NIHR Signal Mechanical clot removal may offer better outcomes for people with stroke

Published on 28 June 2016

Mechanical clot removal alongside standard clot-busting drug treatment may offer better functional outcomes for people who have suffered a stroke caused by a blood clot than drug treatment alone. This review found that 44% of patients receiving mechanical clot removal had a good functional outcome after 90 days, compared to 33% of those who didn’t.

However, these benefits only apply to a subset of patients. Prior brain scan is essential in order to identify if the clot is amenable to mechanical removal. Also, newer technology was associated with better outcomes.

Given these implementation challenges, the cost-effectiveness of the approach remains unknown. Mechanical clot removal is a highly skilled operation that should be performed within six to eight hours after the stroke. Patients would need early access to stroke units with the necessary diagnostics, technology and specialist expertise. Therefore a pragmatic NHS trial and cost-effectiveness analysis would be informative.

Mechanical clot removal may offer better outcomes for people with stroke

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Why was this study needed?

Stroke is the UK’s third largest cause of death, after heart disease and cancer, and a major cause of adult disability. The health and social care costs of stroke in the UK are approximately £4.38 billion a year.

Around 85% of all cases of stroke are ischaemic stroke, where a blood clot obstructs the flow of blood to the brain. If diagnosis of ischaemic stroke is made within hours of symptom onset, drugs can be injected to dissolve the clot and restore the flow of blood to the brain (thrombolysis). However, these only benefit around 1 in 7 people treated.

Another option is a type of keyhole surgery to physically remove the blood clot (thrombectomy). The use of this mechanical clot removal approach alongside thrombolysis may help to improve clinical outcomes. This review set out to evaluate the efficacy and safety of mechanical clot removal in patients with ischaemic stroke.

What did this study do?

This was a systematic review and meta-analysis including 10 randomised controlled trials in 2925 adults with ischaemic stroke comparing keyhole treatments alongside thrombolysis, with thrombolysis alone. Keyhole treatments included not only mechanical clot retrieval but also the injection of drugs directly into the artery at the site of the clot.

Most trials required drug treatment to be given within three to 4.5 hours of symptom onset, and mechanical clot removal between five and 12 hours. Eight of the 10 trials required imaging confirmation before treatment.

Average patient age was 62 to 71 years and severity of stroke ranged from moderate to moderate to severe. Six studies were international; the remaining four were European. Three of the studies were published in 2013 and five in 2015. Six studies were stopped early, mostly because of positive results. The overall risk of bias across trials was moderate.

What did it find?

  • Patients receiving keyhole treatment, including mechanical clot removal, were more likely to achieve a good functional outcome at 90 days (44% with keyhole treatment vs. 33% with thrombolysis alone; risk ratio 1.37, 95% confidence interval 1.14 to 1.64)
  • There was no statistically significant difference in mortality at 90 days (16% vs. 17%).
  • When pooled separately, the seven trials published in 2015 showed better outcomes than the 2013 trials. Keyhole treatment significantly increased the chance of good functional outcome in the 2015 trials (47% vs. 30%), but there was no between-group difference in the 2013 trials.
  • There were a number of differences between the 2013 and 2015 trials. First, all of the 2015 trials required a brain scan before enrolment in the trial; only one of three 2013 trials did. Second, a higher percentage of patients in the 2015 intervention arms received mechanical clot removal rather than other keyhole interventions. Third, 2015 trials were more likely to use newer technology, in particular a device called a “stent retriever”. This is a new device that is more effective at grabbing and removing the clot.

What does current guidance say on this issue?

The NICE stroke guideline published in 2008 recommends that all people with suspected stroke should be admitted directly to a specialist acute stroke unit following initial assessment. Thrombolysis is recommended if specific criteria are met.

Later, 2016 NICE guidance specifically on mechanical clot removal recommends its use for acute ischaemic stroke. The guidance recommends that selection and treatment of patients should be done by experienced and trained specialists within appropriate facilities and support.

What are the implications?

The evidence suggests that for certain patients with ischaemic stroke, mechanical clot removal alongside drug thrombolysis may offer better functional outcomes than thrombolysis alone. A prior brain scan is crucial, as it allows assessment of the position of the clot, and therefore how amenable it is to mechanical removal. It can also assess how much brain tissue is salvageable.

Mechanical clot removal is a highly skilled operation. It benefits from having the latest technology available, such as the use of stent retrievers. It also needs to be performed within about six to eight hours of stroke onset. For mechanical clot removal to be viable, patients need to have early access to stroke units with the necessary diagnostics and technology to hand, along with the expertise to use them. The technique shows promise but because of the financial and workforce implications is likely to need further evaluation before full adoption in the NHS.

