Anticoagulation Hub

Patients with acute ischemic stroke who test positive for aspirin resistance had both larger stroke volume and increased severity, compared with patients without resistance, in an observational study of 311 patients at Korean centers.

Given that previous studies have shown that the use of aspirin is associated with lower stroke severity and decreased infarction growth, the current study’s findings may help to define the effect of aspirin resistance (AR) on stroke severity, since previous studies had provided inconclusive results, Dr. Mi Sun Oh and colleagues at Hallym University Sacred Heart Hospital, Anyang, South Korea, wrote in their abstract. The findings were released Feb. 23 in advance of the annual meeting in April of the American Academy of Neurology.

The investigators enrolled patients with acute ischemic stroke confirmed by diffusion-weighted imaging (DWI) who had received at least 7 days of aspirin therapy before initial stroke symptoms and had been checked for AR within 24 hours of hospital admission. Patients with high prestroke disability scores (modified Rankin Scale score > 2) were excluded, as were those who were taking another antiplatelet or anticoagulant medication concurrently with aspirin on hospital admission.

The abstract did not report detailed patient characteristics or information about type or dose of aspirin; the full results of the study will be presented at the meeting in Washington.

Enrollees were deemed aspirin resistant if a rapid assay detected greater than 550 Aspirin Reaction Units. DWI-observed stroke volume was assessed via a semiautomated threshold technique, and investigators employed the National Institutes of Health Stroke Scale (NIHSS) score to measure initial stroke severity.

Seventy-eight of the 311 patients (25.1%) had AR. Dr. Oh and colleagues reported that median stroke volume was higher for these patients, compared with the aspirin-sensitive group (2.8 cc vs. 1.6 cc), as was least-square mean on multivariate analysis (1.6 cc [95% CI, 1.1-2.1] vs. 1.1 cc [95% CI, 0.7-1.4], P = .036). Median NIHSS scores were also higher for the AR group (4 vs. 3), indicating greater stroke severity, a result that was confirmed by multivariate analysis.

Aspirin resistance is a complicated and heterogeneous concept, and not a well defined entity, according to vascular neurologist Dr. Philip Gorelick, head of the Hauenstein Neuroscience Center at St. Mary’s Health Care in Grand Rapids, Mich. Dr. Gorelick is an honorary member of the Korean Stroke Society but was not involved in the present study. In an interview, he expanded on the diverse mechanisms that can impede the stroke prevention effect of antiplatelet agents such as aspirin (Stroke Res. Treat. 2013;Article ID 727842 [doi:10.1155/2013/727842]).

In contrast to the traditional notion of “resistance” as an inherent or acquired defense or chemical blockage of a drug, whether by a microbe or the host, aspirin resistance may be either a laboratory-defined lack of inhibition of thromboxane A2, or a clinically-defined entity. In either case, a host of factors may contribute, Dr. Gorelick said. Poor adherence to an aspirin therapy regimen may be a primary contributor to AR. Further, enterically coated aspirin may not be as well absorbed in the gut, leading to lower effective aspirin dosing. A host of other factors, including concurrent medication administration, comorbidities impacting platelet turnover, and genetic polymorphisms may also contribute to aspirin failure.

Although patient characteristics were not reported in this study, Dr. Gorelick did issue a general note of caution: “Another major issue in these types of studies,” he noted, is to determine if “patients are similar in terms of background factors. Patients on aspirin therapy may be more likely to have more severe preexisting vascular disease,” predisposing them to more severe stroke.

The Korea Healthcare Technology R&D Project, Ministry of Health and Family Welfare, and the Republic of Korea supported the study. The authors had no disclosures.

Patients with acute ischemic stroke who test positive for aspirin resistance had both larger stroke volume and increased severity, compared with patients without resistance, in an observational study of 311 patients at Korean centers.

Given that previous studies have shown that the use of aspirin is associated with lower stroke severity and decreased infarction growth, the current study’s findings may help to define the effect of aspirin resistance (AR) on stroke severity, since previous studies had provided inconclusive results, Dr. Mi Sun Oh and colleagues at Hallym University Sacred Heart Hospital, Anyang, South Korea, wrote in their abstract. The findings were released Feb. 23 in advance of the annual meeting in April of the American Academy of Neurology.

The investigators enrolled patients with acute ischemic stroke confirmed by diffusion-weighted imaging (DWI) who had received at least 7 days of aspirin therapy before initial stroke symptoms and had been checked for AR within 24 hours of hospital admission. Patients with high prestroke disability scores (modified Rankin Scale score > 2) were excluded, as were those who were taking another antiplatelet or anticoagulant medication concurrently with aspirin on hospital admission.

The abstract did not report detailed patient characteristics or information about type or dose of aspirin; the full results of the study will be presented at the meeting in Washington.

Enrollees were deemed aspirin resistant if a rapid assay detected greater than 550 Aspirin Reaction Units. DWI-observed stroke volume was assessed via a semiautomated threshold technique, and investigators employed the National Institutes of Health Stroke Scale (NIHSS) score to measure initial stroke severity.

Seventy-eight of the 311 patients (25.1%) had AR. Dr. Oh and colleagues reported that median stroke volume was higher for these patients, compared with the aspirin-sensitive group (2.8 cc vs. 1.6 cc), as was least-square mean on multivariate analysis (1.6 cc [95% CI, 1.1-2.1] vs. 1.1 cc [95% CI, 0.7-1.4], P = .036). Median NIHSS scores were also higher for the AR group (4 vs. 3), indicating greater stroke severity, a result that was confirmed by multivariate analysis.

Aspirin resistance is a complicated and heterogeneous concept, and not a well defined entity, according to vascular neurologist Dr. Philip Gorelick, head of the Hauenstein Neuroscience Center at St. Mary’s Health Care in Grand Rapids, Mich. Dr. Gorelick is an honorary member of the Korean Stroke Society but was not involved in the present study. In an interview, he expanded on the diverse mechanisms that can impede the stroke prevention effect of antiplatelet agents such as aspirin (Stroke Res. Treat. 2013;Article ID 727842 [doi:10.1155/2013/727842]).

In contrast to the traditional notion of “resistance” as an inherent or acquired defense or chemical blockage of a drug, whether by a microbe or the host, aspirin resistance may be either a laboratory-defined lack of inhibition of thromboxane A2, or a clinically-defined entity. In either case, a host of factors may contribute, Dr. Gorelick said. Poor adherence to an aspirin therapy regimen may be a primary contributor to AR. Further, enterically coated aspirin may not be as well absorbed in the gut, leading to lower effective aspirin dosing. A host of other factors, including concurrent medication administration, comorbidities impacting platelet turnover, and genetic polymorphisms may also contribute to aspirin failure.

Although patient characteristics were not reported in this study, Dr. Gorelick did issue a general note of caution: “Another major issue in these types of studies,” he noted, is to determine if “patients are similar in terms of background factors. Patients on aspirin therapy may be more likely to have more severe preexisting vascular disease,” predisposing them to more severe stroke.

The Korea Healthcare Technology R&D Project, Ministry of Health and Family Welfare, and the Republic of Korea supported the study. The authors had no disclosures.

Patients with acute ischemic stroke who test positive for aspirin resistance had both larger stroke volume and increased severity, compared with patients without resistance, in an observational study of 311 patients at Korean centers.

Given that previous studies have shown that the use of aspirin is associated with lower stroke severity and decreased infarction growth, the current study’s findings may help to define the effect of aspirin resistance (AR) on stroke severity, since previous studies had provided inconclusive results, Dr. Mi Sun Oh and colleagues at Hallym University Sacred Heart Hospital, Anyang, South Korea, wrote in their abstract. The findings were released Feb. 23 in advance of the annual meeting in April of the American Academy of Neurology.

The investigators enrolled patients with acute ischemic stroke confirmed by diffusion-weighted imaging (DWI) who had received at least 7 days of aspirin therapy before initial stroke symptoms and had been checked for AR within 24 hours of hospital admission. Patients with high prestroke disability scores (modified Rankin Scale score > 2) were excluded, as were those who were taking another antiplatelet or anticoagulant medication concurrently with aspirin on hospital admission.

The abstract did not report detailed patient characteristics or information about type or dose of aspirin; the full results of the study will be presented at the meeting in Washington.

Enrollees were deemed aspirin resistant if a rapid assay detected greater than 550 Aspirin Reaction Units. DWI-observed stroke volume was assessed via a semiautomated threshold technique, and investigators employed the National Institutes of Health Stroke Scale (NIHSS) score to measure initial stroke severity.

Seventy-eight of the 311 patients (25.1%) had AR. Dr. Oh and colleagues reported that median stroke volume was higher for these patients, compared with the aspirin-sensitive group (2.8 cc vs. 1.6 cc), as was least-square mean on multivariate analysis (1.6 cc [95% CI, 1.1-2.1] vs. 1.1 cc [95% CI, 0.7-1.4], P = .036). Median NIHSS scores were also higher for the AR group (4 vs. 3), indicating greater stroke severity, a result that was confirmed by multivariate analysis.

Aspirin resistance is a complicated and heterogeneous concept, and not a well defined entity, according to vascular neurologist Dr. Philip Gorelick, head of the Hauenstein Neuroscience Center at St. Mary’s Health Care in Grand Rapids, Mich. Dr. Gorelick is an honorary member of the Korean Stroke Society but was not involved in the present study. In an interview, he expanded on the diverse mechanisms that can impede the stroke prevention effect of antiplatelet agents such as aspirin (Stroke Res. Treat. 2013;Article ID 727842 [doi:10.1155/2013/727842]).

