Abstract
General Interest Sessions
Official Welcome & Large Clinical Trials
ESOC19-2374
RESTORE BRAIN STUDY: A RANDOMIZED EFFICACY AND SAFETY TRIAL WITH ORAL S 44819 AFTER RECENT ISCHEMIC STROKE EVENT
1Lariboisière Hospital- APHP, Neurology Department, Paris, France
2University Hospital Inselspital Bern, Neurology Department, Bern, Switzerland
3Institut de Recherches Internationales Servier, Neuropsychiatry Department, Suresnes, France
4University Hospital of Essen, Neurology Department, Essen, Germany
Background and Aims
Thrombolysis and mechanical thrombectomy are well established treatments of acute ischemic stroke. Add-on treatments that can enhance post stroke recovery are still lacking. S44819 is a novel competitive antagonist of the GABAA α5 receptor expected to improve functional and cognitive recovery in patients after a recent ischemic stroke.
Methods
RESTORE Brain is a 3-month international, randomized, double-blind, parallel group, placebo-controlled phase II study which is being conducted in 14 countries.
The main inclusion criteria are patients from 18 to 85 years, who had a recent ischemic cortical or combined cortical-subcortical stroke diagnosed on brain MRI or CT-scan with a National Institute of Health Stroke Scale (NIHSS) score between 7 and 20 (both inclusive) and without previous disability. Patients could be included from 3 to 8 (both inclusive) days after the stroke event. They are randomized either to one of the two S44819 dose groups (150 or 300mg b.i.d.) or placebo. The primary efficacy endpoint is the modified Rankin Scale (mRS) score at 3 months, also expressed as dichotomized mRS scores (0–1 versus 2–6) and (0–2 versus 3–6). Secondary efficacy endpoints are the NIHSS, Barthel Index, Montreal Cognitive Assessment scale, Trail Making Tests, safety and tolerability parameters.
Results
585 patients have been enrolled from December 2016 until November 2018. Study results are currently processed.
Conclusions
The results will evaluate the potential of S44819 to enhance functional post stroke recovery
Trial registration number
NCT02877615.
ESOC19-2377
MRI-GUIDED THROMBOLYSIS WITH ALTEPLASE AT 0.6MG/KG FOR STROKE WITH UNKNOWN TIME OF ONSET: THAWS RANDOMIZED CONTROLLED TRIAL
1National Cerebral and Cardiovascular Center, Department of Cerebrovascular Medicine, Suita, Japan
2National Cerebral and Cardiovascular Center, Center for Advancing Clinical and Translational Sciences, Suita, Japan
3National Cerebral and Cardiovascular Center, Department of Data Science, Suita, Japan
4Nippon Medical School, Department of Neurology- Graduate School of Medicine, Tokyo, Japan
5Mihara Memorial Hospital, Department of Stroke Medicine- Institute of Brain and Blood Vessels, Isesaki, Japan
6Yamagata City Hospital Saiseikan, Department of Neurosurgery, Yamagata, Japan
7Obihiro Kosei Hospital, Department of Neurosurgery, Obihiro, Japan
8Kohnan Hospital, Department of Stroke Neurology, Sendai, Japan
9Nakamura Memorial Hospital, Department of Neurosurgery, Sapporo, Japan
10Gifu University School of Medicine, Department of Neurosurgery, Gifu, Japan
11Research Institute for Brain and Blood Vessels, Department of Stroke Science, Akita, Japan
12Saga University Faculty of Medicine, Division of Neurology- Department of Internal Medicine, Saga, Japan
13Niigata City General Hospital, Department of Neurology, Niigata, Japan
14Kyoto Second Red Cross Hospital, Department of Neurology, Kyoto, Japan
15Tokai University School of Medicine, Division of Neurology- Department of Internal Medicine, Isehara, Japan
16National Hospital Organization Kyushu Medical Center, Department of Cerebrovascular Medicine and Neurology- Cerebrovascular Center, Fukuoka, Japan
17Iwate Prefectural Central Hospital, Department of Neurology, Morioka, Japan
18Nagasaki University Graduate School of Biomedical Sciences, Department of Neurology and Strokology, Nagasaki, Japan
19TOYOTA Memorial Hospital, Department of Neurology, Toyota, Japan
20Ohnishi Neurological Center, Department of Neurosurgery, Akashi, Japan
21Kawasaki Medical School General Medical Center, Department of Stroke Medicine, Okayama, Japan
22Tokushima University, Department of Neurosurgery, Tokushima, Japan
23St. Marianna University School of Medicine, Department of Neurology, Kawasaki, Japan
24Kyorin University School of Medicine, Department of Neurosurgery, Mitaka, Japan
25Kobe City Medical Center General Hospital, Department of Neurosurgery, Kobe, Japan
26Steel Memorial Yawata Hospital, Department of Cerebrovascular Medicine- Stroke Center, Kitakyushu, Japan
27Toranomon Hospital, Department of Neurology, Tokyo, Japan
28Hyogo College of Medicine, Department of Neurosurgery, Nishinomiya, Japan
29Juntendo University Urayasu Hospital, Department of Neurology, Urayasu, Japan
30St. Marianna University Toyoko Hospital, Department of Strokology- Stroke Center, Kawasaki, Japan
31National Cerebral and Cardiovascular Center, Department of Neurology, Suita, Japan
32Kyushu University, Department of Medicine and Clinical Science- Graduate School of Medical Sciences, Fukuoka, Japan
33Iwate Medical University, Institute for Biomedical Sciences, Yahaba, Japan
Background and Aims
The WAKE-UP trial recently revealed the efficacy of MRI-based intravenous thrombolysis with alteplase at 0.9mg/kg in acute ischemic stroke patients with unknown time of onset. We tested whether alteplase at 0.6mg/kg is effective and safe in patients with the same condition.
Methods
This was an investigator-initiated, multicenter, randomized, open label, blinded endpoint trial. Patients met the standard indication for intravenous thrombolysis otherwise time window more than 4.5 hours since last-known-well (e.g., wake-up stroke). They were randomly assigned (1:1) to receive alteplase at 0.6mg/kg or standard medical treatment if MRI showed acute ischemic lesion on DWI and no remarkable corresponding hyperintensity on FLAIR.
Results
Following the early stop and positive results of the WAKE-UP trial, this was prematurely terminated with 131 of an anticipated 300 patients (55 women; mean age: 74.4 ± 12.2 years; median NIHSS: 7, IQR: 4–13). Primary outcome (mRS score of 0–1 at 90 days) was comparable between the alteplase group (32/68, 47.1%) and the control group (28/58, 48.3%) (RR, 0.97; 95% CI, 0.68 to 1.41; p = 0.892). Symptomatic intracranial hemorrhage within 22–36 hours occurred in 1/71 (1.4%) and 0/60 (0%) (RR, infinity; 95% CI, 0.06 to infinity; p = 1.0), respectively. Death at 90 days occurred in 2/71 (2.8%) and 2/60 (3.3%) (RR, 0.85; 95% CI, 0.06 to 12.58; p = 1.0), respectively.
Conclusions
There was no difference of favorable outcome between the alteplase and control groups in ischemic stroke patients with unknown time of onset. The safety of alteplase at 0.6mg/kg was comparable to that of standard treatment.
Trial registration number
ClinicalTrials.gov Identifier: NCT02002325
UMIN trial ID: UMIN000011630.
ESOC19-2384
EFFECTS OF ANTIPLATELET THERAPY AFTER STROKE DUE TO INTRACEREBRAL HAEMORRHAGE: MAIN RESULTS OF THE RESTART OR STOP ANTITHROMBOTICS RANDOMISED TRIAL (RESTART)
1University of Edinburgh, Centre for Clinical Brain Sciences, Edinburgh, United Kingdom
Background and Aims
Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest sub-type of intracranial haemorrhage – intracerebral haemorrhage – are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events.
Methods
RESTART was a prospective, randomised, open, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived 24 hours. Computerised randomisation incorporating minimisation allocated participants 1:1 to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage), secondary outcomes (all major vascular events) and other serious adverse events for up to five years. We performed intention-to-treat analyses using Cox proportional hazards regression, adjusted for minimisation covariates. We prospectively registered RESTART.
