NIHR Signal Mechanical clot removal for stroke reduces disability at two years

Published on 1 August 2017

Timely mechanical removal of the blood clots from inside vessels in the brain after a stroke reduces disability and improves quality of life at two years compared with usual care.

Over a third of those in the thrombectomy group had good functional outcome compared with less than a quarter of the standard care group who received clot busting drugs. This was similar to the results at 90 days and was associated with improved quality of life in terms of self-care and mobility. Findings came from a trial of almost 400 people followed up over two years in the Netherlands.

The results strengthen the evidence that mechanical thrombectomy leads to good long-term outcomes, but it must be delivered promptly. Public awareness of early signs of stroke enables early medical attention. The procedure is currently planned for 24 specialist centres in England and will be available around the clock to facilitate urgent diagnosis and effective treatment.

Mechanical clot removal for stroke reduces disability at two years

Why was this study needed?

Stroke is the fourth leading cause of death in the UK and the leading cause of disability. There are over 100,000 strokes in the UK each year, costing the NHS in England around £1.7 billion.

Eighty five per cent of strokes are ischaemic (due to a clot) and can be treated with drugs to dissolve the clot (thrombolysis). Thrombolysis must be given within four-and-a-half hours of stroke onset. Thrombectomy may be an option for some kinds of stroke, where an incision is made into the leg artery and the clot removed either by suction or by advancing a mesh basket to remove the clot. This endovascular treatment must be carried out within five or six hours of symptom onset.

Efficient, well-resourced stroke services are therefore essential to effective treatment. The NIHR themed review, Roads to Recovery, highlighted the organisational requirements for an effective stroke service.

This paper reports an extension to the 2016 trial, which found that thrombectomy improved a stroke survivor’s outcomes after the first 90 days of that trial. Researchers aimed to collect further data on patient outcomes to see if the benefits were sustained. This adds to earlier evidence, including a meta-analysis in 2016, showing the effectiveness of thrombectomies. This pooled the evidence from five trials, including one part-funded by NIHR.

What did this study do?

The Multicentre Randomized Clinical Trial of Endovascular Treatment for Acute Ischaemic Stroke in the Netherlands (MR CLEAN) trial included 500 adults with ischaemic stroke. They were assigned to thrombectomy (within six hours of stroke onset) or standard care alone, which could include thrombolysis.

Participants were originally followed up to 90 days. Three hundred and ninety one people (78.2%) agreed to take part in a telephone interview two years later, when disability was re-assessed using the modified Rankin Scale (mRS).

The loss to follow-up may introduce some bias. Patients not taking part in the two-year assessments were reported to have had poorer outcomes at 90 days, and most were in the standard care group. However, statistical methods were used to allow for this missing data.

What did it find?

  • At two years, participants who received thrombectomy scored a median of three (slight disability) on the six point mRS scale, compared with four (moderate disability) in the standard care group. Thrombectomy was associated with improved likelihood of a better functional score by two years (adjusted odds ratio [aOR] 1.68, 95% confidence interval [CI] 1.15 to 2.45). This was similar to the odds for improved scores at 90 days (aOR 1.67, CI 1.21 to 2.30).
  • More participants in the thrombectomy group achieved a good outcome (mRS score 0 to 2) by two years (37.1%) compared with standard care (23.9%) (aOR 2.21, 95% CI 1.30 to 3.73). There was no difference in the proportion achieving an excellent outcome score of 0 or 1 (7.2% vs 6.1%).
  • Participants in the thrombectomy group had a better quality of life at two years, with a mean healthy utility score of 0.48 on the EQ-5D-3L tool compared with 0.38 in the standard care group (mean difference 0.10, 95% CI 0.03 to 0.16). The difference was mainly in domains of mobility, self-care and performing usual activities.
  • There was no statistical difference in the death rate at two years, which occurred in 26% of the endovascular group and 31% of the standard care group.

What does current guidance say on this issue?

NICE 2008 guidelines recommend that thrombolysis for acute ischaemic stroke is administered only within a well organised stroke service and is given as soon as possible and within 4.5 hours.

