ESOC 2019 (European Stroke Conference)
The 5th European Stroke Organisation Conference (ESOC 2019) was held last week in Milan, Italy between the 22-24 May.
More than 5,650 participants from almost 100 different countries attended and found the scientific programme both stimulating and enriching.
We have summarised some of the key results from the trials presented below.
Video interviews with the investigators can be found here.
ESOC 2019 summary
- PASTA: Paramedic Acute Stroke Treatment Assessment
Thrombolysis is a highly effective treatment for acute ischaemic strokes within 4.5 hours of onset, but optimising a service to provide rapid and cost-effective delivery can be challenging. This trial tested whether a dedicated assessment delivered by attending paramedics improved the rate thrombolysis and its cost-effectiveness in the UK health service.
Of 1214 patients enrolled across 3 ambulance services and 15 hospitals in the UK, 500 were assessed by trained ‘PASTA’ paramedics, whilst 714 were assessed by standard care paramedics.
The PASTA intervention did not increase the number of patients receiving thrombolysis, and there was actually a non-significant trend for fewer patients to receive thrombolysis. However, there was a non-significant improvement in outcome at 3 months. This resulted in an improvement in cost-effectiveness through shorter stays in hospital and less need for rehabilitation.
Presenting the results, Dr Christopher Price commented: “There was cost-saving with the intervention, specifically lower rehabilitation costs and length of stay in hospital, despite lower rates of thrombolysis.” Co-presenter, Prof Gary Ford added: “This is a complex intervention which has put a lot of information into the decision-making, providing better overall care.”
- Extending the thrombolytic time window using perfusion imaging selection – Meta-analysis of individual patient data from EXTEND, ECASS-4 and EPITHET
Endovascular treatment is indicated in patients with large vessel occlusion, but intravenous thrombolysis continues to be the mainstay of treatment for most patients with ischaemic stroke. However, thrombolysis is currently recommended only up to 4.5 hours after stroke onset.
This meta-analysis pooled individual data of 414 patients with acute ischaemic stroke who were imaged with perfusion-diffusion MRI or CT-perfusion and then randomised to treatment with alteplase or placebo after >4.5 hours after onset, or last time seen well, in RCTs testing intravenous thrombolysis versus placebo.
In the pooled analysis, alteplase improved functional outcomes at 3 months when administered 4.5-9 hours after onset or after waking-up with a stroke in patients with perfusion mismatch on imaging (OR 1.86, p=0.011). Although symptomatic intracerebral haemorrhage occurred more often in alteplase-treated patients (4.7% vs. 0.5%), mortality was not significantly different between groups (14% vs. 9%), and this did not negate the net benefit of treatment.
Professor Ma said, “Now is the time to change clinical practice to extend the thrombolysis time window to benefit more stroke patients globally. Importantly, benefit predominantly was seen in patients with automated perfusion mismatch.”
Published in The Lancet.
- RESILIENT: A randomised trial demonstrating efficacy and feasibility of endovascular treatment in resource limited healthcare systems
Randomization of Endovascular Treatment with Stent-Retriever and/or Thromboaspiration vs Best Medical Therapy in Acute Ischemic Stroke due to Large Vessel Occlusion Trial – Final Results
There are many reasons why the health services in some low and middle-income countries do not routinely provide endovascular treatment (EVT) to patients with Large Vessel Occlusion (LVO). This trial in Brazil sought to provide local validation of findings from landmark clinical trials conducted in high-income countries, which demonstrate the benefit of this approach. RESILIENT is a Brazilian Stroke Network/Ministry of Health collaboration.
This multicentre, randomised, controlled trial compared mechanical thrombectomy to medical management in patients with LVO ≤8hours from ischaemic stroke onset (NIHSS ≥8 and ASPECTS ≥6). The trial’s Data Safety Monitory Board recommended early termination due to “clear crossing of the boundary for efficacy at the first interim analysis”. At this time, 221 patients had been enrolled and 174 patients had completed 90-day-follow-up.
Despite the acknowledged limitations of the healthcare system, including reduced availability of experienced endovascular centres and outpatient rehabilitation; RESILIENT showed that EVT was clearly superior to medical management in this setting. Principal investigator Dr Sheila Martins presented the trial’s results on behalf of the RESILIENT collaborative: “We hope these results will encourage more low and middle-income countries to increase the use of EVT to improve outcomes for more LVO patients.” She received clamorous applause from the audience.
- VIST, VAST and SAMMPRIS (pooled analysis): Opening up extracranial stenotic vessels of posterior circulation arteries outside of the brain may be beneficial, and larger clinical trials are needed
Although symptomatic vertebral artery stenosis has been associated with a high risk of recurrent stroke, particularly in the first few weeks after symptoms, there is still controversy whether or not it should be the preferred therapeutic approach in patients with this condition.
