Alison Halliday

10-year stroke prevention after successful carotid endarterectomy for asymptomatic stenosis (ACST-1): a multicentre randomised trial.

Summary Background If carotid artery narrowing remains asymptomatic (ie, has caused no recent stroke or other neurological symptoms), successful carotid endarterectomy (CEA) reduces stroke incidence for some years. We assessed the long-term effects of successful CEA. Methods Between 1993 and 2003, 3120 asymptomatic patients from 126 centres in 30 countries were allocated equally, by blinded minimised randomisation, to immediate CEA (median delay 1 month, IQR 0·3–2·5) or to indefinite deferral of any carotid procedure, and were followed up until death or for a median among survivors of 9 years (IQR 6–11). The primary outcomes were perioperative mortality and morbidity (death or stroke within 30 days) and non-perioperative stroke. Kaplan-Meier percentages and logrank p values are from intention-to-treat analyses. This study is registered, number ISRCTN26156392. Findings 1560 patients were allocated immediate CEA versus 1560 allocated deferral of any carotid procedure. The proportions operated on while still asymptomatic were 89·7% versus 4·8% at 1 year (and 92·1% vs 16·5% at 5 years). Perioperative risk of stroke or death within 30 days was 3·0% (95% CI 2·4–3·9; 26 non-disabling strokes plus 34 disabling or fatal perioperative events in 1979 CEAs). Excluding perioperative events and non-stroke mortality, stroke risks (immediate vs deferred CEA) were 4·1% versus 10·0% at 5 years (gain 5·9%, 95% CI 4·0–7·8) and 10·8% versus 16·9% at 10 years (gain 6·1%, 2·7–9·4); ratio of stroke incidence rates 0·54, 95% CI 0·43–0·68, p<0·0001. 62 versus 104 had a disabling or fatal stroke, and 37 versus 84 others had a non-disabling stroke. Combining perioperative events and strokes, net risks were 6·9% versus 10·9% at 5 years (gain 4·1%, 2·0–6·2) and 13·4% versus 17·9% at 10 years (gain 4·6%, 1·2–7·9). Medication was similar in both groups; throughout the study, most were on antithrombotic and antihypertensive therapy. Net benefits were significant both for those on lipid-lowering therapy and for those not, and both for men and for women up to 75 years of age at entry (although not for older patients). Interpretation Successful CEA for asymptomatic patients younger than 75 years of age reduces 10-year stroke risks. Half this reduction is in disabling or fatal strokes. Net benefit in future patients will depend on their risks from unoperated carotid lesions (which will be reduced by medication), on future surgical risks (which might differ from those in trials), and on whether life expectancy exceeds 10 years. Funding UK Medical Research Council, BUPA Foundation, Stroke Association.

Asymptomatic Carotid Surgery Trial-2 (ACST-2): rationale for a randomised clinical trial comparing carotid endarterectomy with carotid artery stenting in patients with asymptomatic carotid artery stenosis.

OBJECTIVESnTo compare carotid endarterectomy with carotid artery stenting in the prevention of stroke in patients with asymptomatic carotid stenosis.nnnDESIGNnA large, simple, pragmatic international trial of at least 5000 patients with asymptomatic carotid stenosis in whom intervention is thought to be needed but where there is substantial uncertainty about the appropriate choice of treatment. The trial is designed to fit in easily with normal clinical practice.nnnMATERIALS & METHODSnA short (approximately 2 min) telephone call is made to randomise patients to either carotid endarterectomy (CEA) or stenting (CAS). Follow-up by the collaborator will be at one month after the procedure (simple 1-page form) and by the ACST office for 5-years post-procedure. Data will be analysed on an intention-to-treat basis; main outcomes will be 30-day myocardial infarction, stroke and death, and 5-year stroke rates. In addition, appropriate subgroup analyses will be undertaken, and health economic evaluation will consider procedural and stroke-related healthcare costs and quality of life.nnnCONCLUSIONnCollaborators who routinely undertake CEA and CAS are encouraged to participate in ACST-2. This trial, now funded and open for randomisation, will provide important evidence comparing the immediate and long-term safety and efficacy of carotid endarterectomy and stenting in patients with asymptomatic carotid stenosis.

