Mortality in a Multiethnic Population Attending a One-Stop TIA Clinic.

INTRODUCTION: Studies indicate a 13-27% mortality rate following a transient ischaemic attack (TIA). However, outcomes following TIA/minor stroke since the introduction of rapid-access TIA clinics and prompt vascular risk factor intervention are not known. Specifically, there is paucity of data comparing outcomes between people who are diagnosed with an "acute cerebrovascular" (CV) event or an alternative non-cardiovascular diagnosis (non-CV) in a rapid-access TIA clinic. We aimed to assess the mortality in such a setting. METHODS: A retrospective observational study was undertaken at the Leicester rapid-access secondary care TIA clinic. Data included information collected at the first clinic visit (including comorbidities, and primary diagnosis, categorized as CV and non-CV) and the date of death for people dying during follow-up. RESULTS: 11,524 subjects were included with 33,164 years of follow-up data; 4,746 (41.2%) received a CV diagnosis. The median follow-up time was 2.75 years (interquartile range 1.36-4.32). The crude mortality rate was 37.3 (95% CI: 35.3-39.5) per 1,000 person-years (PTPY). The mortality rate was higher following a CV diagnosis (50.8 [47.2-54.7] PTPY) compared to a non-CV diagnosis (27.9 [25.7-30.4] PTPY), and for males, older people, those of white ethnicity, and people with orthostatic hypotension (OH). DISCUSSION: This study identified possible risk factors associated with a higher mortality in TIA clinic attendees, who may benefit from specific intervention. Future research should explore the underlying causes and the effect of specific targeted management strategies.

Pathophysiological and clinical considerations in the perioperative care of patients with a previous ischaemic stroke: a multidisciplinary narrative review.

With an ageing population and increasing incidence of cerebrovascular disease, an increasing number of patients presenting for routine and emergency surgery have a prior history of stroke. This presents a challenge for pre-, intra-, and postoperative management as the neurological risk is considerably higher. Evidence is lacking around anaesthetic practice for patients with vascular neurological vulnerability. Through understanding the pathophysiological changes that occur after stroke, insight into the susceptibilities of the cerebral vasculature to intrinsic and extrinsic factors can be developed. Increasing understanding of post-stroke systemic and cerebral haemodynamics has provided improved outcomes from stroke and more robust secondary prevention, although this knowledge has yet to be applied to our delivery of anaesthesia in those with prior stroke. This review describes the key pathophysiological and clinical considerations that inform clinicians providing perioperative care for patients with a prior diagnosis of stroke.

Interventions for improving modifiable risk factor control in the secondary prevention of stroke.

