Sheth and his associates used data collected by the Florida Agency for Health Care Administration on 3,890 acute ischemic stroke patients treated with EST at 56 Florida hospitals and on 42,505 such patients in the NIS database treated at 2,260 U.S. hospitals. During the 11-year period for Florida data collection, the number of centers performing EST in the state rose steadily at an average rate of about four new centers per year. Although the number of EST procedures done also rose sharply, in general over time a higher percentage of patients underwent treatment at lower-volume centers. Similar patterns existed in the national data. The Florida data showed a statistically significant 10% improvement in good discharge outcomes for every 10 additional EST patients a center treated a year, consistent with the NIS data.
Concurrently with Dr. Sheth’s report, the results also appeared in an article published online (Stroke. 2019 Feb 6. doi: 10.1161/STROKEAHA.118.023967).
Dr. Sheth reported no disclosures.
SOURCE: Sheth SA et al. ISC 2019, Abstract 002.
HONOLULU – The well-documented link between higher procedure volumes and better procedure efficacy also applies to endovascular thrombectomy for acute ischemic stroke.
in analysis of data from two different U.S. sources: the National Inpatient Sample (NIS) and the state of Florida, Sunil A. Sheth, MD, said at the International Stroke Conference sponsored by the American Heart Association.
The finding raises questions about how to best triage patients with an acute ischemic stroke, suggesting that, in at least some situations, patients might be better served being taken to a higher-volume center even if it’s not the closest, noted Dr. Sheth, The results also suggest that the findings in the trials proving the value of EST run primarily at large, tertiary care, referral centers might not be generalizable to all centers that start an endovascular program.
The study looked at data collected during 2006-2016 in Florida and during 2012-2016 in the NIS, and found that in both databases the rate of EST procedures performed showed steadily increasing use over time, with a sharp increase in the number of centers performing EST in 2015. Each of the two data sets also showed that better discharge outcomes occurred in patients treated at centers with the highest procedural volumes.
In the nationwide NIS data, for every 10 additional patients a center treated with EST annually, the incidence of a “good” hospital-discharge outcome (defined as either discharge home or to an acute rehabilitation hospital) rose by 30%, compared with lower-volume centers in a multivariate regression analysis, a statistically significant relationship, said Dr. Sheth, a neurologist at the University of Texas, Houston. This volume-outcome relationship held fairly constant through volumes up to about 50 EST cases annually. “The more the better,” he observed.
“The data suggest that EST outcomes are not always the same,” but right now most emergency medical service systems do not take EST case volume into account when deciding where to take an acute stroke patient, Dr. Sheth said in an interview. But he cautioned against an oversimplified focus on just EST case volume.
A link between volume and better outcomes “is easy to understand and not surprising. We see this relationship for a variety of procedures. The data suggest we need to consider procedure volumes. But volume is only part of makes for good outcomes; it’s not the only factor,” he stressed.
Dr. Sheth and his associates used data collected by the Florida Agency for Health Care Administration on 3,890 acute ischemic stroke patients treated with EST at 56 Florida hospitals and on 42,505 such patients in the NIS database treated at 2,260 U.S. hospitals. During the 11-year period for Florida data collection, the number of centers performing EST in the state rose steadily at an average rate of about four new centers per year. Although the number of EST procedures done also rose sharply, in general over time a higher percentage of patients underwent treatment at lower-volume centers. Similar patterns existed in the national data. The Florida data showed a statistically significant 10% improvement in good discharge outcomes for every 10 additional EST patients a center treated a year, consistent with the NIS data.
Concurrently with Dr. Sheth’s report, the results also appeared in an article published online (Stroke. 2019 Feb 6. doi: 10.1161/STROKEAHA.118.023967).
Dr. Sheth reported no disclosures.
SOURCE: Sheth SA et al. ISC 2019, Abstract 002.
REPORTING FROM ISC 2019
Noncardiac surgery has 7% covert stroke rate in elderly
HONOLULU – Covert strokes are relatively common in elderly patients who undergo noncardiac surgery, with a 7% incidence among a group of prospectively followed but generally unselected patients in a multicenter, international study.
By definition, these covert strokes were acutely asymptomatic, but showed evidence of clinical effects during the subsequent year. Twelve months after surgery, patients with acute, perioperative covert strokes found by systematic collection of postoperative MRI brain scans had a twofold increased rate of cognitive decline and a greater than twofold increased rate of delirium, compared with the patients who did not have evidence of a covert stroke, Marko Mrkobrada, MD, said at the International Stroke Conference sponsored by the American Heart Association.
The message from these findings is that, when elderly patients exhibit confusion or delirium after noncardiac surgery, their physicians should have a high index of suspicion that a covert stroke may have occurred, Dr. Mrkobrada said in a video interview. It’s possible that typical stroke symptoms do not appear in many of the covert stroke patients because they are masked in the immediate postoperative period, he added.
Right now, the only way to screen for a covert stroke is with a brain MR, a test that generally costs several hundred dollars, which is too expensive for routine screening. Dr. Mrkobrada said that his team hopes further study will identify a biomarker that can flag patients with a covert stroke at a lower cost. For example, colleagues of Dr. Mrkobrada have successfully used high-sensitivity troponin T, a biomarker of myocardial injury, to identify patients who have myocardial injury after noncardiac surgery (MINS; JAMA. 2017 April 25;371[16]:1642-51). Study results also established that treating MINS patients with dabigatran improved their long-term clinical outcomes (Lancet. 2018 June 9;391[10137]:2325-34).
Covert stroke after noncardiac surgery “is the same concept” as MINS, said Dr. Mrkobrada, a researcher at the London Health Sciences Centre in Canada. “We find strokes that do not get picked up after noncardiac surgery just like MIs that are not picked up,” he said. It’s also possible that certain interventions may improve outcomes in patients with covert strokes, just as they have helped MINS patients, he suggested. Potentially helpful interventions could include aspirin, a statin, and improved blood pressure control. A major goal for his research group is finding a biomarker that makes diagnosing covert stroke as easy as using high sensitivity troponin T to diagnose MINS.
The NeuroVISION (Detection and Neurological Impact of Cerebrovascular Events In Noncardiac Surgery Patients: A Cohort EvaluatioN) study enrolled and tested 1,114 people aged 65 years or older scheduled for elective noncardiac surgery anticipated to keep them hospitalized for at least 2 days at any of 12 participating centers in nine countries. Patients underwent cognitive function testing before surgery and had a brain MR scan 2-9 days after surgery, and they were excluded if they developed an overt stroke prior to the scan. Patients underwent a second round of cognitive testing a year after surgery. Patients averaged 73 years old.
The screening MR scans identified covert strokes in 78 of the study subjects (7%). The 1-year cognitive tests showed measurable drops in cognitive function in 42% of those who had experience covert strokes and in 29% of everyone else. Those rates translated to a doubled odds ratio for cognitive decline after covert stroke, compared with people without covert stroke after adjustment for baseline between-group differences, a highly statistically significant between-group difference for the study’s primary endpoint. Delirium occurred 2.2-fold more often in the covert stroke patients after adjustment, and overt strokes during 1-year follow-up were 4.1-fold more common patients who’d experienced a covert stroke, compared with everyone else, after adjustment, Dr. Mrkobrada reported. NeuroVISION is the first large-scale study to assess the incidence and associations of covert strokes after noncardiac surgery, he noted.
