Papers by Peter Sandercock
Stroke, 2006
We wish to thank Dr Sanossian et al for their interest in our article and for their kind words. T... more We wish to thank Dr Sanossian et al for their interest in our article and for their kind words. They are certainly right when they say that our study has some limitations: in fact, we have no information on prior vascular events, admission temperature or diabetes of patients randomized in International Stroke Trial (IST). We do not know about baseline dementia, but IST patients could have been randomized if they were independent before their stroke, so it seems unlikely that this is a real problem. Also, premorbid statin use should have been very rare at the time IST was conducted. We would also say that, given the huge number of patients we have analyzed, factors like diabetes, temperature, etc, should result to be equally distributed in the 2 groups, attributable to the effect of randomization; obviously, this does not apply to prior vascular events, as we have discussed in our article. As far as the way we measured stroke severity, to our knowledge there is no direct comparison between Oxford Community Stroke Project (OCSP) method and National Institutes of Health Stroke Scale (NIHSS), and therefore, while waiting for such a study (which will be possible with data from IST 3!), the use of one method instead of the other is a matter of subjective preference; we respect the preference of our American Col-Disclosures None.
European Stroke Journal, 2020
Professor Eivind Berge, MD, PhD died from cancer on 6 February 2020. He was a highly respected st... more Professor Eivind Berge, MD, PhD died from cancer on 6 February 2020. He was a highly respected stroke expert, clinical trialist and clinician scientist who made substantial contributions to evidence-based stroke medicine and the work of the European Stroke Organisation.
Current Neurology and Neuroscience Reports, 2017
Purpose of Review The purpose of the review is to examine recent evidence on the effects of intra... more Purpose of Review The purpose of the review is to examine recent evidence on the effects of intravenous thrombolysis and identify the remaining uncertainties. Recent Findings We review the results of two large trials (the third International Stroke Trial (IST-3) and The Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED)) and the publications from the individual patient data analyses of the trials of alteplase conducted by the Stroke Thrombolysis Trialists Collaboration. Summary Despite about a 2% risk of fatal intracerebral haemorrhage, on average, adult patients of all ages treated with 0.9 mg/kg alteplase within 4.5 h will have better long-term functional outcome. The use of a lower dose of alteplase (0.6 mg/kg) is associated with a lower risk of haemorrhage but its effect on functional outcome has not been proven to be non-inferior to standard dose therapy. Some clinicians feel confident to treat selected patients who present beyond 4.5 h or have unknown time of onset, but many also agree that the current trials and other research is needed to reliably define the optimum imaging methods and treatment eligibility criteria.
International Journal of Stroke, 2015
The idea that different patients will respond differently to the same treatment is not new. The r... more The idea that different patients will respond differently to the same treatment is not new. The recent advances in genomics and laboratory medicine have led to the hope that it will be possible to maximize the benefit and minimize the harms of each medical therapy by using an individuals' biomarker status to ‘personalize’ their treatment. The selection of treatment for each individual would then be determined, not just by their disease status (or an estimate of the risk of developing a disease or disease progression), but also by their genetic makeup or by other measurable characteristics, such as the level of a particular biomarker in the blood. This review discusses the extent to which personalized medicine might be applied in stroke, and the implications for global stroke health care.
The Lancet, 1996
Background Many clinical trials have evaluated the benefit of long-term use of antiplatelet drugs... more Background Many clinical trials have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of clinical thrombotic events. Aspirin and ticlopidine have been shown to be effective, but both have potentially serious adverse effects. Clopidogrel, a new thienopyridine derivative similar to ticlopidine, is an inhibitor of platelet aggregation induced by adenosine diphosphate. Methods CAPRIE was a randomised, blinded, international trial designed to assess the relative efficacy of clopidogrel (75 mg once daily) and aspirin (325 mg once daily) in reducing the risk of a composite outcome cluster of ischaemic stroke, myocardial infarction, or vascular death; their relative safety was also assessed. The population studied comprised subgroups of patients w ith atherosclerotic vascular disease manifested as either recent ischaemic stroke, recent myocardial infarction, or symptomatic peripheral arterial disease. Patients were followed for 1 to 3 years. Findings 19 185 patients, with more than 6300 in each of the clinical subgroups, were recruited over 3 years, with a mean follow-up of 1•91 years. There were 1960 first events included in the outcome cluster on which an intention-totreat analysis showed that patients treated with clopidogrel had an annual 5•32% risk of ischaemic stroke, myocardial infarction, or vascular death compared with 5•83% with aspirin. These rates reflect a statisticaly significant (p=0•043) relative-risk reduction of 8•7% in favour of clopidogrel (95% CI 0•3-16•5). Corresponding on-treatment analysis yielded a relative-risk reduction of 9•4%. There were no major differences in terms of safety. Reported adverse experiences in the clopidogrel and aspirin groups judged to be severe included rash (0•26% vs 0•10%), diarrhoea (0•23% vs 0•11%), upper gastrointestinal discomfort (0•97% vs 1•22%), intracranial haemorrhage (0•33% vs 0•47%), and gastrointestinal haemorrhage (0•52% vs 0•72%) , respectively. There were ten (0•10%) patients in the clopidogrel group with significant reductions in neutrophils (<1•2 ϫ 10 9 /L) and 16 (0•17%) in the aspirin group. Interpretation Long-term administration of clopidogrel to patients with atherosclerotic vascular disease is more effective than aspirin in reducing the combined risk of ischaemic stroke, myocardial infarction, or vascular death. The overall safety profile of clopidogrel is at least as good as that of medium-dose aspirin.