Citation and Funding

Rodrigues FB, Neves JB, Caldeira D, et al. Endovascular treatment versus medical care alone for ischaemic stroke: systematic review and meta-analysis. BMJ. 2016;353:i1754.

No funding information was provided for this study.

Bibliography

NICE. Alteplase for treating acute ischaemic stroke. TA264. London: National Institute for Health and Care Excellence; 2012.

NICE. Mechanical clot retrieval for treating acute ischaemic stroke. IPG548. London: National Institute for Health and Care Excellence; 2016.

NICE. NICE greenlights clot removal procedure for use on NHS. London: National Institute for Health and Care Excellence; 2016.

NICE. Stroke and transient ischaemic attack in over 16s: diagnosis and initial management. CG68. London: National Institute for Health and Care Excellence; 2008.

Stroke Association. State of the nation stroke statistics. London: Stroke Association; 2015.

Why was this study needed?

Stroke is the UK’s third largest cause of death, after heart disease and cancer, and a major cause of adult disability. The health and social care costs of stroke in the UK are approximately £4.38 billion a year.

Around 85% of all cases of stroke are ischaemic stroke, where a blood clot obstructs the flow of blood to the brain. If diagnosis of ischaemic stroke is made within hours of symptom onset, drugs can be injected to dissolve the clot and restore the flow of blood to the brain (thrombolysis). However, these only benefit around 1 in 7 people treated.

Another option is a type of keyhole surgery to physically remove the blood clot (thrombectomy). The use of this mechanical clot removal approach alongside thrombolysis may help to improve clinical outcomes. This review set out to evaluate the efficacy and safety of mechanical clot removal in patients with ischaemic stroke.

What did this study do?

This was a systematic review and meta-analysis including 10 randomised controlled trials in 2925 adults with ischaemic stroke comparing keyhole treatments alongside thrombolysis, with thrombolysis alone. Keyhole treatments included not only mechanical clot retrieval but also the injection of drugs directly into the artery at the site of the clot.

Most trials required drug treatment to be given within three to 4.5 hours of symptom onset, and mechanical clot removal between five and 12 hours. Eight of the 10 trials required imaging confirmation before treatment.

Average patient age was 62 to 71 years and severity of stroke ranged from moderate to moderate to severe. Six studies were international; the remaining four were European. Three of the studies were published in 2013 and five in 2015. Six studies were stopped early, mostly because of positive results. The overall risk of bias across trials was moderate.

What did it find?

  • Patients receiving keyhole treatment, including mechanical clot removal, were more likely to achieve a good functional outcome at 90 days (44% with keyhole treatment vs. 33% with thrombolysis alone; risk ratio 1.37, 95% confidence interval 1.14 to 1.64)
  • There was no statistically significant difference in mortality at 90 days (16% vs. 17%).
  • When pooled separately, the seven trials published in 2015 showed better outcomes than the 2013 trials. Keyhole treatment significantly increased the chance of good functional outcome in the 2015 trials (47% vs. 30%), but there was no between-group difference in the 2013 trials.
  • There were a number of differences between the 2013 and 2015 trials. First, all of the 2015 trials required a brain scan before enrolment in the trial; only one of three 2013 trials did. Second, a higher percentage of patients in the 2015 intervention arms received mechanical clot removal rather than other keyhole interventions. Third, 2015 trials were more likely to use newer technology, in particular a device called a “stent retriever”. This is a new device that is more effective at grabbing and removing the clot.

What does current guidance say on this issue?

The NICE stroke guideline published in 2008 recommends that all people with suspected stroke should be admitted directly to a specialist acute stroke unit following initial assessment. Thrombolysis is recommended if specific criteria are met.

Later, 2016 NICE guidance specifically on mechanical clot removal recommends its use for acute ischaemic stroke. The guidance recommends that selection and treatment of patients should be done by experienced and trained specialists within appropriate facilities and support.

What are the implications?

The evidence suggests that for certain patients with ischaemic stroke, mechanical clot removal alongside drug thrombolysis may offer better functional outcomes than thrombolysis alone. A prior brain scan is crucial, as it allows assessment of the position of the clot, and therefore how amenable it is to mechanical removal. It can also assess how much brain tissue is salvageable.

Mechanical clot removal is a highly skilled operation. It benefits from having the latest technology available, such as the use of stent retrievers. It also needs to be performed within about six to eight hours of stroke onset. For mechanical clot removal to be viable, patients need to have early access to stroke units with the necessary diagnostics and technology to hand, along with the expertise to use them. The technique shows promise but because of the financial and workforce implications is likely to need further evaluation before full adoption in the NHS.