In contrast to the traditional notion of “resistance” as an inherent or acquired defense or chemical blockage of a drug, whether by a microbe or the host, aspirin resistance may be either a laboratory-defined lack of inhibition of thromboxane A2, or a clinically-defined entity. In either case, a host of factors may contribute, Dr. Gorelick said. Poor adherence to an aspirin therapy regimen may be a primary contributor to AR. Further, enterically coated aspirin may not be as well absorbed in the gut, leading to lower effective aspirin dosing. A host of other factors, including concurrent medication administration, comorbidities impacting platelet turnover, and genetic polymorphisms may also contribute to aspirin failure.

Although patient characteristics were not reported in this study, Dr. Gorelick did issue a general note of caution: “Another major issue in these types of studies,” he noted, is to determine if “patients are similar in terms of background factors. Patients on aspirin therapy may be more likely to have more severe preexisting vascular disease,” predisposing them to more severe stroke.

The Korea Healthcare Technology R&D Project, Ministry of Health and Family Welfare, and the Republic of Korea supported the study. The authors had no disclosures.

NASHVILLE, TENN. – The risk of a peripartum thrombotic event is rare, but significantly increased for women who have a cardioseptal defect. In a large national sample, the rate of thrombotic events was seven times higher among women with an atrial or ventral septal defect.

Advanced maternal age also was a significant independent predictor of this complication; among more than 7,000 women who developed a thrombotic complication, 81% were older than 45 years.

Dr. Ali Razmara of the University of Southern California, Los Angeles, mined the National Inpatient Sample for data linking peripartum thrombotic events to patient demographics and medical comorbidities. His cohort comprised 4.3 million normal vaginal and cesarean deliveries from 2000 to 2010. Events of interest included transient ischemic attack, ischemic stroke, hemorrhagic stroke, acute MI, and venous thromboembolism.

There were 7,242 peripartum thrombotic events (0.17%).The majority occurred in women who were older than 45 years (81%); white (58%); and admitted through the emergency department (67%). Women with thrombotic events were more likely to have hypertension (52% vs. 2%), dyslipidemia (26% vs. 0.52%), diabetes (20% vs. 2%), atrial fibrillation (10% vs. 0.23%), and heart failure (10% vs. 0.26%), he said at the International Stroke Conference.

A multivariate regression model controlled for patient demographics and comorbidities, including, among others, preeclampsia, hypercoagulable states, chorioamnionitis, renal and liver disease, hypertension, diabetes, and cardiovascular disorders including atrial fibrillation, heart failure, and atrial/ventral septal defects.

In a multivariate regression analysis, maternal age shook out as the most powerful independent risk factor; the rate of thrombosis was 91 times greater among women older than age 45 years.

Other significant independent predictors included emergency vs. routine admission (RR 3.3), cardiac septal defect (RR 7), preeclampsia (RR 3.3), and hypercoagulability (RR 3).

Dyslipidemia and hypertension doubled the rate of a thrombotic event. Hypertension, migraine, renal disease, heart disease, atrial fibrillation, and heart failure were also significant factors, increasing the rate of thrombosis by 40%-50%, Dr. Razmara said at the meeting, which was sponsored by the American Heart Association.

“Our goal is development of targeted interventions for screening, prevention, and treatment of thrombosis related to pregnancy.”

Dr. Razmara had no relevant financial disclosures.

[email protected]

NASHVILLE, TENN. – The risk of a peripartum thrombotic event is rare, but significantly increased for women who have a cardioseptal defect. In a large national sample, the rate of thrombotic events was seven times higher among women with an atrial or ventral septal defect.

Advanced maternal age also was a significant independent predictor of this complication; among more than 7,000 women who developed a thrombotic complication, 81% were older than 45 years.

Dr. Ali Razmara of the University of Southern California, Los Angeles, mined the National Inpatient Sample for data linking peripartum thrombotic events to patient demographics and medical comorbidities. His cohort comprised 4.3 million normal vaginal and cesarean deliveries from 2000 to 2010. Events of interest included transient ischemic attack, ischemic stroke, hemorrhagic stroke, acute MI, and venous thromboembolism.

There were 7,242 peripartum thrombotic events (0.17%).The majority occurred in women who were older than 45 years (81%); white (58%); and admitted through the emergency department (67%). Women with thrombotic events were more likely to have hypertension (52% vs. 2%), dyslipidemia (26% vs. 0.52%), diabetes (20% vs. 2%), atrial fibrillation (10% vs. 0.23%), and heart failure (10% vs. 0.26%), he said at the International Stroke Conference.

A multivariate regression model controlled for patient demographics and comorbidities, including, among others, preeclampsia, hypercoagulable states, chorioamnionitis, renal and liver disease, hypertension, diabetes, and cardiovascular disorders including atrial fibrillation, heart failure, and atrial/ventral septal defects.

In a multivariate regression analysis, maternal age shook out as the most powerful independent risk factor; the rate of thrombosis was 91 times greater among women older than age 45 years.

Other significant independent predictors included emergency vs. routine admission (RR 3.3), cardiac septal defect (RR 7), preeclampsia (RR 3.3), and hypercoagulability (RR 3).

Dyslipidemia and hypertension doubled the rate of a thrombotic event. Hypertension, migraine, renal disease, heart disease, atrial fibrillation, and heart failure were also significant factors, increasing the rate of thrombosis by 40%-50%, Dr. Razmara said at the meeting, which was sponsored by the American Heart Association.

“Our goal is development of targeted interventions for screening, prevention, and treatment of thrombosis related to pregnancy.”

Dr. Razmara had no relevant financial disclosures.

[email protected]

NASHVILLE, TENN. – The risk of a peripartum thrombotic event is rare, but significantly increased for women who have a cardioseptal defect. In a large national sample, the rate of thrombotic events was seven times higher among women with an atrial or ventral septal defect.

Advanced maternal age also was a significant independent predictor of this complication; among more than 7,000 women who developed a thrombotic complication, 81% were older than 45 years.

Dr. Ali Razmara of the University of Southern California, Los Angeles, mined the National Inpatient Sample for data linking peripartum thrombotic events to patient demographics and medical comorbidities. His cohort comprised 4.3 million normal vaginal and cesarean deliveries from 2000 to 2010. Events of interest included transient ischemic attack, ischemic stroke, hemorrhagic stroke, acute MI, and venous thromboembolism.

There were 7,242 peripartum thrombotic events (0.17%).The majority occurred in women who were older than 45 years (81%); white (58%); and admitted through the emergency department (67%). Women with thrombotic events were more likely to have hypertension (52% vs. 2%), dyslipidemia (26% vs. 0.52%), diabetes (20% vs. 2%), atrial fibrillation (10% vs. 0.23%), and heart failure (10% vs. 0.26%), he said at the International Stroke Conference.

A multivariate regression model controlled for patient demographics and comorbidities, including, among others, preeclampsia, hypercoagulable states, chorioamnionitis, renal and liver disease, hypertension, diabetes, and cardiovascular disorders including atrial fibrillation, heart failure, and atrial/ventral septal defects.

In a multivariate regression analysis, maternal age shook out as the most powerful independent risk factor; the rate of thrombosis was 91 times greater among women older than age 45 years.

Other significant independent predictors included emergency vs. routine admission (RR 3.3), cardiac septal defect (RR 7), preeclampsia (RR 3.3), and hypercoagulability (RR 3).

Dyslipidemia and hypertension doubled the rate of a thrombotic event. Hypertension, migraine, renal disease, heart disease, atrial fibrillation, and heart failure were also significant factors, increasing the rate of thrombosis by 40%-50%, Dr. Razmara said at the meeting, which was sponsored by the American Heart Association.

“Our goal is development of targeted interventions for screening, prevention, and treatment of thrombosis related to pregnancy.”

Dr. Razmara had no relevant financial disclosures.

[email protected]

SAN FRANCISCO – Reducing factor XI levels with the experimental antisense oligonucleotide FXI-ASO lowered venous thromboembolism rates after total knee arthroplasty without increasing bleeding in a phase II study.

Venous thromboembolism (VTE) rates were 30% among controls (21/69) on enoxaparin (Lovenox) 40 mg, compared with 27% for patients (36/134) given FXI-ASO 200 mg and 4% for those (3/71) given FXI-ASO 300 mg. Low-dose FXI-ASO was noninferior to enoxaparin (P = .59), while the high-dose regimen was superior (P < .001).

Patrice Wendling/Frontline Medical News

A 4% VTE rate “has never ever been seen before in patients undergoing knee surgery,” Dr. Harry Büller said during the late-breaking abstract session at the annual meeting of the American Society of Hematology.

The strategy of targeting factor XI is based on the understanding that patients with factor XI deficiency (plasma levels < 20% of normal) have a reduced risk of deep vein thrombosis (DVT). Experimental data in mice and primates also suggest that reducing factor XI attenuates thrombosis without excess bleeding.

Among the 300 patients in the open-label study, major or clinically relevant bleeding occurred in 3% of both FXI-ASO groups and 8% of the enoxaparin group (P = .09).

The findings provide the first evidence in humans that the factor XI intrinsic pathway is one of the drivers of postoperative thrombosis and support the concept that thrombosis and hemostasis can be dissociated, said Dr. Büller of the Academic Medical Center, Amsterdam.

“FXI-ASO is a promising new investigational antithrombotic agent and I believe you are witnessing the birth of a new class of antithrombotic agents,” he concluded.

During a press conference, Dr. Büller confided to reporters that he felt like a boy in a candy store, finally able to reveal the superb study findings.

