TPA Plus Solitaire Gives Better Outcomes Than IMS-III?

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TPA Plus Solitaire Gives Better Outcomes Than IMS-III?

Sue Hughes

Mar 22, 2013San Diego, California — A regimen of thrombolysis plus endovascular therapy similar to that tested in the recent Interventional Management of Stroke III (IMS-III) trial but using a more modern device has shown impressive results in a registry series of patients with acute ischemic stroke.

These data from the North American SOLITAIRE Acute Stroke (NASA) Registry, presented here at the American Academy of Neurology (AAN) 65th Annual Meeting, evaluated the use of thrombolysis with tissue plasminogen activator (tPA) followed by endovascular therapy with the Solitaire-FR mechanical thrombectomy device (Covidien) in 156 patients.

Lead investigator Osama O. Zaidat, MD, Medical College of Wisconsin, Milwaukee, says the data suggested a better outcome than shown with the combination of thrombolysis and endovascular therapy in the IMS-III trial. Results of that trial showed no benefit of the combined approach over thrombolysis alone. Dr. Zaidat said the better results in the current study may be explained by the use of the newer device.

“In IMS-III, any type of endovascular device could be used, and older devices such as the Merci retriever were used in most patients. But now more modern devices are becoming available and our data suggest they give better results,” Dr. Zaidat commented to Medscape Medical News.

Commenting on these data for Medscape Medical News, Joseph Broderick, MD, University of Cincinnati, Ohio, who was lead investigator of IMS-III, pointed out that this was a registry study with all the associated limitations and could therefore not be compared with the randomized IMS-III trial results.

“Bottom line, new stent retriever technology is an advance over older technology in terms of reperfusion but still needs to be demonstrated to be more effective than IV [intravenous] t-PA alone in randomized trials,” Dr. Broderick said.

NASA Registry

The new data come from the NASA Registry; which is a repository database of the Solitaire Stent-retriever in real life practice.

For the current study, which was investigator-initiated and led, Zaidat explained that an “IMS-III–like group” was identified as the cohort within the NASA registry that received IV tPA plus Solitaire-FR and had an National Institutes of Health Stroke Scale (NIHSS) score of 8 or higher. “This is the largest IMS-III–like group analysis using the newer thrombectomy devices,” he said.

Baseline NIHSS scores were 19 for the NASA tPA plus Solitaire patients versus 17 for the IMS-lll combination group and 18 for the IMS-III tPA alone group.

In this “IMS-III–like group” from the NASA registry, a good clinical outcome (defined as a 90-day modified Rankin scale score [mRS] of 2 or less) was achieved in more patients than those who received the combination approach or tPA alone in the IMS-III trial, Dr. Zaidat reported.

Table 1. Major Results From NASA Database of tPA Plus Solitaire vs IMS-III Results

Endpoint tPA Plus Solitaire (From NASA Registry) IMS-III Combination Group IMS-III tPA Alone Group
Good clinical outcome (90-d mRS score 2 or less) (%) 51.5 40.8 38.7
Mortality (%) 24.6 19.1 21.6

 

Dr. Zaidat suggested the better rate of good clinical outcome in the NASA tPA plus Solitaire patients could be related to a higher recanalization rates.

Table 2. Recanalization Rates: NASA Registry vs IMS-III

Recanalization Rate tPA Plus Solitaire (From NASA Registry) IMS-III Combination Group
mTICI score, 2b-3 (%) 70 40
mTICI score, 3 (%) 41 2

 

mTICI = Modified Thrombosis in Cerebral Infarction.

“The results of the IMS-III raise the question of the efficacy of combined thrombolysis plus endovascular therapy versus thrombolysis only,” Dr. Zaidat said. “But one of the criticisms of the IMS-III is the use of historical interventional approaches that are no longer used in clinical practice. Here, an ‘IMS-III–like group’ was analyzed from newer-generation thrombectomy device database, and results suggested a better outcome.”

He added that both studies demonstrated the importance of time to treatment and that large blinded adjudicated studies may provide additional insight on the effect of newer technology on outcome in the combined tPA plus endovascular approach.