Results
Between May 22 2013 and May 31 2018, 537 patients were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset. Participants were followed for median 2·0 years (completeness 99·3%).
Conclusions
The results will be presented and published simultaneously in The Lancet.
Trial registration number
ISRCTN71907627
ESOC19-2392
EXTENDING THROMBOLYSIS TO 9 HOURS AND WAKE-UP STROKE USING PERFUSION IMAGING: A META-ANALYSIS OF INDIVIDUAL PATIENT DATA FROM EXTEND, ECASS4-EXTEND AND EPITHET
1Monash University, Neurology, Clayton, Australia
2Royal Melbourne Hospital, Neurology, Melbourne, Australia
3Ruprecht Karls University Heidelberg, Neurology, Heidelberg, Germany
Background and Aims
Stroke thrombolysis is currently recommended 0–4·5h after stroke onset. Perfusion imaging may identify patients with salvageable brain who could benefit from thrombolysis beyond 4·5h or with symptoms on waking.
Methods
We performed a systematic review and individual patient data meta-analysis of randomised trials of alteplase versus placebo in ischaemic stroke patients treated >4·5h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT-perfusion. The primary outcome was excellent functional outcome (modified Rankin Score, mRS0–1) at 3 months, adjusted for baseline age and clinical severity. Secondary outcomes included functional independence (mRS0–2) and functional improvement (≥1 point reduction in mRS). Safety outcomes were death and symptomatic intracerebral haemorrhage (sICH).
Results
Of 414 patients randomised 4·5–9h or with wake-up stroke in 3 trials, 213 received alteplase and 201 placebo. In intention-to-treat analysis, the primary outcome occurred in 76/211(36%) alteplase-treated patients versus 58/199(29%) with placebo (adjusted odds ratio, aOR = 1·86, 95% confidence interval [CI] 1·15–2·99, p = 0·011). Functional independence occurred in 103/211(49%) alteplase-treated patients versus 87/199(44%) with placebo (aOR = 1·74, 95%CI 1·08–2·81, p = 0·022); Functional improvement was significantly increased with alteplase (common OR = 1·6, 95%CI 1·12–2·27, p = 0·009). sICH occurred in 10/213(4·7%) of alteplase-treated patients versus 1/201(0·5%) with placebo (aOR = 9·7, 95%CI 1·23–76·55, p = 0·031). Mortality occurred in 29/213(14%) of alteplase-treated patients versus 18/201(9%) with placebo (aOR = 1·55, 95%CI 0·81–2·96, p = 0·66).
Conclusions
Ischemic stroke patients with salvageable brain treated with alteplase 4·5–9h from onset, or with wake-up stroke, achieved better functional outcomes. An increase in sICH with alteplase did not significantly increase mortality.
Trial registration number
PROSPERO ID128036
ESOC19-2403
RANDOMIZATION OF ENDOVASCULAR TREATMENT WITH STENT-RETRIEVER AND/OR THROMBOASPIRATION VS. BEST MEDICAL THERAPY IN ACUTE ISCHEMIC STROKE DUE TO LARGE VESSEL OCCLUSION TRIAL (RESILIENT): FINAL RESULTS
1Hospital de Clínicas de Porto Alegre da Faculdade de Medicina da Universidade Federal do Rio Grande do Sul, Neurology, Porto Alegre, Brazil
2Hospital Geral de Fortaleza, Neuroendovascular, Fortaleza, Brazil
3Hospital das Clinicas da Faculdade de Medicina de Ribeirão Preto, Neurology, Ribeirão Preto, Brazil
4Hospital de Base de Brasília, Neurology, Brasília, Brazil
5Hospital São Paulo Universidade Federal de São Paulo, Neurology, São Paulo, Brazil
6Hospital Geral de Fortaleza, Neurology, Fortaleza, Brazil
7Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Neuroendovascular, Ribeirão Preto, Brazil
8Hospital de Base de Brasília, Neuroendovascular, Brasília, Brazil
9Hospital São Paulo Universidade Federal de São Paulo, Neuroendovascular, São Paulo, Brazil
10Hospital de Clinicas de Porto Alegre, Neuroendovascular, Porto Alegre, Brazil
11Hospital de Clinicas da Universidade Federal do Paraná, Neurology, Curitiba, Brazil
12Hospital Estadual de Vitória, Neuroendovascular, Vitória, Brazil
13Hospital das Clínicas da Universidade de Campinas, Neuroendovascular, Campinas, Brazil
14Universidade Federal da Bahia, Neurology, Salvador, Brazil
15Hospital Pró-Cardíaco, Neurology, Rio de Janeiro, Brazil
16University of California Los Angeles, Neuroradiology, Los Angeles, USA
17Grady Memorial Hospital Emory University, Neuroendovascular, Atlanta, USA
Background and Aims
Randomized clinical trials have consistently demonstrated the benefit of Mechanical Thrombectomy (MT) for the treatment of Large Vessel Occlusion Strokes (LVOS). However, these studies were performed in “First-World” countries and have had minimal impact on the public healthcare of low-and-middle-income-countries as the costs of MT were deemed too high and its benefit not properly validated in these countries. RESILIENT is a Brazilian Stroke Network/Ministry of Health collaboration with the objective of evaluating MT in the Public Healthcare System.
Methods
Prospective, multi-center, randomized, controlled trial of MT versus medical management (including IV-tPA if applicable) in anterior circulation LVOS (ICA and/or MCA-M1) ≤8 hours from onset. Key inclusion criteria included NIHSS≥8 and ASPECTS≥6 at baseline. The primary outcome was the distribution of the 90-day mRS scores (ordinal-shift analysis) as evaluated by a blinded core lab through video interviews. Sample size was 690 patients for a 10% treatment effect difference.
Results
221 patients were randomized (111MT vs. 110controls;age,64 ± 4;NIHSS,18 ± 5;tPA,65%;ICA-occlusions,18%) over 25 months. On 3/23/2019, the DSMB recommended the trial termination due to “clear crossing of the boundary for efficacy at the first interim analysis” after 174 patients had completed 90-day-follow-up. Amongst the particularities are the use of single-plane angiography, lack of outpatient rehabilitation, and previous MT experience in only one out of the 12 participating centers. The final results will be presented at theESOC.
Conclusions
The efficacy of MT persists despite of the many limitations encountered in the public system of a developing country.
