European Stroke Organisation Conference
May 22–24, 2019

Aristeidis H. Katsanos, MD, PhD

Thursday, May 23

In the first presentation of the second day of the Large Clinical Trials section, Dr. Hatem Wafa presented a study on the burden of stroke in Europe: 30-year projections of incidence, prevalence, deaths and disability-adjusted life years (DALYs). Dr. Wafa presented data on the epidemiological trends and demographic changes in stroke epidemiology across Europe, using data from the global burden of disease (GBD) between 1990 and 2017. Future trajectories up to 2047 were based on population projections and GDP prospects. Investigators found that the absolute burden of stroke increased between the years 1990 and 2017 and will continue to increase through 2047 in most EU countries. Lithuania was found to be the country with the largest increase in both stroke incidence (+0.48%) and prevalence (+0.7%), while Portugal was found to have the greatest reductions in both metrics (-1.57% and -1.3%, respectively). Stroke survivors are expected to increase by 27%, posing the need for more rehabilitation services and care homes.

In the presentation of a post-hoc analysis from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) trial on the interaction of blood pressure (BP) lowering and alteplase dose in thrombolysis-eligible acute ischemic stroke (AIS) patients, it was reported that in thrombolysis-treated AIS patients, low (0.6 mg/kg) vs. standard-dose alteplase (0.9 mg/kg) does not clearly modify the treatment effects of intensive (systolic BP<130-140mmHg) vs. guideline BP lowering (SBP<180mmHg) on the primary outcome of functional outcome, intracranial hemorrhage (ICH), death or serious adverse events. Investigators concluded that intensive BP lowering does not improve functional recovery or ICH risk with either low or standard-dose alteplase.

Dr. Tom Moullaali presented the results of an individual patient data (IPD) meta-analysis of the intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT) and Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) II trial on the utility of systolic BP control after acute intracerebral hemorrhage (ICH). After analyzing data from a total of 3,829 patients from both trials (mean age 63 years, median NIHSS score 11 points, median time from ICH onset to randomization 3.6 hours), investigators found that achieved systolic BP and BP variability in the first 24 hours after ICH onset is significantly associated with the probability of 3-month functional independence, suggesting that sustained and careful lowering of systolic BP to the level of 120-130 mmHg in the first 24 hours after ICH may be optimal for improved functional outcomes.

Dr. Nikola Sprigg presented the one-year follow-up data from the tranexamic acid for intracerebral haemorrhage (TICH-2) trial, a multicenter, double-blind, placebo-controlled trial with 2,325 participants assessing the impact of tranexamic acid (1g bolus, 1g infusion) in patients with spontaneous ICH presenting within 8 hours from symptom onset. In this sub-study, TICH-2 investigators analyzed data only from UK centers (1,910 participants). Although no significant difference was found in the functional outcomes at 1 year in this subgroup of patients, participants randomized in the intervention group were found to have 23% reduced cumulative mortality rates compared to those randomized in the placebo arm. Interestingly, the only significant interaction that was uncovered in the pre-defined subgroup analyses was the lower mortality risk in patients with baseline systolic BP less than 170 mmHg.

Dr. Deborah Levine presented a pooled analysis of IPD from 5 longitudinal cohorts in the United States, which were conducted between the years 1971 and 2017 and recruited a total of 19,378 participants (20% black, 55% females) free of stroke and dementia. Investigators found significant racial disparities in later-life cognitive decline associated with increased BP levels over the life course, concluding that adult population, and especially black, warrant strict BP management to reduce the risk of cognitive decline in addition to cardiovascular risk.

Dr. David Werring presented on behalf of the Microbleeds International Collaborative Network the results of a pooled IPD analysis from 15 cohort studies (5,068 total participants) on the association of cerebral microbleeds (CMBs) with stroke risk after ischemic stroke or transient ischaemic attack (TIA). Microbleeds International Collaborative Network investigators found that although the rate of ICH rises more steeply than that of ischemic stroke as CMB burden rises, the absolute risk of ischemic stroke exceeds that of ICH independently of CMB burden, anatomical distribution antithrombotic drug intake and ethnicity. Therefore, according to the results of this analysis, CMBs can inform on the hazard for ICH in patients with recent ischemic stroke or TIA but should not be used as a reason to withhold antithrombotic treatment.

Dr. Mike Sharma presented the results of the NAVIGATE MIND MRI sub-study, a protocol with the primary aim to determine the effect of rivaroxaban compared to acetylsalicylic acid (ASA) on the MRI-defined covert and clinical infarcts in patients with recent embolic strokes of undetermined source (ESUS). After analyzing data from a total of 1,060 patients (mean age 67 years, 61% males) investigators found no difference on the rates of baseline ischemic infarcts or CMBs between patients randomized to rivaroxaban or ASA. In the follow-up period, incident infarcts occurred in 11% of the participants, with 72% of them being only covert infarcts. Rivaroxaban treatment was neither found to reduce MRI infarcts, nor was associated with increased CMB incidence compared to ASA.