Considering this, the authors performed an individual patient pooled analysis of the 354 participants included in three previous large randomised controlled clinical trials – VIST, VAST AND SAMMPRIS – that compared vertebral stenting with medical treatment for symptomatic vertebral stenosis.
There was no evidence of significant benefit of vertebral stenting over medical treatment, although there was a trend towards lower recurrence rates in patients receiving stenting for extracranial vertebral stenosis. Further larger trials are required to ascertain whether there is benefit in this subgroup.
Principal investigator Prof Hugh Markus commented: “Stenting for intracranial stenosis did not show benefit from either strategy. Stenting for extracranial stenosis might be beneficial, so we are planning the VIST 2 – interested investigators please contact firstname.lastname@example.org!”
Published in Lancet Neurology.
- Gender differences: Although commonly presenting with similar, non-specific symptoms at the time of a TIA or stroke, women were more likely to be given an alternative diagnosis
It has been shown that women are less likely than men to be diagnosed with heart attack, but what about stroke? This Canadian study of 1,648 patients showed women and men were equally likely to present with non-focal symptoms, but women were still more likely to be diagnosed with a stroke mimic. The risk of recurrent stroke within 90 days, however, were similar in men and women. Dr Yu’s findings raise questions about missed opportunities in preventing vascular events in women.
“What’s important to recognize in stroke is that the brain has so many different functions, so that when a stroke is happening, people can feel different things beyond the typical stroke symptoms,” said Dr Yu. “Accurately diagnosing TIA and stroke would change a patient’s treatment plan and could help prevent another stroke from happening.”
Published in the Journal of the American Medical Association (JAMA).
- RATULS: Robot Assisted Training for the Upper Limb After Stroke
Robot-assisted training could be a promising treatment for improving upper limb recovery following stroke. The RATULS trial is the largest trial to assess whether robot-assisted training improves upper limb function recovery after stroke. 770 participants enrolled from four study centres were randomly allocated to: i) robot-assisted training ii) enhanced upper limb therapy iii) standard NHS care.
Robot-assisted training did not significantly improve upper limb function at 3 months after stroke compared to the other two treatments, for the primary outcome, although there were some improvements on secondary outcomes. However, enhanced care improved the ability to carry out activities of daily living at 3 and 6 months.
Although RATULS had a neutral overall outcome, Principal Investigator Prof Helen Rodgers stated that robot assisted training demonstrated a potential clinically-significant improvement in function. “There were statistically significant differences in a number of other factors, but none of these were clinically meaningful.
However, the study has generated a lot of interesting information about the potential benefits of robot-assisted training.”
Published in The Lancet.
Combined use of contact aspiration and the stent retriever technique versus stent retriever alone for recanalization in acute cerebral infarction
Mechanical thrombectomy is the cornerstone of acute ischaemic stroke treatment in the subgroup of patients with large vessel occlusion and salvageable tissue. However, successful recanalisation is not achieved in all patients.
ASTER2 was the first head-to-head randomised controlled study directly comparing the combined use of contact aspiration (CA) and stent-retriever (SR) with stent-retriever alone on revascularisation rates in acute stroke patients receiving thrombectomy, with suspected anterior circulation ischaemic stroke secondary to large vessel occlusion and onset of symptoms <8 hours
250 patients were included in this multicentre open-label blinded study and the primary endpoint was the rate of perfect reperfusion (mTICI score 2c/3) at the end of the endovascular procedure.
The study’s results showed that the rate of perfect recanalization was 65% with the combined approach and 58% in the stent retriever arm as a first line approach (p=0.17). There was also no significant difference regarding the first-pass effect. However, in the subgroup analysis, the combined strategy was associated with an increased rate of successful recanalization in patients with intracranial carotid occlusion or T occlusion.
Principal investigator, Professor Bertrand Lapergue, commented: “Perfect recanalization [TICI 2c/3] should be the target of endovascular treatment of ischaemic stroke. Further studies should address whether a specific clot location or type can benefit from a combined approach first line. Importantly, no safety concerns were observed during the trial.”
- RESTART: Effects of Antiplatelet Therapy After Stroke due to Intracerebral Haemorrhage Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage: Main results of the REstart or Stop Antithrombotics Randomised Trial
Patients who have suffered an acute bleed in the brain are at risk of both recurrent bleeds in the brain or ischaemic strokes due to blood clots. This trial sought to answer whether restarting antiplatelet drugs that reduce the chance of ischaemic strokes would make these patients more likely to suffer another bleed in the brain.
537 patients from 122 hospitals across the UK who had suffered a bleed in the brain whilst taking medications to stop blood clotting were randomised to either take antiplatelet medications or avoid these medications for 5 years.