SOURCE: Mrkobrada M. ISC 2019, Late-Breaking Abstract LB18.
HONOLULU – Covert strokes are relatively common in elderly patients who undergo noncardiac surgery, with a 7% incidence among a group of prospectively followed but generally unselected patients in a multicenter, international study.
By definition, these covert strokes were acutely asymptomatic, but showed evidence of clinical effects during the subsequent year. Twelve months after surgery, patients with acute, perioperative covert strokes found by systematic collection of postoperative MRI brain scans had a twofold increased rate of cognitive decline and a greater than twofold increased rate of delirium, compared with the patients who did not have evidence of a covert stroke, Marko Mrkobrada, MD, said at the International Stroke Conference sponsored by the American Heart Association.
The message from these findings is that, when elderly patients exhibit confusion or delirium after noncardiac surgery, their physicians should have a high index of suspicion that a covert stroke may have occurred, Dr. Mrkobrada said in a video interview. It’s possible that typical stroke symptoms do not appear in many of the covert stroke patients because they are masked in the immediate postoperative period, he added.
Right now, the only way to screen for a covert stroke is with a brain MR, a test that generally costs several hundred dollars, which is too expensive for routine screening. Dr. Mrkobrada said that his team hopes further study will identify a biomarker that can flag patients with a covert stroke at a lower cost. For example, colleagues of Dr. Mrkobrada have successfully used high-sensitivity troponin T, a biomarker of myocardial injury, to identify patients who have myocardial injury after noncardiac surgery (MINS; JAMA. 2017 April 25;371[16]:1642-51). Study results also established that treating MINS patients with dabigatran improved their long-term clinical outcomes (Lancet. 2018 June 9;391[10137]:2325-34).
Covert stroke after noncardiac surgery “is the same concept” as MINS, said Dr. Mrkobrada, a researcher at the London Health Sciences Centre in Canada. “We find strokes that do not get picked up after noncardiac surgery just like MIs that are not picked up,” he said. It’s also possible that certain interventions may improve outcomes in patients with covert strokes, just as they have helped MINS patients, he suggested. Potentially helpful interventions could include aspirin, a statin, and improved blood pressure control. A major goal for his research group is finding a biomarker that makes diagnosing covert stroke as easy as using high sensitivity troponin T to diagnose MINS.
The NeuroVISION (Detection and Neurological Impact of Cerebrovascular Events In Noncardiac Surgery Patients: A Cohort EvaluatioN) study enrolled and tested 1,114 people aged 65 years or older scheduled for elective noncardiac surgery anticipated to keep them hospitalized for at least 2 days at any of 12 participating centers in nine countries. Patients underwent cognitive function testing before surgery and had a brain MR scan 2-9 days after surgery, and they were excluded if they developed an overt stroke prior to the scan. Patients underwent a second round of cognitive testing a year after surgery. Patients averaged 73 years old.
The screening MR scans identified covert strokes in 78 of the study subjects (7%). The 1-year cognitive tests showed measurable drops in cognitive function in 42% of those who had experience covert strokes and in 29% of everyone else. Those rates translated to a doubled odds ratio for cognitive decline after covert stroke, compared with people without covert stroke after adjustment for baseline between-group differences, a highly statistically significant between-group difference for the study’s primary endpoint. Delirium occurred 2.2-fold more often in the covert stroke patients after adjustment, and overt strokes during 1-year follow-up were 4.1-fold more common patients who’d experienced a covert stroke, compared with everyone else, after adjustment, Dr. Mrkobrada reported. NeuroVISION is the first large-scale study to assess the incidence and associations of covert strokes after noncardiac surgery, he noted.
SOURCE: Mrkobrada M. ISC 2019, Late-Breaking Abstract LB18.
HONOLULU – Covert strokes are relatively common in elderly patients who undergo noncardiac surgery, with a 7% incidence among a group of prospectively followed but generally unselected patients in a multicenter, international study.
By definition, these covert strokes were acutely asymptomatic, but showed evidence of clinical effects during the subsequent year. Twelve months after surgery, patients with acute, perioperative covert strokes found by systematic collection of postoperative MRI brain scans had a twofold increased rate of cognitive decline and a greater than twofold increased rate of delirium, compared with the patients who did not have evidence of a covert stroke, Marko Mrkobrada, MD, said at the International Stroke Conference sponsored by the American Heart Association.
The message from these findings is that, when elderly patients exhibit confusion or delirium after noncardiac surgery, their physicians should have a high index of suspicion that a covert stroke may have occurred, Dr. Mrkobrada said in a video interview. It’s possible that typical stroke symptoms do not appear in many of the covert stroke patients because they are masked in the immediate postoperative period, he added.
Right now, the only way to screen for a covert stroke is with a brain MR, a test that generally costs several hundred dollars, which is too expensive for routine screening. Dr. Mrkobrada said that his team hopes further study will identify a biomarker that can flag patients with a covert stroke at a lower cost. For example, colleagues of Dr. Mrkobrada have successfully used high-sensitivity troponin T, a biomarker of myocardial injury, to identify patients who have myocardial injury after noncardiac surgery (MINS; JAMA. 2017 April 25;371[16]:1642-51). Study results also established that treating MINS patients with dabigatran improved their long-term clinical outcomes (Lancet. 2018 June 9;391[10137]:2325-34).
Covert stroke after noncardiac surgery “is the same concept” as MINS, said Dr. Mrkobrada, a researcher at the London Health Sciences Centre in Canada. “We find strokes that do not get picked up after noncardiac surgery just like MIs that are not picked up,” he said. It’s also possible that certain interventions may improve outcomes in patients with covert strokes, just as they have helped MINS patients, he suggested. Potentially helpful interventions could include aspirin, a statin, and improved blood pressure control. A major goal for his research group is finding a biomarker that makes diagnosing covert stroke as easy as using high sensitivity troponin T to diagnose MINS.
The NeuroVISION (Detection and Neurological Impact of Cerebrovascular Events In Noncardiac Surgery Patients: A Cohort EvaluatioN) study enrolled and tested 1,114 people aged 65 years or older scheduled for elective noncardiac surgery anticipated to keep them hospitalized for at least 2 days at any of 12 participating centers in nine countries. Patients underwent cognitive function testing before surgery and had a brain MR scan 2-9 days after surgery, and they were excluded if they developed an overt stroke prior to the scan. Patients underwent a second round of cognitive testing a year after surgery. Patients averaged 73 years old.
The screening MR scans identified covert strokes in 78 of the study subjects (7%). The 1-year cognitive tests showed measurable drops in cognitive function in 42% of those who had experience covert strokes and in 29% of everyone else. Those rates translated to a doubled odds ratio for cognitive decline after covert stroke, compared with people without covert stroke after adjustment for baseline between-group differences, a highly statistically significant between-group difference for the study’s primary endpoint. Delirium occurred 2.2-fold more often in the covert stroke patients after adjustment, and overt strokes during 1-year follow-up were 4.1-fold more common patients who’d experienced a covert stroke, compared with everyone else, after adjustment, Dr. Mrkobrada reported. NeuroVISION is the first large-scale study to assess the incidence and associations of covert strokes after noncardiac surgery, he noted.
SOURCE: Mrkobrada M. ISC 2019, Late-Breaking Abstract LB18.
REPORTING FROM ISC 2019
Key clinical point:
Major finding: Elderly patients who underwent noncardiac surgery had a 7% incidence of covert stroke.