Dr. Robert Flaumenhaft of Harvard Medical School, Boston, was far less effusive in an editorial that accompanied the simultaneous publication of the study in the New England Journal of Medicine.

“Do these finding prove that reduction in factor XI levels inhibits thrombosis without affecting bleeding? The conservative answer is no,” he wrote.

Dr. Flaumenhaft observed that the incidence of clinically relevant bleeding is relatively low after knee arthroplasty, even when patients receive anticoagulants, and that this safety outcome did not differ significantly between the enoxaparin and 300-mg FXI-ASO groups.

“These results also do not make a compelling case for the clinical use of the factor XI antisense oligonucleotide over anticoagulants that are currently used for prophylaxis in patients undergoing knee arthroplasty,” he wrote.

Central to this argument are issues of convenience and questions regarding reversibility. Treatment began 36 days before surgery and was associated with a high incidence of adverse events at the injection site and factor XI levels remained about 60% lower 70 days after initiation of therapy.

The half-life of FXI-ASO is about 22 days, “which in the classical setting in terms of bleeding could be seen as something of a disadvantage,” Dr. Büller told reporters. “But if we do the next study and it shows to be safe, it turns into an advantage” … because there is the possibility of giving FXI-ASO once every 3 weeks.

Dr. Flaumenhaft closed the editorial by acknowledging that the study challenges “the current paradigm” regarding the primary mechanism responsible for fibrin formation during thrombosis. “The striking observation that reducing factor XI levels prevents thrombosis after knee arthroplasty provides the best clinical evidence to date that the intrinsic pathway is essential for thrombus formation,” he wrote.

The study was conducted at 19 centers in five countries and randomly assigned 300 patients scheduled for elective primary unilateral total-knee arthroplasty to daily enoxaparin 40 mg or three doses of FXI-ASO. The protocol was amended early on to exclude a 100-mg FXI-ASO dose.

FXI-ASO 200 mg or 300 mg was given subcutaneously beginning 36 days before surgery on days 1, 3, 5, 8, 15, 22, and 29, and 6 hours postoperatively, with a final dose on day 39.

Enoxaparin 40 mg was given subcutaneously once daily, beginning the evening before or 6-8 hours after surgery, according to investigator preference, and was continued for at least 8 days postoperatively.

The primary efficacy point was a composite of asymptomatic DVT, detected by venography, and confirmed symptomatic VTE.

At baseline, the average factor XI level was 1.23 units/mL in the enoxaparin group, 1.20 U/mL in the 200-mg group, and 1.16 U/mL in the 300-mg group.

In patients with an average factor XI level of 0.2 U/mL or less, the incidence of the primary efficacy outcome was 5%.

Isis Pharmaceuticals funded the study. Dr. Büller disclosed ties with Isis, Daiichi-Sankyo, Bayer Healthcare, Pfizer, and Bristol-Myers Squibb. Dr. Flaumenhaft reported having no disclosures.

[email protected]

SAN FRANCISCO – Reducing factor XI levels with the experimental antisense oligonucleotide FXI-ASO lowered venous thromboembolism rates after total knee arthroplasty without increasing bleeding in a phase II study.

Venous thromboembolism (VTE) rates were 30% among controls (21/69) on enoxaparin (Lovenox) 40 mg, compared with 27% for patients (36/134) given FXI-ASO 200 mg and 4% for those (3/71) given FXI-ASO 300 mg. Low-dose FXI-ASO was noninferior to enoxaparin (P = .59), while the high-dose regimen was superior (P < .001).

Patrice Wendling/Frontline Medical News

A 4% VTE rate “has never ever been seen before in patients undergoing knee surgery,” Dr. Harry Büller said during the late-breaking abstract session at the annual meeting of the American Society of Hematology.

The strategy of targeting factor XI is based on the understanding that patients with factor XI deficiency (plasma levels < 20% of normal) have a reduced risk of deep vein thrombosis (DVT). Experimental data in mice and primates also suggest that reducing factor XI attenuates thrombosis without excess bleeding.

Among the 300 patients in the open-label study, major or clinically relevant bleeding occurred in 3% of both FXI-ASO groups and 8% of the enoxaparin group (P = .09).

The findings provide the first evidence in humans that the factor XI intrinsic pathway is one of the drivers of postoperative thrombosis and support the concept that thrombosis and hemostasis can be dissociated, said Dr. Büller of the Academic Medical Center, Amsterdam.

“FXI-ASO is a promising new investigational antithrombotic agent and I believe you are witnessing the birth of a new class of antithrombotic agents,” he concluded.

During a press conference, Dr. Büller confided to reporters that he felt like a boy in a candy store, finally able to reveal the superb study findings.

Dr. Robert Flaumenhaft of Harvard Medical School, Boston, was far less effusive in an editorial that accompanied the simultaneous publication of the study in the New England Journal of Medicine.

“Do these finding prove that reduction in factor XI levels inhibits thrombosis without affecting bleeding? The conservative answer is no,” he wrote.

Dr. Flaumenhaft observed that the incidence of clinically relevant bleeding is relatively low after knee arthroplasty, even when patients receive anticoagulants, and that this safety outcome did not differ significantly between the enoxaparin and 300-mg FXI-ASO groups.

“These results also do not make a compelling case for the clinical use of the factor XI antisense oligonucleotide over anticoagulants that are currently used for prophylaxis in patients undergoing knee arthroplasty,” he wrote.

Central to this argument are issues of convenience and questions regarding reversibility. Treatment began 36 days before surgery and was associated with a high incidence of adverse events at the injection site and factor XI levels remained about 60% lower 70 days after initiation of therapy.

The half-life of FXI-ASO is about 22 days, “which in the classical setting in terms of bleeding could be seen as something of a disadvantage,” Dr. Büller told reporters. “But if we do the next study and it shows to be safe, it turns into an advantage” … because there is the possibility of giving FXI-ASO once every 3 weeks.

Dr. Flaumenhaft closed the editorial by acknowledging that the study challenges “the current paradigm” regarding the primary mechanism responsible for fibrin formation during thrombosis. “The striking observation that reducing factor XI levels prevents thrombosis after knee arthroplasty provides the best clinical evidence to date that the intrinsic pathway is essential for thrombus formation,” he wrote.

The study was conducted at 19 centers in five countries and randomly assigned 300 patients scheduled for elective primary unilateral total-knee arthroplasty to daily enoxaparin 40 mg or three doses of FXI-ASO. The protocol was amended early on to exclude a 100-mg FXI-ASO dose.

FXI-ASO 200 mg or 300 mg was given subcutaneously beginning 36 days before surgery on days 1, 3, 5, 8, 15, 22, and 29, and 6 hours postoperatively, with a final dose on day 39.

Enoxaparin 40 mg was given subcutaneously once daily, beginning the evening before or 6-8 hours after surgery, according to investigator preference, and was continued for at least 8 days postoperatively.

The primary efficacy point was a composite of asymptomatic DVT, detected by venography, and confirmed symptomatic VTE.

At baseline, the average factor XI level was 1.23 units/mL in the enoxaparin group, 1.20 U/mL in the 200-mg group, and 1.16 U/mL in the 300-mg group.

In patients with an average factor XI level of 0.2 U/mL or less, the incidence of the primary efficacy outcome was 5%.

Isis Pharmaceuticals funded the study. Dr. Büller disclosed ties with Isis, Daiichi-Sankyo, Bayer Healthcare, Pfizer, and Bristol-Myers Squibb. Dr. Flaumenhaft reported having no disclosures.

[email protected]

SAN FRANCISCO – Reducing factor XI levels with the experimental antisense oligonucleotide FXI-ASO lowered venous thromboembolism rates after total knee arthroplasty without increasing bleeding in a phase II study.

Venous thromboembolism (VTE) rates were 30% among controls (21/69) on enoxaparin (Lovenox) 40 mg, compared with 27% for patients (36/134) given FXI-ASO 200 mg and 4% for those (3/71) given FXI-ASO 300 mg. Low-dose FXI-ASO was noninferior to enoxaparin (P = .59), while the high-dose regimen was superior (P < .001).

Patrice Wendling/Frontline Medical News

A 4% VTE rate “has never ever been seen before in patients undergoing knee surgery,” Dr. Harry Büller said during the late-breaking abstract session at the annual meeting of the American Society of Hematology.

The strategy of targeting factor XI is based on the understanding that patients with factor XI deficiency (plasma levels < 20% of normal) have a reduced risk of deep vein thrombosis (DVT). Experimental data in mice and primates also suggest that reducing factor XI attenuates thrombosis without excess bleeding.

Among the 300 patients in the open-label study, major or clinically relevant bleeding occurred in 3% of both FXI-ASO groups and 8% of the enoxaparin group (P = .09).

The findings provide the first evidence in humans that the factor XI intrinsic pathway is one of the drivers of postoperative thrombosis and support the concept that thrombosis and hemostasis can be dissociated, said Dr. Büller of the Academic Medical Center, Amsterdam.

“FXI-ASO is a promising new investigational antithrombotic agent and I believe you are witnessing the birth of a new class of antithrombotic agents,” he concluded.

During a press conference, Dr. Büller confided to reporters that he felt like a boy in a candy store, finally able to reveal the superb study findings.

Dr. Robert Flaumenhaft of Harvard Medical School, Boston, was far less effusive in an editorial that accompanied the simultaneous publication of the study in the New England Journal of Medicine.

“Do these finding prove that reduction in factor XI levels inhibits thrombosis without affecting bleeding? The conservative answer is no,” he wrote.