The study showed that patients on antiplatelet medications actually experienced fewer bleeds in the brain than patients not receiving antiplatelets (12 vs 23 patients, HR 0.51, p=0.06) over an average of 2 years, suggesting that antiplatelet medications may actually reduce the risk of bleeds in the brain in this setting. Differences in all vascular events were reduced with antiplatelet therapy, as expected from previous studies (HR 0.65, p=0.025).
Principal Investigator, Prof Rustam Al-Shahi Salman said: “These findings are reassuring for clinicians. If there is any increased risk of brain haemorrhage it is not large enough to exceed the established benefits of antiplatelet therapy.”
Published in The Lancet.
- RESCUE BRAIN: A neutral trial of remote ischaemic conditioning within 6 hours of stroke; however, ongoing trials will determine if the method is efficient in a different setting
This prospective randomised open, blinded end-point trial (PROBE) of patients who had experienced an acute ischaemic stroke in the preceding 6 hours assessed whether or not applying transient ischaemia remote from the brain (i.e. remote per-conditioning) reduces ischaemic lesion size (visible on MRI) over time compared to no intervention. This elegant non-invasive therapeutic strategy uses brief cycles of blood pressure cuff inflation and deflation at a lower extremity to protect the brain against ischaemia–reperfusion injury has shown to be successful in several animal models as well as in patients with myocardial ischaemia.
200 patients were randomized 1:1 to receive either 4 cycles of blood pressure cuff inflation 110 mm Hg above systolic blood pressure for 5 minutes followed by 4 cycles of deflation versus no intervention. The primary endpoint was change in lesion volume from baseline to day one after the infarction, assessed by a core lab using a validated software blinded to clinical data.
RESCUE BRAIN demonstrated no significant change in lesion volume within 24 hours of acute stroke in patients with remote ischaemic conditioning compared to patients without, although the intervention was safe. Three ongoing trials will help answer the question if the method is efficient when applied earlier or when using multiple cycles.
Principal investigator, Professor Fernando Pico, commented: “RESCUE brain is a neutral trial of remote ischaemic conditioning within 6 hours of ischaemic stroke. However, ongoing trials will determine if the method is efficient in a different setting.”
- TAKE CHARGE (TaCAS): Statistically significant improvements in quality of life, independence and activities of daily living with this low-cost self-management approach
Take Charge’ is a community-based, self-management rehabilitation program that aims to enable people to take charge of their own recovery after stroke, thereby improving their health-related quality of life. A ‘Take Charge’ session is delivered as talking therapy in the patient’s home by a trained clinician to facilitate self-directed rehabilitation in an inquiring but non-directional way.
400 people from 7 centres, living in the community within 16 weeks of their stroke, were randomly allocated to one of three groups: i) A single ‘Take Charge’ session , ii) two ‘Take Charge’ sessions 6 weeks apart, or iii) control (Stroke Foundation pamphlets).
The ‘Take Charge’ program, whether delivered as a single session or two, resulted in improvement in patient-reported health-related quality of life after stroke. The results suggest that ‘Take Charge’ could potentially be a low cost, self-management intervention.
Principal investigator, Dr Vivian Fu, commented, “Take Charge was superior to control for quality of life, independence, and activities of daily living. Our combined meta-analysis showed that for every eight patients treated with ‘Take Charge’ (at ~60 euros/session), one of them becomes independent at 12 months.”
- THAWS: MRI-guided thrombolysis with alteplase at 0.6mg/kg for stroke with unknown time of onset.
Clot-busting thrombolysis is an effective treatment for acute strokes within 4.5 hours of onset, but there remains uncertainty as how to treat patients who wake up with symptoms, or for whom the time of symptom onset is unknown. This Phase III clinical trial aimed to test whether a lower dose of thrombolysis was effective and safe in this group of patients, when ‘mismatch’ on MRI imaging suggested the stroke was not well-established.
131 of the enrolment target of 300 patients were recruited until the trial was stopped early following the publication of the similarly designed ‘WAKE-UP’ trial. THAWS showed no difference in the proportion of patients with no symptoms or mild non-disabling symptoms (mRS 0-1) at 3 months, risk of bleeding in the brain or death.
Early termination precludes definitive conclusions about effectiveness of lower dose thrombolysis in patients who wake up with stroke selected by mismatch
Principal Investigator, Professor Koga, commented: “There was no difference in favourable outcome between the groups … and the safety was comparable to that of standard treatment. Early study termination precludes any definitive conclusions and additional research may be warranted.”
Other study results
- IMPACT-24B: Sphenopalatine ganglion stimulation improves outcome from Acute Ischaemic Stroke in a Dose-Dependent Manner in a subgroup of ischaemic stroke patients
- COMPASS – No significant effect with different anti-coagulation strategies on stroke lesion burden
- INSPIRE-TMS & STROKE-CARD CARE PROGRAMME: Specially-designed multi-component support programmes offer promising secondary prevention optio
Information courtesy of https://eso-conference.org/2019
Look out for next years 2020 Conference in Vienna.