Efficacy of nitric oxide, with or without continuing antihypertensive treatment, for management of high blood pressure in acute stroke (ENOS): a partial-factorial randomised controlled trial.

Summary Thrombolysis with alteplase administered within a narrow therapeutic window provides an effective therapy for acute ischaemic stroke. However, mainly because of prehospital delay, patients often arrive too late for treatment, and no more than 1–8% of patients with stroke obtain this treatment. We recommend that all links in the prehospital stroke rescue chain must be optimised so that in the future more than a small minority of patients can profit from time-sensitive acute stroke therapy. Measures for improvement include continuous public awareness campaigns, education of emergency medical service personnel, the use of standardised, validated scales for recognition of stroke symptoms and for triaging to the appropriate institution, and advance notification to the receiving hospital. In the future, use of telemedicine technologies for interaction between the emergency site and hospital, and the strategy of treatment directly at the emergency site (mobile stroke unit concept), could contribute to more efficient use of resources and reduce the time taken to instigate treatment to within 60 min—the golden hour—of the onset of the symptoms of stroke.

Streamlining of prehospital stroke management: the golden hour.

The close relationship between stroke and dementia is an important health issue. Ischaemic stroke can facilitate the onset of vascular dementia as well as aggravate pre-existing cognitive decline. The onset of cognitive decline may become manifest immediately following the onset of ischaemic stroke, but often there is a delay in the development of cognitive decline after a stroke. This delay can be seen as a therapeutic time window allowing interventions to be applied to preserve cognition following stroke. Both neurodegenerative and vascular mechanisms are activated and probably result in overlapping processes within the neurovascular unit. This review focuses on the incidence and prevalence of cognitive decline following stroke, predisposing stroke aetiologies, pre-stroke decline, imaging factors and biomarkers. Outcomes are discussed in relation to timing of assessment and neuropsychological tests used for evaluation of cognitive decline in ischaemic stroke patients. Including such tests in routine evaluations of stroke patients after some weeks or months is recommended. Finally, an outlook on ongoing and planned intervention trials is added and some recommendations for future research are proposed.

Post-stroke Cognitive Decline: An Update and Perspectives for Clinical Research

Background and Purpose—The practicalities of doing ambulance-based trials where paramedics perform all aspects of a clinical trial involving patients with ultra-acute stroke have not been assessed. Methods—We performed a randomized controlled trial with screening, consent, randomization, and treatment performed by paramedics prior to hospitalization. Patients with probable ultra-acute stroke ( 140 mm Hg were randomized to transdermal glyceryl trinitrate (GTN; 5 mg/24 hours) or none (blinding under gauze dressing) for 7 days with the first dose given by paramedics. The primary outcome was SBP at 2 hours. Results—Of a planned 80 patients, 41 (25 GTN, 16 no GTN) were enrolled >22 months with median age [interquartile range] 79 [16] years; men 22 (54%); SBP 168 [46]; final diagnosis: stroke 33 (80%) and transient ischemic attack 3 (7%). Time to randomization was 55 [75] minutes. After treatment with GTN versus no GTN, SBP at 2 hours was 153 [31] versus 174 [27] mm Hg, respectively, with difference −18 [30] mm Hg (P=0.030). GTN improved functional outcome with a shift in the modified Rankin Scale by 1 [3] point (P=0.040). The rates of death, 4 (16%) versus 6 (38%; P=0.15), and serious adverse events, 14 (56%) versus 10 (63%; P=0.75), did not differ between GTN and no GTN. Conclusions—Paramedics can successfully enroll patients with ultra-acute stroke into an ambulance-based trial. GTN reduces SBP at 2 hours and seems to be safe in ultra-acute stroke. A larger trial is needed to assess whether GTN improves functional outcome. Clinical Trial Registration—URL: http://www.controlled-trials.com/ISRCTN66434824/66434824. Unique identifier: 66434824. (Stroke. 2013;44:3120-3128.)