Dr. Flaumenhaft observed that the incidence of clinically relevant bleeding is relatively low after knee arthroplasty, even when patients receive anticoagulants, and that this safety outcome did not differ significantly between the enoxaparin and 300-mg FXI-ASO groups.

“These results also do not make a compelling case for the clinical use of the factor XI antisense oligonucleotide over anticoagulants that are currently used for prophylaxis in patients undergoing knee arthroplasty,” he wrote.

Central to this argument are issues of convenience and questions regarding reversibility. Treatment began 36 days before surgery and was associated with a high incidence of adverse events at the injection site and factor XI levels remained about 60% lower 70 days after initiation of therapy.

The half-life of FXI-ASO is about 22 days, “which in the classical setting in terms of bleeding could be seen as something of a disadvantage,” Dr. Büller told reporters. “But if we do the next study and it shows to be safe, it turns into an advantage” … because there is the possibility of giving FXI-ASO once every 3 weeks.

Dr. Flaumenhaft closed the editorial by acknowledging that the study challenges “the current paradigm” regarding the primary mechanism responsible for fibrin formation during thrombosis. “The striking observation that reducing factor XI levels prevents thrombosis after knee arthroplasty provides the best clinical evidence to date that the intrinsic pathway is essential for thrombus formation,” he wrote.

The study was conducted at 19 centers in five countries and randomly assigned 300 patients scheduled for elective primary unilateral total-knee arthroplasty to daily enoxaparin 40 mg or three doses of FXI-ASO. The protocol was amended early on to exclude a 100-mg FXI-ASO dose.

FXI-ASO 200 mg or 300 mg was given subcutaneously beginning 36 days before surgery on days 1, 3, 5, 8, 15, 22, and 29, and 6 hours postoperatively, with a final dose on day 39.

Enoxaparin 40 mg was given subcutaneously once daily, beginning the evening before or 6-8 hours after surgery, according to investigator preference, and was continued for at least 8 days postoperatively.

The primary efficacy point was a composite of asymptomatic DVT, detected by venography, and confirmed symptomatic VTE.

At baseline, the average factor XI level was 1.23 units/mL in the enoxaparin group, 1.20 U/mL in the 200-mg group, and 1.16 U/mL in the 300-mg group.

In patients with an average factor XI level of 0.2 U/mL or less, the incidence of the primary efficacy outcome was 5%.

Isis Pharmaceuticals funded the study. Dr. Büller disclosed ties with Isis, Daiichi-Sankyo, Bayer Healthcare, Pfizer, and Bristol-Myers Squibb. Dr. Flaumenhaft reported having no disclosures.

[email protected]

NASHVILLE, TENN. – A 1 million–patient analysis of the Get With the Guidelines database found striking improvements in outcomes after ischemic stroke.

Despite the proven benefits of new-generation clot-retrieval devices, however, only about 2% of such stroke patients undergo endovascular therapy.

In a video interview at the International Stroke Conference, Dr. Bijoy Menon of the department of clinical neurosciences at the University of Calgary (Alta.), who presented the findings at the conference, discussed this apparent clinical paradox.

Dr. Menon’s study echoes findings of the landmark Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) trial, which found dramatically improved stroke outcomes after endovascular therapy.

But the benefits of such treatment should never outweigh the need for thoroughly screening patients and carefully considering their recovery prospects, Dr. Michael Hill, professor of neurology at the University of Calgary and primary investigator on the ESCAPE study, cautioned in another video interview at the meeting.

[email protected]

On Twitter @alz_gal

NASHVILLE, TENN. – A 1 million–patient analysis of the Get With the Guidelines database found striking improvements in outcomes after ischemic stroke.

Despite the proven benefits of new-generation clot-retrieval devices, however, only about 2% of such stroke patients undergo endovascular therapy.

In a video interview at the International Stroke Conference, Dr. Bijoy Menon of the department of clinical neurosciences at the University of Calgary (Alta.), who presented the findings at the conference, discussed this apparent clinical paradox.

Dr. Menon’s study echoes findings of the landmark Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) trial, which found dramatically improved stroke outcomes after endovascular therapy.

But the benefits of such treatment should never outweigh the need for thoroughly screening patients and carefully considering their recovery prospects, Dr. Michael Hill, professor of neurology at the University of Calgary and primary investigator on the ESCAPE study, cautioned in another video interview at the meeting.

[email protected]

On Twitter @alz_gal

NASHVILLE, TENN. – A 1 million–patient analysis of the Get With the Guidelines database found striking improvements in outcomes after ischemic stroke.

Despite the proven benefits of new-generation clot-retrieval devices, however, only about 2% of such stroke patients undergo endovascular therapy.

In a video interview at the International Stroke Conference, Dr. Bijoy Menon of the department of clinical neurosciences at the University of Calgary (Alta.), who presented the findings at the conference, discussed this apparent clinical paradox.

Dr. Menon’s study echoes findings of the landmark Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) trial, which found dramatically improved stroke outcomes after endovascular therapy.

But the benefits of such treatment should never outweigh the need for thoroughly screening patients and carefully considering their recovery prospects, Dr. Michael Hill, professor of neurology at the University of Calgary and primary investigator on the ESCAPE study, cautioned in another video interview at the meeting.

[email protected]

On Twitter @alz_gal

LAKE BUENA VISTA, FLA. – Trauma patients on contact isolation were nearly six times more likely to develop venous thromboembolism (VTE) as those who were not isolated, based on an analysis of 4,317 patients.

VTE occurred in 17.5% (44/251) of patients on contact isolation and 3.5% (141/4,066) of patients who were not isolated (P < .0001). Injury Severity Score (ISS), age, male gender, and obesity also were significantly associated with the risk of VTE.

The relationship between VTE risk and contact isolation remained significant after adjusting for gender, age, ISS, and comorbidities (odds ratio, 3.28; P < .0001), Dr. Robert Ferguson reported at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.

Odds ratios also were significantly elevated for obesity (OR, 2.35; P < .006), male gender (OR, 2.1; P < .0001), ISS (OR, 1.08; P < .0001), and age (OR, 1.02; P < .0001). The presence of diabetes, dementia/Alzheimer’s, history of cerebrovascular accident, psychiatric disease, cirrhosis, cancer, or alcohol abuse was not statistically significant.

The increased risk for VTE in trauma patients on contact isolation “is likely multifactorial in nature and is related but not limited to decreased ambulation, noncompliance with prophylaxis, and restricted access by staff,” said Dr. Ferguson, a third-year resident at the Virginia Tech, Roanoke.

The risk:benefit ratio of contact isolation in the trauma population needs to be reevaluated, the researchers concluded. “We encourage hospital committees to alter protocols and supplement strategies such as staff education, dedicated ambulation areas and/or isolation wards, and eliminate contact isolation following routine methicillin-resistant Staphylococcus aureus surveillance screening.”

Dr. Ferguson and his coauthors reported having no financial disclosures.

[email protected]

LAKE BUENA VISTA, FLA. – Trauma patients on contact isolation were nearly six times more likely to develop venous thromboembolism (VTE) as those who were not isolated, based on an analysis of 4,317 patients.

VTE occurred in 17.5% (44/251) of patients on contact isolation and 3.5% (141/4,066) of patients who were not isolated (P < .0001). Injury Severity Score (ISS), age, male gender, and obesity also were significantly associated with the risk of VTE.

The relationship between VTE risk and contact isolation remained significant after adjusting for gender, age, ISS, and comorbidities (odds ratio, 3.28; P < .0001), Dr. Robert Ferguson reported at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.

Odds ratios also were significantly elevated for obesity (OR, 2.35; P < .006), male gender (OR, 2.1; P < .0001), ISS (OR, 1.08; P < .0001), and age (OR, 1.02; P < .0001). The presence of diabetes, dementia/Alzheimer’s, history of cerebrovascular accident, psychiatric disease, cirrhosis, cancer, or alcohol abuse was not statistically significant.

The increased risk for VTE in trauma patients on contact isolation “is likely multifactorial in nature and is related but not limited to decreased ambulation, noncompliance with prophylaxis, and restricted access by staff,” said Dr. Ferguson, a third-year resident at the Virginia Tech, Roanoke.

The risk:benefit ratio of contact isolation in the trauma population needs to be reevaluated, the researchers concluded. “We encourage hospital committees to alter protocols and supplement strategies such as staff education, dedicated ambulation areas and/or isolation wards, and eliminate contact isolation following routine methicillin-resistant Staphylococcus aureus surveillance screening.”

Dr. Ferguson and his coauthors reported having no financial disclosures.

[email protected]

LAKE BUENA VISTA, FLA. – Trauma patients on contact isolation were nearly six times more likely to develop venous thromboembolism (VTE) as those who were not isolated, based on an analysis of 4,317 patients.

VTE occurred in 17.5% (44/251) of patients on contact isolation and 3.5% (141/4,066) of patients who were not isolated (P < .0001). Injury Severity Score (ISS), age, male gender, and obesity also were significantly associated with the risk of VTE.

The relationship between VTE risk and contact isolation remained significant after adjusting for gender, age, ISS, and comorbidities (odds ratio, 3.28; P < .0001), Dr. Robert Ferguson reported at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.

Odds ratios also were significantly elevated for obesity (OR, 2.35; P < .006), male gender (OR, 2.1; P < .0001), ISS (OR, 1.08; P < .0001), and age (OR, 1.02; P < .0001). The presence of diabetes, dementia/Alzheimer’s, history of cerebrovascular accident, psychiatric disease, cirrhosis, cancer, or alcohol abuse was not statistically significant.