Trial registration number
ClinicalTrials.gov:NCT02216643
Presidential Symposium – Awards & Trials
ESOC19-2406
RESULTS OF THE CARDIOVASCULAR OUTCOMES FOR PEOPLE USING ANTICOAGULATION STRATEGIES (COMPASS) RANDOMIZED TRIAL MRI AND NEUROCOGNITIVE DETERIORATION SUBSTUDY (COMPASS MIND)
1Population Health Research Institute/McMaster University/Hamilton Health Sciences, Stroke & Cognition Program/Division of Neurology/Department of Neurology, Hamilton, Canada
2Hotchkiss Brain Institute – University of Calgary, Clinical Neurosciences, Calgary, Canada
3Population Health Research Institute/McMaster University/Hamilton Health Sciences, CVD Prevention and Risk Factors Program/School of Rehabilitation Science, Hamilton, Canada
4Population Health Research Institute/McMaster University/Hamilton Health Sciences, Statistics, Hamilton, Canada
5Population Health Research Institute/McMaster University/Hamilton Health Sciences, CVD Prevention and Risk Factors Program/Medicine Hematology/Department of Hematology, Hamilton, Canada
6Population Health Research Institute/McMaster University/Hamilton Health Sciences, Arrhythmia & Thrombosis Program/Medicine Cardiology/Department of Cardiology, Hamilton, Canada
7Estudios Clı´nicos Latino America and Instituto Cardiovascular de Rosario, Prevención Cardiovascular, Rosario, Argentina
8Research Institute- FOSCAL-Bucaramanga, Metabolic Syndrome and Diabetes, Bucaramanga, Colombia
9Comprehensive Heart Failure Center- University and University Hospital Wuerzburg, Department of Cardiology, Wuerzburg, Germany
10Comprehensive Heart Failure Center- University and University Hospital Wuerzburg, Department of Clinical Research and Epidemiology, Wuerzburg, Germany
11Institut Universitaire de Cardiologie et Pneumologie de Quebec, Cardiologie, Quebec City, Canada
12Population Health Research Institute/McMaster University/Hamilton Health Sciences, CVD Prevention and Risk Factors Program/Medicine Cardiology/Department of Cardiology, Hamilton, Canada
13Karolinska Institutet, Department of Cardiology, Stockholm, Sweden
14Monash University, Department of Epidemiology and Preventive Medicine, Melbourne, Australia
15Monash University, Department of Public Health and Preventative Medicine, Melbourne, Australia
16Brigham and Women’s Hospital Heart and Vascular Center – Harvard Medical School, Division of Cardiovascular Medicine, Boston, USA
17University of Washington Medical Centre, Department of Cardiology, Seattle, USA
18University of Washington, Clinical Trials Service Unit – Division of Cardiology, Seattle, USA
19The Catholic University of Korea, Cardiology, Seoul, Republic of Korea
20National University of Ireland, Department of Translational Medicine, Galway, Ireland
21University of Medicine and Pharmacology Carol Davila University and Emergency Hospital, Department of Cardiology, Bucharest, Romania
22Centre for Cardiovascular Science – University of Edinburgh, Department of Cardiology, Edinburgh, United Kingdom
23FuWai Hospital, Department of Cardiology, Beijing, China
24National Research Centre for Preventative Medicine Moscow, Department of Cardiology, Moscow, Russia
25ANMCO Research Center, Cardiology, Florence, Italy
26Instituto Dante Pazzanese de Cardiologia, Cardiologia, Sao Paulo, Brazil
27University of Sao Paulo, Cardiologia, Sao Paulo, Brazil
28Semmelweis University, Department of Cardiology, Budapest, Hungary
29Bayer AG, TA Thrombosis & Hematology, Wuppertal, Germany
30Bayer AG, Thrombosis, Whippany, USA
31Population Health Research Institute/McMaster University/Hamilton Health Sciences, CVD Prevention and Risk Factors Program, Hamilton, Canada
32Population Health Research Institute/McMaster University/Hamilton Health Sciences, Executive Director/Medicine/Chief Scientist, Hamilton, Canada
Background and Aims
MRI-defined covert infarcts are common and associated with cognitive decline. COMPASS compared the effects of rivaroxaban alone or combined with aspirin in 27,395 patients with stable coronary artery or peripheral artery disease and was stopped early for efficacy. Ischemic stroke was significantly reduced for participants treated with rivaroxaban 2.5 mg BID combined with aspirin 100 mg OD (HR 0.51;95% CI 0.38–0.68). We assessed the effect of rivaroxaban on incident covert brain infarcts.
Methods
Standardized baseline and end-study MRIs were obtained and interpreted by blinded central readers for incident infarcts, cerebral microbleeds (CMBs) and WHI. Covert infarcts were defined using the STRIVE consensus criteria.
Results
1761 baseline MRI scans were completed at 83 centers in 16 countries; 1445 (82%) had a follow up scan. After a mean (SD) of 2.0 (0.7) years, incident covert infarcts occurred in 2.7% on rivaroxaban and aspirin vs 3.5% on aspirin alone OR 0.77(0.37–1.60). Covert infarcts or ischemic stroke occurred in 2.9% on the combination and 5.3% on aspirin alone OR 0.53(0.27–1.03). Incident CMBs occurred in 6.6% of participants; combination vs aspirin OR 1.49(0.88–2.52). Overall, 65.7% of participants experienced WHI increase; in these patients, median (IQR) increase was 2.2 ml (0.9–4.3) with no significant difference by treatment.
Conclusions
Although the rate of covert infarcts was not significantly reduced, this is likely due to the size of the substudy, and short duration due to early termination of the study. When taken together with clinical stroke, the data suggest the effect on covert and clinical stroke may be similar.
Trial registration number
NCT01776424
Large Clinical Trials 2
ESOC19-2376
EFFECTS OF A MULTICOMPONENT SUPPORT PROGRAM FOR INTENSIFIED SECONDARY PREVENTION IN PATIENTS WITH TRANSIENT ISCHEMIC ATTACK AND MINOR STROKE THE INSPIRE-TMS TRIAL
1Charité Universitätsmedizin Berlin, Department of Neurology, Berlin, Germany
2Charité – Universitätsmedizin Berlin, Neurology- Center for Stroke Research, Berlin, Germany
3Klinikum Ludwigshafen, Neurology, Ludwigshafen, Germany
4The Danish Stroke Centre – Aarhus University Hospital, Neurology, Aarhus, Denmark
5Klinikum Rechts der Isar- Technical University Munich, Neurology, Ludwigshafen, Germany
6The Danish Stroke Center- University Hospital Aarhus, Neurology, Aarhus, Denmark
7Praxis für Neurologie und Psychiatrie am Prinzregentenplatz, Neurology, Munich, Germany
8University Medical Center Utrecht, Utrecht Stroke Center- Neurology and Neurosurgery and Julius Center, Utrecht, The Netherlands
9Bichat Hospital- Université Paris Diderot- Sorbonne Paris, Neurology and Stroke Centre, Paris, France
10Deutsche Schlaganfallgesellschaft, Neurolgoy, Berlin, Germany
11Charité – Universitätsmedizin Berlin, Cardiology- Center for Cardiovascular Telemedicine, Berlin, Germany
12Charité – Universitätsmedizin Berlin, Neurology, Berlin, Germany
Background and Aims
Patients with recent ischaemic stroke or transient ischaemic attack (TIA) are at high risk of suffering a new cerebro- or cardiovascular event possibly leading to permanent disability or death. Although evidence-based treatments for secondary prevention of stroke are available, many patients do not achieve recommended risk factor control, behavioural modifications and pharmaceutical prevention in the long-term. They may therefore benefit from a support program for enhanced secondary prevention.
Methods
In a randomized, controlled trial, we included 2098 patients of eight German and Danish centers with non-disabling stroke or TIA and at least one evidence-based modifiable risk factor. Patients were either assigned to the support program (plus usual care) with eight outpatient visits planned over two years and based on feedback and motivational interviewing strategies or to receive usual care by family doctors only (control group). The primary outcome was the composite of stroke, acute coronary syndrome and vascular death. Key secondary outcomes were total number of primary outcome events (including repeated events in same patients), all-cause death and effects on risk factor targets.
Results
Patients of the support program group achieved higher rates of prevention targets in follow-up, e.g. at 1-year: 59% versus 48% for blood pressure, 62% versus 54% for low-density lipoprotein, 33% versus 19% for physical activity, 50% versus 35% for smoking cessation (all p < 0.01) and 83% versus 75% for effective oral anticoagulation in patients with atrial fibrillation (p = 0.055).
Conclusions
The results on primary and secondary outcomes will be presented at the ESOC 2019.
Trial registration number
NCT01586702
ESOC19-2396
ORGANISING SUPPORT FOR CARERS OF STROKE SURVIVORS (OSCARSS): FIRST RELEASE OF FINDINGS FROM A CLUSTER RANDOMISED CONTROLLED TRIAL
1University of Manchester- Manchester Academic Health Science Centre MAHSC, Faculty of Biological and Medical Sciences- Division of Neuroscience and Experimental Psychology, Manchester, United Kingdom
2NIHR Collaboration for Leadership in Applied Health Research and Care CLAHRC Greater Manchester, Stroke Programme, Manchester, United Kingdom
3University of Manchester- Manchester Academic Health Science Centre MAHSC, Centre for Biostatistics- Institute of Population Health, Manchester, United Kingdom
4University of Manchester, Alliance Manchester Business School, Manchester, United Kingdom
5University of Manchester- Manchester Academic Health Science Centre MAHSC, Division of Nursing- Midwifery and Social Work, Manchester, United Kingdom
6University of Cambridge, Centre for Family Research, Cambridge, United Kingdom
7Stroke Association, Stroke Support, Manchester, United Kingdom
Background and Aims
We investigated the effectiveness of training staff to provide an adapted, person-centred approach to supporting informal caregivers of stroke survivors.