BACKGROUND: People with stroke or transient ischaemic attack (TIA) are at increased risk of future stroke and other cardiovascular events. Stroke services need to be configured to maximise the adoption of evidence-based strategies for secondary stroke prevention. Smoking-related interventions were examined in a separate review so were not considered in this review. This is an update of our 2014 review. OBJECTIVES: To assess the effects of stroke service interventions for implementing secondary stroke prevention strategies on modifiable risk factor control, including patient adherence to prescribed medications, and the occurrence of secondary cardiovascular events. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (April 2017), the Cochrane Effective Practice and Organisation of Care Group Trials Register (April 2017), CENTRAL (the Cochrane Library 2017, issue 3), MEDLINE (1950 to April 2017), Embase (1981 to April 2017) and 10 additional databases including clinical trials registers. We located further studies by searching reference lists of articles and contacting authors of included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that evaluated the effects of organisational or educational and behavioural interventions (compared with usual care) on modifiable risk factor control for secondary stroke prevention. DATA COLLECTION AND ANALYSIS: Four review authors selected studies for inclusion and independently extracted data. The quality of the evidence as 'high', 'moderate', 'low' or 'very low' according to the GRADE approach (GRADEpro GDT).Three review authors assessed the risk of bias for the included studies. We sought missing data from trialists.The results are presented in 'Summary of findings' tables. MAIN RESULTS: The updated review included 16 new studies involving 25,819 participants, resulting in a total of 42 studies including 33,840 participants. We used the Cochrane risk of bias tool and assessed three studies at high risk of bias; the remainder were considered to have a low risk of bias. We included 26 studies that predominantly evaluated organisational interventions and 16 that evaluated educational and behavioural interventions for participants. We pooled results where appropriate, although some clinical and methodological heterogeneity was present.Educational and behavioural interventions showed no clear differences on any of the review outcomes, which include mean systolic and diastolic blood pressure, mean body mass index, achievement of HbA1c target, lipid profile, mean HbA1c level, medication adherence, or recurrent cardiovascular events. There was moderate-quality evidence that organisational interventions resulted in improved blood pressure control, in particular an improvement in achieving target blood pressure (odds ratio (OR) 1.44, 95% confidence interval (CI) 1.09 to1.90; 13 studies; 23,631 participants). However, there were no significant changes in mean systolic blood pressure (mean difference (MD), -1.58 mmHg 95% CI -4.66 to 1.51; 16 studies; 17,490 participants) and mean diastolic blood pressure (MD -0.91 mmHg 95% CI -2.75 to 0.93; 14 studies; 17,178 participants). There were no significant changes in the remaining review outcomes. AUTHORS' CONCLUSIONS: We found that organisational interventions may be associated with an improvement in achieving blood pressure target but we did not find any clear evidence that these interventions improve other modifiable risk factors (lipid profile, HbA1c, medication adherence) or reduce the incidence of recurrent cardiovascular events. Interventions, including patient education alone, did not lead to improvements in modifiable risk factor control or the prevention of recurrent cardiovascular events.

Managing uncertainty: a qualitative study of GPs' views on the diagnosis and immediate management of transient ischaemic attack and the potential of a diagnostic tool.

Background: Most patients with transient ischaemic attack (TIA) present to their GP. Early identification and treatment reduces the risk of subsequent stroke and consequent disability and mortality. Objective: To explore GPs' views on the diagnosis and immediate management of suspected TIA, and the potential utility of a diagnostic tool. Methods: This is a qualitative interview study based in Leicestershire, UK. A purposive sample of 10 GPs participated in 30-minute semi-structured telephone interviews. Data were analysed thematically. Results: GPs reported that TIA was more likely to be suspected when patients were more obvious candidates for TIA based on their history, characteristics and symptom presentation. Referrals were in part a strategy to manage risk under conditions of uncertainty and to seek reassurance. GPs valued using a TIA risk stratification tool but felt this did not inform their diagnostic decision making. A diagnostic tool for TIA in primary care was seen to have potential to improve the decision-making process about diagnosis and management and enhance confidence of GPs, particularly in ruling out TIAs. GPs saw benefits of using hard thresholds, but remained concerned about missing TIAs and saw a tool as an adjunct to clinical judgement. Conclusions: GPs weigh up the likelihood of TIA in the context of assessments of candidacy and diverse, often vague, symptoms. A diagnostic tool could support GPs in this process and help reduce reliance on referrals to TIA clinics for reassurance, provided the tool was designed to support decision making in cases of less 'typical' presentations.

Short-term blood pressure variability in acute stroke: post hoc analysis of the controlling hypertension and hypotension immediately post stroke and continue or stop post-stroke antihypertensives collaborative study trials.