The increased risk for VTE in trauma patients on contact isolation “is likely multifactorial in nature and is related but not limited to decreased ambulation, noncompliance with prophylaxis, and restricted access by staff,” said Dr. Ferguson, a third-year resident at the Virginia Tech, Roanoke.

The risk:benefit ratio of contact isolation in the trauma population needs to be reevaluated, the researchers concluded. “We encourage hospital committees to alter protocols and supplement strategies such as staff education, dedicated ambulation areas and/or isolation wards, and eliminate contact isolation following routine methicillin-resistant Staphylococcus aureus surveillance screening.”

Dr. Ferguson and his coauthors reported having no financial disclosures.

[email protected]

Patients hospitalized with non–ST-segment myocardial infarction who received fondaparinux had significantly lower risk of suffering a major bleed or dying in the hospital, compared with those treated with low-molecular-weight heparin, investigators reported online Feb. 17 in JAMA.

The differences persisted 1 and 6 months after hospitalization, said Dr. Karolina Szummer at Karolinska University Hospital in Stockholm, and her associates. However, fondaparinux was not linked to lower rates of stroke or recurrent heart attack, compared with low-molecular-weight heparin (LMWH), the researchers said.

The European Society of Cardiology changed its NSTEMI guidelines in 2011, recommending fondaparinux as a first-choice anticoagulant for both patients treated either noninvasively or with PCI, spurring a “rapid switch” from LMWH to the indirect factor Xa inhibitor fondaparinux for treating non–ST-segment myocardial infarction (NSTEMI), said the investigators. (American Heart Association/American College of Cardiology guidelines, issued in 2012, do not favor fondaparinux over LMWH.) To study the effects of ESC’s change, they analyzed registry data from 40,616 patients hospitalized with NSTEMI between 2006 and 2010, of whom 36% of patients received fondaparinux and 64% received LMWH (JAMA 2015 Feb. 17;313:707-16).

Only 3.7% of the fondaparinux group suffered severe bleeding events or died in the hospital, compared with 5.5% of the heparin group (adjusted odds ratio, 0.67; 95% confidence interval, 0.58-0.78), the study found. Significant differences in bleeding and death rates persisted 30 days and 6 months after hospitalization, but rates of recurrent heart attack and stroke were similar between the treatment groups at all time points, the researchers said.

“This is not a randomized trial; therefore, residual confounding is very likely,” the investigators cautioned, adding that because the study used registry data, it probably underestimated bleeding events.

The work was funded by the Swedish Foundation for Strategic Research, the Swedish Heart and Lung Foundation, ALF Medicin, and the Swedish Medical Research Council. Dr. Szummer has received lecture fees from AstraZeneca. One coauthor reported financial relationships with GlaxoSmithKline, which markets fondaparinux. Other coauthors reported funding from numerous pharmaceutical companies.

Patients hospitalized with non–ST-segment myocardial infarction who received fondaparinux had significantly lower risk of suffering a major bleed or dying in the hospital, compared with those treated with low-molecular-weight heparin, investigators reported online Feb. 17 in JAMA.

The differences persisted 1 and 6 months after hospitalization, said Dr. Karolina Szummer at Karolinska University Hospital in Stockholm, and her associates. However, fondaparinux was not linked to lower rates of stroke or recurrent heart attack, compared with low-molecular-weight heparin (LMWH), the researchers said.

The European Society of Cardiology changed its NSTEMI guidelines in 2011, recommending fondaparinux as a first-choice anticoagulant for both patients treated either noninvasively or with PCI, spurring a “rapid switch” from LMWH to the indirect factor Xa inhibitor fondaparinux for treating non–ST-segment myocardial infarction (NSTEMI), said the investigators. (American Heart Association/American College of Cardiology guidelines, issued in 2012, do not favor fondaparinux over LMWH.) To study the effects of ESC’s change, they analyzed registry data from 40,616 patients hospitalized with NSTEMI between 2006 and 2010, of whom 36% of patients received fondaparinux and 64% received LMWH (JAMA 2015 Feb. 17;313:707-16).

Only 3.7% of the fondaparinux group suffered severe bleeding events or died in the hospital, compared with 5.5% of the heparin group (adjusted odds ratio, 0.67; 95% confidence interval, 0.58-0.78), the study found. Significant differences in bleeding and death rates persisted 30 days and 6 months after hospitalization, but rates of recurrent heart attack and stroke were similar between the treatment groups at all time points, the researchers said.

“This is not a randomized trial; therefore, residual confounding is very likely,” the investigators cautioned, adding that because the study used registry data, it probably underestimated bleeding events.

The work was funded by the Swedish Foundation for Strategic Research, the Swedish Heart and Lung Foundation, ALF Medicin, and the Swedish Medical Research Council. Dr. Szummer has received lecture fees from AstraZeneca. One coauthor reported financial relationships with GlaxoSmithKline, which markets fondaparinux. Other coauthors reported funding from numerous pharmaceutical companies.

Patients hospitalized with non–ST-segment myocardial infarction who received fondaparinux had significantly lower risk of suffering a major bleed or dying in the hospital, compared with those treated with low-molecular-weight heparin, investigators reported online Feb. 17 in JAMA.

The differences persisted 1 and 6 months after hospitalization, said Dr. Karolina Szummer at Karolinska University Hospital in Stockholm, and her associates. However, fondaparinux was not linked to lower rates of stroke or recurrent heart attack, compared with low-molecular-weight heparin (LMWH), the researchers said.

The European Society of Cardiology changed its NSTEMI guidelines in 2011, recommending fondaparinux as a first-choice anticoagulant for both patients treated either noninvasively or with PCI, spurring a “rapid switch” from LMWH to the indirect factor Xa inhibitor fondaparinux for treating non–ST-segment myocardial infarction (NSTEMI), said the investigators. (American Heart Association/American College of Cardiology guidelines, issued in 2012, do not favor fondaparinux over LMWH.) To study the effects of ESC’s change, they analyzed registry data from 40,616 patients hospitalized with NSTEMI between 2006 and 2010, of whom 36% of patients received fondaparinux and 64% received LMWH (JAMA 2015 Feb. 17;313:707-16).

Only 3.7% of the fondaparinux group suffered severe bleeding events or died in the hospital, compared with 5.5% of the heparin group (adjusted odds ratio, 0.67; 95% confidence interval, 0.58-0.78), the study found. Significant differences in bleeding and death rates persisted 30 days and 6 months after hospitalization, but rates of recurrent heart attack and stroke were similar between the treatment groups at all time points, the researchers said.

“This is not a randomized trial; therefore, residual confounding is very likely,” the investigators cautioned, adding that because the study used registry data, it probably underestimated bleeding events.

The work was funded by the Swedish Foundation for Strategic Research, the Swedish Heart and Lung Foundation, ALF Medicin, and the Swedish Medical Research Council. Dr. Szummer has received lecture fees from AstraZeneca. One coauthor reported financial relationships with GlaxoSmithKline, which markets fondaparinux. Other coauthors reported funding from numerous pharmaceutical companies.

Age is the most important risk factor for stroke in patients with atrial fibrillation, and not all stroke risk factors in the CHA2DS2-VASc score carry equal risk, a retrospective, population-based study showed.

Analysis of data from 186,570 Taiwanese patients with atrial fibrillation (AF) found that the risk of ischemic stroke ranged from 1.96% per year for men with vascular diseases to 3.5% per year for those aged 65-74 years. In women, the risk increased from 1.91% per year for women with hypertension to 3.34% per year for those aged 65-74 years, wrote Dr. Tze-Fan Chao of Taipei (Taiwan) Veterans General Hospital and coauthors (J. Am. Coll. Cardiol. 2015;65:635-42 [doi: 10.1016/j.jacc.2014.11.046]).

The study results showed that male AF patients with a CHA2DS2-VASc score of 1 had an annual stroke rate of 2.75%; women with a CHA2DS2-VASc score of 2 had a greater than two-fold increase in stroke risk, compared with women with a score of 1.

“Our study is the first population-based investigation analyzing the risk of ischemic stroke in nonanticoagulated AF male patients with a CHA2DS2-VASc score of 1 and female patients with a CHA2DS2-VASc score of 2, according to the specific covariates composing the CHA2DS2-VASc score,” Dr. Chao wrote.

The investigators cited several limitations. One is that they were unable to determine whether the cause of ischemic stroke was tied to AF-related thromboembolism or atherosclerosis and thrombosis of the cerebral artery. This limitation, however, was common among previous randomized trials, they noted.

The study was partly supported by grants from the National Science Council and Taipei (Taiwan) Veterans General Hospital. One author declared consultancies and speakers fees from private industry. No other conflicts of interest were declared.

Age is the most important risk factor for stroke in patients with atrial fibrillation, and not all stroke risk factors in the CHA2DS2-VASc score carry equal risk, a retrospective, population-based study showed.

Analysis of data from 186,570 Taiwanese patients with atrial fibrillation (AF) found that the risk of ischemic stroke ranged from 1.96% per year for men with vascular diseases to 3.5% per year for those aged 65-74 years. In women, the risk increased from 1.91% per year for women with hypertension to 3.34% per year for those aged 65-74 years, wrote Dr. Tze-Fan Chao of Taipei (Taiwan) Veterans General Hospital and coauthors (J. Am. Coll. Cardiol. 2015;65:635-42 [doi: 10.1016/j.jacc.2014.11.046]).

