Does Intra-Arterial Treatment Benefit Patients With Ischemic Stroke?

Intra-arterial treatment is effective and safe when administered within six hours of acute ischemic stroke resulting from a proximal intracranial occlusion of the anterior circulation, according to research published online ahead of print December 17, 2014, in the New England Journal of Medicine. The treatment aids functional recovery and increases functional independence by three months, researchers said. This study follows several similar investigations that yielded mixed or negative results regarding the benefits of this therapy.

Examining Intra-Arterial Treatment and Standard Therapy
Olvert A. Berkhemer, MD, of the Department of Neurology at Erasmus University Medical Center in Rotterdam, the Netherlands, and colleagues initiated the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) to compare intra-arterial treatment plus standard care with standard care alone. Eligible patients were 18 or older and had an acute ischemic stroke. The investigators enrolled patients with an occlusion of the distal intracranial carotid artery, middle cerebral artery, or anterior cerebral artery that had been established with CT angiography, magnetic resonance angiography, or digital-subtraction angiography. Eligible patients also had a score of 2 or higher on the NIH Stroke Scale (NIHSS). According to the study protocol, initiation of intra-arterial treatment had to be possible within six hours of stroke onset.

The researchers randomized patients using a Web-based tool. Local interventionists chose the method of intra-arterial treatment, which consisted of arterial catheterization with a microcatheter to the level of occlusion and delivery of a thrombolytic agent, mechanical thrombectomy, or both. The investigators permitted a maximum dose of 90 mg of alteplase or 1,200,000 IU of urokinase to be administered for intra-arterial thrombolysis. The dose was restricted to 30 mg of alteplase or 400,000 IU of urokinase if IV alteplase was given. Methods of mechanical treatment included thrombus retraction, aspiration, wire disruption, and the use of a retrievable stent.

The study’s primary outcome was modified Rankin scale score at 90 days. Secondary outcomes included NIHSS score at 24 hours and at five to seven days or discharge (if earlier), activities of daily living measured with the Barthel index, and the health-related quality of life measured with the EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D) at 90 days. Safety variables included hemorrhagic complications, progression of ischemic stroke, new ischemic stroke into a different vascular territory, and death.

Intervention Improved Modified Rankin Scale Score
Dr. Berkhemer and colleagues randomized 502 patients at 16 medical centers. Two patients withdrew consent and were not included in the intention-to-treat analysis. The study population’s mean age was 65, and 58.4% of participants were men. In all, 233 patients were assigned to the intervention group and 267 patients were assigned to the control group. Risk factors for a poor outcome, clinical risk factors for stroke, and aspects of rerandomization treatment were evenly distributed between the two treatment groups.

The median modified Rankin scale score at 90 days was 3 for patients who received intra-arterial treatment plus standard care, compared with 4 for patients who received standard care alone. Approximately 33% of patients in the intervention group had a modified Rankin score of 0 to 2 at 90 days, compared with 19% of the control group.

Median NIHSS score at five to seven days or discharge was 8 for the intervention group and 14 for the control group. Approximately 46% of patients who received intra-arterial therapy plus standard care had a Barthel index of 19 or 20 at 90 days, compared with 30% of patients who received standard care alone. Median EQ-5D score at 90 days was 0.69 for the intervention group and 0.66 for the control group.

An absence of residual occlusion at the target site was more common in the intervention group (75.4%) than in the control group (32.9%). Infarct volume was 19 mL smaller in the intervention group than in the control group, and good reperfusion was achieved in 58.7% of patients in the intervention group.

The rate of serious adverse events during follow-up did not differ significantly between the two groups. Thirteen of the 233 patients (5.6%) in the intervention group, however, had clinical signs of a new ischemic stroke in a different vascular territory within 90 days, compared with one of the 267 patients (0.4%) in the control group.

Results Diverged From Those of Previous Studies
“Our findings stand in clear distinction to those of recent randomized, controlled trials that failed to show a benefit of intra-arterial treatment,” said Dr. Berkhemer. Unlike some of those studies, MR CLEAN required participants to have a radiologically proven intracranial occlusion. “It is likely that intra-arterial treatment will not alter the natural history of acute ischemic stroke in the absence of a proximal arterial occlusion,” added Dr. Berkhemer.

“Our study benefited from the widespread availability of retrievable stents, which were used in 82% of the patients in the intervention group. These devices were recently shown to be superior to the first-generation Merci device for both revascularization and clinical outcomes.” Yet the study was limited by slightly unbalanced randomization, a relatively low reperfusion rate, and patients’ awareness of their treatment group assignments, Dr. Berkhemer said.

One Small Step?
“MR CLEAN is the first step in the right direction,” said Werner Hacke, MD, PhD, Professor and Chairman of the Department of Neurology at the University of Heidelberg in Germany, in an accompanying editorial. Other investigators are conducting similar trials, and “it is premature to conclude that there is no longer equipoise regarding thrombectomy,” he added. “We need and will get results from other well-designed trials, not only to confirm or refute the results of MR CLEAN, but also to look at effects in subgroups (according to stroke severity, occlusion site, or time to treatment initiation), for which most single trials are underpowered.”