Cochrane Database of Systematic Reviews, 2002
Much of the brain swelling in ischaemic stroke is due to cytotoxic oedema, which is related to ce... more Much of the brain swelling in ischaemic stroke is due to cytotoxic oedema, which is related to cell membrane dysfunction. Early treatment with corticosteroids may help reduce the swelling and improve the outcomes after a stroke. The objective of this review was to assess the effect of corticosteroids in acute presumed ischaemic stroke. We searched the Cochrane Stroke Group trials register and contacted investigators in the field. Published randomised trials comparing corticosteroids with placebo or control in people with acute (presumed or definite) ischaemic stroke. Trials were included if treatment began within 48 hours of stroke onset and if clinical outcome was assessed. Two reviewers independently applied the inclusion criteria, assessed trial quality and extracted the data. Seven trials involving 453 people were included. Details of trial quality that may relate to bias were not available from most trials. No difference was shown in the odds of death within one year (odds ratio 1.08, 95% confidence interval 0.68 to 1.72). Treatment did not appear to improve functional outcome in survivors. Six trials reported neurological impairment but pooling the data was impossible because no common scale or time interval was used. The results were inconsistent between individual trials. The only adverse effects reported were small numbers of gastrointestinal bleeds, infections and deterioration of hyperglycaemia across both groups. There is not enough evidence to evaluate corticosteroid treatment for people with acute presumed ischaemic stroke.
Journal of Stroke and Cerebrovascular Diseases, 2002
Background Endovascular detachable coil treatment is being increasingly used as an alternative to... more Background Endovascular detachable coil treatment is being increasingly used as an alternative to craniotomy and clipping for some ruptured intracranial aneurysms, although the relative benefits of these two approaches have yet to be established. We undertook a randomised, multicentre trial to compare the safety and efficacy of endovascular coiling with standard neurosurgical clipping for such aneurysms judged to be suitable for both treatments. Methods We enrolled 2143 patients with ruptured intracranial aneurysms and randomly assigned them to neurosurgical clipping (n=1070) or endovascular treatment by detachable platinum coils (n=1073). Clinical outcomes were assessed at 2 months and at 1 year with interim ascertainment of rebleeds and death. The primary outcome was the proportion of patients with a modified Rankin scale score of 3-6 (dependency or death) at 1 year. Trial recruitment was stopped by the steering committee after a planned interim analysis. Analysis was per protocol. Findings 190 of 801 (23•7%) patients allocated endovascular treatment were dependent or dead at 1 year compared with 243 of 793 (30•6%) allocated neurosurgical treatment (p=0•0019). The relative and absolute risk reductions in dependency or death after allocation to an endovascular versus neurosurgical treatment were 22•6% (95% CI 8•9-34•2) and 6•9% (2•5-11•3), respectively. The risk of rebleeding from the ruptured aneurysm after 1 year was two per 1276 and zero per 1081 patient-years for patients allocated endovascular and neurosurgical treatment, respectively. Interpretation In patients with a ruptured intracranial aneurysm, for which endovascular coiling and neurosurgical clipping are therapeutic options, the outcome in terms of survival free of disability at 1 year is significantly better with endovascular coiling. The data available to date suggest that the long-term risks of further bleeding from the treated aneurysm are low with either therapy, although somewhat more frequent with endovascular coiling.