Feasibility of an Ambulance-Based Stroke Trial, and Safety of Glyceryl Trinitrate in Ultra-Acute Stroke: The Rapid Intervention With Glyceryl Trinitrate in Hypertensive Stroke Trial (RIGHT, ISRCTN66434824)

BackgroundCurrent guidelines suggest treating blood pressure above 180/105 mm Hg during the first 24 hours in patients with acute ischemic stroke undergoing any form of recanalization therapy Curr

Systolic blood pressure within 24 hours after thrombectomy for acute Ischemic stroke correlates with outcome

Background. Time from acute stroke to enrolment in clinical trials needs to be reduced to improve the chances of finding effective treatments. No completed randomised controlled trials of ambulance-based treatment for acute stroke have been reported in the UK, and the practicalities of recruiting, consenting, and treating patients are unknown. Methods. RIGHT is an ambulance based, single-blind, randomised controlled trial with blinded-outcome assessment. The trial will assess feasibility of using ambulance services to deliver ultra-acute stroke treatments; a secondary aim is to assess the effect of glyceryl trinitrate (GTN) on haemodynamic variables and functional outcomes. Initial consent, randomisation, and treatment are performed by paramedics prior to hospitalisation. Patients with ultra-acute stroke (≤4 hours of onset) are randomised to transdermal GTN (5 mg/24 hours) or gauze dressing daily for 7 days. The primary outcome is systolic blood pressure at 2 hours. Secondary outcomes include feasibility, haemodynamics, dependency, and other functional outcomes. A nested qualitative study is included. Trial Status. The trial has all relevant ethics and regulatory approvals and recruitment started on February 15, 2010. The trial stopped recruitment in December 2011 after 41 patients were recruited. Trial Registration. The trial registration number is ISRCTN66434824 and EudraCT number is 2007-004766-40.

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Determining the feasibility of ambulance-based randomised controlled trials in patients with ultra-acute stroke:study protocol for the “Rapid Intervention with GTN in Hypertensive Stroke Trial” (RIGHT, ISRCTN66434824)

Background: The safety of nitric oxide donors in patients with ultraacute stroke has yet to be reported. Methods: RIGHT was an ambulance-based, single-centre, single-blind, randomised controlled trial with blinded outcome assessment. The trial determined the feasibility of using the ambulance services to deliver ultra-acute (<4 hours) treatment with transdermal glyceryl trinitrate (GTN) or control. Initial consent, randomisation and treatment was delivered by paramedics prior to hospitalisation. Numbers are median (IQR) or frequency (%). Results: 41 patients were randomised over 22 months: age 79 (17) years; male 51%; hypertension 66%; baseline FAST 3 (1); systolic BP 168 (46) mmHg; time from stroke to enrolment 55 minutes; final diagnosis ischaemic 56%, haemorrhage 20%, TIA 10% and non stroke 12%. GTN lowered systolic BP at 15 minutes, 153 (30) vs 180 (47) mmHg (p=0.046), and 120 minutes (primary outcome), 153 (31) vs 174 (27) mmHg (p=0.027). Rates of hypotension, deterioration and death at 7 days did not differ between GTN and no GTN. 75 paramedics (11 ambulance stations) were trained, and 5 paramedics recruited 3 or more patients. Conclusion: The trial confirmed that paramedics can deliver a trial in patients with ultra-acute presumed stroke. Only a minority of patients had non-stroke. GTN lowered blood pressure at 15 and 120 minutes, and appears safe to administer. A large multicentre trial is now in design to test the effect of lowering blood pressure ultra-acutely after stroke.

348 rapid intervention with glyceryl trinitrate (gtn) in hypertensive stroke trial (right): determining the safety of gtn and potential of ambulance-based randomised controlled trials in patients with ultra-acute stroke

Michael Fuller

Papers

Feasibility of an Ambulance-Based Stroke Trial, and Safety of Glyceryl Trinitrate in Ultra-Acute Stroke: The Rapid Intervention With Glyceryl Trinitrate in Hypertensive Stroke Trial (RIGHT, ISRCTN66434824)

Determining the feasibility of ambulance-based randomised controlled trials in patients with ultra-acute stroke:study protocol for the “Rapid Intervention with GTN in Hypertensive Stroke Trial” (RIGHT, ISRCTN66434824)

348 rapid intervention with glyceryl trinitrate (gtn) in hypertensive stroke trial (right): determining the safety of gtn and potential of ambulance-based randomised controlled trials in patients with ultra-acute stroke