Methods
Longitudinal, multi-site cluster randomised controlled trial (cRCT), health economic and process evaluation. Clusters were UK NHS-commissioned services, randomised to person-centred training (intervention) or usual care (control). Adult carers referred to participating clusters were eligible.
cRCT carer participants provided study entry and outcome data at three and six months, through postal questionnaires. Primary outcome: three month caregiver strain from the Family Appraisal of Caregiving Questionnaire. Secondary outcomes included mood and satisfaction with stroke services.
The process evaluation explored intervention implementation and carers’ experiences in both arms.
Results
35 randomised clusters (18 intervention; 17 control) recruited 414 cRCT carers. Study entry characteristics were balanced between arms. Intention to treat analyses, based on primary outcomes from 175 (84%) and 174 (84%) intervention and control carers respectively, found mean (SD) strain at 3 months was 3.03 (0.90) versus 3.11 (0.87) in controls, adjusted mean difference −0.04 (95% CI −0.20 to 0.13). Secondary outcomes had similarly small differences and tight CIs. In both arms, mood difficulties were low and satisfaction high, on average. Sensitivity analyses suggested robust findings. The process evaluation found that carers were positive about support in both arms and staff valued the intervention but did not implement all components.
Conclusions
The intervention as implemented conferred no clinical benefits above usual care for carers. Training was not sufficient to shift staff to the intended approach. Valuable learning informed future implementation research and service development.
Trial registration number
ISRCTN58414120
ESOC19-2398
PRAGMATIC TRIAL OF A MULTIFACETED INTERVENTION (STROKE-CARD CARE PROGRAMME) TO PREVENT FUTURE CARDIOVASCULAR EVENTS AND IMPROVE QUALITY OF LIFE AFTER ACUTE ISCHAEMIC STROKE OR TIA
1Medical University of Innsbruck, Department of Neurology, Innsbruck, Austria
2University of Cambridge, Department of Public Health and Primary Care, Cambridge, United Kingdom
3St. John’s of God Hospital, Department of Neurology, Vienna, Austria
4Medical University of Innsbruck, Department of Medical Psychology, Innsbruck, Austria
5University Hospital of Innsbruck, Central Institute of Medical and Chemical Laboratory Diagnostics, Innsbruck, Austria
Background and Aims
Patients with ischaemic stroke or transient ischaemic attack (TIA) are at high risk of recurrent stroke and other cardiovascular diseases, which may be preventable with an intensified post-stroke disease management programme.
Methods
We enrolled patients with acute ischaemic stroke or TIA (ABCD2 score ≥3) between January 2014 and December 2017. We randomly assigned patients in a 2:1 ratio to the multifaceted disease management programme STROKE-CARD or to standard care. Co-primary outcomes were (i) incident cardiovascular disease defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death occurring between hospital discharge and 12 months, and (ii) health-related quality of life quantified with the EQ-5D-3L overall utility score at 12 months.
Results
Of 2149 patients enrolled (mean age 69 years, 41% female, 83% with ischaemic stroke, 17% with TIA), 1438 were assigned to STROKE-CARD care and 711 to standard care. Incident cardiovascular disease occurred in 78 patients in the STROKE-CARD care group (5.4%) and in 59 patients in the standard care group (8.3%) (hazard ratio, 0.63; 95% CI: 0.45–0.88; P = 0.007). At 12 months, the median EQ-5D-3L score was 78.3 (IQR 68.7–100) in the STROKE-CARD care group and 77.9 (IQR 57.3–100) in standard care group (difference in medians, +0.4; P<0.001). Among pre-specified secondary outcomes, STROKE-CARD care improved individual EQ-5D-3L dimensions and the modified Rankin Scale. Risk of major bleeding, syncope, fractures, or rhabdomyolysis did not differ between trial arms.
Conclusions
The STROKE-CARD care programme reduced cardiovascular risk and improved quality of life in patients with acute ischaemic stroke or TIA.
Trial registration number
NCT02156778 (ClinicalTrials.gov)
Scientific Communications (Oral Abstract Presentation Session)
Scientific Communications 02-Epidemiology
ESOC19-2369
PREDICTORS OF RECURRENT ISCHEMIC STROKE IN PATIENTS WITH EMBOLIC STROKES OF UNDETERMINED SOURCE AND EFFECTS OF RIVAROXABAN VERSUS ASPIRIN BY RISK STATUS: NAVIGATE ESUS TRIAL
1McMaster University/Population Health Research Institute, Medicine Neurology, Hamilton, Canada
2Imperial College London, Neurology, London, United Kingdom
3Population Health Research Institute, Statistics, Hamilton, Canada
4University of Pennsylvania, Department of Neurology, Philadelphia, USA
5McMaster University/Population Health Research Institute, Department of Health Research Methods- Evidence and Impact, Hamilton, Canada
6University of Thessaly, Department of Medicine, Larissa, Greece
7Institute for Neurological Research, Neurology, Buenos Aires, Argentina
8“Sapienza” University of Rome, Department of Neurology and Psychiatry, Rome, Italy
9Medical University of Warsaw, 2nd Department of Neurology, warsaw, Poland
10Lund University, Department of Neurology and Rehabilitation Medicine, Lund, Sweden
11University of Western Australia, Neurology, Perth, Australia
12University of Alberta Hospital, Department of Neurology, Alberta, Canada
13Hotchkiss Brain Institute, Department of Clinical Neurosciences- Radiology- and Community Health Sciences, Calgary, Canada
14Irmandade da Santa Casa de Misericórdia de São Paulo, Neurology, Sao Paulo, Brazil
15Bayer U.S. L.L.C., Research, Whippany, USA
16Bayer AG, Research, Wuppertal, Germany
17Janssen Research and Development- LLC, Research and Development, Spring House, USA
18McMaster University/Population Health Research Institute, Medicine Cardiology, Hamilton, Canada
Background and Aims
ESUS identifies patients with cryptogenic ischemic stroke (IS) presumed due to embolism from unidentified sources. We sought to determine independent predictors of recurrent IS, among patients with ESUS, during treatment with aspirin or rivaroxaban and to assess the relative effects of these treatments according to risk.
Methods
Exploratory analyses of 7213 participants in NAVIGATE ESUS trial randomized to aspirin 100mg/day or rivaroxaban 15mg/day and followed for a median of 11 months, during which time 309 first recurrent IS (4.6%/year) occurred. Baseline features were correlated with recurrent IS by multivariate analysis.
Results
Prior stroke/TIA (HR 2.03,95%CI 1.58–2.60), current tobacco user (HR 1.62,95%CI 1.24–2.12), age (HR 1.02 per year increase, 95%CI 1.01–1.03), diabetes (HR 1.28, 95%CI 1.01–1.64), multiple acute infarcts on neuroimaging (HR 1.49, 95%CI 1.09–2.02), aspirin use prior to qualifying stroke (HR 1.34, 95%CI 1.02–1.76), and time from qualifying stroke to randomization (HR 1.00, 95%CI 0.99–1.00) were independent predictors of recurrent IS. Recurrent stroke rate was 2.6%/yr and 7.8%/yr respectively for participants without any of these risk factors and those with three or more risk factors. There were no significant interactions between treatment effects and independent stroke predictors or stroke risk status.
Conclusions
In this large cohort of ESUS patients, prior stroke/TIA, advanced age, current tobacco use, multiple acute infarcts on neuroimaging, and diabetes (among others) independently identified those with an increased risk of ischemic stroke recurrence. The relative effects of rivaroxaban and aspirin were similar across the spectrum of independent stroke predictors and recurrent stroke risk status.