Limitations of Registry Data

In his comments on the NASA data for Medscape Medical News, Dr. Broderick highlighted the limitations of registry data. “Registries provide us useful information but the quality of information increases substantially from registry to single-arm controlled clinical trials to randomized trials. Patients enrolled in registries almost always have better outcomes than ‘the same patients’ in randomized trials,” he said. “Reasons for this is that some patients who have poor outcome prior to consent to participate in a registry, may not be enrolled (not an intent-to-treat group).”

Dr. Broderick also made the point that registry patients often don’t have a very well-defined follow-up done by an investigator who is certified in the assessment tool, such as the mRS, and thus more patients are lost to follow-up.

For example, in this NASA Registry, 12% of patients were lost to follow-up, and these patients were more likely to have poor outcomes, he noted. “In a clinical trial such as IMS-III, these patients are counted as poor outcomes. If these are included as poor outcomes in the registry, the mRS 0-2 would be 46%,” he added.

He also pointed out that this registry had a more conservative definition of symptomatic intracerebral hemorrhage (ICH), and the rate of symptomatic ICH was 12%, compared with 6% in IMS-III.

In addition, the mortality rate was 5% lower in IMS-III. However, none of these differences were statistically significant. “The investigators don’t comment on these differences in the conclusions,” he noted. But he added that the registry patients were a little sicker than patients in IMS-III, “so I would expect a little higher mortality and a bit higher symptomatic ICH rate.”

On the reperfusion data, Dr. Broderick said: “The increased reperfusion rates with the new technology are real and IMS-III didn’t have many new devices before the trial was stopped. However, it is not clear [in the SOLITAIRE registry] if the reperfusion rates were determined by central reading laboratory or by on-site investigator. The latter always tends to overcall reperfusion rates compared to central reading laboratory in prior trials.”

Dr. Broderick also stressed that randomized controlled trials are the gold standard because they ensure that the population of patients under study is similar with regard to key variables and other therapies.

“In IMS III, patients weren’t selected by CT [computed tomography] perfusion studies.  Some of the patients in this SOLITARE registry may have been selected by CT or MR perfusion and thus may have been a patient group with a greater likelihood of a good outcome, regardless of treatment,” he said.

American Academy of Neurology (AAN) 65th Annual Meeting. Emerging Science Abstract 011. Presented March 20, 2013.

Sue HughesMar 22, 2013San Diego, California — A regimen of thrombolysis plus endovascular therapy similar to that tested in the recent Interventional Management of Stroke III (IMS-III) trial but using a more modern device has shown impressive results in a registry series of patients with acute ischemic stroke.

These data from the North American SOLITAIRE Acute Stroke (NASA) Registry, presented here at the American Academy of Neurology (AAN) 65th Annual Meeting, evaluated the use of thrombolysis with tissue plasminogen activator (tPA) followed by endovascular therapy with the Solitaire-FR mechanical thrombectomy device (Covidien) in 156 patients.

Lead investigator Osama O. Zaidat, MD, Medical College of Wisconsin, Milwaukee, says the data suggested a better outcome than shown with the combination of thrombolysis and endovascular therapy in the IMS-III trial. Results of that trial showed no benefit of the combined approach over thrombolysis alone. Dr. Zaidat said the better results in the current study may be explained by the use of the newer device.

“In IMS-III, any type of endovascular device could be used, and older devices such as the Merci retriever were used in most patients. But now more modern devices are becoming available and our data suggest they give better results,” Dr. Zaidat commented to Medscape Medical News.

Commenting on these data for Medscape Medical News, Joseph Broderick, MD, University of Cincinnati, Ohio, who was lead investigator of IMS-III, pointed out that this was a registry study with all the associated limitations and could therefore not be compared with the randomized IMS-III trial results.

“Bottom line, new stent retriever technology is an advance over older technology in terms of reperfusion but still needs to be demonstrated to be more effective than IV [intravenous] t-PA alone in randomized trials,” Dr. Broderick said.

NASA Registry

The new data come from the NASA Registry; which is a repository database of the Solitaire Stent-retriever in real life practice.

For the current study, which was investigator-initiated and led, Zaidat explained that an “IMS-III–like group” was identified as the cohort within the NASA registry that received IV tPA plus Solitaire-FR and had an National Institutes of Health Stroke Scale (NIHSS) score of 8 or higher. “This is the largest IMS-III–like group analysis using the newer thrombectomy devices,” he said.