Study details: NeuroVISION, a prospective, multicenter, observational study with 1,114 patients.
Disclosures: NeuroVISION did not receive commercial funding. Dr. Mrkobrada had no disclosures.
Source: Mrkobrada M. ISC 2019, Late-Breaking Abstract LB18.
Hormone therapy in transgender individuals may up risk of CV events
when compared with the general population, according to a study that analyzed medical records of more than 6,000 patients.
“In light of our results, we urge both physicians and transgender individuals to be aware of this increased cardiovascular risk,” first author Nienke M. Nota, MD, said in a press release for the study, which was published online Feb. 18 in Circulation. “It may be helpful to reduce risk factors by stopping smoking, exercising, eating a healthy diet, and losing weight, if needed, before starting therapy, and clinicians should continue to evaluate patients on an ongoing basis thereafter.”Dr. Nota and her colleagues at the Amsterdam University Medical Center analyzed the risk of cardiovascular events by comparing the medical records of 6,793 individuals, including only patients who received hormone therapy at their center or affiliate. They did not include those who had discontinued hormone therapy for an extended period or had alternated female and male sex hormones.
They defined transmen as indiviuals assigned female sex at birth but who had male gender identity, and transwomen as those assigned male sex at birth but with female gender identity.*
Researchers analyzed 2,517 transwomen (median age 30 years) and 1,358 transmen (median age 23 years) who received hormone therapy (defined as estrogen with and without androgen-suppressors for transwomen and testosterone for transmen) at the center gender’s clinic between 1972 and 2015. These records were compared with those of cisgender women and men (individuals whose gender identity matches their assigned birth gender).
The mean follow-up duration was 9.07 years for transwomen and 8.10 years for transmen. The researchers compared observed cases of stroke, myocardial infarction (MI), and venous thromboembolism (VTE) with expected cases using cisgender reference women and men. There were 29 stroke events, 30 MIs, and 73 VTE events for transwomen and 6 stroke, 11 MIs, and 2 VTE events for transmen.
There was a greater risk of stroke for transwomen, compared with cisgender women (standardized incidence ratio [SIR] = 2.42) and cisgender men (1.80), and a significantly greater risk of VTE, compared with cisgender women (5.52) and cisgender men (4.55).
The rate of MI was also significantly higher in transwomen, compared with cisgender women (2.64) and in transmen compared with cisgender women (3.69).
In a subgroup analysis, the researchers found ethinylestradiol use prior to 2001 did not significantly change the incident rate of cardiovascular events, but noted there was a lower rate of VTE when transwomen who began hormone therapy prior to 2001 were excluded from the analysis.
The researchers noted that hormone therapy may increase the risk of cardiovascular events in transgender individuals, in part, due to hormone therapy’s effect on cardiovascular risk factors such as lipid levels. Although a previous study analyzed the risk of cardiovascular events in transwomen and transmen, the researchers said that study could not conclude there was an increased risk of cardiovascular events for transmen.
The researchers said the results may be limited by study design, and their analysis of medical records could not account for potential confounders such as psychosocial stressors and smoking, as well as the decreasing risk of cardiovascular events over the period of the study, and assessing cardiovascular events differently than reference studies used.
The study had no specific funding, and the authors reported no relevant conflicts of interest.
SOURCE: Nota NM et al. Circulation. 2019 Feb 18. doi: 10.1161/CIRCULATIONAHA.118.038584
*Correction 2/25/2019: An earlier version of this story incorrectly defined transwomen and transmen. The definitions are now accurate.
when compared with the general population, according to a study that analyzed medical records of more than 6,000 patients.
“In light of our results, we urge both physicians and transgender individuals to be aware of this increased cardiovascular risk,” first author Nienke M. Nota, MD, said in a press release for the study, which was published online Feb. 18 in Circulation. “It may be helpful to reduce risk factors by stopping smoking, exercising, eating a healthy diet, and losing weight, if needed, before starting therapy, and clinicians should continue to evaluate patients on an ongoing basis thereafter.”Dr. Nota and her colleagues at the Amsterdam University Medical Center analyzed the risk of cardiovascular events by comparing the medical records of 6,793 individuals, including only patients who received hormone therapy at their center or affiliate. They did not include those who had discontinued hormone therapy for an extended period or had alternated female and male sex hormones.
They defined transmen as indiviuals assigned female sex at birth but who had male gender identity, and transwomen as those assigned male sex at birth but with female gender identity.*
Researchers analyzed 2,517 transwomen (median age 30 years) and 1,358 transmen (median age 23 years) who received hormone therapy (defined as estrogen with and without androgen-suppressors for transwomen and testosterone for transmen) at the center gender’s clinic between 1972 and 2015. These records were compared with those of cisgender women and men (individuals whose gender identity matches their assigned birth gender).
The mean follow-up duration was 9.07 years for transwomen and 8.10 years for transmen. The researchers compared observed cases of stroke, myocardial infarction (MI), and venous thromboembolism (VTE) with expected cases using cisgender reference women and men. There were 29 stroke events, 30 MIs, and 73 VTE events for transwomen and 6 stroke, 11 MIs, and 2 VTE events for transmen.
There was a greater risk of stroke for transwomen, compared with cisgender women (standardized incidence ratio [SIR] = 2.42) and cisgender men (1.80), and a significantly greater risk of VTE, compared with cisgender women (5.52) and cisgender men (4.55).
The rate of MI was also significantly higher in transwomen, compared with cisgender women (2.64) and in transmen compared with cisgender women (3.69).
In a subgroup analysis, the researchers found ethinylestradiol use prior to 2001 did not significantly change the incident rate of cardiovascular events, but noted there was a lower rate of VTE when transwomen who began hormone therapy prior to 2001 were excluded from the analysis.
The researchers noted that hormone therapy may increase the risk of cardiovascular events in transgender individuals, in part, due to hormone therapy’s effect on cardiovascular risk factors such as lipid levels. Although a previous study analyzed the risk of cardiovascular events in transwomen and transmen, the researchers said that study could not conclude there was an increased risk of cardiovascular events for transmen.
The researchers said the results may be limited by study design, and their analysis of medical records could not account for potential confounders such as psychosocial stressors and smoking, as well as the decreasing risk of cardiovascular events over the period of the study, and assessing cardiovascular events differently than reference studies used.
The study had no specific funding, and the authors reported no relevant conflicts of interest.
SOURCE: Nota NM et al. Circulation. 2019 Feb 18. doi: 10.1161/CIRCULATIONAHA.118.038584
*Correction 2/25/2019: An earlier version of this story incorrectly defined transwomen and transmen. The definitions are now accurate.
when compared with the general population, according to a study that analyzed medical records of more than 6,000 patients.
“In light of our results, we urge both physicians and transgender individuals to be aware of this increased cardiovascular risk,” first author Nienke M. Nota, MD, said in a press release for the study, which was published online Feb. 18 in Circulation. “It may be helpful to reduce risk factors by stopping smoking, exercising, eating a healthy diet, and losing weight, if needed, before starting therapy, and clinicians should continue to evaluate patients on an ongoing basis thereafter.”Dr. Nota and her colleagues at the Amsterdam University Medical Center analyzed the risk of cardiovascular events by comparing the medical records of 6,793 individuals, including only patients who received hormone therapy at their center or affiliate. They did not include those who had discontinued hormone therapy for an extended period or had alternated female and male sex hormones.