Likewise, in the COMPASS MIND sub-study of the cardiovascular outcomes for people using anticoagulation strategies (COMPASS) randomized trial, presented also by Dr. Mike Sharma, low rivaroxan dose was not found to have a significant effect on covert infarcts, which were found to be 6-times more common than symptomatic infarcts in the analysis of readable baseline and follow-up MRI scans from 1,445 patients (mean age 71 years, 77% males).

Friday, May 24

Dr. Keun-Sik Hong presented a subgroup analysis of the prevention of cardiovascular events in Asian patients with ischaemic stroke at high risk of cerebral hemorrhage (PICASSO) trial, with the aim to explore the safety and efficacy of cilostazol vs. ASA between patients with 2 or more CMBs and in those with clinical or radiological evidence of prior ICH. After analyzing data from 1,512 total patients and a median follow-up of 1.9 years, PICASSO investigators found that cilostazol substantially lowered ICH risk in patients with CMBs, but not in patients with prior ICH. Cilostazol treatment was also found to have a trend for lower risk of major vascular events in patients with CMBs, but not in patients with prior ICH, suggesting that cilostazol might be a better treatment option compared to ASA in ischemic stroke patients with multiple CMBs.

Dr. Jeffrey Saver presented on behalf of ImpACT-24B Trial Investigators the results from a pivotal, phase 2, randomized, double-blind, sham-controlled trial assessing the impact of sphenopalatine ganglion stimulation in the outcomes of AIS patients. After randomizing a total of 1,000 acute ischemic stroke patients (mean age 70 years, median NIHSS score 12 points, median time from symptom onset to randomization: 17 hours), ImpACT-24B investigators found that sphenopalatine ganglion stimulation was safe, while showing evidence of benefit in the presence of cortical involvement. A strong, inverted U-shaped dose-benefit relationship was present consistently for all primary and secondary outcomes.

Dr. Guillaume Turc presented an IPD meta-analysis from the medical arms of two randomized trials (CLOSE and DEFENSE-PFO) and two prospective observational cohort studies, with the aim to investigate the influence of atrial septal aneurysm and shunt size on the risk of recurrent stroke in patients with patent foramen ovale. After analyzing data from 898 total patients (mean age 45 years, 60% males), investigators found that in patients with PFO-associated stroke treated with medical therapy alone, atrial septal aneurysm presence was associated with stroke recurrence, an association that was not found for patients with large shunt.

Dr. Jochen Fiebach presented a post-hoc analysis from the WAKE-UP trial to assess the utility of intravenous thrombolysis in eligible patients with large vessel occlusion and unknown stroke onset time. After analyzing data from 485 patients with available baseline magnetic resonance angiography (20% with large vessel occlusion), WAKE-UP investigators found that intravenous alteplase is effective in patients with large vessel occlusion and unknown symptom onset and is associated with about 2-times higher likelihood of 3-month favorable outcome, suggesting that there is no reason to withhold intravenous thrombolysis in wake-up patients with DWI-FLAIR mismatch even if thrombectomy is planned.

Dr. Salwa El Tawil presented the results of the penumbra and recanalisation acute computed tomography in ischaemic stroke evaluation (PRACTISE) trial, a randomized clinical trial assessing the utility of multimodal computed tomography (CT) with CT angiography and perfusion in the outcomes of intravenous thrombolysis. After randomizing a total of 272 patients (mean age 67.5 years, median NIHSS score 6 points), PRACTISE investigators found that although multimodal CT did not affect time to treatment, it was associated with a significant reduction in the rate of intravenous thrombolysis administration. Moreover, functional outcomes at 3-months were not different between patients receiving multimodal CT and those receiving only plain non-contrast CT scans on admission.

Dr. Heinrich Audebert presented the results of the INSPIRE trial, a multicenter, prospective randomized trial including patients with minor stroke or TIA within 14 days and at least one treatable vascular risk factor. After recruitment of a total of 2,098 patients (mean age 67 years, 34% females) in 7 German and 1 Danish centers, INSPIRE investigators found that although patients randomized in the support program were more successful in the achievement of all secondary prevention targets compared to patients receiving conventional care, the two groups had no significant differences in the rates of major vascular events during follow-up. 

Dr. Peter Willeit presented the results of the STROKE-CARD Care program, a pragmatic trial of a multifaced intervention to prevent future cardiovascular events and improve quality of life after acute ischemic stroke or TIA. After including 2,149 patients (mean age 69 years, median NIHSS score 3 points) from two centers in Austria, STROKE-CARD investigators found reduced cardiovascular risk, improved health-related quality of life and better functional outcomes in patients randomized to the STROKE-CARD Care program compared to conventional care, highlighting that optimal stroke care does not end with hospital discharge but should extend to a comprehensive 3-month reassessment performed by the same multidisciplinary team.

Dr. Emma Patchwood presented the first findings from the Organising Support for Carers of Stroke Survivors (OSCARSS) trial, a national cluster randomized controlled trial. After analyzing data from 319 patients (76% females), OSCARSS investigators found no meaningful difference among intervention and standard support groups, concluding that potentially intervention was not fully implemented and suggesting that future implementations should be based on person-centered approaches.