The study results showed that male AF patients with a CHA2DS2-VASc score of 1 had an annual stroke rate of 2.75%; women with a CHA2DS2-VASc score of 2 had a greater than two-fold increase in stroke risk, compared with women with a score of 1.

“Our study is the first population-based investigation analyzing the risk of ischemic stroke in nonanticoagulated AF male patients with a CHA2DS2-VASc score of 1 and female patients with a CHA2DS2-VASc score of 2, according to the specific covariates composing the CHA2DS2-VASc score,” Dr. Chao wrote.

The investigators cited several limitations. One is that they were unable to determine whether the cause of ischemic stroke was tied to AF-related thromboembolism or atherosclerosis and thrombosis of the cerebral artery. This limitation, however, was common among previous randomized trials, they noted.

The study was partly supported by grants from the National Science Council and Taipei (Taiwan) Veterans General Hospital. One author declared consultancies and speakers fees from private industry. No other conflicts of interest were declared.

Age is the most important risk factor for stroke in patients with atrial fibrillation, and not all stroke risk factors in the CHA2DS2-VASc score carry equal risk, a retrospective, population-based study showed.

Analysis of data from 186,570 Taiwanese patients with atrial fibrillation (AF) found that the risk of ischemic stroke ranged from 1.96% per year for men with vascular diseases to 3.5% per year for those aged 65-74 years. In women, the risk increased from 1.91% per year for women with hypertension to 3.34% per year for those aged 65-74 years, wrote Dr. Tze-Fan Chao of Taipei (Taiwan) Veterans General Hospital and coauthors (J. Am. Coll. Cardiol. 2015;65:635-42 [doi: 10.1016/j.jacc.2014.11.046]).

The study results showed that male AF patients with a CHA2DS2-VASc score of 1 had an annual stroke rate of 2.75%; women with a CHA2DS2-VASc score of 2 had a greater than two-fold increase in stroke risk, compared with women with a score of 1.

“Our study is the first population-based investigation analyzing the risk of ischemic stroke in nonanticoagulated AF male patients with a CHA2DS2-VASc score of 1 and female patients with a CHA2DS2-VASc score of 2, according to the specific covariates composing the CHA2DS2-VASc score,” Dr. Chao wrote.

The investigators cited several limitations. One is that they were unable to determine whether the cause of ischemic stroke was tied to AF-related thromboembolism or atherosclerosis and thrombosis of the cerebral artery. This limitation, however, was common among previous randomized trials, they noted.

The study was partly supported by grants from the National Science Council and Taipei (Taiwan) Veterans General Hospital. One author declared consultancies and speakers fees from private industry. No other conflicts of interest were declared.

Strenuous daily exercise actually increased the risk of coronary heart disease, venous thromboembolism, and cerebrovascular disease, compared with moderate physical activity, according to new data from the Million Women Study.

At baseline, the 1.1 million women who participated in the study were 55.9 years old on average, with a mean body mass index of 26 kg/m². Over the next 9 years, those reporting moderate activity had significantly lower risks of all three conditions than did inactive women, according to a study published online Feb. 16 in Circulation [doi:10.1161/CIRCULATIONAHA.114.010296].

©Monkey Business Images/thinkstockphotos.com

However, women who undertook daily strenuous activity had a 15% increase in their risk of coronary heart disease, a 25% increase in cerebrovascular disease risk, and a 29% increase in venous thromboembolism (VTE) risk, compared with those who exercised strenuously two to three times a week, judging from the findings of Cox regression models that controlled for BMI, smoking, and alcohol consumption.

“Among active women, there was little evidence of progressive reductions in risk with more frequent activity, and even an increase in risk for CHD, cerebrovascular disease, and VTE in the most active group,” wrote Dr. Miranda E. G. Armstrong of the University of Oxford, England, and colleagues.

The study was supported by the UK Medical Research Council, Cancer Research UK, and the BHF Centre of Research Excellence. There were no other conflicts of interest declared.

Strenuous daily exercise actually increased the risk of coronary heart disease, venous thromboembolism, and cerebrovascular disease, compared with moderate physical activity, according to new data from the Million Women Study.

At baseline, the 1.1 million women who participated in the study were 55.9 years old on average, with a mean body mass index of 26 kg/m². Over the next 9 years, those reporting moderate activity had significantly lower risks of all three conditions than did inactive women, according to a study published online Feb. 16 in Circulation [doi:10.1161/CIRCULATIONAHA.114.010296].

©Monkey Business Images/thinkstockphotos.com

However, women who undertook daily strenuous activity had a 15% increase in their risk of coronary heart disease, a 25% increase in cerebrovascular disease risk, and a 29% increase in venous thromboembolism (VTE) risk, compared with those who exercised strenuously two to three times a week, judging from the findings of Cox regression models that controlled for BMI, smoking, and alcohol consumption.

“Among active women, there was little evidence of progressive reductions in risk with more frequent activity, and even an increase in risk for CHD, cerebrovascular disease, and VTE in the most active group,” wrote Dr. Miranda E. G. Armstrong of the University of Oxford, England, and colleagues.

The study was supported by the UK Medical Research Council, Cancer Research UK, and the BHF Centre of Research Excellence. There were no other conflicts of interest declared.

Strenuous daily exercise actually increased the risk of coronary heart disease, venous thromboembolism, and cerebrovascular disease, compared with moderate physical activity, according to new data from the Million Women Study.

At baseline, the 1.1 million women who participated in the study were 55.9 years old on average, with a mean body mass index of 26 kg/m². Over the next 9 years, those reporting moderate activity had significantly lower risks of all three conditions than did inactive women, according to a study published online Feb. 16 in Circulation [doi:10.1161/CIRCULATIONAHA.114.010296].

©Monkey Business Images/thinkstockphotos.com

However, women who undertook daily strenuous activity had a 15% increase in their risk of coronary heart disease, a 25% increase in cerebrovascular disease risk, and a 29% increase in venous thromboembolism (VTE) risk, compared with those who exercised strenuously two to three times a week, judging from the findings of Cox regression models that controlled for BMI, smoking, and alcohol consumption.

“Among active women, there was little evidence of progressive reductions in risk with more frequent activity, and even an increase in risk for CHD, cerebrovascular disease, and VTE in the most active group,” wrote Dr. Miranda E. G. Armstrong of the University of Oxford, England, and colleagues.

The study was supported by the UK Medical Research Council, Cancer Research UK, and the BHF Centre of Research Excellence. There were no other conflicts of interest declared.

NASHVILLE, TENN. – Newly reported results from three trials showing “profound” benefit from endovascular embolectomy in selected patients with acute ischemic stroke “will have a major impact on how we treat stroke patients,” Dr. Lee H. Schwamm said during an interview at the International Stroke Conference.

“Many centers already provide this treatment, but this is the first time we have data on which patients to select” for catheter-based embolectomy, said Dr. Schwamm, professor of neurology at Harvard Medical School and director of acute stroke services at Massachusetts General Hospital in Boston. “Because we already have the capability in many centers, the first focus will be to extend the number of centers that can do this,” Dr. Schwamm noted.

An important part of that will be “changing the public health system to route patients to appropriate facilities” that can perform embolectomy, he said at the conference, sponsored by the American Heart Association.

Dr. Schwamm also noted that intravenous, thrombolytic treatment with tissue plasminogen activator (TPA) remains unchanged as the key first treatment for all patients with acute ischemic stroke. Following that, selected patients who do not fully respond to TPA should proceed to embolectomy. However, the new findings “do not suggest that you should avoid TPA and go directly to the catheter,” Dr. Schwamm cautioned.

[email protected]

On Twitter @mitchelzoler

NASHVILLE, TENN. – Newly reported results from three trials showing “profound” benefit from endovascular embolectomy in selected patients with acute ischemic stroke “will have a major impact on how we treat stroke patients,” Dr. Lee H. Schwamm said during an interview at the International Stroke Conference.

“Many centers already provide this treatment, but this is the first time we have data on which patients to select” for catheter-based embolectomy, said Dr. Schwamm, professor of neurology at Harvard Medical School and director of acute stroke services at Massachusetts General Hospital in Boston. “Because we already have the capability in many centers, the first focus will be to extend the number of centers that can do this,” Dr. Schwamm noted.

An important part of that will be “changing the public health system to route patients to appropriate facilities” that can perform embolectomy, he said at the conference, sponsored by the American Heart Association.

Dr. Schwamm also noted that intravenous, thrombolytic treatment with tissue plasminogen activator (TPA) remains unchanged as the key first treatment for all patients with acute ischemic stroke. Following that, selected patients who do not fully respond to TPA should proceed to embolectomy. However, the new findings “do not suggest that you should avoid TPA and go directly to the catheter,” Dr. Schwamm cautioned.

[email protected]

On Twitter @mitchelzoler

NASHVILLE, TENN. – Newly reported results from three trials showing “profound” benefit from endovascular embolectomy in selected patients with acute ischemic stroke “will have a major impact on how we treat stroke patients,” Dr. Lee H. Schwamm said during an interview at the International Stroke Conference.

“Many centers already provide this treatment, but this is the first time we have data on which patients to select” for catheter-based embolectomy, said Dr. Schwamm, professor of neurology at Harvard Medical School and director of acute stroke services at Massachusetts General Hospital in Boston. “Because we already have the capability in many centers, the first focus will be to extend the number of centers that can do this,” Dr. Schwamm noted.

An important part of that will be “changing the public health system to route patients to appropriate facilities” that can perform embolectomy, he said at the conference, sponsored by the American Heart Association.