Trial registration number
NCT02313909
Scientific Communications 03-Heart & Brain
ESOC19-2405
EFFECT OF A QUALITY IMPROVEMENT INTERVENTION ON THE PRESCTIPTION OF CARDIOVASCULAR PREVENTION TREATMENTS IN STROKE PATIENTS: INSIGHTS FROM THE BRIDGE CARDIOVASCULAR PREVENTION CLUSTER RANDOMIZED TRIAL
1Hospital do Coração, Research Institute, São Paulo, Brazil
2Ribeirão Preto School of Medicine, Ribeirão Preto School of Medicine, Ribeirão Preto, Brazil
3Federal University of São Paulo, School of Medicine, São Paulo, Brazil
4Instituto Dante Pazzanese, Cardiology, São Paulo, Brazil
5Duke University School of Medicine, Duke Clinical Research Institute, Durham, USA
6Universidade Federal de Ciências da Saúde de Porto Alegre, School of Medicine, Porto Alegre, Brazil
Background and Aims
We assessed the hypothesis that a multifaceted educational intervention can improve the adherence to evidence-based therapies for cardiovascular prevention in stroke patients.
Methods
The BRIDGE Cardiovascular Prevention study was a cluster randomized trial including 1,623 patients with stroke, coronary artery disease or peripheral artery disease from 40 outpatient clinics in Brazil. Clusters were randomized to receive a multifaceted quality improvement intervention or to routine practice (control). The quality improvement intervention include: reminders, care algorithms, training of a case manager, audit and feedback reports, and distribution of educational materials to health care providers. The primary endpoint is the adherence to combined evidence-based therapies (statins, antiplatelet therapy and ACE inhibitors or angiotensin receptor blockers) using the “all or none” approach at 12 months in patients without contra-indications.
Results
: Among the 1619 patients enrolled in the original sample, 355(21,9%) were stroke patients. The mean age was 66.6 (SD = 11) and 214 (60.3%) were men. Table 1 presents the main trial findings. There was a significant difference in the combined adherence to evidence-based therapies between the intervention and the control groups (73.3% versus 53.8% respectively, Odds ratio, 2.57 [95% CI, 1.33 – 4.95], p < 0.01). Patients in the intervention group were more likely to receive statins (94.1% vs. 79.6%%; Odds ratio 4.05 [95% CI, 1.77 – 9.27], p < 0.01) and antiplatelet (93.3% vs. 80.1%%; Odds ratio 4.54 [95% CI, 1.73 – 11.90], p < 0.01).
Conclusions
Among stroke patients treated in Brazil, a quality improvement intervention resulted in improved prescription of evidence-based therapies for cardiovascular prevention
Trial registration number
Clinicaltrials.gov: NCT02851732.
Scientific Communications 08-Reperfusion Treatment (IVT)
ESOC19-2379
CEREBROLYSIN REGISTRY STUDY IN STROKE (CREGS-S): FINAL RESULTS
1University of Glasgow, School of Medicine, Dentistry & Nursing, Glasgow, United Kingdom
2Elias Sourasky Medical Centre, Department of Neurology, Tel Aviv, Israel
3Danube University, Department Neurosciences and Preventive Medicinie, Krems, Austria
4University of Glasgow, Institute of Cardiovascular & Medical Sciences, Glasgow, United Kingdom
5Klinikum der Universität München, Institut für Schlaganfall und Demenzforschung ISD, Munich, Germany
6Max Planck Institute, Institute for Metabolism Research, Cologne, Germany
7Karolinska Institutet, Department of Clinical Neurosciences, Stockholm, Sweden
Background and Aims
CREGS-S (NCT02541227) was a rigorously controlled registry-based study to assess outcomes after cerebrolysin use in routine clinical practice versus otherwise comparable untreated patients.
Methods
We registered patients’ use versus non-use of cerebrolysin within hospitals where approved, recording baseline data at admission; and outcome at three months through video recording of modified Rankin (mRS) interview by certified raters. These videos were independently adjudicated at Glasgow University, blinded to treatment and outcome. Treated versus untreated patients were matched for baseline data 1:1 by propensity scores, locking the match before releasing outcomes. Primary analysis was mRS distribution in the matched population. Sensitivity analyses considered the unmatched intent-to-include population; patients with NIHSS≥8; unadjudicated outcomes; use of approved dosage.
Results
From 1828 registrations, 1179 patients (age 64 ± 11; NIHSS 7 ± 6) had recorded outcomes, permitting matching of 427 treated with 427 untreated cases, achieving excellent correspondence of baseline prognostic variables. Outcomes were not better in the cerebrolysin group: MannWhitney OR = 1.05, 95% CI 0.90–1.22, p = 0.52. Unmatched analysis was also neutral: MWOR = 1.09, 95% CI 0.96–1.25, p = 0.18. In 358 matched patients with NIHSS ≥ 8, outcomes remained neutral: MWOR = 0.84, 95% CI 0.67–1.06, p = 0.15. Dose had no impact. Analysis of unadjudicated outcomes favoured cerebrolysin despite matching: MWOR = 1.35, 95% CI 1.18–1.55, p < 0.001, n = 1080; serious AE reports appeared selectively submitted.
Conclusions
Adjudicated review consistently found neutrality versus controls. Local raters recorded better functional outcomes after cerebrolysin and imbalanced SAE reports: propensity matching populations alone is insufficient to control bias. Blinded central adjudication of outcomes is crucial to rigorous interpretation of registry data.
Trial registration number
NCT02541227
Scientific Communications 08-Reperfusion Treatment (IVT)
ESOC19-2383
EFFECT OF GLYCERYL TRINITRATE (GTN) IN PRE-HOSPITAL ULTRA-ACUTE ISCHAEMIC EVENTS: A SUB-GROUP ANALYSIS OF THE RAPID INTERVENTION WITH GLYCERYL TRINITRATE IN HYPERTENSIVE STROKE TRIAL-2 (RIGHT-2)
1University of Nottingham, Stroke- Division of Clinical Neuroscience, Nottingham, United Kingdom
2University of Edinburgh, Centre for Clinical Brain Sciences- UK Dementia Research Institute, Edinburgh, United Kingdom
Background and Aims
Glyceryl trinitrate (GTN, a nitrovasodilator) had no overall effect on outcome when administered before hospital. Here we assess the safety and efficacy of GTN in patients with ischaemic events (IE, ischaemic stroke and transient ischaemic attack).
Methods
RIGHT-2 was an ambulance-based multicentre single-masked blinded-endpoint trial. Patients were randomised to GTN or sham patch <4 hours of onset. The primary outcome was the shift in modified Rankin Scale (mRS) at 90 days. Secondary outcomes included death; a global analysis (Wei-Lachin test) encompassing mRS, Barthel Index, Zung depression scale, telephone interview for cognitive status-modified and EuroQol-5D; and imaging. Data are adjusted common odds ratio (acOR) with 95% confidence intervals (CI).
Results
706/1149 (61%) patients had a final diagnosis of an IE (ischaemic stroke 597, transient ischaemic attack 109); mean age 74.8 (standard deviation; 12.5), median National Institutes of Health Stroke Scale score 7.5 [interquartile range, IQR;4–15] and median time from onset to randomisation was 70 [IQR;45–107] minutes. At day 90, GTN did not have an effect on the primary outcome (acOR 1.15, 95% CI 0.88–1.51).
Conclusions
In IE patients, very early administration of GTN was safe but did not affect dependency. Further results regarding imaging and clinical outcomes will be ready to present in May 2019.
Trial registration number
ISRCTN26986053
Scientific Communications 10- Intracerebral Haemorrhage
ESOC19-2373
GLYCERYL TRINITRATE (GTN) FOR PRE-HOSPITAL ULTRA-ACUTE INTRACEREBRAL HAEMORRHAGE (ICH): A SUB-GROUP ANALYSIS OF THE RAPID INTERVENTION WITH GLYCERYL TRINITRATE IN HYPERTENSIVE STROKE TRIAL-2 (RIGHT-2)
1University of Nottingham, Stroke- Division of Clinical Neuroscience, Nottingham, United Kingdom
2University of Edinburgh, Centre for Clinical Brain Sciences- UK Dementia Research Institute, Edinburgh, United Kingdom
Background and Aims
Glyceryl trinitrate (GTN, a nitrovasodilator) had no overall effect on outcome when administered before hospital. Here we assess the safety and efficacy of GTN in patients with intracerebral haemorrhage (ICH).