NICE 2016 interventional procedures guidance says that current evidence supports the use of mechanical clot retrieval for ischaemic stroke, when performed by experienced clinicians with appropriate facilities.

The Royal College of Physicians guideline for stroke states thrombectomy is best performed within five hours of stroke onset, although some people meeting set criteria may be considered for treatment up 12 hours after onset.

What are the implications?

This extended trial data shows that endovascular clot removal, called mechanical thrombectomy, within six hours of stroke onset is an important treatment option and provides a sustained reduction of disability for patients.

As with thrombolysis, thrombectomy needs to be delivered quickly. It is important that public health campaigns such as FAST help to ensure that people with stroke symptoms receive medical attention as quickly as possible. Adequately provisioned specialist stroke services are essential to ensure that patients eligible for endovascular therapy can be diagnosed urgently and treatment commenced.

If thrombectomy reduces long-term disability this potentially could save NHS and social care resources, though cost effectiveness remains to be assessed.

In April 2017 it was agreed that endovascular thrombectomy will be available through specialised commissioning at 24 designated neuroscience centres in England. It is estimated that the service will be used by about 8000 patients a year.

Citation and Funding

Van den Berg LA, Dijkgraaf MG, Berkhemer OA, et al. Two-Year Outcome after Endovascular Treatment for Acute Ischemic Stroke. N Engl J Med. 2017;376(14):1341-49.

Funded by the Netherlands Organization for Health Research and Development.

Bibliography

Berkhemer OA, Fransen PSS, BEumer D, et al. A randomized trial of intraarterial treatment for acute ischaemic stroke. N Engl J Med. 2015;372(1):11-20.

Goyal M, Menon BK, van Zwam WH, et al; HERMES collaborators. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016;387(10029):1723-31.

Intercollegiate Stroke Working Party. National Clinical Guideline for Stroke. London: Royal College of Physicians; 2016.

Muir KW, Ford GA, Messow CM, et al; PISTE Investigators. Endovascular therapy for acute ischaemic stroke: the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) randomised, controlled trial. J Neurol Neurosurg Psychiatry. 2017;88(1):38-44.

NHS England. Stroke patients in England set to receive revolutionary new treatment. London: Department of Health; 2017.

NHS Choices. Stroke – treatment. London: Department of Health; 2017

NICE. Mechanical clot removal for treating acute ischaemic stroke. IPG548. 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; 2017.

Public Health England. Act fast campaign. London: GOV.UK; 2014.

Stroke Association. State of the Nation: stroke statistics. London: Stroke Association; 2017.

Why was this study needed?

Stroke is the fourth leading cause of death in the UK and the leading cause of disability. There are over 100,000 strokes in the UK each year, costing the NHS in England around £1.7 billion.

Eighty five per cent of strokes are ischaemic (due to a clot) and can be treated with drugs to dissolve the clot (thrombolysis). Thrombolysis must be given within four-and-a-half hours of stroke onset. Thrombectomy may be an option for some kinds of stroke, where an incision is made into the leg artery and the clot removed either by suction or by advancing a mesh basket to remove the clot. This endovascular treatment must be carried out within five or six hours of symptom onset.

Efficient, well-resourced stroke services are therefore essential to effective treatment. The NIHR themed review, Roads to Recovery, highlighted the organisational requirements for an effective stroke service.

This paper reports an extension to the 2016 trial, which found that thrombectomy improved a stroke survivor’s outcomes after the first 90 days of that trial. Researchers aimed to collect further data on patient outcomes to see if the benefits were sustained. This adds to earlier evidence, including a meta-analysis in 2016, showing the effectiveness of thrombectomies. This pooled the evidence from five trials, including one part-funded by NIHR.

What did this study do?

The Multicentre Randomized Clinical Trial of Endovascular Treatment for Acute Ischaemic Stroke in the Netherlands (MR CLEAN) trial included 500 adults with ischaemic stroke. They were assigned to thrombectomy (within six hours of stroke onset) or standard care alone, which could include thrombolysis.