They defined transmen as indiviuals assigned female sex at birth but who had male gender identity, and transwomen as those assigned male sex at birth but with female gender identity.*
Researchers analyzed 2,517 transwomen (median age 30 years) and 1,358 transmen (median age 23 years) who received hormone therapy (defined as estrogen with and without androgen-suppressors for transwomen and testosterone for transmen) at the center gender’s clinic between 1972 and 2015. These records were compared with those of cisgender women and men (individuals whose gender identity matches their assigned birth gender).
The mean follow-up duration was 9.07 years for transwomen and 8.10 years for transmen. The researchers compared observed cases of stroke, myocardial infarction (MI), and venous thromboembolism (VTE) with expected cases using cisgender reference women and men. There were 29 stroke events, 30 MIs, and 73 VTE events for transwomen and 6 stroke, 11 MIs, and 2 VTE events for transmen.
There was a greater risk of stroke for transwomen, compared with cisgender women (standardized incidence ratio [SIR] = 2.42) and cisgender men (1.80), and a significantly greater risk of VTE, compared with cisgender women (5.52) and cisgender men (4.55).
The rate of MI was also significantly higher in transwomen, compared with cisgender women (2.64) and in transmen compared with cisgender women (3.69).
In a subgroup analysis, the researchers found ethinylestradiol use prior to 2001 did not significantly change the incident rate of cardiovascular events, but noted there was a lower rate of VTE when transwomen who began hormone therapy prior to 2001 were excluded from the analysis.
The researchers noted that hormone therapy may increase the risk of cardiovascular events in transgender individuals, in part, due to hormone therapy’s effect on cardiovascular risk factors such as lipid levels. Although a previous study analyzed the risk of cardiovascular events in transwomen and transmen, the researchers said that study could not conclude there was an increased risk of cardiovascular events for transmen.
The researchers said the results may be limited by study design, and their analysis of medical records could not account for potential confounders such as psychosocial stressors and smoking, as well as the decreasing risk of cardiovascular events over the period of the study, and assessing cardiovascular events differently than reference studies used.
The study had no specific funding, and the authors reported no relevant conflicts of interest.
SOURCE: Nota NM et al. Circulation. 2019 Feb 18. doi: 10.1161/CIRCULATIONAHA.118.038584
*Correction 2/25/2019: An earlier version of this story incorrectly defined transwomen and transmen. The definitions are now accurate.
FROM CIRCULATION
ICYMI: Andexanet alfa reduces anti–factor Xa activity from apixaban, rivaroxaban
Patients with acute major bleeding associated with factor Xa inhibitor usage who received andexanet alfa experienced a significant decrease in anti–factor Xa activity, with more than three-quarters of patients experiencing good or excellent hemostatic efficiency after 12 hours. That finding emerged from the multicenter, prospective, open-label, single-group ANNEXA-4 trial published in the New England Journal of Medicine (2019 Feb 11. doi: 10.1056/NEJMoa1814051).
We reported this story at the annual meeting of the American College of Cardiology before it was published in the journal. Find our coverage at the link below.
Patients with acute major bleeding associated with factor Xa inhibitor usage who received andexanet alfa experienced a significant decrease in anti–factor Xa activity, with more than three-quarters of patients experiencing good or excellent hemostatic efficiency after 12 hours. That finding emerged from the multicenter, prospective, open-label, single-group ANNEXA-4 trial published in the New England Journal of Medicine (2019 Feb 11. doi: 10.1056/NEJMoa1814051).
We reported this story at the annual meeting of the American College of Cardiology before it was published in the journal. Find our coverage at the link below.
Patients with acute major bleeding associated with factor Xa inhibitor usage who received andexanet alfa experienced a significant decrease in anti–factor Xa activity, with more than three-quarters of patients experiencing good or excellent hemostatic efficiency after 12 hours. That finding emerged from the multicenter, prospective, open-label, single-group ANNEXA-4 trial published in the New England Journal of Medicine (2019 Feb 11. doi: 10.1056/NEJMoa1814051).
We reported this story at the annual meeting of the American College of Cardiology before it was published in the journal. Find our coverage at the link below.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Minimally invasive ICH lysis safely helps when clot adequately shrinks
HONOLULU – A minimally invasive approach to lysing an intracerebral hemorrhage clot was safe but failed to produce a statistically significant improvement in long-term functional outcome when compared with usual medical management in a phase 3 randomized trial of 499 patients. However, the results also showed that when the procedure met its acute goal of cutting residual clot to a volume of 15 mL or less, it significantly boosted the percentage of patients with a modified Rankin Scale score of 0-3 when assessed a year after treatment, Daniel F. Hanley Jr., MD, said at the International Stroke Conference, sponsored by the American Heart Association.
“Improved function and increased survival was produced by surgical [clot] reduction to 15 mL or less,” said Dr. Hanley, professor of neurology at Johns Hopkins University, Baltimore, and one of the organizers of the MISTIE III trial.
When assessed by another measure, treated patients showed significant, long-term functional improvement compared with controls when their clot burden dropped by at least 70% following the lytic procedure.
“This is the first description of specific thresholds of hematoma evacuation that impact functional outcomes in intracerebral hemorrhage surgery trials,” said Issam A. Awad, MD, professor of surgery and director of neurovascular surgery at the University of Chicago and coprincipal investigator of the trial.
The problem in the trial was that the surgeons who performed the interventions did not treat many patients aggressively enough to reach these thresholds. They achieved the prespecified goal of residual clot of 15 mL or less in 59% of patients, Dr. Hanley reported, even though the study protocol called for serial infusions of 1 mg of tissue plasminogen activator (Alteplase) into the clot via a placed catheter as many as nine times, administered at 8 hour intervals, with treatment to continue until patients reached the goal residual volume or until they had received all nine doses. In actual practice during the study, operators administered a median of four lytic doses.
“We showed that this goal was important, but not all sites embraced the goal,” Dr. Hanley said. Even though the participating clinicians had a specific interest in intracerebral hemorrhage patients and in this procedure, several nonetheless “had a poor understanding of the goal,” he said in an interview. He attributed the less-than-aggressive approach many operators took to the safety concern that further doses of the lytic drug could trigger recurrent hemorrhage.
“We showed that the goal was important. I think they will embrace the [hematoma evacuation] goal when they see these data,” Dr. Hanley predicted.
An as-treated analysis of the data that focused on the 145 of 246 patients who were treated with minimally invasive lysis and reached the target residual volume and who were then functionally assessed a year later, showed that the rate of patients with a modified Rankin Scale score of 0-3 was 53%, compared with 42% among the controls, an 11% difference.
This shows “a large treatment effect. This is a big, transformative treatment,” Dr. Hanley said. “Our data clearly show that more than half the patients had a positive outcome when their surgeons were more aggressive about clot removal.” He cautioned that the trial was not just about the volume of clot removed but was also about doing it in a gentle way, with a minimum of tissue trauma. Other approaches to reducing hematoma volume may be faster or more complete but they cannot now match the record of safety and efficacy documented in MISTIE III for minimally invasive clot lysis, Dr. Hanley noted.