Methods
RIGHT-2 was an ambulance-based multicentre single-masked blinded-endpoint trial. Patients were randomised to GTN or sham patch <4 hours of onset. The primary outcome was shift in modified Rankin Scale (mRS) at 90 days. Secondary outcomes included a global analysis (Wei-Lachin test) encompassing mRS, Barthel Index, Zung depression scale, telephone interview for cognitive status-modified and EuroQol-5D; and imaging. Data are adjusted common odds ratio (acOR) with 95% confidence intervals (CI).
Results
145/1149 (13%) patients had an ICH diagnosis; mean age 73 (standard deviation; 13) years, National Institutes of Health Stroke Scale score median 16 [interquartile range, IQR;10–20], time onset to randomisation median 74 [IQR;45–110] minutes. At day 90, GTN was associated with a non-significant shift to a worse functional outcome (mRS acOR 1.87, 95% CI 0.98–3.57).
Conclusions
In ICH patients, very early administration of GTN was associated with non-significant worse functional outcome. This and further results on other clinical and imaging outcomes will be available to present in May 2019; they have profound implications for ultra-acute blood pressure lowering in ICH.
Trial registration number
ISRCTN26986053
Scientific Communications 14-Rehabilitation – Interventions
ESOC19-2388
CONSENSUS-BASED CORE SET OF OUTCOME MEASURES FOR CLINICAL STROKE REHABILITATION – A DELPHI STUDY
1University Hospital Zurich, Neurology, Zurich, Switzerland
2Cereneo, Center for Neurology and Rehabilitation- Vitznau, Vitznau, Switzerland
Background and Aims
Outcome measures (OMs) are key to tailor rehabilitation goals to individual stroke patient’s needs and to monitor recovery. The large number of available OMs is leading to high variability in clinical use. The goal was to develop a core set of OMs for the motor domain to serve as a quality standard for stroke rehabilitation.
Methods
119 OMs for the upper and lower extremities, and activities of daily living (ADL)/generic were presented to 30 European stroke rehabilitation experts in a Delphi study. In round 1, their clinical feasibility and relevance were rated. In round 2, those rated at least as “very relevant” and “very feasible” were prioritised through ranking within ICF-domains, and measurement timing had to be indicated. In round 3, answers were reviewed in reference to overall results to reach final consensus.
Results
The recommended core set for the upper extremity includes the Fugl-Meyer Motor Assessment (FMMA) and Action Research Arm Test. For the lower extremity, the FMMA, 10-Meter Walk Test Timed-up-and-Go test and Berg Balance Scale were recommended. Selected ADL/generic measures were the National Institutes of Health Stroke Scale, and Barthel Index or Functional Independence Measure, and Stroke Impairment Scale. Recommended time points are seven days; two, four, six, twelve and twenty-six weeks poststroke; and every sixth month.
Conclusions
Agreement was found upon a set of nine OMs, with measurement time points following stages of poststroke recovery. In a next step, this core set should be implemented to improve transparency, comparability, and quality of European stroke rehabilitation care.
Trial registration number
Basec-Nr.-Req-2018-00601
Scientific Communications 17-Prevention
ESOC19-2370
EFFECT OF CAROTID ENDARTERECTOMY ON DEMENTIA INCIDENCE: 20-YEAR FOLLOW-UP OF THE ASYMPTOMATIC CAROTID SURGERY TRIAL (ACST-1)
1University of Oxford, Nuffield Department of Population Health, Oxford, United Kingdom
2University of Lund, Department of Vascular Diseases, Lund, Sweden
3University of Oxford, Nuffield Department of Surgical Sciences, Oxford, United Kingdom
4University of Edinburgh, Centre for Clinical Brain Sciences, Edinburgh, United Kingdom
5University of Oxford, Nuffield Department of Clinical Neurosciences, Oxford, United Kingdom
6University of Uppsala, Department of Surgical Sciences, Uppsala, Sweden
Background and Aims
Carotid endarterectomy (CEA) might protect against dementia, by reducing future stroke risk and improving cerebral blood flow. In ACST-1, using linkage of randomised trial participants to electronic health records, we aimed to measure the long-term effect of CEA on recorded dementia.
Methods
Patients with severe carotid stenosis and no recent stroke/TIA were randomly allocated in ACST-1 to immediate or deferred CEA (control). Known dementia precluded trial entry.
To ascertain dementia, we linked 1601 participants to electronic health records and registries. Additionally, cognitive function in UK participants will be assessed via questionnaire.
We compared time to dementia between randomised groups using Kaplan-Meier and logrank analysis, censoring at death, outward migration and date of linkage.
Results
796 (49.7%) participants were allocated to immediate surgery and 805 (50.3%) to deferred CEA. Data linkage confirmed 1233 (77.0%) participants had died. Median survivor follow-up was 18 years (IQR16–21). There were 210 (13.1%) confirmed cases of incident dementia. Comparing those allocated immediate CEA versus deferral, absolute dementia risk was 3.0% vs 1.5% at 5 years, 9.3% vs 9.3% at 10 years and 18.6% vs 20.0% at 15 years. The hazard ratio of annual dementia rates between immediate CEA and control was 1.00 (95% CI 0.76–1.32, 2p = 1.0); 1.3% per year (101/7932) vs 1.3% (109/8236).
Conclusions
In ACST-1, carotid endarterectomy reduced long-term stroke risk, but may not significantly reduce risk of dementia, although for this final analysis the highest risk groups for stroke may also be at higher risk of dementia.
Trial registration number
ISRCTN26156392
Scientific Communications 17-Prevention
ESOC19-2385
EFFECTS OF ANTIPLATELET THERAPY ON STROKE RISK BY BRAIN IMAGING FEATURES OF INTRACEREBRAL HAEMORRHAGE AND CEREBRAL SMALL VESSEL DISEASES: SUB-GROUP ANALYSES OF THE RESTART TRIAL
1University of Edinburgh, Centre for Clinical Brain Sciences, Edinburgh, United Kingdom
2Newcastle-upon-Tyne Hospitals NHS Trust, Department of Neuroradiology, Newcastle-upon-Tyne, United Kingdom
3NHS Lothian, Department of Neuroradiology, Edinburgh, United Kingdom
4Addenbrooke’s Hospital, Department of Radiology, Cambridge, United Kingdom
5University of Edinburgh, Usher Institute of Population Health Sciences and Informatics, Edinburgh, United Kingdom
6University of Edinburgh, Centre for Cardiovascular Science, Edinburgh, United Kingdom
7University of Nottingham, Division of Clinical Neurosciences- Faculty of Medicine & Health Sciences, Nottingham, United Kingdom
8University College London, Stroke Research Group- Department of Brain Repair & Rehabilitation, London, United Kingdom
9Newcastle University, Institute of Neuroscience and Newcastle University Institute for Ageing, Newcastle-upon-Tyne, United Kingdom
Background and Aims
Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with up to five-fold proportional increases in recurrent intracerebral haemorrhage, but whether they modify the effects of antiplatelet therapy is unclear.
Methods
The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open, blinded endpoint, parallel-group trial including adults who were taking antithrombotic therapy for prevention of occlusive vascular diseases when they had intracerebral haemorrhage, and randomly allocated them 1:1 to start or avoid antiplatelet therapy. Consultant neuroradiologists masked to treatment allocation reviewed brain CT or MRI performed before randomisation to confirm participant eligibility and rate features of the intracerebral haemorrhage and surrounding brain. We followed participants for primary (recurrent symptomatic intracerebral haemorrhage) and secondary (ischaemic stroke) outcomes for up to five years. We analysed eligible participants with intracerebral haemorrhage according to their treatment allocation in primary sub-group analyses of cerebral microbleeds on MRI, and exploratory sub-group analyses of other features on CT or MRI. We prospectively registered RESTART.