Participants were originally followed up to 90 days. Three hundred and ninety one people (78.2%) agreed to take part in a telephone interview two years later, when disability was re-assessed using the modified Rankin Scale (mRS).

The loss to follow-up may introduce some bias. Patients not taking part in the two-year assessments were reported to have had poorer outcomes at 90 days, and most were in the standard care group. However, statistical methods were used to allow for this missing data.

What did it find?

  • At two years, participants who received thrombectomy scored a median of three (slight disability) on the six point mRS scale, compared with four (moderate disability) in the standard care group. Thrombectomy was associated with improved likelihood of a better functional score by two years (adjusted odds ratio [aOR] 1.68, 95% confidence interval [CI] 1.15 to 2.45). This was similar to the odds for improved scores at 90 days (aOR 1.67, CI 1.21 to 2.30).
  • More participants in the thrombectomy group achieved a good outcome (mRS score 0 to 2) by two years (37.1%) compared with standard care (23.9%) (aOR 2.21, 95% CI 1.30 to 3.73). There was no difference in the proportion achieving an excellent outcome score of 0 or 1 (7.2% vs 6.1%).
  • Participants in the thrombectomy group had a better quality of life at two years, with a mean healthy utility score of 0.48 on the EQ-5D-3L tool compared with 0.38 in the standard care group (mean difference 0.10, 95% CI 0.03 to 0.16). The difference was mainly in domains of mobility, self-care and performing usual activities.
  • There was no statistical difference in the death rate at two years, which occurred in 26% of the endovascular group and 31% of the standard care group.

What does current guidance say on this issue?

NICE 2008 guidelines recommend that thrombolysis for acute ischaemic stroke is administered only within a well organised stroke service and is given as soon as possible and within 4.5 hours.

NICE 2016 interventional procedures guidance says that current evidence supports the use of mechanical clot retrieval for ischaemic stroke, when performed by experienced clinicians with appropriate facilities.

The Royal College of Physicians guideline for stroke states thrombectomy is best performed within five hours of stroke onset, although some people meeting set criteria may be considered for treatment up 12 hours after onset.

What are the implications?

This extended trial data shows that endovascular clot removal, called mechanical thrombectomy, within six hours of stroke onset is an important treatment option and provides a sustained reduction of disability for patients.

As with thrombolysis, thrombectomy needs to be delivered quickly. It is important that public health campaigns such as FAST help to ensure that people with stroke symptoms receive medical attention as quickly as possible. Adequately provisioned specialist stroke services are essential to ensure that patients eligible for endovascular therapy can be diagnosed urgently and treatment commenced.

If thrombectomy reduces long-term disability this potentially could save NHS and social care resources, though cost effectiveness remains to be assessed.

In April 2017 it was agreed that endovascular thrombectomy will be available through specialised commissioning at 24 designated neuroscience centres in England. It is estimated that the service will be used by about 8000 patients a year.

Citation and Funding

Van den Berg LA, Dijkgraaf MG, Berkhemer OA, et al. Two-Year Outcome after Endovascular Treatment for Acute Ischemic Stroke. N Engl J Med. 2017;376(14):1341-49.

Funded by the Netherlands Organization for Health Research and Development.

Bibliography

Berkhemer OA, Fransen PSS, BEumer D, et al. A randomized trial of intraarterial treatment for acute ischaemic stroke. N Engl J Med. 2015;372(1):11-20.

Goyal M, Menon BK, van Zwam WH, et al; HERMES collaborators. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016;387(10029):1723-31.

Intercollegiate Stroke Working Party. National Clinical Guideline for Stroke. London: Royal College of Physicians; 2016.

Muir KW, Ford GA, Messow CM, et al; PISTE Investigators. Endovascular therapy for acute ischaemic stroke: the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) randomised, controlled trial. J Neurol Neurosurg Psychiatry. 2017;88(1):38-44.