MISTIE III (Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III) enrolled patients at 78 centers in the United States and several other countries during 2013-2017. Patients had to enroll 12-72 hours after onset and present with a hematoma volume of at least 30 mL. Participating neurosurgeons used image-guided neuronavigation to place a 4- to 6-mm cannula through the clot, ideally straight through the hematoma’s long axis and with the tip placed within the largest clot segment. Among the 110 surgeons who performed this procedure during the study, 88% had never done it before, and operator and site experience linked with better performance. No surgeon who had already performed four minimally invasive lytic cases, and no center that had already performed seven cases, had a subsequent patient with a residual volume that exceeded 30 mL, Dr. Awad said. The surgical experience during the trial showed that catheter repositioning and using a second catheter were both safe ways to maximize evacuation of the hematoma, he added.
The trial’s primary endpoint, the rate of patients with a modified Rankin Scale score of 0-3 at 1 year after treatment in a modified intention-to-treat analysis that included all patients regardless of the amount of hematoma evacuation they received, showed a 45% rate among the patients who underwent minimally invasive lysis and a 41% rate among those in the control arm, a difference that was not statistically significant. Safety assessments showed that patients treated with the investigational approach had significantly lower mortality 7 days after treatment: 0.8% compared with 4.0%. By 1 year after treatment, mortality was cut by one-third in the minimally invasive patients, compared with the control patients, also a statistically significant difference. The rates of symptomatic bleeds and brain infections were similar in the two treatment groups, Dr. Hanley reported. Concurrently with his talk at the conference, a paper with the primary study results appeared online (Lancet. 2019 Feb 7. doi: 10.1016/S0140-6736[19]30195-3).
MISTIE III was supported by the National Institute of Neurological Disorders and Stroke. The trial received no commercial support aside from free tissue plasminogen activator (Alteplase) supplied by Genentech. Dr. Hanley has been a consultant to BrainScope, Neurotrope, Portola, and Op2Lysis, and he has served as an expert witness on behalf of Medtronic. Dr. Awad had no disclosures.
SOURCE: Hanley DF et al. ISC 2019, Abstract LB4; Awad IS et al. ISC 2019, Abstract LB5.
The MISTIE III results showed that this approach to clot lysis is safe and feasible for surgeons to perform even if they have had limited experience with the procedure. I think that based on these findings, minimally-invasive clot lysis will become widely adopted. It’s pretty simple to perform in most patients. At my center in Houston, we already use it on a routine basis in patients like those enrolled in MISTIE III.
Some people may focus on the neutral primary endpoint result from the MISTIE III trial, but the study made two very important findings. First, the results showed that we have improved medical management of patients who have an intracerebral hemorrhage. The 1-year functional outcomes of patients in the control group of the study who had a 41% rate of scoring 0-3 on the modified Rankin Scale after 1 year was much better than we have seen in these patients in the past. Second, the results gave a clear signal that the more clot an operator can lyse to get the residual clot to 15 mL or less, the better patients do. Faster clot lysis might also be important.
It’s hard to call the minimally-invasive approach used in MISTIE III the new standard-of-care approach for these patients given the neutral primary endpoint of the study. On the other hand, if you have a treatment that poses little risk to patients and that you know could benefit them if it succeeds in minimizing residual clot volume, then it makes sense to try it. It’s a low-risk treatment with reasonable potential for benefit. Its demonstrated safety is very important.
Louise D. McCullough, MD, PhD , is a professor of neurology and chair of neurology at the University of Texas, Houston. She had no disclosures. She made these comments in an interview.
The MISTIE III results showed that this approach to clot lysis is safe and feasible for surgeons to perform even if they have had limited experience with the procedure. I think that based on these findings, minimally-invasive clot lysis will become widely adopted. It’s pretty simple to perform in most patients. At my center in Houston, we already use it on a routine basis in patients like those enrolled in MISTIE III.
Some people may focus on the neutral primary endpoint result from the MISTIE III trial, but the study made two very important findings. First, the results showed that we have improved medical management of patients who have an intracerebral hemorrhage. The 1-year functional outcomes of patients in the control group of the study who had a 41% rate of scoring 0-3 on the modified Rankin Scale after 1 year was much better than we have seen in these patients in the past. Second, the results gave a clear signal that the more clot an operator can lyse to get the residual clot to 15 mL or less, the better patients do. Faster clot lysis might also be important.
It’s hard to call the minimally-invasive approach used in MISTIE III the new standard-of-care approach for these patients given the neutral primary endpoint of the study. On the other hand, if you have a treatment that poses little risk to patients and that you know could benefit them if it succeeds in minimizing residual clot volume, then it makes sense to try it. It’s a low-risk treatment with reasonable potential for benefit. Its demonstrated safety is very important.
Louise D. McCullough, MD, PhD , is a professor of neurology and chair of neurology at the University of Texas, Houston. She had no disclosures. She made these comments in an interview.
The MISTIE III results showed that this approach to clot lysis is safe and feasible for surgeons to perform even if they have had limited experience with the procedure. I think that based on these findings, minimally-invasive clot lysis will become widely adopted. It’s pretty simple to perform in most patients. At my center in Houston, we already use it on a routine basis in patients like those enrolled in MISTIE III.
Some people may focus on the neutral primary endpoint result from the MISTIE III trial, but the study made two very important findings. First, the results showed that we have improved medical management of patients who have an intracerebral hemorrhage. The 1-year functional outcomes of patients in the control group of the study who had a 41% rate of scoring 0-3 on the modified Rankin Scale after 1 year was much better than we have seen in these patients in the past. Second, the results gave a clear signal that the more clot an operator can lyse to get the residual clot to 15 mL or less, the better patients do. Faster clot lysis might also be important.
It’s hard to call the minimally-invasive approach used in MISTIE III the new standard-of-care approach for these patients given the neutral primary endpoint of the study. On the other hand, if you have a treatment that poses little risk to patients and that you know could benefit them if it succeeds in minimizing residual clot volume, then it makes sense to try it. It’s a low-risk treatment with reasonable potential for benefit. Its demonstrated safety is very important.
Louise D. McCullough, MD, PhD , is a professor of neurology and chair of neurology at the University of Texas, Houston. She had no disclosures. She made these comments in an interview.
HONOLULU – A minimally invasive approach to lysing an intracerebral hemorrhage clot was safe but failed to produce a statistically significant improvement in long-term functional outcome when compared with usual medical management in a phase 3 randomized trial of 499 patients. However, the results also showed that when the procedure met its acute goal of cutting residual clot to a volume of 15 mL or less, it significantly boosted the percentage of patients with a modified Rankin Scale score of 0-3 when assessed a year after treatment, Daniel F. Hanley Jr., MD, said at the International Stroke Conference, sponsored by the American Heart Association.
“Improved function and increased survival was produced by surgical [clot] reduction to 15 mL or less,” said Dr. Hanley, professor of neurology at Johns Hopkins University, Baltimore, and one of the organizers of the MISTIE III trial.
When assessed by another measure, treated patients showed significant, long-term functional improvement compared with controls when their clot burden dropped by at least 70% following the lytic procedure.
“This is the first description of specific thresholds of hematoma evacuation that impact functional outcomes in intracerebral hemorrhage surgery trials,” said Issam A. Awad, MD, professor of surgery and director of neurovascular surgery at the University of Chicago and coprincipal investigator of the trial.