—Erik Greb

Intra-arterial treatment is effective and safe when administered within six hours of acute ischemic stroke resulting from a proximal intracranial occlusion of the anterior circulation, according to research published online ahead of print December 17, 2014, in the New England Journal of Medicine. The treatment aids functional recovery and increases functional independence by three months, researchers said. This study follows several similar investigations that yielded mixed or negative results regarding the benefits of this therapy.

Examining Intra-Arterial Treatment and Standard Therapy
Olvert A. Berkhemer, MD, of the Department of Neurology at Erasmus University Medical Center in Rotterdam, the Netherlands, and colleagues initiated the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) to compare intra-arterial treatment plus standard care with standard care alone. Eligible patients were 18 or older and had an acute ischemic stroke. The investigators enrolled patients with an occlusion of the distal intracranial carotid artery, middle cerebral artery, or anterior cerebral artery that had been established with CT angiography, magnetic resonance angiography, or digital-subtraction angiography. Eligible patients also had a score of 2 or higher on the NIH Stroke Scale (NIHSS). According to the study protocol, initiation of intra-arterial treatment had to be possible within six hours of stroke onset.

The researchers randomized patients using a Web-based tool. Local interventionists chose the method of intra-arterial treatment, which consisted of arterial catheterization with a microcatheter to the level of occlusion and delivery of a thrombolytic agent, mechanical thrombectomy, or both. The investigators permitted a maximum dose of 90 mg of alteplase or 1,200,000 IU of urokinase to be administered for intra-arterial thrombolysis. The dose was restricted to 30 mg of alteplase or 400,000 IU of urokinase if IV alteplase was given. Methods of mechanical treatment included thrombus retraction, aspiration, wire disruption, and the use of a retrievable stent.

The study’s primary outcome was modified Rankin scale score at 90 days. Secondary outcomes included NIHSS score at 24 hours and at five to seven days or discharge (if earlier), activities of daily living measured with the Barthel index, and the health-related quality of life measured with the EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D) at 90 days. Safety variables included hemorrhagic complications, progression of ischemic stroke, new ischemic stroke into a different vascular territory, and death.

Intervention Improved Modified Rankin Scale Score
Dr. Berkhemer and colleagues randomized 502 patients at 16 medical centers. Two patients withdrew consent and were not included in the intention-to-treat analysis. The study population’s mean age was 65, and 58.4% of participants were men. In all, 233 patients were assigned to the intervention group and 267 patients were assigned to the control group. Risk factors for a poor outcome, clinical risk factors for stroke, and aspects of rerandomization treatment were evenly distributed between the two treatment groups.

The median modified Rankin scale score at 90 days was 3 for patients who received intra-arterial treatment plus standard care, compared with 4 for patients who received standard care alone. Approximately 33% of patients in the intervention group had a modified Rankin score of 0 to 2 at 90 days, compared with 19% of the control group.

Median NIHSS score at five to seven days or discharge was 8 for the intervention group and 14 for the control group. Approximately 46% of patients who received intra-arterial therapy plus standard care had a Barthel index of 19 or 20 at 90 days, compared with 30% of patients who received standard care alone. Median EQ-5D score at 90 days was 0.69 for the intervention group and 0.66 for the control group.

An absence of residual occlusion at the target site was more common in the intervention group (75.4%) than in the control group (32.9%). Infarct volume was 19 mL smaller in the intervention group than in the control group, and good reperfusion was achieved in 58.7% of patients in the intervention group.

The rate of serious adverse events during follow-up did not differ significantly between the two groups. Thirteen of the 233 patients (5.6%) in the intervention group, however, had clinical signs of a new ischemic stroke in a different vascular territory within 90 days, compared with one of the 267 patients (0.4%) in the control group.

Results Diverged From Those of Previous Studies
“Our findings stand in clear distinction to those of recent randomized, controlled trials that failed to show a benefit of intra-arterial treatment,” said Dr. Berkhemer. Unlike some of those studies, MR CLEAN required participants to have a radiologically proven intracranial occlusion. “It is likely that intra-arterial treatment will not alter the natural history of acute ischemic stroke in the absence of a proximal arterial occlusion,” added Dr. Berkhemer.

“Our study benefited from the widespread availability of retrievable stents, which were used in 82% of the patients in the intervention group. These devices were recently shown to be superior to the first-generation Merci device for both revascularization and clinical outcomes.” Yet the study was limited by slightly unbalanced randomization, a relatively low reperfusion rate, and patients’ awareness of their treatment group assignments, Dr. Berkhemer said.

One Small Step?
“MR CLEAN is the first step in the right direction,” said Werner Hacke, MD, PhD, Professor and Chairman of the Department of Neurology at the University of Heidelberg in Germany, in an accompanying editorial. Other investigators are conducting similar trials, and “it is premature to conclude that there is no longer equipoise regarding thrombectomy,” he added. “We need and will get results from other well-designed trials, not only to confirm or refute the results of MR CLEAN, but also to look at effects in subgroups (according to stroke severity, occlusion site, or time to treatment initiation), for which most single trials are underpowered.”