NHS England. Stroke patients in England set to receive revolutionary new treatment. London: Department of Health; 2017.

NHS Choices. Stroke – treatment. London: Department of Health; 2017

NICE. Mechanical clot removal for treating acute ischaemic stroke. IPG548. 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; 2017.

Public Health England. Act fast campaign. London: GOV.UK; 2014.

Stroke Association. State of the Nation: stroke statistics. London: Stroke Association; 2017.

Two-Year Outcome after Endovascular Treatment for Acute Ischemic Stroke

Published on 6 April 2017

van den Berg, L. A.,Dijkgraaf, M. G.,Berkhemer, O. A.,Fransen, P. S.,Beumer, D.,Lingsma, H. F.,Majoie, C. B.,Dippel, D. W.,van der Lugt, A.,van Oostenbrugge, R. J.,van Zwam, W. H.,Roos, Y. B.

N Engl J Med Volume 376 , 2017

Background Several trials involving patients with acute ischemic stroke have shown better functional outcomes with endovascular treatment than with conventional treatment at 90 days after initiation of treatment. However, results on long-term clinical outcomes are lacking. Methods We assessed clinical outcomes 2 years after patients were randomly assigned to receive either endovascular treatment (intervention group) or conventional treatment (control group) for acute ischemic stroke. The primary outcome was the score on the modified Rankin scale at 2 years; this scale measures functional outcome, with scores ranging from 0 (no symptoms) to 6 (death). Secondary outcomes included all-cause mortality and the quality of life at 2 years, as measured by means of a health utility index that is based on the European Quality of Life-5 Dimensions questionnaire (scores range from -0.329 to 1, with higher scores indicating better health). Results Of the 500 patients who underwent randomization in the original trial, 2-year data for this extended follow-up trial were available for 391 patients (78.2%) and information on death was available for 459 patients (91.8%). The distribution of outcomes on the modified Rankin scale favored endovascular treatment over conventional treatment (adjusted common odds ratio, 1.68; 95% confidence interval [CI], 1.15 to 2.45; P=0.007). There was no significant difference between the treatment groups in the percentage of patients who had an excellent outcome (i.e., a modified Rankin scale score of 0 or 1). The mean quality-of-life score was 0.48 among patients randomly assigned to endovascular treatment as compared with 0.38 among patients randomly assigned to conventional treatment (mean difference, 0.10; 95% CI, 0.03 to 0.16; P=0.006). The cumulative 2-year mortality rate was 26.0% in the intervention group and 31.0% in the control group (adjusted hazard ratio, 0.9; 95% CI, 0.6 to 1.2; P=0.46). Conclusions In this extended follow-up trial, the beneficial effect of endovascular treatment on functional outcome at 2 years in patients with acute ischemic stroke was similar to that reported at 90 days in the original trial. (Funded by the Netherlands Organization for Health Research and Development and others; MR CLEAN Current Controlled Trials number, ISRCTN10888758 , and Netherlands Trial Register number, NTR1804 , and MR CLEAN extended follow-up trial Netherlands Trial Register number, NTR5073 .).

The modified Rankin Scale (mRS) has a score ranging from 0, meaning no symptoms at all to 6, death. 1 means no significant disability and able to carry out all usual activities. 2 means slight disability and unable to carry out all previous activities but doesn’t require assistance. 3 means moderate disability and needing help, but able to walk unassisted. 4 means moderately severe disability, unable to walk or attend to own needs without help. 5 means severely disabled, bedridden and needing constant care.

Expert commentary

Recent research has shown that mechanical thrombectomy, the direct removal of a blood clot blocking the main artery to the brain and causing stroke, results in better outcome for patients, with people treated less disabled when assessed at 90 days compared to those who had thrombolysis (clot busting injections).

This paper is important because it shows that this treatment benefit is still present when the patients were assessed again two years later, providing more evidence for the benefit of thrombectomy in stroke and supporting the investment needed to be able to deliver this service to those who need it.

Professor Philippa Tyrrell, Chair in Stroke Medicine, University of Manchester

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