Results
525 (98%) of the 537 participants randomised in RESTART had intracerebral haemorrhage: 507 (97%) diagnosed on CT and 254 (48%) underwent the required brain MRI protocol.
Conclusions
The final analyses have been performed and will be presented at the conference.
Trial registration number
ISRCTN71907627
Scientific Communications 18- Atrial Fibrillation
ESOC19-2393
POST-EMBOLIC RHYTHM DETECTION WITH IMPLANTABLE VERSUS EXTERNAL MONITORING (PER DIEM)
1University of Alberta, Department of Medicine, Edmonton, Canada
2University of Calgary, Department of Clinical Neurosciences, Calgary, Canada
3University of Calgary, Libin Cardiovascular Institute, Calgary, Canada
Background and Aims
Current guidelines recommend patients with recent ischemic stroke or TIA and no apparent cause should undergo prolonged rhythm monitoring (> 30 days) to assess for the presence of atrial fibrillation (AF) to guide the prescription of oral anticoagulant (OAC) therapy. The incremental benefit of detecting AF with a longer-duration implantable loop recorder (ILR) versus an external loop recorder (ELR) is unknown.
Methods
PER DIEM was a prospective, open-label, randomized study with blinded expert endpoint adjudication, conducted in Alberta, Canada. Patients ≥18 years of age, with ischemic stroke within 6 months, and a baseline ECG showing sinus rhythm were included. Those with a history of AF were excluded. Patients were randomized (1:1) to 4-weeks of cardiac monitoring with an ELR (Sorin SpiderFlash™) or 1-year monitoring with an ILR (Medtronic Reveal LINQ™ with CareLink™). The primary outcome was the detection of clinically actionable AF (≥ 2 minutes) at 1-year. OAC prescription was a secondary outcome. Data were analyzed using the intention-to-treat principle.
Results
The 300 ischemic stroke patients were randomized equally to ELR or ILR, the baseline characteristics were well matched (ELR vs ILR): mean age (SD) 62.8 (12.6) vs 64.9 (13.0), female 40.3% vs 40.7%, cryptogenic stroke 71.0 vs 68.2%, median CHADS2-VASc (IQR) 4 (3-5) vs 4 (3–5). The PER DIEM primary and secondary outcomes will be presented.
Conclusions
These results will determine if cardiac monitoring after ischemic stroke with an ILR for 1-year significantly increases AF detection rates compared to a much shorter 4 weeks of monitoring with an ELR.
Trial registration number
ClinicalTrials.gov Identifier: NCT02428140
Scientific Communications 20-Large Artery Disease and Treatment
ESOC19-2411
CLOPIDOGREL ANTIPLATELET LOADING IN ISCHEMIC STROKE OF RECENT ONSET (CAIRO) TRIAL
1Ain Shams University, Neurology, Cairo, Egypt
2Matareya Hospital, Neurology, Cairo, Egypt
Background and Aims
Intravenous thrombolysis and thrombectomy are the approved medical treatments for acute stroke. However with time restriction and multiple contraindications, their use is still limited. Clopidogrel has a dose dependent, intense and rapid antiplatelet effect with a loading dose and may be used in acute stroke setting.
Methods
Double blind RCT to assess safety and efficacy of clopidogrel in acute ischaemia stroke. Patients who are not eligible for IV TPA were randomised within 9 hours from symptom onset to clopidogrel 900 mg, 600 mg or aspirin 300 mg (groups 1,2 and 3 respectively). Outcome was assessed using NIHSS, defining improvement as = >4 points, and Modified Rankin scale (MRS) at 3 months. Secondary outcome was haemorrhagic transformation and peripheral bleeding
Results
A total of 188 patients were recuited. among the 3 groups 41/63, 44/62 and 16/58 showed significant improvement. ANOVA confirmed a groupXtime interaction. There was significant difference for MRS < 2 in group 1 and 2 compared to group 3 (p = 0.04 for group 1 vs. group 3, p = 0.02 for group 2 vs. group 3). One patient in group 1 and 2 patients in group 2 had non-significant haemorrhagic transformation.
Conclusions
Loading clopidogrel is safe and superior to aspirin in acute ischemic stroke within 9 hours.
Trial registration number
NCT02776540
Scientific Communications 22-Risk Factors and Prognosis
ESOC19-2402
DIFFERENTIAL TEMPORAL TREND FOR MORTALITY AMONG PATIENTS WITH INTRACEREBRAL HEMORRHAGE OR ISCHEMIC STROKE AT YOUNG AGE
1Radboud University Medical Centre- Donders Institute for Brain- Cognition and Behaviour, Department of Neurology, Nijmegen, The Netherlands
2Brain Center Rudolf Magnus- University Medical Center Utrecht- Utrecht- The Netherlands, Department of Neurology and Neurosurgery, Utrecht, The Netherlands
Background and Aims
Over two million people suffer an ischaemic stroke at young age (18-50 years) yearly, with incidence increasing. Especially at young age, with a long life-expectancy ahead, information on prognosis and mortality is urgently needed, but limited.
Methods
A registry- and population-based study in the Netherlands of 15257 young patients with first-ever stroke between 1998 and 2010, with follow-up until January 1st, 2017. Outcomes were (risk factors for) all-cause cumulative mortality stratified by age, sex and stroke-subtype, and compared to the general population.
Results
Among the 15257 patients (median age 44 years, 53.3% women), 3540 (23.2%) cumulative deaths had occurred during a median follow-up of 9.3 years.45–49 Year olds were at highest risk of mortality (HR 3.8; 95%CI 2.4–5.9), male sex (HR 1.5; 95%CI 1.4–1.7) and higher Charlson Comorbidity Index (index > = 3; range 0–6) HR 9.4 95%CI 7.5–11.7) were also associated with increased mortality. Long-term mortality after ischemic stroke was 5.1 (95%CI 4.7–5.4) times higher compared to peers from the general population, mortality after intracerebral hemorrhage was 8.4 (95%CI 7.4–9.3) times higher. After ischemic stroke 1- and 5-year mortality decreased significantly from 1998 to 2010 (annual average decrease of 2.2% and 3.1% respectively), whereas 1- and 5-year mortality after intracerebral hemorrhage remained stable.
Conclusions
Among young adults aged 18–49 years in the Netherlands with first-ever stroke, mortality risk compared to the general population remained elevated up to 15 years later. Mortality remained at an unaltered high level after an intracerebral hemorrhage during the follow-up, whereas it significantly decreased after an ischemic stroke.
Trial registration number
NA.
E-Poster Viewing
E-Poster Viewing – May 22 – 24
Clinical Trial Results – Rehabilitation & Recovery
ESOC19-2397
PROCESS EVALUATION OF ORGANISING SUPPORT FOR CARERS OF STROKE SURVIVORS (OSCARSS): HELPING UNDERSTAND THE TRIAL’S FINDINGS
1NIHR Collaboration for Leadership in Applied Health Research and Care CLAHRC Greater Manchester, Stroke Programme, Manchester, United Kingdom
2University of Manchester, Alliance Manchester Business School, Manchester, United Kingdom
3University of Manchester- Manchester Academic Health Science Centre, Division of Neuroscience and Experimental Psychology- School of Biological Sciences, Manchester, United Kingdom
4University of Manchester- Manchester Academic Health Science Centre, Centre for Biostatistics- Institute of Population Health, Manchester, United Kingdom
5University of Manchester- Manchester Academic Health Science Centre, Division of Nursing. Midwifery and Social Work- School of Health Sciences, Manchester, United Kingdom
6University of Cambridge, Centre for Family Research, Cambridge, United Kingdom
Background and Aims
OSCARSS includes a cluster randomised controlled trial investigating the effectiveness of a comprehensive, person-centred intervention to support carers, implemented within NHS commissioned stroke specialist services. The embedded process evaluation examines intervention fidelity, feasibility and acceptability to providers and service users (informal caregivers).