Baseline NIHSS scores were 19 for the NASA tPA plus Solitaire patients versus 17 for the IMS-lll combination group and 18 for the IMS-III tPA alone group.

In this “IMS-III–like group” from the NASA registry, a good clinical outcome (defined as a 90-day modified Rankin scale score [mRS] of 2 or less) was achieved in more patients than those who received the combination approach or tPA alone in the IMS-III trial, Dr. Zaidat reported.

Table 1. Major Results From NASA Database of tPA Plus Solitaire vs IMS-III Results

Endpoint tPA Plus Solitaire (From NASA Registry) IMS-III Combination Group IMS-III tPA Alone Group
Good clinical outcome (90-d mRS score 2 or less) (%) 51.5 40.8 38.7
Mortality (%) 24.6 19.1 21.6

 

Dr. Zaidat suggested the better rate of good clinical outcome in the NASA tPA plus Solitaire patients could be related to a higher recanalization rates.

Table 2. Recanalization Rates: NASA Registry vs IMS-III

Recanalization Rate tPA Plus Solitaire (From NASA Registry) IMS-III Combination Group
mTICI score, 2b-3 (%) 70 40
mTICI score, 3 (%) 41 2

 

mTICI = Modified Thrombosis in Cerebral Infarction.

“The results of the IMS-III raise the question of the efficacy of combined thrombolysis plus endovascular therapy versus thrombolysis only,” Dr. Zaidat said. “But one of the criticisms of the IMS-III is the use of historical interventional approaches that are no longer used in clinical practice. Here, an ‘IMS-III–like group’ was analyzed from newer-generation thrombectomy device database, and results suggested a better outcome.”

He added that both studies demonstrated the importance of time to treatment and that large blinded adjudicated studies may provide additional insight on the effect of newer technology on outcome in the combined tPA plus endovascular approach.

Limitations of Registry Data

In his comments on the NASA data for Medscape Medical News, Dr. Broderick highlighted the limitations of registry data. “Registries provide us useful information but the quality of information increases substantially from registry to single-arm controlled clinical trials to randomized trials. Patients enrolled in registries almost always have better outcomes than ‘the same patients’ in randomized trials,” he said. “Reasons for this is that some patients who have poor outcome prior to consent to participate in a registry, may not be enrolled (not an intent-to-treat group).”

Dr. Broderick also made the point that registry patients often don’t have a very well-defined follow-up done by an investigator who is certified in the assessment tool, such as the mRS, and thus more patients are lost to follow-up.

For example, in this NASA Registry, 12% of patients were lost to follow-up, and these patients were more likely to have poor outcomes, he noted. “In a clinical trial such as IMS-III, these patients are counted as poor outcomes. If these are included as poor outcomes in the registry, the mRS 0-2 would be 46%,” he added.

He also pointed out that this registry had a more conservative definition of symptomatic intracerebral hemorrhage (ICH), and the rate of symptomatic ICH was 12%, compared with 6% in IMS-III.

In addition, the mortality rate was 5% lower in IMS-III. However, none of these differences were statistically significant. “The investigators don’t comment on these differences in the conclusions,” he noted. But he added that the registry patients were a little sicker than patients in IMS-III, “so I would expect a little higher mortality and a bit higher symptomatic ICH rate.”

On the reperfusion data, Dr. Broderick said: “The increased reperfusion rates with the new technology are real and IMS-III didn’t have many new devices before the trial was stopped. However, it is not clear [in the SOLITAIRE registry] if the reperfusion rates were determined by central reading laboratory or by on-site investigator. The latter always tends to overcall reperfusion rates compared to central reading laboratory in prior trials.”

Dr. Broderick also stressed that randomized controlled trials are the gold standard because they ensure that the population of patients under study is similar with regard to key variables and other therapies.

“In IMS III, patients weren’t selected by CT [computed tomography] perfusion studies.  Some of the patients in this SOLITARE registry may have been selected by CT or MR perfusion and thus may have been a patient group with a greater likelihood of a good outcome, regardless of treatment,” he said.

American Academy of Neurology (AAN) 65th Annual Meeting. Emerging Science Abstract 011. Presented March 20, 2013.

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