BACKGROUND AND PURPOSE: Short-term blood pressure variability (BPV) may predict outcome in acute stroke. We undertook a post hoc analysis of data from 2 randomized controlled trials to determine the effect of short-term BPV on 2-week outcome. METHODS: Controlling Hypertension and Hypotension Immediately Post Stroke (CHHIPS) was a trial of BP-lowering, enrolling 179 acute stroke patients (onset<36 hours). Continue or Stop Post-Stroke Antihypertensives Collaborative Study (COSSACS) compared a strategy of continuation versus temporarily stopping prestroke antihypertensive therapy in 763 acute stroke patients (onset<48 hours). BPV at baseline (defined as SD, coefficient of variation, variation independent of the mean, and average real variability) was derived from standardized casual cuff BP measures (6 readings<30 minutes). Adjusted logistic regression models were used to assess the relation between BPV and death and disability (modified Rankin scale>3) at 2 weeks. RESULTS: Seven hundred six (92.5%) and 171 (95.5%) participants were included in the analysis for the COSSACS and CHHIPS data sets, respectively. Adjusted logistic regression analyses revealed no statistically significant associations between any of the included BPV parameters with 2-week death or disability in either study data set: COSSACS, odds ratio SD systolic BP 0.98 (0.78-1.23); CHHIPS, odds ratio SD systolic BP 0.97 (0.90-1.11). CONCLUSIONS: When derived from casual cuff BP measures, short-term BPV is not a useful predictor of early (2 weeks) outcome after acute stroke. Differing methodology may account for the discordance with previous studies indicating long-term (casual BPV) and short-term (beat-to-beat BPV) prognostic value. CLINICAL TRIAL REGISTRATION: COSSACS was registered on the International Standard Randomised Controlled Trial Register; URL: http://www.isrctn.com. Unique identifier: ISRCTN89712435. CHHIPS was registered on the National Research Register; URL: http://public.ukcrn.org.uk. Unique identifier: N0484128008.

Interventions for improving modifiable risk factor control in the secondary prevention of stroke.

BACKGROUND: People with stroke or transient ischaemic attack (TIA) are at increased risk of future stroke and other cardiovascular events. Evidence-based strategies for secondary stroke prevention have been established. However, the implementation of prevention strategies could be improved. OBJECTIVES: To assess the effects of stroke service interventions for implementing secondary stroke prevention strategies on modifiable risk factor control, including patient adherence to prescribed medications, and the occurrence of secondary cardiovascular events. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (April 2013), the Cochrane Effective Practice and Organisation of Care Group Trials Register (April 2013), CENTRAL (The Cochrane Library 2013, issue 3), MEDLINE (1950 to April 2013), EMBASE (1981 to April 2013) and 10 additional databases. We located further studies by searching reference lists of articles and contacting authors of included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that evaluated the effects of organisational or educational and behavioural interventions (compared with usual care) on modifiable risk factor control for secondary stroke prevention. DATA COLLECTION AND ANALYSIS: Two review authors selected studies for inclusion and independently extracted data. One review author assessed the risk of bias for the included studies. We sought missing data from trialists. MAIN RESULTS: This review included 26 studies involving 8021 participants. Overall the studies were of reasonable quality, but one study was considered at high risk of bias. Fifteen studies evaluated predominantly organisational interventions and 11 studies evaluated educational and behavioural interventions for patients. Results were pooled where appropriate, although some clinical and methodological heterogeneity was present. The estimated effects of organisational interventions were compatible with improvements and no differences in the modifiable risk factors mean systolic blood pressure (mean difference (MD) -2.57 mmHg; 95% confidence interval (CI) -5.46 to 0.31), mean diastolic blood pressure (MD -0.90 mmHg; 95% CI -2.49 to 0.68), blood pressure target achievement (OR 1.24; 95% CI 0.94 to 1.64) and mean body mass index (MD -0.68 kg/m(2); 95% CI -1.46 to 0.11). There were no significant effects of organisational interventions on lipid profile, HbA1c, medication adherence or recurrent cardiovascular events. Educational and behavioural interventions were not generally associated with clear differences in any of the review outcomes, with only two exceptions. AUTHORS' CONCLUSIONS: Pooled results indicated that educational interventions were not associated with clear differences in any of the review outcomes. The estimated effects of organisational interventions were compatible with improvements and no differences in several modifiable risk factors. We identified a large number of ongoing studies, suggesting that research in this area is increasing. The use of standardised outcome measures would facilitate the synthesis of future research findings.