Methods
Embedded longitudinal mixed-methods process evaluation to support interpretation of trial findings (see separate abstract). Methods included: online questionnaires with frontline staff at three time points (pre-cluster-randomisation, 12 and 24 months post-randomisation); qualitative interviews with frontline staff, managers and carers. Data were synthesised and thematically analysed using components of Normalisation Process Theory: Coherence, Cognitive Participation, Collective Action, Reflexive Monitoring.
Results
141 survey responses and 64 interviews across both intervention and control arms were analysed. There was high Coherence regarding the need to support carers and the value of a structured approach, and high Cognitive Participation in believing frontline staff were well placed to support carers. However, not all components of the intervention were delivered as intended (Collective Action). Staff interviews highlighted the need for essential additions to staff training and explicit organisational buy-in to change practice sufficiently to achieve differentiation. Carers’ interviews suggested they were satisfied with the support they received in both control and intervention arms (Reflexive Monitoring), consistent with the trial’s generally positive outcome measurements.
Conclusions
Process evaluation helps interpret the trial’s findings and identified implementation challenges. Future implementation of the comprehensive, carer-centred intervention requires enhanced staff training and systems level change to ensure delivery of key intervention components and should precede a further trial.
Trial registration number
ISRCTN58414120
Late Breaking
WITHDRAWN
ESOC19-2389
MRI-DWI POSITIVITY AFTER MILD, NONDISABLING ACUTE CEREBRAL ISCHEMIA: AN ANCILLARY STUDY OF THE PRISMS TRIAL
1University of Cincinnati, Radiology, Cincinnati, USA
2Northwestern University, Neurology, Chicago, USA
3Cincinnati Children’s Hospital Medical Center, Biostatistics and Epidemiology, Cincinnati, USA
4University of Cincinnati, Neurology, Cincinnati, USA
5Emory University, Neurology, Atlanta, USA
6University of Missouri Kansas City, Neurology, Kansas City, USA
7SUNY Downstate, Neurology, Brooklyn, USA
8University of Miami, Neurology, Miami, USA
9University of California Los Angeles, Neurology, Los Angeles, USA
10Medical University of South Carolina, Public Health Sciences, Charleston, USA
Background and Aims
In patients with acute cerebral ischemia (ACI) and mild deficit, reports of detection of acute infarction on MRI (DWI-positivity) range from 67–75%. We tested the hypothesis that white matter hyperintensity (WMH) would independently predispose patients to DWI-positivity. We also developed an exploratory, multivariable model of independent predictive factors of DWI positivity.
Methods
The phase 3b, randomized PRISMS trial compared intravenous alteplase to aspirin for mild (NIHSS0–5), nondisabling stroke at ≤3 h from onset. For the current, prespecified study, patients with a final diagnosis of neurovascular mimic were excluded. Central readers assessed Day 2 MRIs for prior infarct, WMH burden [graded quantitatively (volume) and qualitatively (Fazekas)], and presence of DWI-positivity (primary outcome). Randomization assignment, demographics, and clinical covariates were prespecified for adjustment in regression modeling.
Results
Of 313 patients enrolled, 273 (87%) had a final diagnosis of ACI. Of 212/273 (77%) with MRI scans, 109 (51%) had DWI positivity (median lesion volume 1.20 cc, IQR 0.57–2.50 cc). Univariately, higher Fazekas grade (67%2–3 vs 47%0–1; p = 0.02) and prior infarct (45% vs 27%, p < 0.01) were associated with DWI positivity. WMH was not associated with DWI positivity in adjusted analysis (Table). The final, exploratory model of independent factors yielded nearly identical results, also showing alteplase treatment to be inversely associated with DWI-positivity.
Conclusions
Among patients presenting with mild, nondisabling ACI, the presence of WMH is not associated with DWI-positivity. A hypothesis emerges that alteplase treatment may reduce DWI positivity in mild, nondisabling ACI.
Trial registration number
NCT02072226
Rehabilitation – Excluding Clinical Trial Results
ESOC19-2401
AN INTERNATIONAL AND INTER-PROFESSIONAL SURVEY ON THE SCREENING AND DIAGNOSIS OF POST-STROKE UNILATERAL SPATIAL NEGLECT
1The University of Manchester – Manchester Academic Health Science Centre, Division of Neuroscience & Experimental Psychology, Manchester, United Kingdom
2The Kessler Foundation, Center for Stroke Rehabilitation Research, West Orange NJ, USA
3The University of Texas, Division of Rehabilitation Sciences, Galveston TX, USA
4Umeå University, Department of Pharmacology and Clinical Neuroscience, Umeå, Sweden
5The University of Manchester – Manchester Academic Health Science Centre, Division of Population Health- Health Services Research & Primary Care, Manchester, United Kingdom
6Ospedale Santa Maria alla Gruccia, Clinica di Riabilitazione della Toscane, Montevarchi, Italy
7Dalhousie University, Department of Psychiatry, Halifax, Canada
8The University of Geneva, Department of Fundamental Neurosciences, Geneva, Switzerland
Background and Aims
Unilateral spatial neglect (inattention of contralesional space) is a disabling syndrome that often follows stroke. Identifying neglect is an important step for clinicians before formulating a clinical care plan. There is no universally-agreed standard for diagnosis and no universally-agreed operational definition of neglect for guidance. As a first step to achieving consensus we began with an international survey of stroke clinicians’ current use of neglect assessments.
Methods
Using an online survey, we targeted international clinicians with current experience in screening/diagnosing neglect. We distributed the survey via professional bodies and networks representing various specialities. We asked respondents to indicate their use of neglect assessments categorised as cognitive, functional, and neurological, whether these choices were guided by professional choice or institutional policy, and also invited further suggestions and comments.
Results
The survey attracted 454 responses from 12 professional groups across 25 countries, predominantly occupational therapy (179), psychology (84), medicine (70) and physiotherapy (55) with most respondents from the UK (172), USA (99) and Italy (76). Respondents had a median 120 months experience, typically worked exclusively in in-patient settings (50%) and saw more than one patient with neglect every two months (67%). Data cleaning is complete: quality is good with very little missing data. We are finalising analyses to examine the most frequently used assessments and explore potential differences in clinical practice e.g. between professions and countries.
Conclusions
Results from this inter-professional, international survey will form a useful starting point for consensus discussions regarding screening and diagnosing neglect.
Trial registration number
n/a
Small Vessel Disease
ESOC19-2409
REPRESENTATION OF BLOOD FLOW IN PERFORATING BASAL GANGLIA ARTERIES OF PATIENTS WITH CEREBRAL SMALL VESSEL DISEASE (CSVD) AT 7 TESLA MRI.
1Otto-von-Guericke University, Department of Neurology, Magdeburg, Germany
2Helmholtz Association, German Center for Neurodegenerative Diseases DZNE, Magdeburg, Germany
Background and Aims
Interest in the small vessels’ pathology is growing because of its contribution to cognitive impairment (Pantoni et al., 2009) and its possible interaction with AD-related pathology (Boyle et al., 2018). CSVD affects small vessels, including the perforating arteries of the basal ganglia. Because of their small dimension, in vivo analysis of blood flow in these arteries is challenging.
Methods
We applied an innovative 2D-Flow sequence at 7 Tesla MRI (Bouvy et al., 2016) in order to assess the blood flow velocity and pulsatility index (PI) of these arteries in 20 CSVD patients (mean [SD] age 71 [9] years, 65% male) and 28 healthy elderly controls (70 [9] years, 62% male). Vascular risk factors were also available in this cohort. Furthermore, we obtained MRI measures of 8 participants approximately a year from baseline. Using a MATLAB-based tool, we calculated the individual and average blood flow velocity curve and the PI value.
Results
A positive correlation between age and PI (r = 0.57, p < 0.001) was demonstrated, irrespective of presence of CSVD.
Conclusions
Our results suggest that age might be a main factor influencing small vessels’ stiffness, as it has already been shown in larger vessels (Zarrinkoob et al., 2016). We possibly failed to observe differences between groups because not all CSVD subjects in our cohort were severely affected by the disease, when compared to previous studies (Geurts et al., 2018).
Trial registration number
no number