JAMA, 2008
Introduction, 1 2 Development of knowledge about cerebrovascular disease, 7 3 Is it a vascular ev... more Introduction, 1 2 Development of knowledge about cerebrovascular disease, 7 3 Is it a vascular event and where is the lesion?, 35 4 Which arterial territory is involved?, 131 5 What pathological type of stroke is it, cerebral ischaemic or haemorrhage?, 181 6 What caused this transient or persisting ischaemic event?, 259 7 Unusual causes of ischaemic stroke and transient ischaemic attack, 353 8 What caused this intracerebral haemorrhage?, 411 9 What caused this subarachnoid haemorrhage?, 457 10 A practical approach to the management of stroke and transient ischaemic attack patients, 503 11 What are this person's problems? A problem-based approach to the general management of stroke, 537 12 Specific treatments for acute ischaemic stroke, 635 13 Specific treatment of intracerebral haemorrhage, 703 14 Specific treatment of aneurismal subarachnoid haemorrhage, 719 15 Specific interventions to prevent intracranial haemorrhage, 767 16 Preventing recurrent stroke and other serious vascular events, 789 17 The organization of stroke services, 903 18 Reducing the impact of stroke and improving the public health, 953 Index, 980 Colour plates are found facing p.550
International Journal of Stroke, 2013
Rationale Thrombolysis with intravenous alteplase is both effective and safe when administered to... more Rationale Thrombolysis with intravenous alteplase is both effective and safe when administered to particular types of patient within 4·5 hours of having an ischemic stroke. However, the extent to which effects might vary in different types of patient is uncertain. Aims and Design We describe the protocol for an updated individual patient data meta-analysis of trials of intravenous alteplase, including results from the recently reported third International Stroke Trial, in which a wide range of patients enrolled up to six-hours after stroke onset were randomized to alteplase vs. control. Study Outcomes This protocol will specify the primary outcome for efficacy, specified prior to knowledge of the results from the third International Stroke Trial, as the proportion of patients having a ‘favorable’ stroke outcome, defined by modified Rankin Score 0–1 at final follow-up at three- to six-months. The primary analysis will be to estimate the extent to which the known benefit of alteplase ...
International Journal of Stroke, 2006
High blood pressure (BP) is common in acute stroke and is independently associated with a poor ou... more High blood pressure (BP) is common in acute stroke and is independently associated with a poor outcome. Many patients with acute stroke are taking antihypertensive medications. To test the safety and efficacy of 7 days of transdermal glyceryl trinitrate (GTN, 5 mg/day) vs. no GTN in patients with acute stroke; patients taking antihypertensive therapy immediately before their stroke are also randomised to continue vs. stop this temporarily. ENOS is a prospective international multicentre single-blind randomised-controlled trial in 5000 patients with acute (< 48 h of onset) ischaemic or haemorrhagic stroke. The primary outcome is combined death and dependency (modified Rankin scale > 2) at 90 days measured by blinded central telephone follow-up. Secondary outcomes include: BP over the 7 days of treatment; death, impairment (Scandinavian stroke scale), recurrence, and neuroimaging at 7 days; discharge disposition, disability (Barthel index), cognition (mini-mental status examinat...
European Heart Journal, 1999
Aims In observational studies, prolonged lower blood total cholesterol levels-down at least to 3 ... more Aims In observational studies, prolonged lower blood total cholesterol levels-down at least to 3 mmol. l 1-are associated with lower risks of coronary heart disease. Cholesterol-lowering therapy may, therefore, be worthwhile for individuals at high risk of coronary heart disease events irrespective of their presenting cholesterol levels. Observational studies also suggest that increased dietary intake of antioxidant vitamins may be associated with lower risks of coronary heart disease. The present randomized trial aims to assess reliably the effects on mortality and major morbidity of cholesterol-lowering therapy and of antioxidant vitamin supplementation in a wide range of different categories of high-risk patients. Conclusion The Heart Protection Study is large, it has included a wide range of patients at high risk of vascular events, and the treatment regimens being studied are welltolerated and produce substantial effects on blood lipid and vitamin levels. The study should, therefore, provide reliable evidence about the effects of cholesterol-lowering therapy and of antioxidant vitamin supplements on all-cause or cause-specific mortality and major morbidity in a range of different categories of individuals for whom uncertainty remains about the balance of benefits and risks of these treatments.
BMJ, 1994
To determine the efficacy of antiplatelet therapy in maintaining vascular patency in various cate... more To determine the efficacy of antiplatelet therapy in maintaining vascular patency in various categories of patients. Searching MEDLINE and Current Contents were searched by computer, and journals were manually searched. Additional material was obtained by examining reference lists of trials, review articles, abstracts and meeting proceedings, by collaboration with the trial register of the International Committee on Thrombosis and Haemostasis, and by consulting colleagues and various manufacturers of antiplatelet agents. Both published and unpublished studies, available for review by 30th March 1990, were included. Study selection Study designs of evaluations included in the review Unconfounded randomised controlled trials comparing different antiplatelet therapies or comparing antiplatelet therapy with placebo. Specific interventions included in the review Treatment with agents which act on the vascular system by inhibition of platelet aggregation or adhesion, or both.