The problem in the trial was that the surgeons who performed the interventions did not treat many patients aggressively enough to reach these thresholds. They achieved the prespecified goal of residual clot of 15 mL or less in 59% of patients, Dr. Hanley reported, even though the study protocol called for serial infusions of 1 mg of tissue plasminogen activator (Alteplase) into the clot via a placed catheter as many as nine times, administered at 8 hour intervals, with treatment to continue until patients reached the goal residual volume or until they had received all nine doses. In actual practice during the study, operators administered a median of four lytic doses.
“We showed that this goal was important, but not all sites embraced the goal,” Dr. Hanley said. Even though the participating clinicians had a specific interest in intracerebral hemorrhage patients and in this procedure, several nonetheless “had a poor understanding of the goal,” he said in an interview. He attributed the less-than-aggressive approach many operators took to the safety concern that further doses of the lytic drug could trigger recurrent hemorrhage.
“We showed that the goal was important. I think they will embrace the [hematoma evacuation] goal when they see these data,” Dr. Hanley predicted.
An as-treated analysis of the data that focused on the 145 of 246 patients who were treated with minimally invasive lysis and reached the target residual volume and who were then functionally assessed a year later, showed that the rate of patients with a modified Rankin Scale score of 0-3 was 53%, compared with 42% among the controls, an 11% difference.
This shows “a large treatment effect. This is a big, transformative treatment,” Dr. Hanley said. “Our data clearly show that more than half the patients had a positive outcome when their surgeons were more aggressive about clot removal.” He cautioned that the trial was not just about the volume of clot removed but was also about doing it in a gentle way, with a minimum of tissue trauma. Other approaches to reducing hematoma volume may be faster or more complete but they cannot now match the record of safety and efficacy documented in MISTIE III for minimally invasive clot lysis, Dr. Hanley noted.
MISTIE III (Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III) enrolled patients at 78 centers in the United States and several other countries during 2013-2017. Patients had to enroll 12-72 hours after onset and present with a hematoma volume of at least 30 mL. Participating neurosurgeons used image-guided neuronavigation to place a 4- to 6-mm cannula through the clot, ideally straight through the hematoma’s long axis and with the tip placed within the largest clot segment. Among the 110 surgeons who performed this procedure during the study, 88% had never done it before, and operator and site experience linked with better performance. No surgeon who had already performed four minimally invasive lytic cases, and no center that had already performed seven cases, had a subsequent patient with a residual volume that exceeded 30 mL, Dr. Awad said. The surgical experience during the trial showed that catheter repositioning and using a second catheter were both safe ways to maximize evacuation of the hematoma, he added.
The trial’s primary endpoint, the rate of patients with a modified Rankin Scale score of 0-3 at 1 year after treatment in a modified intention-to-treat analysis that included all patients regardless of the amount of hematoma evacuation they received, showed a 45% rate among the patients who underwent minimally invasive lysis and a 41% rate among those in the control arm, a difference that was not statistically significant. Safety assessments showed that patients treated with the investigational approach had significantly lower mortality 7 days after treatment: 0.8% compared with 4.0%. By 1 year after treatment, mortality was cut by one-third in the minimally invasive patients, compared with the control patients, also a statistically significant difference. The rates of symptomatic bleeds and brain infections were similar in the two treatment groups, Dr. Hanley reported. Concurrently with his talk at the conference, a paper with the primary study results appeared online (Lancet. 2019 Feb 7. doi: 10.1016/S0140-6736[19]30195-3).
MISTIE III was supported by the National Institute of Neurological Disorders and Stroke. The trial received no commercial support aside from free tissue plasminogen activator (Alteplase) supplied by Genentech. Dr. Hanley has been a consultant to BrainScope, Neurotrope, Portola, and Op2Lysis, and he has served as an expert witness on behalf of Medtronic. Dr. Awad had no disclosures.
SOURCE: Hanley DF et al. ISC 2019, Abstract LB4; Awad IS et al. ISC 2019, Abstract LB5.
HONOLULU – A minimally invasive approach to lysing an intracerebral hemorrhage clot was safe but failed to produce a statistically significant improvement in long-term functional outcome when compared with usual medical management in a phase 3 randomized trial of 499 patients. However, the results also showed that when the procedure met its acute goal of cutting residual clot to a volume of 15 mL or less, it significantly boosted the percentage of patients with a modified Rankin Scale score of 0-3 when assessed a year after treatment, Daniel F. Hanley Jr., MD, said at the International Stroke Conference, sponsored by the American Heart Association.
“Improved function and increased survival was produced by surgical [clot] reduction to 15 mL or less,” said Dr. Hanley, professor of neurology at Johns Hopkins University, Baltimore, and one of the organizers of the MISTIE III trial.
When assessed by another measure, treated patients showed significant, long-term functional improvement compared with controls when their clot burden dropped by at least 70% following the lytic procedure.
“This is the first description of specific thresholds of hematoma evacuation that impact functional outcomes in intracerebral hemorrhage surgery trials,” said Issam A. Awad, MD, professor of surgery and director of neurovascular surgery at the University of Chicago and coprincipal investigator of the trial.
The problem in the trial was that the surgeons who performed the interventions did not treat many patients aggressively enough to reach these thresholds. They achieved the prespecified goal of residual clot of 15 mL or less in 59% of patients, Dr. Hanley reported, even though the study protocol called for serial infusions of 1 mg of tissue plasminogen activator (Alteplase) into the clot via a placed catheter as many as nine times, administered at 8 hour intervals, with treatment to continue until patients reached the goal residual volume or until they had received all nine doses. In actual practice during the study, operators administered a median of four lytic doses.
“We showed that this goal was important, but not all sites embraced the goal,” Dr. Hanley said. Even though the participating clinicians had a specific interest in intracerebral hemorrhage patients and in this procedure, several nonetheless “had a poor understanding of the goal,” he said in an interview. He attributed the less-than-aggressive approach many operators took to the safety concern that further doses of the lytic drug could trigger recurrent hemorrhage.
“We showed that the goal was important. I think they will embrace the [hematoma evacuation] goal when they see these data,” Dr. Hanley predicted.
An as-treated analysis of the data that focused on the 145 of 246 patients who were treated with minimally invasive lysis and reached the target residual volume and who were then functionally assessed a year later, showed that the rate of patients with a modified Rankin Scale score of 0-3 was 53%, compared with 42% among the controls, an 11% difference.
This shows “a large treatment effect. This is a big, transformative treatment,” Dr. Hanley said. “Our data clearly show that more than half the patients had a positive outcome when their surgeons were more aggressive about clot removal.” He cautioned that the trial was not just about the volume of clot removed but was also about doing it in a gentle way, with a minimum of tissue trauma. Other approaches to reducing hematoma volume may be faster or more complete but they cannot now match the record of safety and efficacy documented in MISTIE III for minimally invasive clot lysis, Dr. Hanley noted.
MISTIE III (Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III) enrolled patients at 78 centers in the United States and several other countries during 2013-2017. Patients had to enroll 12-72 hours after onset and present with a hematoma volume of at least 30 mL. Participating neurosurgeons used image-guided neuronavigation to place a 4- to 6-mm cannula through the clot, ideally straight through the hematoma’s long axis and with the tip placed within the largest clot segment. Among the 110 surgeons who performed this procedure during the study, 88% had never done it before, and operator and site experience linked with better performance. No surgeon who had already performed four minimally invasive lytic cases, and no center that had already performed seven cases, had a subsequent patient with a residual volume that exceeded 30 mL, Dr. Awad said. The surgical experience during the trial showed that catheter repositioning and using a second catheter were both safe ways to maximize evacuation of the hematoma, he added.