Citation and Funding

Rodrigues FB, Neves JB, Caldeira D, et al. Endovascular treatment versus medical care alone for ischaemic stroke: systematic review and meta-analysis. BMJ. 2016;353:i1754.

No funding information was provided for this study.

Bibliography

NICE. Alteplase for treating acute ischaemic stroke. TA264. London: National Institute for Health and Care Excellence; 2012.

NICE. Mechanical clot retrieval for treating acute ischaemic stroke. IPG548. London: National Institute for Health and Care Excellence; 2016.

NICE. NICE greenlights clot removal procedure for use on NHS. London: National Institute for Health and Care Excellence; 2016.

NICE. Stroke and transient ischaemic attack in over 16s: diagnosis and initial management. CG68. London: National Institute for Health and Care Excellence; 2008.

Stroke Association. State of the nation stroke statistics. London: Stroke Association; 2015.

Endovascular treatment versus medical care alone for ischaemic stroke: systematic review and meta-analysis

Published on 20 April 2016

Rodrigues, F. B.,Neves, J. B.,Caldeira, D.,Ferro, J. M.,Ferreira, J. J.,Costa, J.

Bmj Volume 353 , 2016

OBJECTIVES: To evaluate the efficacy and safety of endovascular treatment, particularly adjunctive intra-arterial mechanical thrombectomy, in patients with ischaemic stroke. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, Cochrane Central Register of Controlled Trials, Web of Science, SciELO, LILACS, and clinical trial registries from inception to December 2015. Reference lists were crosschecked. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials in adults aged 18 or more with ischaemic stroke comparing endovascular treatment, including thrombectomy, with medical care alone, including intravenous recombinant tissue plasminogen activator (rt-PA). Trial endpoints were functional outcome (modified Rankin scale scores of </=2) and mortality at 90 days after onset of symptoms. No language or time restrictions applied. RESULTS: 10 randomised controlled trials (n=2925) were included. In pooled analysis endovascular treatment, including thrombectomy, was associated with a higher proportion of patients experiencing good (modified Rankin scale scores </=2) and excellent (scores </=1) outcomes 90 days after stroke, without differences in mortality or rates for symptomatic intracranial haemorrhage, compared with patients randomised to medical care alone, including intravenous rt-PA. Heterogeneity was high among studies. The more recent studies (seven randomised controlled trials, published or presented in 2015) proved better suited to evaluate the effect of adjunctive intra-arterial mechanical thrombectomy on its index disease owing to more accurate patient selection, intravenous rt-PA being administered at a higher rate and earlier, and the use of more efficient thrombectomy devices. In most of these studies, more than 86% of the patients were treated with stent retrievers, and rates of recanalisation were higher (>58%) than previously reported. Subgroup analysis of these seven studies yielded a risk ratio of 1.56 (95% confidence interval 1.38 to 1.75) for good functional outcomes and 0.86 (0.69 to 1.06) for mortality, without heterogeneity among the results of the studies. All trials were open label. Risk of bias was moderate across studies. The full results of two trials are yet to be published. CONCLUSIONS: Moderate to high quality evidence suggests that compared with medical care alone in a selected group of patients endovascular thrombectomy as add-on to intravenous thrombolysis performed within six to eight hours after large vessel ischaemic stroke in the anterior circulation provides beneficial functional outcomes, without increased detrimental effects. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015019340.

The modified Rankin scale is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke. It is a widely used clinical outcome measure for stroke clinical trials. The scale gives a score from 0-6. This runs from perfect health without symptoms (0) to death (6).

“Good functional outcome” in the included studies was defined as a modified Rankin scale score of between 0 and 2. These scores represent the following:

  • 0: no symptoms
  • 1: no significant disability (able to carry out all usual activities, despite some symptoms)
  • 2: slight disability (able to look after own affairs without assistance, but unable to carry out all previous activities).

Expert commentary

This systematic review and meta-analysis adds to the evidence supporting the use of thrombectomy for selected patients with large vessel occlusion leading to ischaemic stroke. To its credit, unlike a meta-analysis published in the Lancet earlier this year that only analysed data from recent positive trials, it does include data from older negative trials even though methods of clot retrieval have changed. Despite this, we still only have evidence on a total of 2925 patients which is not enough to be able to answer really important practical questions about which subgroups of patients benefit the most. It is understandable, but a shame that so many of the trials were stopped early by their data monitoring committees, therefore, limiting the data available. The task now is to find ways of delivering the treatment to the standards described in the trials. This has major financial and workforce implications for health services.

Tony Rudd, Professor of Stroke Medicine, Kings College, London; Consultant Stroke Physician, Guy's and St Thomas; National Clinical Director for Stroke NHS England; London Stroke Clinical Director; Stroke Programme Director Royal College Physicians London