—Erik Greb

Intra-arterial treatment is effective and safe when administered within six hours of acute ischemic stroke resulting from a proximal intracranial occlusion of the anterior circulation, according to research published online ahead of print December 17, 2014, in the New England Journal of Medicine. The treatment aids functional recovery and increases functional independence by three months, researchers said. This study follows several similar investigations that yielded mixed or negative results regarding the benefits of this therapy.

Examining Intra-Arterial Treatment and Standard Therapy
Olvert A. Berkhemer, MD, of the Department of Neurology at Erasmus University Medical Center in Rotterdam, the Netherlands, and colleagues initiated the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) to compare intra-arterial treatment plus standard care with standard care alone. Eligible patients were 18 or older and had an acute ischemic stroke. The investigators enrolled patients with an occlusion of the distal intracranial carotid artery, middle cerebral artery, or anterior cerebral artery that had been established with CT angiography, magnetic resonance angiography, or digital-subtraction angiography. Eligible patients also had a score of 2 or higher on the NIH Stroke Scale (NIHSS). According to the study protocol, initiation of intra-arterial treatment had to be possible within six hours of stroke onset.

The researchers randomized patients using a Web-based tool. Local interventionists chose the method of intra-arterial treatment, which consisted of arterial catheterization with a microcatheter to the level of occlusion and delivery of a thrombolytic agent, mechanical thrombectomy, or both. The investigators permitted a maximum dose of 90 mg of alteplase or 1,200,000 IU of urokinase to be administered for intra-arterial thrombolysis. The dose was restricted to 30 mg of alteplase or 400,000 IU of urokinase if IV alteplase was given. Methods of mechanical treatment included thrombus retraction, aspiration, wire disruption, and the use of a retrievable stent.

The study’s primary outcome was modified Rankin scale score at 90 days. Secondary outcomes included NIHSS score at 24 hours and at five to seven days or discharge (if earlier), activities of daily living measured with the Barthel index, and the health-related quality of life measured with the EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D) at 90 days. Safety variables included hemorrhagic complications, progression of ischemic stroke, new ischemic stroke into a different vascular territory, and death.

Intervention Improved Modified Rankin Scale Score
Dr. Berkhemer and colleagues randomized 502 patients at 16 medical centers. Two patients withdrew consent and were not included in the intention-to-treat analysis. The study population’s mean age was 65, and 58.4% of participants were men. In all, 233 patients were assigned to the intervention group and 267 patients were assigned to the control group. Risk factors for a poor outcome, clinical risk factors for stroke, and aspects of rerandomization treatment were evenly distributed between the two treatment groups.

The median modified Rankin scale score at 90 days was 3 for patients who received intra-arterial treatment plus standard care, compared with 4 for patients who received standard care alone. Approximately 33% of patients in the intervention group had a modified Rankin score of 0 to 2 at 90 days, compared with 19% of the control group.

Median NIHSS score at five to seven days or discharge was 8 for the intervention group and 14 for the control group. Approximately 46% of patients who received intra-arterial therapy plus standard care had a Barthel index of 19 or 20 at 90 days, compared with 30% of patients who received standard care alone. Median EQ-5D score at 90 days was 0.69 for the intervention group and 0.66 for the control group.

An absence of residual occlusion at the target site was more common in the intervention group (75.4%) than in the control group (32.9%). Infarct volume was 19 mL smaller in the intervention group than in the control group, and good reperfusion was achieved in 58.7% of patients in the intervention group.

The rate of serious adverse events during follow-up did not differ significantly between the two groups. Thirteen of the 233 patients (5.6%) in the intervention group, however, had clinical signs of a new ischemic stroke in a different vascular territory within 90 days, compared with one of the 267 patients (0.4%) in the control group.

Results Diverged From Those of Previous Studies
“Our findings stand in clear distinction to those of recent randomized, controlled trials that failed to show a benefit of intra-arterial treatment,” said Dr. Berkhemer. Unlike some of those studies, MR CLEAN required participants to have a radiologically proven intracranial occlusion. “It is likely that intra-arterial treatment will not alter the natural history of acute ischemic stroke in the absence of a proximal arterial occlusion,” added Dr. Berkhemer.

“Our study benefited from the widespread availability of retrievable stents, which were used in 82% of the patients in the intervention group. These devices were recently shown to be superior to the first-generation Merci device for both revascularization and clinical outcomes.” Yet the study was limited by slightly unbalanced randomization, a relatively low reperfusion rate, and patients’ awareness of their treatment group assignments, Dr. Berkhemer said.

One Small Step?
“MR CLEAN is the first step in the right direction,” said Werner Hacke, MD, PhD, Professor and Chairman of the Department of Neurology at the University of Heidelberg in Germany, in an accompanying editorial. Other investigators are conducting similar trials, and “it is premature to conclude that there is no longer equipoise regarding thrombectomy,” he added. “We need and will get results from other well-designed trials, not only to confirm or refute the results of MR CLEAN, but also to look at effects in subgroups (according to stroke severity, occlusion site, or time to treatment initiation), for which most single trials are underpowered.”

—Erik Greb