The trial’s primary endpoint, the rate of patients with a modified Rankin Scale score of 0-3 at 1 year after treatment in a modified intention-to-treat analysis that included all patients regardless of the amount of hematoma evacuation they received, showed a 45% rate among the patients who underwent minimally invasive lysis and a 41% rate among those in the control arm, a difference that was not statistically significant. Safety assessments showed that patients treated with the investigational approach had significantly lower mortality 7 days after treatment: 0.8% compared with 4.0%. By 1 year after treatment, mortality was cut by one-third in the minimally invasive patients, compared with the control patients, also a statistically significant difference. The rates of symptomatic bleeds and brain infections were similar in the two treatment groups, Dr. Hanley reported. Concurrently with his talk at the conference, a paper with the primary study results appeared online (Lancet. 2019 Feb 7. doi: 10.1016/S0140-6736[19]30195-3).
MISTIE III was supported by the National Institute of Neurological Disorders and Stroke. The trial received no commercial support aside from free tissue plasminogen activator (Alteplase) supplied by Genentech. Dr. Hanley has been a consultant to BrainScope, Neurotrope, Portola, and Op2Lysis, and he has served as an expert witness on behalf of Medtronic. Dr. Awad had no disclosures.
SOURCE: Hanley DF et al. ISC 2019, Abstract LB4; Awad IS et al. ISC 2019, Abstract LB5.
REPORTING FROM ISC 2019
Key clinical point: Minimally-invasive intracerebral clot lysis was safe and often effective when the residual clot shrank to 15 mL or less.
Major finding: One year after entry, 45% of MISTIE-treated patients and 41% of controls had a modified Rankin Scale score of 0-3.
Study details: MISTIE III, a multicenter, international, randomized trial of 499 patients.
Disclosures: MISTIE III was supported by the National Institute of Neurological Disorders and Stroke. The trial received no commercial support aside from free tissue plasminogen activator (Alteplase) supplied by Genentech. Dr. Hanley has been a consultant to BrainScope, Neurotrope, Portola, and Op2Lysis, and he has served as an expert witness on behalf of Medtronic. Dr. Awad had no disclosures.
Source: Hanley DF et al. ISC 2019, Abstract LB4; Awad IS et al. ISC 2019, Abstract LB5.
Deferoxamine does not improve 90-day outcomes after ICH
HONOLULU – (ICH), according to trial results described at the International Stroke Conference sponsored by the American Heart Association. However, the drug is safe and well tolerated and data suggest that it may improve outcomes at 180 days.
Animal studies indicate that iron, which is released from hemolyzed red blood cells, accumulates in the brain after ICH and is associated with secondary neuronal injury and death. Researchers have found that deferoxamine, an iron chelator, provides neuroprotection and improves recovery after experimental ICH. The drug also has anti-inflammatory, antiapoptotic, and BP-lowering effects. Deferoxamine has been approved since the 1960s.
Magdy H. Selim, MD, PhD, a neurologist at Beth Israel Deaconess Medical Center in Boston, and colleagues hypothesized that treatment with deferoxamine could improve outcomes in patients with ICH. The researchers conducted a phase 2 clinical trial to evaluate whether deferoxamine should be studied in a phase 3 efficacy trial. In their multicenter, double-blind study, Dr. Selim and his colleagues randomized patients with spontaneous supratentorial ICH in equal groups to 32 mg/kg per day of deferoxamine or saline placebo. Treatments were administered as intravenous infusions for 3 consecutive days, and therapy was initiated within 24 hours after ICH onset. The follow-up period was 6 months.
Eligible participants had an National Institutes of Health Stroke Scale score of 6 or higher, a Glasgow Coma Scale score greater than 6, and had been functionally independent before the hemorrhage. The researchers excluded patients with a secondary cause for ICH or coagulopathy.
The primary endpoint in the futility analysis was the proportion of participants with a good clinical outcome – defined as a modified Rankin Scale (mRS) score of 0-2 – at 90 days and 180 days. The secondary endpoint was good outcome, defined as an mRS score of 0-3, at 90 days. Safety endpoints included all deferoxamine-related adverse events until day 7 or discharge (whichever was earlier) and serious adverse events through day 90.
Dr. Selim and his colleagues enrolled 294 participants in their trial, 3 of whom did not receive treatment. Of these included participants, 147 (50.5%) were randomized to placebo and 144 (49.5%) were randomized to deferoxamine. Participants’ mean age was 60.3 years, and 38.5% of the population was female.
Overall, the two study arms did not differ significantly according to demographic and clinical characteristics, however, there were more nonwhite patients in the deferoxamine arm than in the placebo arm, however. In addition, thalamic hemorrhage and intraventricular hemorrhage were more common in the placebo-treated group and hemorrhages in the putamen and basal ganglia were more common in the deferoxamine-treated group.
The rates of adverse events were comparable between the two study arms. Dr. Selim and his colleagues found no unexpected safety issues. Mortality was low, and the 90-day and 180-day mortality rates were comparable between the two treatment arms.
Approximately 34% of deferoxamine-treated patients and 33% of placebo-treated patients had an mRS score of 0-2 at 90 days. The adjusted absolute risk difference between arms was 0.6%; this result did not surpass the predefined futility threshold. The risk difference between groups for mRS score of 0-2 at 180 days was 8.6% in favor of deferoxamine, which did surpass the futility threshold.
The risk difference for meeting the secondary endpoint was 6.2% in favor of deferoxamine; this result did not surpass the futility threshold. Patients in both treatment groups improved between day 90 and day 180. The likelihood of good outcome was approximately 10% higher in the deferoxamine group at day 90 and 26% higher in the deferoxamine group at day 180.
“It is futile to conduct a phase 3 trial with the anticipation that treatment with deferoxamine would improve outcome, defined as mRS score of 0-2 at 90 days,” said Dr. Selim. “These data, together with the data from MISTIE and CLEAR, suggest that ICH trials need to have a longer follow-up period to capture the full extent of recovery after ICH. Several of our secondary analyses tended to favor deferoxamine over the placebo arm and leave open the possibility that deferoxamine might lead to improved outcome at 180 days.”
The researchers received support from the NIH and the National Institute of Neurological Disorders and Stroke.
SOURCE: Selim MH et al. ISC 2019, Abstract LB22.
HONOLULU – (ICH), according to trial results described at the International Stroke Conference sponsored by the American Heart Association. However, the drug is safe and well tolerated and data suggest that it may improve outcomes at 180 days.
Animal studies indicate that iron, which is released from hemolyzed red blood cells, accumulates in the brain after ICH and is associated with secondary neuronal injury and death. Researchers have found that deferoxamine, an iron chelator, provides neuroprotection and improves recovery after experimental ICH. The drug also has anti-inflammatory, antiapoptotic, and BP-lowering effects. Deferoxamine has been approved since the 1960s.
Magdy H. Selim, MD, PhD, a neurologist at Beth Israel Deaconess Medical Center in Boston, and colleagues hypothesized that treatment with deferoxamine could improve outcomes in patients with ICH. The researchers conducted a phase 2 clinical trial to evaluate whether deferoxamine should be studied in a phase 3 efficacy trial. In their multicenter, double-blind study, Dr. Selim and his colleagues randomized patients with spontaneous supratentorial ICH in equal groups to 32 mg/kg per day of deferoxamine or saline placebo. Treatments were administered as intravenous infusions for 3 consecutive days, and therapy was initiated within 24 hours after ICH onset. The follow-up period was 6 months.