Dr. Schwamm also noted that intravenous, thrombolytic treatment with tissue plasminogen activator (TPA) remains unchanged as the key first treatment for all patients with acute ischemic stroke. Following that, selected patients who do not fully respond to TPA should proceed to embolectomy. However, the new findings “do not suggest that you should avoid TPA and go directly to the catheter,” Dr. Schwamm cautioned.

[email protected]

On Twitter @mitchelzoler

NASHVILLE, TENN. – Treatment of selected patients with acute ischemic stroke underwent a dramatic, sudden shift with reports from three randomized, controlled trials that showed substantial added benefit and no incremental risk with the use of catheter-based embolic retrieval to open blocked intracerebral arteries when performed on top of standard thrombolytic therapy.

The three studies, each run independently and based in different countries, supported the results first reported last October and published online in December (N. Engl. J. Med. 2015;372:11-20) from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) study. These were the first contemporary trial results to show a jump in functional outcomes with use of a stent retriever catheter to pluck out the occluding embolus from an artery in the stroke patient’s brain to restore normal blood flow.

All three of the newly-reported studies stopped before reaching their prespecified enrollment levels because of overwhelming evidence for embolectomy’s incremental efficacy.

With four reports from prospective, randomized trials showing similar benefits and no added harm to patients, experts at the International Stroke Conference uniformly anointed catheter-based embolectomy the new standard of care for the small percentage of acute, ischemic-stroke patients who present with proximal, large-artery obstructions and also match the other strict clinical and imaging inclusion and exclusion criteria used in the studies.

Mitchel L. Zoler/Frontline Medical News

“Starting now, in patients with an acute ischemic stroke due to proximal vessel occlusion, rapid endovascular treatment using a retrieval stent is the standard of care,” Dr. Mayank Goyal declared from the plenary-session podium. He is a professor of diagnostic imaging at the University of Calgary (Canada) and an investigator in two of the three trials presented at the conference, which was sponsored by the American Heart Association.

“Today the world changed. We are now in a new era, the era of highly-effective intravascular recanalization therapy,” said Dr. Jeffrey L. Saver, professor of neurology and director of the Stroke Center at the University of California, Los Angeles, and lead investigator for one of the new studies.

In three of the four studies, the researchers did not report specific numbers on how selective they were in focusing in on the ischemic stroke patients most likely to benefit from this treatment, but the one study that did, EXTEND-IA (Extending the Time for Thrombolysis in Emergency Neurological Deficits – Intra-Arterial), run at nine Australian centers and one in New Zealand, showed the extensive winnowing that occurred. Of 7,796 patients with an acute ischemic stroke who initially presented, 1,044 (13%) were eligible to receive thrombolytic therapy (alteplase in this study). And from among these 1,044 patients, a mere 70 – less than 1% of the initial group – were deemed eligible for randomization into the embolectomy trial. The top three reasons for exclusion of patients who qualified for thrombolytic treatment from the trial was an absence of a major-vessel occlusion (45% of the excluded patients), presentation outside of the times when enrollment personnel were available (22%), and poor premorbid function (16%).

Mitchel L. Zoler/Frontline Medical News

But subgroup analyses in three of the four studies (EXTEND-IA with a total of 70 patients was too small for subgroup analyses) showed no subgroup of patients who failed to benefit from embolectomy, including elderly patients who in some cases were nonagenarians.

The unusual confluence of having four major trials showing remarkably consistent results meant that the stroke experts gathered at the meeting focused their attention not on whether stent retrievers should now be widely and routinely used in appropriate patients but instead on how this technology will roll out worldwide.

“From here on out we are obligated to treat patients with this technology at centers that can do this, and we are obligated to have more centers that can provide it,” said Dr. Kyra J. Becker, professor of neurology and neurological surgery and codirector of the Stroke Center at the University of Washington, Seattle. Dr. Becker had no involvement in any of the stent retriever trials. “I had been a doubter of this technology,” primarily because results reported at the International Stroke Conference a couple of years ago failed to prove the efficacy of clot retrieval in ischemic stroke patients, she noted. “Our ability to select appropriate patients and do it in a timely fashion hadn’t gotten to where it had to be until now,” Dr. Becker said in an interview.

“We only enrolled patients with blockages, we treated them quickly, and we used much better devices to open their arteries,” Dr. Saver added, explaining why the new studies succeeded when earlier studies had not.

The trial led by Dr. Saver, SWIFT-PRIME (SOLITAIRE™ FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke), enrolled 195 patients at 39 sites in the United States and in Europe. At 90 days after treatment, 59 patients (60%) among those treated with thrombolysis plus embolectomy had a modified Rankin Scale score of 0-2, compared with 33 patients (36%) among those treated only with thrombolysis (in this trial intravenous treatment with tissue plasminogen activator), a highly significant difference for the study’s primary endpoint.

Mitchel L. Zoler/Frontline Medical News

“For every two and half patients treated, one more patient had a better disability outcome, and for every four patients treated, one more patient was independent at long-term follow-up,” Dr. Saver said. Safety measures were similar among patients in the study’s two arms.

The EXTEND-IA results showed a 90-day modified Rankin Scale score of 0-2 in 52% of the embolectomy patients, compared with 28% of those treated only with thrombolysis. The study’s co–primary endpoints were median level of reperfusion at 24 hours after treatment, 100% with embolectomy and 37% with thrombolysis only, and early neurologic recovery, defined as at least an 8-point drop from the baseline in the National Institutes of Health Stroke Scale score or a score of 0 or 1 when assessed 3 days after treatment. Patients met this second endpoint at an 80% rate with embolectomy and a 37% rate with thrombolysis only. Results of EXTEND-IA appeared in an article published online concurrently with the meeting report (N. Engl J. Med. 2015 Feb. 11 [doi:10.1056/NEJMoa1414792]).

The third, and largest, of the three studies presented at the conference, ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times), enrolled 316 patients at 11 centers in Canada, 6 in the United States, 3 in South Korea, and 1 in Ireland. After 90 days, 53% of patients in the embolectomy arm had achieved a modified Rankin Scale score of 0-2, this study’s primary endpoint, compared with 29% of patients in the thrombolysis-only arm (treatment with alteplase). These results also appeared in an article published online concurrently with the conference report (N. Engl. J. Med. 2015 Feb. 11 [doi:10.1056/NEJMoa1414905]).

SWIFT PRIME was sponsored by Covidien, which markets the stent retriever used in the study. Dr. Saver and Dr. Goyal are consultants to Covidien. EXTEND-IA used stent retrievers provided by Covidien. ESCAPE received a grant from Covidien. Dr. Becker had no relevant disclosures.

[email protected]

On Twitter @mitchelzoler

NASHVILLE, TENN. – Treatment of selected patients with acute ischemic stroke underwent a dramatic, sudden shift with reports from three randomized, controlled trials that showed substantial added benefit and no incremental risk with the use of catheter-based embolic retrieval to open blocked intracerebral arteries when performed on top of standard thrombolytic therapy.

The three studies, each run independently and based in different countries, supported the results first reported last October and published online in December (N. Engl. J. Med. 2015;372:11-20) from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) study. These were the first contemporary trial results to show a jump in functional outcomes with use of a stent retriever catheter to pluck out the occluding embolus from an artery in the stroke patient’s brain to restore normal blood flow.

All three of the newly-reported studies stopped before reaching their prespecified enrollment levels because of overwhelming evidence for embolectomy’s incremental efficacy.

With four reports from prospective, randomized trials showing similar benefits and no added harm to patients, experts at the International Stroke Conference uniformly anointed catheter-based embolectomy the new standard of care for the small percentage of acute, ischemic-stroke patients who present with proximal, large-artery obstructions and also match the other strict clinical and imaging inclusion and exclusion criteria used in the studies.

Mitchel L. Zoler/Frontline Medical News

“Starting now, in patients with an acute ischemic stroke due to proximal vessel occlusion, rapid endovascular treatment using a retrieval stent is the standard of care,” Dr. Mayank Goyal declared from the plenary-session podium. He is a professor of diagnostic imaging at the University of Calgary (Canada) and an investigator in two of the three trials presented at the conference, which was sponsored by the American Heart Association.

“Today the world changed. We are now in a new era, the era of highly-effective intravascular recanalization therapy,” said Dr. Jeffrey L. Saver, professor of neurology and director of the Stroke Center at the University of California, Los Angeles, and lead investigator for one of the new studies.

In three of the four studies, the researchers did not report specific numbers on how selective they were in focusing in on the ischemic stroke patients most likely to benefit from this treatment, but the one study that did, EXTEND-IA (Extending the Time for Thrombolysis in Emergency Neurological Deficits – Intra-Arterial), run at nine Australian centers and one in New Zealand, showed the extensive winnowing that occurred. Of 7,796 patients with an acute ischemic stroke who initially presented, 1,044 (13%) were eligible to receive thrombolytic therapy (alteplase in this study). And from among these 1,044 patients, a mere 70 – less than 1% of the initial group – were deemed eligible for randomization into the embolectomy trial. The top three reasons for exclusion of patients who qualified for thrombolytic treatment from the trial was an absence of a major-vessel occlusion (45% of the excluded patients), presentation outside of the times when enrollment personnel were available (22%), and poor premorbid function (16%).

Mitchel L. Zoler/Frontline Medical News

But subgroup analyses in three of the four studies (EXTEND-IA with a total of 70 patients was too small for subgroup analyses) showed no subgroup of patients who failed to benefit from embolectomy, including elderly patients who in some cases were nonagenarians.

