Mechanical thrombectomy: can it be safely delivered out of hours in the UK?

BACKGROUND: Mechanical thrombectomy was approved by NICE as a treatment for stroke in 2016. However, most of the evidence is from studies conducted during working hours. Only few centres in the UK perform thrombectomies out-of-hours. The Royal Stoke University Hospital (RSUH) has offered thrombectomies over 24 h (24/7) since 2010. The aim of this service review is to compare the outcomes for patients treated in regular working hours to those treated outside normal working hours within this unit. METHODS: This retrospective service analysis includes all patients treated with mechanical thrombectomy at RSUH since the start of the service in January 2010 to June 2019. Data on key demographics, timings, procedural complications, and long-term outcomes including death and disability at 90 days were collected. In-hours was defined as the time between 8:00-17:00 h, Monday to Friday; out-of-hours was defined as any time outside this period. RESULTS: In total, 516 mechanical thrombectomies were performed in this time period; data were available on 501 of these. Successful recanalization (TICI 2b/3) was achieved in 86% of patients. By 90 days 96 (19%) had died and 234 (47%) were functionally independent (modified Rankin Scale score ≤ 2). 211 (42%) of the procedures were performed in-hours and 290 (58%) out-of-hours. Door-to-CT and door-to-groin times were significantly longer out-of-hours than in-hours, but thrombectomy duration was significantly shorter. There were no significant differences in complications and short- and long-term outcomes. CONCLUSION: Mechanical thrombectomy was delivered safely and effectively 24/7 in this UK hospital, with no difference in clinical outcomes

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Interpretation: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy.Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388.Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16,

Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme

Case costing of mechanical thrombectomy for acute ischaemic stroke in routine clinical setting::cost differences between mothership vs drip and ship

Introduction: Reducing stroke related mortality and morbidity is a Government priority. In 2007, the National Stroke Strategy recommended reviewing stroke survivors at 6 week, 6 months and annually thereafter but there has been limited evaluation. This study focused on the 6-month review when statutory services have withdrawn and patients report feeling abandoned. Methods: A multiple case study approach used interviews, observations and policy analysis. Overall, 46 patients, 30 carers and 27 professionals were interviewed. 29 reviews were observed. Data was analysed within and across sites to develop a theoretical understanding of the review that could be extended to a broader context. Results: The review identified unmet needs and acted as a gateway to further services. 6-month reviews carried out by stroke nurse specialists were underpinned by a biomedical approach whereas those carried out by the Stroke Association focused on social issues. Patients valued both models but their views were influenced by their experiences of the care pathway, orientation to rehabilitation and the nature of their relationships with clinicians during rehabilitation. Self-management was incorporated into the review but was limited by its one-off nature and gaps in community services. Conclusion: The 6-month review needs to be embedded into the care pathway and strategies for secondary prevention reviewed and consolidated at each stage. Reviewers should be allowed the freedom to individualise the process on a needs-led basis. The 6-month review ought to relate back to therapy goals and forward to community services to encourage participation in valued activities and community integration

The cost of providing mechanical thrombectomy in the UK NHS: a micro-costing study

Introduction The clinical efficacy and cost-effectiveness of mechanical thrombectomy (MT) for the treatment of large vessel occlusion stroke is well established, but uncertainty remains around the true cost of delivering this treatment within the NHS. The aim of this study was to establish the cost of providing MT within the hyperacute phase of care and to explore differences in resources used and costs across different neuroscience centres in the UK. Method This was a multicentre retrospective study using micro-costing methods to enable a precise assessment of the costs of MT from an NHS perspective. Data on resources used and their costs were collected from five UK neuroscience centres between 2015 and 2018. Results Data were collected on 310 patients with acute ischaemic stroke treated with MT. The mean total cost of providing MT and inpatient care within 24 hours was £10,846 (95% confidence interval (CI) 10,527–11,165) per patient. The main driver of cost was MT procedure costs, accounting for 73% (£7,943; 95% CI 7,649–8,237) of the total 24-hour cost. Costs were higher for patients treated under general anaesthesia (£11,048; standard deviation (SD) 2,654) than for local anaesthesia (£9,978; SD 2,654), mean difference £1,070 (95% CI 381–1,759; p=0.003); admission to an intensive care unit (ICU; £12,212; SD 3,028) against for admission elsewhere (£10,179; SD 2,415), mean difference £2,032 (95% CI 1,345–2,719; p The mean cost within 72 hours was £12,440 (95% CI 10,628–14,252). The total costs for the duration of inpatient care before discharge from a thrombectomy centre was £14,362 (95% CI 13,603–15,122). Conclusions Major factors contributing to costs of MT for stroke include consumables and staff for intervention, use of general anaesthesia and ICU admissions. These findings can inform the reimbursement, provision and strategic planning of stroke services and aid future economic evaluations.</p

Feasibility of reporting results of large randomised controlled trials to participants:experience from the Fluoxetine or Control under supervision (FOCUS) trial

Objectives Informing research participants of the results of studies in which they took part is viewed as an ethical imperative. However, there is little guidance in the literature about how to do this. The Fluoxetine Or Control Under Supervision trial randomised 3127 patients with a recent acute stroke to 6 months of fluoxetine or placebo and was published in the Lancet on 5 December 2018. The trial team decided to inform the participants of the results at exactly the same time as the Lancet publication, and also whether they had been allocated fluoxetine or placebo. In this report, we describe how we informed participants of the results.Design In the 6-month and 12-month follow-up questionnaires, we invited participants to provide an email address if they wished to be informed of the results of the trial. We re-opened our trial telephone helpline between 5 December 2018 and 31 March 2019.Setting UK stroke services.Participants 3127 participants were randomised. 2847 returned 6-month follow-up forms and 2703 returned 12-month follow-up forms; the remaining participants had died (380), withdrawn consent or did not respond.Results Of those returning follow-up questionnaires, a total of 1845 email addresses were provided and a further 50 people requested results to be sent by post. Results were sent to all email and postal addresses provided; 309 emails were returned unrecognised. Seventeen people replied, of whom three called the helpline and the rest responded by email.Conclusion It is feasible to disseminate results of large trials to research participants, though only around 60% of those randomised wanted to receive the results. The system we developed was efficient and required very little resource, and could be replicated by trialists in the future.Trial registration number ISRCTN83290762; Post-results