Predictors and Outcomes of Neurological Deterioration in Intracerebral Hemorrhage: Results from the TICH-2 Randomized Controlled Trial.

Neurological deterioration is common after intracerebral hemorrhage (ICH). We aimed to identify the predictors and effects of neurological deterioration and whether tranexamic acid reduced the risk of neurological deterioration. Data from the Tranexamic acid in IntraCerebral Hemorrhage-2 (TICH-2) randomized controlled trial were analyzed. Neurological deterioration was defined as an increase in National Institutes of Health Stroke Scale (NIHSS) of ≥ 4 or a decline in Glasgow Coma Scale of ≥ 2. Neurological deterioration was considered to be early if it started ≤ 48 h and late if commenced between 48 h and 7 days after onset. Logistic regression was used to identify predictors and effects of neurological deterioration and the effect of tranexamic acid on neurological deterioration. Of 2325 patients, 735 (31.7%) had neurological deterioration: 590 (80.3%) occurred early and 145 (19.7%) late. Predictors of early neurological deterioration included recruitment from the UK, previous ICH, higher admission systolic blood pressure, higher NIHSS, shorter onset-to-CT time, larger baseline hematoma, intraventricular hemorrhage, subarachnoid extension and antiplatelet therapy. Older age, male sex, higher NIHSS, previous ICH and larger baseline hematoma predicted late neurological deterioration. Neurological deterioration was independently associated with a modified Rankin Scale of > 3 (aOR 4.98, 3.70-6.70; p < 0.001). Tranexamic acid reduced the risk of early (aOR 0.79, 0.63-0.99; p = 0.041) but not late neurological deterioration (aOR 0.76, 0.52-1.11; p = 0.15). Larger hematoma size, intraventricular and subarachnoid extension increased the risk of neurological deterioration. Neurological deterioration increased the risk of death and dependency at day 90. Tranexamic acid reduced the risk of early neurological deterioration and warrants further investigation in ICH. URL: https://www.isrctn.com Unique identifier: ISRCTN93732214.

Acute ischemic stroke diagnosis using brain tissue pulsations.

Healthy brain tissue pulsates with the cardiac cycle, but whether brain tissue pulsations (BTPs) are impaired by tissue ischemia due to ischemic stroke is currently unclear. This study is the first to explore the clinical potential of measuring BTPs using ultrasound in acute ischemic stroke patients. BTPs were measured in 24 healthy volunteers (aged 52-82 years) and 14 acute ischemic stroke patients (aged 51-86 years) using a novel Transcranial Tissue Doppler (TCTD) method. Measurements were quick to perform and were well tolerated by all subjects. A mixed-methods approach was used for blinded analysis of recordings. This identified qualitative disruption of BTPs in acute stroke patients, which were used to create an analysis checklist. Blinded BTP analysis by novices using the checklist resulted in high sensitivity but low specificity for stroke detection. Quantitative analysis also identified differences between stroke and healthy participants, including weaker BTPs in stroke patients. This first study reporting BTP characteristics in acute ischemic stroke revealed weaker brain tissue pulsations and waveform disruption in acute stroke patients. However, further clinical evaluation using a larger sample size is required to confirm these findings and to explore whether TCTD monitoring might be beneficial for clinical neuromonitoring.

What is the optimal blood pressure level for patients with atrial fibrillation treated with direct oral anticoagulants?