The unusual confluence of having four major trials showing remarkably consistent results meant that the stroke experts gathered at the meeting focused their attention not on whether stent retrievers should now be widely and routinely used in appropriate patients but instead on how this technology will roll out worldwide.

“From here on out we are obligated to treat patients with this technology at centers that can do this, and we are obligated to have more centers that can provide it,” said Dr. Kyra J. Becker, professor of neurology and neurological surgery and codirector of the Stroke Center at the University of Washington, Seattle. Dr. Becker had no involvement in any of the stent retriever trials. “I had been a doubter of this technology,” primarily because results reported at the International Stroke Conference a couple of years ago failed to prove the efficacy of clot retrieval in ischemic stroke patients, she noted. “Our ability to select appropriate patients and do it in a timely fashion hadn’t gotten to where it had to be until now,” Dr. Becker said in an interview.

“We only enrolled patients with blockages, we treated them quickly, and we used much better devices to open their arteries,” Dr. Saver added, explaining why the new studies succeeded when earlier studies had not.

The trial led by Dr. Saver, SWIFT-PRIME (SOLITAIRE™ FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke), enrolled 195 patients at 39 sites in the United States and in Europe. At 90 days after treatment, 59 patients (60%) among those treated with thrombolysis plus embolectomy had a modified Rankin Scale score of 0-2, compared with 33 patients (36%) among those treated only with thrombolysis (in this trial intravenous treatment with tissue plasminogen activator), a highly significant difference for the study’s primary endpoint.

Mitchel L. Zoler/Frontline Medical News

“For every two and half patients treated, one more patient had a better disability outcome, and for every four patients treated, one more patient was independent at long-term follow-up,” Dr. Saver said. Safety measures were similar among patients in the study’s two arms.

The EXTEND-IA results showed a 90-day modified Rankin Scale score of 0-2 in 52% of the embolectomy patients, compared with 28% of those treated only with thrombolysis. The study’s co–primary endpoints were median level of reperfusion at 24 hours after treatment, 100% with embolectomy and 37% with thrombolysis only, and early neurologic recovery, defined as at least an 8-point drop from the baseline in the National Institutes of Health Stroke Scale score or a score of 0 or 1 when assessed 3 days after treatment. Patients met this second endpoint at an 80% rate with embolectomy and a 37% rate with thrombolysis only. Results of EXTEND-IA appeared in an article published online concurrently with the meeting report (N. Engl J. Med. 2015 Feb. 11 [doi:10.1056/NEJMoa1414792]).

The third, and largest, of the three studies presented at the conference, ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times), enrolled 316 patients at 11 centers in Canada, 6 in the United States, 3 in South Korea, and 1 in Ireland. After 90 days, 53% of patients in the embolectomy arm had achieved a modified Rankin Scale score of 0-2, this study’s primary endpoint, compared with 29% of patients in the thrombolysis-only arm (treatment with alteplase). These results also appeared in an article published online concurrently with the conference report (N. Engl. J. Med. 2015 Feb. 11 [doi:10.1056/NEJMoa1414905]).

SWIFT PRIME was sponsored by Covidien, which markets the stent retriever used in the study. Dr. Saver and Dr. Goyal are consultants to Covidien. EXTEND-IA used stent retrievers provided by Covidien. ESCAPE received a grant from Covidien. Dr. Becker had no relevant disclosures.

[email protected]

On Twitter @mitchelzoler

NASHVILLE, TENN. – Treatment of selected patients with acute ischemic stroke underwent a dramatic, sudden shift with reports from three randomized, controlled trials that showed substantial added benefit and no incremental risk with the use of catheter-based embolic retrieval to open blocked intracerebral arteries when performed on top of standard thrombolytic therapy.

The three studies, each run independently and based in different countries, supported the results first reported last October and published online in December (N. Engl. J. Med. 2015;372:11-20) from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) study. These were the first contemporary trial results to show a jump in functional outcomes with use of a stent retriever catheter to pluck out the occluding embolus from an artery in the stroke patient’s brain to restore normal blood flow.

All three of the newly-reported studies stopped before reaching their prespecified enrollment levels because of overwhelming evidence for embolectomy’s incremental efficacy.

With four reports from prospective, randomized trials showing similar benefits and no added harm to patients, experts at the International Stroke Conference uniformly anointed catheter-based embolectomy the new standard of care for the small percentage of acute, ischemic-stroke patients who present with proximal, large-artery obstructions and also match the other strict clinical and imaging inclusion and exclusion criteria used in the studies.

Mitchel L. Zoler/Frontline Medical News

“Starting now, in patients with an acute ischemic stroke due to proximal vessel occlusion, rapid endovascular treatment using a retrieval stent is the standard of care,” Dr. Mayank Goyal declared from the plenary-session podium. He is a professor of diagnostic imaging at the University of Calgary (Canada) and an investigator in two of the three trials presented at the conference, which was sponsored by the American Heart Association.

“Today the world changed. We are now in a new era, the era of highly-effective intravascular recanalization therapy,” said Dr. Jeffrey L. Saver, professor of neurology and director of the Stroke Center at the University of California, Los Angeles, and lead investigator for one of the new studies.

In three of the four studies, the researchers did not report specific numbers on how selective they were in focusing in on the ischemic stroke patients most likely to benefit from this treatment, but the one study that did, EXTEND-IA (Extending the Time for Thrombolysis in Emergency Neurological Deficits – Intra-Arterial), run at nine Australian centers and one in New Zealand, showed the extensive winnowing that occurred. Of 7,796 patients with an acute ischemic stroke who initially presented, 1,044 (13%) were eligible to receive thrombolytic therapy (alteplase in this study). And from among these 1,044 patients, a mere 70 – less than 1% of the initial group – were deemed eligible for randomization into the embolectomy trial. The top three reasons for exclusion of patients who qualified for thrombolytic treatment from the trial was an absence of a major-vessel occlusion (45% of the excluded patients), presentation outside of the times when enrollment personnel were available (22%), and poor premorbid function (16%).

Mitchel L. Zoler/Frontline Medical News

But subgroup analyses in three of the four studies (EXTEND-IA with a total of 70 patients was too small for subgroup analyses) showed no subgroup of patients who failed to benefit from embolectomy, including elderly patients who in some cases were nonagenarians.

The unusual confluence of having four major trials showing remarkably consistent results meant that the stroke experts gathered at the meeting focused their attention not on whether stent retrievers should now be widely and routinely used in appropriate patients but instead on how this technology will roll out worldwide.

“From here on out we are obligated to treat patients with this technology at centers that can do this, and we are obligated to have more centers that can provide it,” said Dr. Kyra J. Becker, professor of neurology and neurological surgery and codirector of the Stroke Center at the University of Washington, Seattle. Dr. Becker had no involvement in any of the stent retriever trials. “I had been a doubter of this technology,” primarily because results reported at the International Stroke Conference a couple of years ago failed to prove the efficacy of clot retrieval in ischemic stroke patients, she noted. “Our ability to select appropriate patients and do it in a timely fashion hadn’t gotten to where it had to be until now,” Dr. Becker said in an interview.

“We only enrolled patients with blockages, we treated them quickly, and we used much better devices to open their arteries,” Dr. Saver added, explaining why the new studies succeeded when earlier studies had not.

The trial led by Dr. Saver, SWIFT-PRIME (SOLITAIRE™ FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke), enrolled 195 patients at 39 sites in the United States and in Europe. At 90 days after treatment, 59 patients (60%) among those treated with thrombolysis plus embolectomy had a modified Rankin Scale score of 0-2, compared with 33 patients (36%) among those treated only with thrombolysis (in this trial intravenous treatment with tissue plasminogen activator), a highly significant difference for the study’s primary endpoint.

Mitchel L. Zoler/Frontline Medical News

“For every two and half patients treated, one more patient had a better disability outcome, and for every four patients treated, one more patient was independent at long-term follow-up,” Dr. Saver said. Safety measures were similar among patients in the study’s two arms.

The EXTEND-IA results showed a 90-day modified Rankin Scale score of 0-2 in 52% of the embolectomy patients, compared with 28% of those treated only with thrombolysis. The study’s co–primary endpoints were median level of reperfusion at 24 hours after treatment, 100% with embolectomy and 37% with thrombolysis only, and early neurologic recovery, defined as at least an 8-point drop from the baseline in the National Institutes of Health Stroke Scale score or a score of 0 or 1 when assessed 3 days after treatment. Patients met this second endpoint at an 80% rate with embolectomy and a 37% rate with thrombolysis only. Results of EXTEND-IA appeared in an article published online concurrently with the meeting report (N. Engl J. Med. 2015 Feb. 11 [doi:10.1056/NEJMoa1414792]).

The third, and largest, of the three studies presented at the conference, ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times), enrolled 316 patients at 11 centers in Canada, 6 in the United States, 3 in South Korea, and 1 in Ireland. After 90 days, 53% of patients in the embolectomy arm had achieved a modified Rankin Scale score of 0-2, this study’s primary endpoint, compared with 29% of patients in the thrombolysis-only arm (treatment with alteplase). These results also appeared in an article published online concurrently with the conference report (N. Engl. J. Med. 2015 Feb. 11 [doi:10.1056/NEJMoa1414905]).

SWIFT PRIME was sponsored by Covidien, which markets the stent retriever used in the study. Dr. Saver and Dr. Goyal are consultants to Covidien. EXTEND-IA used stent retrievers provided by Covidien. ESCAPE received a grant from Covidien. Dr. Becker had no relevant disclosures.

[email protected]

On Twitter @mitchelzoler