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.
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.
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.
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