OBJECTIVE: Limited data exist to inform blood pressure (BP) thresholds for patients with atrial fibrillation prescribed direct oral anticoagulants (DOAC) therapy in the real world setting. METHODS: SBP was measured in 9051 primary care patients in England on DOACs for atrial fibrillation with postinitiation BP levels available within the Clinical Practice Research Datalink. The incidence rate for the primary outcome of the first recorded event (defined as a diagnosis of first stroke, recurrent stroke, myocardial infarction, symptomatic intracranial bleed, or significant gastrointestinal bleed) and of secondary outcomes all-cause mortality and cardiovascular mortality were calculated by postinitiation BP groups. RESULTS: The Cox proportional hazard ratio of an event [crude and adjusted hazard ratio 1.04 (95% confidence interval (CI) 1.00-1.08), P = 0.077 and 0.071, respectively] did not differ significantly with a 10 mmHg increase in SBP. The hazard of all-cause mortality [crude hazard ratio 0.83 (95% CI 0.80-0.86), P = 0.000; adjusted hazard ratio 0.84 (95% CI 0.81-0.87), P = 0.000] and cardiovascular mortality [crude hazard ratio 0.92 (95% CI 0.85-0.99), P = 0.021; adjusted hazard ratio 0.93 (95% CI 0.86-1.00), P = 0.041] demonstrated a significant inverse relationship with a 10 mmHg increase in SBP. Patients with a SBP within 161-210 mmHg had the lowest all-cause death rate, while patients with SBP within 121-140 mmHg had the lowest cardiovascular death rate. CONCLUSION: SBP values below 161 mmHg are associated higher all-cause mortality, but lower event risk in patients with atrial fibrillation on DOAC therapy. The nadir SBP for lowest event rate was 120 mmHg, for lowest cardiovascular mortality was 130 mmHg and for lowest all-cause mortality was 160 mmHg. This demonstrates a need for a prospective interventional study of BP control after initiation of anticoagulation.

Clinical Relevance of Orthostatic Hypotension in Patients with Atrial Fibrillation and Suspected Transient Ischemic Attack.

INTRODUCTION: Orthostatic hypotension (OH) and atrial fibrillation (AF) are both regarded as independent risk factors for transient ischemic attack (TIA). However, the clinical implication of OH in the presence of AF is unclear. This study investigates, for the first time, the association between blood pressure (BP), OH and mortality in a cohort of patients with AF and TIA symptoms. AIM: To investigate the incidence of the association between OH, AF and TIA. METHODS: This retrospective observational study utilised the Leicester one-stop transient TIA clinic patient database to consider the initial systolic and diastolic BP of 688 patients with a diagnosis of AF. The primary outcome was time until death. Covariant measures included status of AF diagnosis (known or new AF), cardiovascular risk factors, and primary clinic diagnosis [cerebrovascular (CV) versus non-cerebrovascular (non-CV)]. Statistical models adjusted for sex, age, previous AF diagnosis. RESULTS: Mortality rate was higher in the over 85 age group [191.5 deaths per 1000 person years (py) (95% CI 154.0-238.1)] and lower in the aged 75 and younger age group [40.0 deaths per 1000 py (95% CI 27.0-59.2)] compared to intermediate groups. A 10 mmHg increase in supine diastolic BP was associated with a significant reduction in the hazard of mortality for patients suspected of TIA with AF [adjusted HR 0.79 (95% CI 0.68-0.92), p < 0.001]. The mortality rate for patients with OH was 119.0 deaths per 1000 py compared with a rate of 98.0 for patients without OH (rate ratio 1.2, p = 0.275). CONCLUSION: Higher diastolic BP may be a marker for reduced mortality risk in patients with a previous AF diagnosis and non-CV diagnosis. Lower diastolic BP and the presence of AF pertain to a higher mortality risk. This study raises the importance of opportunistic screening for both OH and AF in patients presenting to TIA clinic.

Incidence and predictors of early seizures in intracerebral haemorrhage and the effect of tranexamic acid.