Archives of Internal Medicine, 1995
, issue of the ARCHIVES, Becker and Ansell1 present a synopsis of the third American College of C... more , issue of the ARCHIVES, Becker and Ansell1 present a synopsis of the third American College of Chest Physicians Consensus Conference on Antithrombotic Therapy. In the clinical guidelines presented, they recommended the routine use of subcutaneous heparin therapy for the prevention of venous thromboembolism in patients with ischemic stroke.
Cochrane Database of Systematic Reviews, 1999
Most ischaemic strokes are caused by blood clots blocking an artery in the brain. Clot prevention... more Most ischaemic strokes are caused by blood clots blocking an artery in the brain. Clot prevention with anticoagulants might improve outcome if bleeding risks were low. This is an update of a Cochrane review first published in 1995, and previously updated in 2004. To assess the effect of anticoagulant therapy versus control in the early treatment (less than 14 days) of patients with acute ischaemic stroke. We searched the Cochrane Stroke Group Trials Register (last searched 2 October 2007), and two Internet clinical trials registries for relevant ongoing studies (last searched October 2007). Randomised trials comparing early anticoagulant therapy (started within two weeks of stroke onset) with control in patients with acute presumed or confirmed ischaemic stroke. Two review authors independently selected trials for inclusion, assessed trial quality, and extracted the data. Twenty-four trials involving 23,748 participants were included. The quality of the trials varied considerably. The anticoagulants tested were standard unfractionated heparin, low-molecular-weight heparins, heparinoids, oral anticoagulants, and thrombin inhibitors. Based on 11 trials (22,776 participants) there was no evidence that anticoagulant therapy reduced the odds of death from all causes (odds ratio (OR) 1.05; 95% confidence interval (CI) 0.98 to 1.12) at the end of follow up. Similarly, based on eight trials (22,125 participants), there was no evidence that anticoagulants reduced the odds of being dead or dependent at the end of follow up (OR 0.99; 95% CI 0.93 to 1.04). Although anticoagulant therapy was associated with fewer recurrent ischaemic strokes (OR 0.76; 95% CI 0.65 to 0.88), it was also associated with an increase in symptomatic intracranial haemorrhages (OR 2.55; 95% CI 1.95 to 3.33). Similarly, anticoagulants reduced the frequency of pulmonary emboli (OR 0.60; 95% CI 0.44 to 0.81), but this benefit was offset by an increase in extracranial haemorrhages (OR 2.99; 95% CI 2.24 to 3.99). Since the last version of the review, neither of the two new relevant studies have provided additional information to change the conclusions. In patients with acute ischaemic stroke, immediate anticoagulant therapy is not associated with net short or long-term benefit. Treatment with anticoagulants reduced recurrent stroke, deep vein thrombosis and pulmonary embolism, but increased bleeding risk. The data do not support the routine use of any the currently available anticoagulants in acute ischaemic stroke.
International Journal of Stroke, 2018
This is the first paper in a series of five on how to do good quality clinical research. It sets ... more This is the first paper in a series of five on how to do good quality clinical research. It sets the scene for the four papers that follow. The aims of the series are to: promote reliable clinical research to inform clinical practice; help people new to research to get started (at any stage of their career); create teaching resources for experienced researchers; and help clinicians working in resource-poor settings to conduct research. We set out in this paper the skills clinicians need to run research projects that are relevant to their clinical practice. We focus on how to get the right training in research methodology, choose and refine a good research question, and then how to ensure the methods and data analysis plan are correct for the question being asked.
The Lancet. Neurology, 2016
The benefi ts and harms of intravenous thrombolysis with recombinant tissue plasminogen activator... more The benefi ts and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the Third International Stroke Trial [IST-3]): a randomised controlled trial.
Stroke, Dec 1, 2016
In patients with acute ischemic stroke, whether involvement of the insular cortex influences outc... more In patients with acute ischemic stroke, whether involvement of the insular cortex influences outcome is controversial. Much of the apparent adverse outcome may relate to such strokes usually being severe. We examined the influence of right and left insular involvement on stroke outcomes among patients from the IST-3 study (Third International Stroke Trial) who had visible ischemic stroke on neuroimaging. We used multiple logistic regression to compare outcomes of left versus right insular and noninsular strokes across strata of stroke severity, on death, proportion dead or dependent, and level of disability (ordinalized Oxford Handicap Score) at 6 months, with adjustment for the effects of age, lesion size, and presence of atrial fibrillation. Of 3035 patients recruited, 2099 had visible ischemic strokes limited to a single hemisphere on computed tomography/magnetic resonance scans. Of these, 566 and 714 had infarction of right and left insula. Six months after randomization, right ...
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Papers by Peter Sandercock