Eligible participants had an National Institutes of Health Stroke Scale score of 6 or higher, a Glasgow Coma Scale score greater than 6, and had been functionally independent before the hemorrhage. The researchers excluded patients with a secondary cause for ICH or coagulopathy.
The primary endpoint in the futility analysis was the proportion of participants with a good clinical outcome – defined as a modified Rankin Scale (mRS) score of 0-2 – at 90 days and 180 days. The secondary endpoint was good outcome, defined as an mRS score of 0-3, at 90 days. Safety endpoints included all deferoxamine-related adverse events until day 7 or discharge (whichever was earlier) and serious adverse events through day 90.
Dr. Selim and his colleagues enrolled 294 participants in their trial, 3 of whom did not receive treatment. Of these included participants, 147 (50.5%) were randomized to placebo and 144 (49.5%) were randomized to deferoxamine. Participants’ mean age was 60.3 years, and 38.5% of the population was female.
Overall, the two study arms did not differ significantly according to demographic and clinical characteristics, however, there were more nonwhite patients in the deferoxamine arm than in the placebo arm, however. In addition, thalamic hemorrhage and intraventricular hemorrhage were more common in the placebo-treated group and hemorrhages in the putamen and basal ganglia were more common in the deferoxamine-treated group.
The rates of adverse events were comparable between the two study arms. Dr. Selim and his colleagues found no unexpected safety issues. Mortality was low, and the 90-day and 180-day mortality rates were comparable between the two treatment arms.
Approximately 34% of deferoxamine-treated patients and 33% of placebo-treated patients had an mRS score of 0-2 at 90 days. The adjusted absolute risk difference between arms was 0.6%; this result did not surpass the predefined futility threshold. The risk difference between groups for mRS score of 0-2 at 180 days was 8.6% in favor of deferoxamine, which did surpass the futility threshold.
The risk difference for meeting the secondary endpoint was 6.2% in favor of deferoxamine; this result did not surpass the futility threshold. Patients in both treatment groups improved between day 90 and day 180. The likelihood of good outcome was approximately 10% higher in the deferoxamine group at day 90 and 26% higher in the deferoxamine group at day 180.
“It is futile to conduct a phase 3 trial with the anticipation that treatment with deferoxamine would improve outcome, defined as mRS score of 0-2 at 90 days,” said Dr. Selim. “These data, together with the data from MISTIE and CLEAR, suggest that ICH trials need to have a longer follow-up period to capture the full extent of recovery after ICH. Several of our secondary analyses tended to favor deferoxamine over the placebo arm and leave open the possibility that deferoxamine might lead to improved outcome at 180 days.”
The researchers received support from the NIH and the National Institute of Neurological Disorders and Stroke.
SOURCE: Selim MH et al. ISC 2019, Abstract LB22.
HONOLULU – (ICH), according to trial results described at the International Stroke Conference sponsored by the American Heart Association. However, the drug is safe and well tolerated and data suggest that it may improve outcomes at 180 days.
Animal studies indicate that iron, which is released from hemolyzed red blood cells, accumulates in the brain after ICH and is associated with secondary neuronal injury and death. Researchers have found that deferoxamine, an iron chelator, provides neuroprotection and improves recovery after experimental ICH. The drug also has anti-inflammatory, antiapoptotic, and BP-lowering effects. Deferoxamine has been approved since the 1960s.
Magdy H. Selim, MD, PhD, a neurologist at Beth Israel Deaconess Medical Center in Boston, and colleagues hypothesized that treatment with deferoxamine could improve outcomes in patients with ICH. The researchers conducted a phase 2 clinical trial to evaluate whether deferoxamine should be studied in a phase 3 efficacy trial. In their multicenter, double-blind study, Dr. Selim and his colleagues randomized patients with spontaneous supratentorial ICH in equal groups to 32 mg/kg per day of deferoxamine or saline placebo. Treatments were administered as intravenous infusions for 3 consecutive days, and therapy was initiated within 24 hours after ICH onset. The follow-up period was 6 months.
Eligible participants had an National Institutes of Health Stroke Scale score of 6 or higher, a Glasgow Coma Scale score greater than 6, and had been functionally independent before the hemorrhage. The researchers excluded patients with a secondary cause for ICH or coagulopathy.
The primary endpoint in the futility analysis was the proportion of participants with a good clinical outcome – defined as a modified Rankin Scale (mRS) score of 0-2 – at 90 days and 180 days. The secondary endpoint was good outcome, defined as an mRS score of 0-3, at 90 days. Safety endpoints included all deferoxamine-related adverse events until day 7 or discharge (whichever was earlier) and serious adverse events through day 90.
Dr. Selim and his colleagues enrolled 294 participants in their trial, 3 of whom did not receive treatment. Of these included participants, 147 (50.5%) were randomized to placebo and 144 (49.5%) were randomized to deferoxamine. Participants’ mean age was 60.3 years, and 38.5% of the population was female.
Overall, the two study arms did not differ significantly according to demographic and clinical characteristics, however, there were more nonwhite patients in the deferoxamine arm than in the placebo arm, however. In addition, thalamic hemorrhage and intraventricular hemorrhage were more common in the placebo-treated group and hemorrhages in the putamen and basal ganglia were more common in the deferoxamine-treated group.
The rates of adverse events were comparable between the two study arms. Dr. Selim and his colleagues found no unexpected safety issues. Mortality was low, and the 90-day and 180-day mortality rates were comparable between the two treatment arms.
Approximately 34% of deferoxamine-treated patients and 33% of placebo-treated patients had an mRS score of 0-2 at 90 days. The adjusted absolute risk difference between arms was 0.6%; this result did not surpass the predefined futility threshold. The risk difference between groups for mRS score of 0-2 at 180 days was 8.6% in favor of deferoxamine, which did surpass the futility threshold.
The risk difference for meeting the secondary endpoint was 6.2% in favor of deferoxamine; this result did not surpass the futility threshold. Patients in both treatment groups improved between day 90 and day 180. The likelihood of good outcome was approximately 10% higher in the deferoxamine group at day 90 and 26% higher in the deferoxamine group at day 180.
“It is futile to conduct a phase 3 trial with the anticipation that treatment with deferoxamine would improve outcome, defined as mRS score of 0-2 at 90 days,” said Dr. Selim. “These data, together with the data from MISTIE and CLEAR, suggest that ICH trials need to have a longer follow-up period to capture the full extent of recovery after ICH. Several of our secondary analyses tended to favor deferoxamine over the placebo arm and leave open the possibility that deferoxamine might lead to improved outcome at 180 days.”
The researchers received support from the NIH and the National Institute of Neurological Disorders and Stroke.
SOURCE: Selim MH et al. ISC 2019, Abstract LB22.
REPORTING FROM ISC 2019
Key clinical point: Deferoxamine does not improve disability at 90 days after intracranial hemorrhage.
Major finding: Approximately one-third of patients in both treatment groups had a good outcome.
Study details: A multicenter, randomized, double-blind study of 294 participants with intracranial hemorrhage.
Disclosures: The National Institutes of Health and National Institute of Neurological Disorders and Stroke supported this study.
Source: Selim MH et al. ISC 2019, Abstract LB22.