INTRODUCTION: Seizures are common after intracerebral haemorrhage. Tranexamic acid increases the risk of seizures in non-intracerebral haemorrhage population but its effect on post-intracerebral haemorrhage seizures is unknown. We explored the risk factors and outcomes of seizures after intracerebral haemorrhage and if tranexamic acid increased the risk of seizures in the Tranexamic acid for IntraCerebral Haemorrhage-2 trial. PATIENTS AND METHODS: Seizures were reported prospectively up to day 90. Cox regression analyses were used to determine the predictors of seizures within 90 days and early seizures (≤7 days). We explored the effect of early seizures on day 90 outcomes. RESULTS: Of 2325 patients recruited, 193 (8.3%) had seizures including 163 (84.5%) early seizures and 30 (15.5%) late seizures (>7 days). Younger age (adjusted hazard ratio (aHR) 0.98 per year increase, 95% confidence interval (CI) 0.97-0.99; p = 0.008), lobar haematoma (aHR 5.84, 95%CI 3.58-9.52; p < 0.001), higher National Institute of Health Stroke Scale (aHR 1.03, 95%CI 1.01-1.06; p = 0.014) and previous stroke (aHR 1.66, 95%CI 1.11-2.47; p = 0.013) were associated with early seizures. Tranexamic acid did not increase the risk of seizure within 90 days. Early seizures were associated with worse modified Rankin Scale (adjusted odds ratio (aOR) 1.79, 95%CI 1.12-2.86, p = 0.015) and increased risk of death (aOR 3.26, 95%CI 1.98-5.39; p < 0.001) at day 90.Discussion and conclusion: Lobar haematoma was the strongest independent predictor of early seizures after intracerebral haemorrhage. Tranexamic acid did not increase the risk of post-intracerebral haemorrhage seizures in the first 90 days. Early seizures resulted in worse functional outcome and increased risk of death.

Pressor therapy in acute ischemic stroke: systematic review.

BACKGROUND AND PURPOSE: Systolic blood pressure (SBP) levels below 140 mm Hg after acute stroke occur in 18% to 25% of patients, and may be associated with adverse outcome, in terms of death and disability. It has thus been proposed that BP elevation in acute ischemic stroke may be beneficial by increasing perfusion to the peri-infarct penumbra, though not only in those with low BP levels. METHODS: All articles studying BP elevation in the context of acute stroke were identified using a structured search strategy. RESULTS: Two reviewers independently searched the databases, and 12 relevant publications were identified. All identified publications related to acute ischemic stroke and no articles on pressor therapy in primary hemorrhagic stroke were found. The review included 319 subjects (age: 42 to 88 years, 46% male), with phenylephrine being the most commonly used pressor agent, though 8 studies incorporated volume expansion. Because of small numbers, and varying entry/outcome criteria, no meta-analysis of outcome measures was possible. Overall, in these few studies undertaken, pressor therapy in acute stroke appears feasible and well-tolerated. The benefit and risks in terms of clinical outcomes remains unknown, but intensive monitoring is advised if such therapy is undertaken. CONCLUSIONS: Theoretical arguments exist for inducing BP elevation in acute ischemic stroke to increase blood flow to the ischemic penumbra across patients with a broad BP range. To date, there have only been a few small trials with inconclusive results. Many questions are still unanswered about the safety and potential benefits of pressor therapy in acute stroke. Hopefully, ongoing trials will answer some of these important questions.

Is dynamic cerebral autoregulation measurement using transcranial Doppler ultrasound reproducible in the presence of high concentration oxygen and carbon dioxide?

Reliability of cerebral blood flow velocity (CBFV) and dynamic cerebral autoregulation estimates (expressed as autoregulation index: ARI) using spontaneous fluctuations in blood pressure (BP) has been demonstrated. However, reliability during co-administration of O2 and CO2 is unknown. Bilateral CBFV (using transcranial Doppler), BP and RR interval recordings were performed in healthy volunteers (seven males, four females, age: 54 ± 10 years) on two occasions over 9 ± 4 d. Four 5 min recordings were made whilst breathing air (A), then 5%CO2 (C), 80%O2 (O) and mixed O2 + CO2 (M), in random order. CBFV was recorded; ARI was calculated using transfer function analysis. Precision was quantified as within-visit standard error of measurement (SEM) and the coefficient of variation (CV). CBFV and ARI estimates with A (SEM: 3.85 & 0.87; CV: 7.5% & 17.8%, respectively) were comparable to a previous reproducibility study. The SEM and CV with C and O were similar, though higher values were noted with M; Bland-Altman plots indicated no significant bias across all gases for CBFV and ARI (bias <0.06 cm s(-1) and <0.05, respectively). Thus, transcranial-Doppler-ultrasound-estimated CBFV and ARI during inhalation of O2 and CO2 have acceptable levels of reproducibility and can be used to study the effect of these gases on cerebral haemodynamics.

