Ammad Mahmood, MBChB

European Stroke Organisation-World Stroke Organization 2020 Virtual Conference
November 7-9, 2020

Profs. Jesse Dawson and Michael Brainin welcomed all the delegates to the virtual conference and a chance to bring stroke care back into focus after a difficult year focusing on the COVID-19 pandemic. They spoke about the hard work that has gone into the rearrangement of this year’s conference into a virtual experience, and we thank them and their teams for their efforts in bringing the conference to us in these difficult times.

Fluoxetine after stroke
The first two presentations focused on the use of fluoxetine after stroke to assess any benefit in stroke rehabilitation and functional outcome. These trials came from an international collaboration of 3 trials focusing on this topic. First, Erik Lundstrom from Sweden presented the results of the EFFECTS trial. 1500 patients, at 35 Swedish centers, with ischemic or hemorrhagic stroke in the last 2-15 days but no history of depression were randomized 1:1 to receive either fluoxetine or placebo. The primary outcome of modified Rankin scale at 6 months demonstrated a neutral result with odds ratio 0.94 (0.78-1.13) at 6 months. Secondary outcomes demonstrated a small decrease in depression after stroke but a small increase in rates of fractures. Next, Graeme Hankey from Australia presented the 12-month results from the AFFINITY trial, which had also shown neutral results when the main trial results for 6 months outcome were previously published. The 12-month outcomes also showed a neutral effect of fluoxetine in functional outcome showing there is no delayed benefit. A small reduction in the rate of recurrent ischemic stroke in the fluoxetine group was seen in the AFFINITY trial, but not in the two other larger trials; therefore, this was felt to be a random effect. Overall, the results of the EFFECTS, AFFINITY, and FOCUS trials demonstrated that there is no benefit of fluoxetine after stroke in improving rehabilitation and functional outcome.

Ticagrelor in minor stroke and TIA
Next, Clay Johnston from Texas presented the results of the THALES trial. Dual antiplatelet therapy with aspirin and clopidogrel has become common practice after the POINT and CHANCE trials. The SOCRATES trial did not show any benefit on ticagrelor monotherapy versus aspirin monotherapy, and the THALES trial now examined dual antiplatelet therapy with ticagrelor and aspirin versus aspirin alone in minor stroke (NIHSS ≤5) and high-risk TIA (ABCD2≥6 or >50% symptomatic arterial stenosis) within 24 hours. 11016 patients were randomized 1:1 at 414 sites in 28 countries. Results showed a benefit of ticagrelor and aspirin over aspirin alone in the primary outcome of reduction in recurrent stroke or death at 30 days with a hazard ratio of 0.83 (0.71-0.96); most of the benefit was attributable to reduction in recurrent stroke in the first 7 days. However, there was a significant additional risk of hemorrhage in the ticagrelor group with a hazard ratio of 3.99 (1.74-9.14), though a small absolute difference. Overall, the authors helpfully summarized the effect as “for every 1000 patients treated, 11 strokes or deaths were prevented but 4 severe hemorrhages were produced.”

EVT in basilar artery occlusion
Wouter Schonewille from the Netherlands presented the results of the BASICS trial tackling one of the most difficult clinical problems in acute stroke, basilar artery occlusion. The trial randomized patients to either endovascular treatment plus best medical management (EVT + BMM) or best medical management (BMM) alone within 6 hours of the estimated time of basilar artery occlusion. They allowed inclusion of cases with stuttering onset as the time of basilar artery occlusion was taken as the point of acute severe deterioration. 300 patients were randomized in Europe and Brazil. The primary outcome of favorable functional outcome was neutral with 44.2% of EVT + BMM and 37.7% of BMM achieving mRS 0-3 with a risk ratio of 1.18 (0.92-1.50). There was no significant difference in rate of symptomatic ICH or mortality. The absolute risk reduction of 6.5% in the EVT group suggested a trend towards benefit of EVT. In subgroup analysis, patients presenting with NIHSS >10 showed a significant benefit of EVT. The authors concluded that EVT was safe within 6 hours and may be a better option for patients with NIHSS>10. The role of EVT beyond 6 hours and with minor deficit remains unclear.

LVO – where to?
Planning of stroke services worldwide involves deciding whether patients should be taken by the ambulance initially to the nearest stroke center or direct to a comprehensive stroke center where EVT is available. Next, Natalia Perez de la Ossa and Marc Ribo from Catalonia presented the results of the RACECAT trial. 1401 patients who resided in areas served by non-EVT stroke centers with suspected LVO according to the RACE score were randomized while in the ambulance to either proceed to the local stroke center (drip and ship) or direct to the EVT-capable center (mothership). The primary outcome of functional outcome measured by mRS in patients with ischemic stroke only was neutral. Mean time from symptom onset to arrival at the first center was 142 minutes in the drip-and-ship model and 216 minutes in the mothership model. Two-thirds of patients identified by the RACE score had ischemic stroke and two-thirds of these had LVO. Symptom onset to IV thrombolysis and EVT was 120 minutes and 270 minutes, respectively, in the drip and ship patients, and 155 minutes and 214 minutes, respectively, in the mothership patients. Overall, this well-designed trial answers an important question, and although planning of stroke services will always depend upon local needs, the validation of both drip-and-ship and mothership models is valuable.

Cryptogenic stroke – PFO closure vs antiplatelets
Next, Scott Kasner presented long-term outcomes from the REDUCE study of PFO closure vs antiplatelet therapy. Patients aged 18-59 with cryptogenic stroke and a PFO confirmed by echocardiography were randomized to either PFO closure plus antiplatelet therapy or antiplatelet therapy alone. In keeping with the previously published results in earlier follow up, the PFO closure group had a lower rate of recurrent ischemic stroke with a hazard ratio of 0.31 (0.13-0.76) though the absolute numbers of recurrent events are small especially in the latter years of the 5-year follow-up period. Significantly, more patients in the PFO group developed atrial fibrillation in the follow-up period. Most AF was peri-procedure though 2.7% of the PFO group (vs 0.4% in antiplatelet only) developed persistent or permanent AF and required anticoagulation. 

A Q&A panel was held to close out the session with speakers exploring some of the points of interest. Overall, despite the neutral results of many of the trials presented, important take-home messages about issues that the stroke community grapples with on a day-to-day basis — such as ‘mothership vs drip-and-ship’ care pathways, optimal management of basilar artery occlusion, and cryptogenic stroke — all contributed to an informative opening session at the conference. Of note, whilst this year’s conference aimed for greater gender balance and wider geographic representation, the large clinical trials sessions were noticeably lacking in this regard and demonstrate areas of improvement for the stroke community. More female representation and experiences of stroke care in the developing world shared on the largest stage at global conferences should continue to be in our collective aims for future conferences.