Blood pressure management in acute stroke

Blood pressure (BP) is elevated in 75% or more of patients with acute stroke and is associated with poor outcomes. Whether to modulate BP in acute stroke has long been debated. With the loss of normal cerebral autoregulation, theoretical concerns are twofold: high BP can lead to cerebral oedema, haematoma expansion or haemorrhagic transformation; and low BP can lead to increased cerebral infarction or perihaematomal ischaemia. Published evidence from multiple large, high-quality, randomised trials is increasing our understanding of this challenging area, such that BP lowering is recommended in acute intracerebral haemorrhage and is safe in ischaemic stroke. Here we review the evidence for BP modulation in acute stroke, discuss the issues raised and look to on-going and future research to identify patient subgroups who are most likely to benefit

Acute treatment of stroke (except thrombectomy)

Purpose of Review: The management of patients with acute stroke has been revolutionized in recent years with the advent of new effective treatments. In this rapidly evolving field, we provide an update on the management of acute stroke excluding thrombectomy, looking to recent, ongoing, and future trials.Recent Findings: Large definitive trials have provided insight into acute stroke care including broadening the therapeutic window for thrombolysis, alternatives to standard dose alteplase, the use of dual antiplatelet therapy early after minor ischemic stroke, and treating elevated blood pressure in intracerebral hemorrhage. Further ongoing and future trials are eagerly awaited in this ever-expanding area.Summary: Although definitive trials have led to improvements in acute stroke care, there remains a need for further research to improve our understanding of pathophysiological mechanisms underlying different stroke types with the potential for treatments to be tailored to the individual

Blood pressure management in acute stroke

Blood pressure (BP) is elevated in 75% or more of patients with acute stroke and is associated with poor outcomes. Whether to modulate BP in acute stroke has long been debated. With the loss of normal cerebral autoregulation, theoretical concerns are twofold: high BP can lead to cerebral oedema, haematoma expansion or haemorrhagic transformation; and low BP can lead to increased cerebral infarction or perihaematomal ischaemia. Published evidence from multiple large, high-quality, randomised trials is increasing our understanding of this challenging area, such that BP lowering is recommended in acute intracerebral haemorrhage and is safe in ischaemic stroke. Here we review the evidence for BP modulation in acute stroke, discuss the issues raised and look to on-going and future research to identify patient subgroups who are most likely to benefit

Hypercholesterolaemia and vascular dementia

Vascular dementia (VaD) is the second commonest cause of dementia. Stroke is the leading cause of disability in adults in developed countries, the second major cause of dementia and the third commonest cause of death. Traditional vascular risk factors–diabetes, hypercholesterolaemia, hypertension and smoking–are implicated as risk factors for VaD. The associations between cholesterol and small vessel disease (SVD), stroke, cognitive impairment and subsequent dementia are complex and as yet not fully understood. Similarly, the effects of lipids and lipid-lowering therapy on preventing or treating dementia remain unclear; the few trials that have assessed lipid-lowering therapy for preventing (two trials) or treating (four trials) dementia found no evidence to support the use of lipid-lowering therapy for these indications. It is appropriate to treat those patients with vascular risk factors that meet criteria for lipid-lowering therapy for the primary and secondary prevention of cardiovascular and cerebrovascular events, and in line with current guidelines. Managing the individual patient in a holistic manner according to his or her own vascular risk profile is recommended. Although the paucity of randomized controlled evidence makes for challenging clinical decision making, it provides multiple opportunities for on-going and future research, as discussed here

Results from the tranexamic acid for primary intracerebral haemorrhage-2 (TICH-2) trial

Background: Haematoma expansion leads to worse outcome in intracerebral haemorrhage (ICH). Tranexamic acid (TXA) is a promising haemostatic agent to prevent haematoma expansion and improve outcome after ICH. Methods: TICH-2 is a multicentre prospective double blind randomised controlled trial, which recruited patients presenting within 8 hours of primary ICH to receive intravenous TXA or placebo. Primary outcome is modified Rankin Scale at day 90 and will be analysed using ordinal logistic regression, adjusted for minimisation criteria. Secondary outcomes will be analysed using adjusted binary logistic regression and multiple linear regression; these include haematoma expansion at 24 hours, day 7 National Institute of Health Stroke Scale (NIHSS), day 90 Barthel Index, quality of life, cognition and mood. Results: A total of 2325 patients were recruited between 14th March 2013 and 30th September 2017, from 12 countries: United Kingdom (n= 1910), Italy, Georgia, Switzerland, Malaysia, Hungary, Poland, Ireland, Turkey, Sweden, Denmark and Spain. Randomisation characteristics included: age 68.9 (13.8) years; male 1301 (56.0%); time from onset to randomisation 3.6 hours [2.6, 5.0]; NIHSS 13 (7.5); Glasgow coma scale 13.4 (2.1); systolic blood pressure 172.6 (27.2) mmHg; intraventricular haemorrhage 745 (32.0%) and prior antiplatelet use 610 (26.2%). Conclusion: TICH-2 is the largest trial of TXA in spontaneous ICH and recruited over its original target of 2000 patients. The results will be available in May 2018 and will inform whether TXA should be recommended for the treatment of acute spontaneous ICH

Serum amyloid protein is associated with outcome following acute ischaemic stroke: data from the REmote ischaemic Conditioning After Stroke Trial (RECAST)

Background: Remote ischaemic per-conditioning (RIC) in experimental ischaemic stroke is neuroprotective. Several neurohumoral, vascular and inflammatory mediators are implicated. Methods: The REmote ischaemic Conditioning After Stroke Trial (RECAST) was a pilot blinded sham-controlled trial in patients with ischaemic stroke, randomised to receive four 5-minute cycles of RIC within 24 hours of ictus. Plasma taken pre-intervention, immediately post-intervention and on day 4 was analysed for nitric oxide (nitrate/nitrite) levels using chemiluminescence and other biomarkers were analysed by enzyme-linked immunosorbent assay (ELISA): alpha-2-macroglobulin (A2M), serum amyloid protein (SAP), e-selectin, vascular endothelial growth factor (VEGF). Biomarkers were correlated with outcome (Day 90 National Institutes of Health Stroke Scale [NIHSS], modified Rankin scale [mRS], Barthel index [BI]) using Pearson’s correlation coefficient. Results: In all 26 patients, an increase in SAP (pre- to post-intervention) positively correlated with worse day 90 mRS (r=0.429, p=0.029) and negatively with worse BI (r=-0.392, p=0.048), whilst an increase in SAP from day 0 to 4 positively correlated with worse day 90 NIHSS (r=0.400, p=0.043), mRS (r=0.505, p=0.008) and negatively with worse BI (r=-0.439, p=0.025). RIC reduced SAP levels from pre- to post-intervention (n=13, 2-way ANOVA, p<0.05), whilst sham did not. No significant changes over time or by treatment, or correlations with outcome were seen for A2M, e-selectin, nitric oxide or VEGF. Conclusion: Increased plasma levels of SAP are associated with worse clinical outcomes after ischaemic stroke. RIC reduced SAP levels from pre- to post-intervention. Larger studies assessing biomarkers and efficacy of RIC in acute ischaemic stroke are warranted