Current status of statin therapy for stroke prevention.

Stroke is a leading cause of mortality and long-term disability in the Western world. Lipid abnormalities are a key risk factor for stroke, elevated LDL-cholesterol being the most common abnormality. No clear association has been demonstrated between elevated LDL-cholesterol and stroke incidence, possibly due to the lack of appropriate etiopathophysiological classification of stroke in most studies. Nonetheless, statin therapy is associated with significant reduction in first and recurrent stroke, and there remains a net benefit despite a significant but small increase in hemorrhagic stroke. Following a stroke, indirect evidence supports continuation of prestroke statin therapy while the impact of de novo statin therapy in acute stroke remains uncertain. International guidelines advise an objective assessment of cardiovascular risk to determine the appropriateness of statins for primary prevention and near universal use of statins for secondary prevention after the acute phase of ischemic stroke. There is lack of consensus with regard to the choice of agent, timing of initiation, dose and duration of therapy. Some guidelines advocate high-dose atorvastatin while others suggest the use of simvastatin owing to generic availability and low cost. While the benefits of preventive interventions for stroke are well established and clearly outlined in international guidelines, there is poor application of such measures in clinical practice. This article summarizes the current understanding of the role of statins in stroke prevention and early studies of potential interventions to overcome the barriers to effective statin therapy for secondary prevention. There is a clear need for further research into identifying deficiencies in long-term management, barriers to optimal secondary prevention and novel interventions to overcome these barriers.

Thrombolysis in acute ischaemic stroke: an update.

Stroke is a major cause of mortality and morbidity, and thrombolysis has served as a catalyst for major changes in the management of acute ischaemic stroke. Intravenous alteplase (recombinant tissue plasminogen activator) is the only approved thrombolytic agent at present indicated for acute ischaemic stoke. While the licensed time window extends to 3h from symptom onset, recent data suggest that the trial window can be extended up to 4.5 h with overall benefit. Nonetheless, 'time is brain' and every effort must be made to reduce the time delay to thrombolysis. Intracranial haemorrhage is the major complication associated with thrombolysis, and key factors increasing risk of haemorrhage include increasing age, high blood pressure, diabetes and stroke severity. Currently, there is no direct evidence to support thrombolysis in patients >80 years of age, with a few case series indicating no overt harm. Identification of viable penumbra based on computed tomography/magnetic resonance imaging may allow future extension of the time window. Adjuvant transcranial Doppler ultrasound has the potential to improve reperfusion rates. While intra-arterial thrombolysis has been in vogue for a few decades, there is no clear advantage over intravenous thrombolysis. The evidence base for thrombolysis in specific situations (e.g. dissection, pregnancy) is inadequate, and individualized decisions are needed, with a clear indication to the patient/carer about the lack of direct evidence, and the risk-benefit balance. Patient-friendly information leaflets may facilitate the process of consent for thrombolysis. This article summarizes the recent advances in thrombolysis for acute ischaemic stroke. Key questions faced by clinicians during the decision-making process are answered based on the evidence available.

Measurement of cerebral blood flow responses to the thigh cuff maneuver: a comparison of TCD with a novel MRI method.

Cerebral autoregulation (CA) describes the mechanism responsible for maintaining cerebral blood flow (CBF) relatively constant, despite changes in mean arterial blood pressure (ABP). This paper introduces a novel method for assessing CA using magnetic resonance imaging (MRI). Images are rapidly and repeatedly acquired using a gradient-echo echo-planar imaging pulse sequence for a period of 4 minutes, during which a transient decrease in ABP is induced by rapid release of bilateral thigh cuffs. The method was validated by comparing the observed MRI signal intensity change with the CBF velocity change in the middle cerebral arteries, as measured by transcranial Doppler (TCD) ultrasound, using a standardized thigh cuff maneuver in both cases. Cross-correlation analysis of the response profiles from the left and right hemispheres showed a greater consistency for MRI measures than for TCD, both for interhemisphere comparisons and for repeated measures. The new MRI method may provide opportunities for assessing regional autoregulatory changes following acute stroke, and in other conditions in which poor autoregulation is implicated.

Current status of blood pressure management after stroke.

Stroke is a leading cause of mortality and long-term disability in the western world, accounting for 5% of the UK health budget. Consequently, it has been the major focus of recent healthcare advances. Physiological disturbances are common following an acute stroke, chiefly blood pressure (BP) abnormalities (high and 'relatively' low BP), which indicate adverse prognosis. While pilot studies suggest that early intervention to moderate both extremes of BP may improve outcomes, definitive evidence is awaited from ongoing research. Long-term elevated BP is the most prevalent risk factor for future stroke, with a comprehensive evidence base supporting BP reduction to reduce the risk of vascular events, including stroke. However, adherence to secondary preventive medications, including antihypertensive agents, remains poor. This article summarizes the current understanding of the role of BP in stroke, focusing on the management of BP for secondary prevention. Further emphasis is placed on identifying deficiencies in long-term management; barriers to improved application and potential interventions to overcome these barriers are summarized.

Effects of antihypertensive treatment after acute stroke in the Continue or Stop Post-Stroke Antihypertensives Collaborative Study (COSSACS): a prospective, randomised, open, blinded-endpoint trial.

BACKGROUND: Up to 50% of patients with acute stroke are taking antihypertensive drugs on hospital admission. However, whether such treatment should be continued during the immediate post-stroke period is unclear. We therefore aimed to assess the efficacy and safety of continuing or stopping pre-existing antihypertensive drugs in patients who had recently had a stroke. METHODS: The Continue or Stop Post-Stroke Antihypertensives Collaborative Study (COSSACS) was a UK multicentre, prospective, randomised, open, blinded-endpoint trial. Patients were recruited at 49 UK National Institute for Health Research Stroke Research Network centres from January 1, 2003, to March 31, 2009. Patients aged over 18 years who were taking antihypertensive drugs were enrolled within 48 h of stroke and the last dose of antihypertensive drug. Patients were randomly assigned (1:1) by secure internet central randomisation to either continue or stop pre-existing antihypertensive drugs for 2 weeks. Patients and clinicians who randomly assigned patients were unmasked to group allocation. Clinicians who assessed 2-week outcomes and 6-month outcomes were masked to group allocation. The primary endpoint was death or dependency at 2 weeks, with dependency defined as a modified Rankin scale score greater than 3 points. Analysis was by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Register, number ISRCTN89712435. FINDINGS: 763 patients were assigned to continue (n=379) or stop (n=384) pre-existing antihypertensive drugs. 72 of 379 patients in the continue group and 82 of 384 patients in the stop group reached the primary endpoint (relative risk 0.86, 95% CI 0.65-1.14; p=0.3). The difference in systolic blood pressure at 2 weeks between the continue group and the stop group was 13 mm Hg (95% CI 10-17) and the difference in diastolic blood pressure was 8 mm Hg (6-10; difference between groups p<0.0001). No substantial differences were observed between groups in rates of serious adverse events, 6-month mortality, or major cardiovascular events. INTERPRETATION: Continuation of antihypertensive drugs did not reduce 2-week death or dependency, cardiovascular event rate, or mortality at 6 months. Lower blood pressure levels in those who continued antihypertensive treatment after acute mild stroke were not associated with an increase in adverse events. These neutral results might be because COSSACS was underpowered owing to early termination of the trial, and support the continuation of ongoing research trials. FUNDING: The Health Foundation and The Stroke Association.