Waiting times for carotid endarterectomy in UK: observational study

Objectives To assess timeliness of carotid endarterectomy services in the United Kingdom. Design Observational study with follow-up to March 2008. Setting UK hospitals performing carotid endarterectomy. Participants UK surgeons undertaking carotid endarterectomy from December 2005 to December 2007. Main outcome measures Provision and speed of delivery of appropriate assessments of patients; carotid endarterectomy and operative mortality; 30 day postoperative mortality. Results 240 (61% of those eligible) consultant surgeons took part from 102 (76%) hospitals and trusts. Of 9913 carotid endarterectomies recorded on hospital episode statistics, 5513 (56%) were included. Of the patients who underwent endarterectomy, 83% had a history of transient ischaemic attack or stroke. Of these recently symptomatic patients, 20% had their operation within two weeks of onset of symptoms and 30% waited more than 12 weeks. Operative mortality was 0.5% during the inpatient stay and 1.0% (95% confidence interval 0.7% to 1.3%) by 30 days. Conclusion Only 20% of symptomatic patients had surgery within the two week target time set by the National Institute for Health and Clinical Excellence (NICE). Although operative mortality rates are comparable with those in other countries, some patients might experience disabling or fatal stroke while waiting for surgery and hence not be included in operative statistics. Major improvements in services are necessary to enable early surgery in appropriate patients in order to prevent strokes.

The prevalence of thrombophilia in patients with symptomatic peripheral vascular disease.

The aim of this prospective study was to establish the prevalence of thrombophilia and hyperhomocysteinaemia using a comprehensive screen in patients with peripheral vascular disease.

Is Ultrasound Sufficient for Vascular Imaging Prior to Carotid Endarterectomy

Clinical trials of carotid endarterectomy (CEA) published over the last decade in both symptomatic and asymptomatic patients have emphasized the importance of accurate vascular imaging prior to operation. Different methods of evaluating carotid stenosis using digital subtraction angiography (DSA)1 and between ultrasound and angiographic measurements2 explain many of the discrepancies between clinical outcomes of the different surgical trials.nnDSA is usually considered the “gold standard” but has a 1% to 2% stroke and death rate, which significantly impacts on surgical results in centers of excellence, where the combined mortality and morbidity of carotid endarterectomy is as low as 1.5%.3 However, no consensus has yet been arrived at for noninvasive imaging alternatives (ultrasound alone, magnetic resonance angiography [MRA] alone, or both combined) to replace DSA. In a recent “Controversies” section of this journal, strongly contrasting viewpoints on the value of ultrasound and MRA3,4 were followed by comments by the section editors, who even disagreed with each other.5nnDifferent surgical specialties also differ from each other in presurgical imaging assessment. In a recent survey in Canada6 of surgeons specializing in carotid endarterectomy, 50% still used DSA as their method of choice, but whereas 46% of vascular surgeons used ultrasound alone, this was used as the sole method of neurovascular imaging in only 11% of neurosurgeons (a significant difference, P =0.002). Published data comparing …

Conveying Equipoise during Recruitment for Clinical Trials: Qualitative Synthesis of Clinicians’ Practices across Six Randomised Controlled Trials

Background Randomised controlled trials (RCTs) are essential for evidence-based medicine and increasingly rely on front-line clinicians to recruit eligible patients. Clinicians’ difficulties with negotiating equipoise is assumed to undermine recruitment, although these issues have not yet been empirically investigated in the context of observable events. We aimed to investigate how clinicians conveyed equipoise during RCT recruitment appointments across six RCTs, with a view to (i) identifying practices that supported or hindered equipoise communication and (ii) exploring how clinicians’ reported intentions compared with their actual practices. Methods and Findings Six pragmatic UK-based RCTs were purposefully selected to include several clinical specialties (e.g., oncology, surgery) and types of treatment comparison. The RCTs were all based in secondary-care hospitals (n = 16) around the UK. Clinicians recruiting to the RCTs were interviewed (n = 23) to understand their individual sense of equipoise about the RCT treatments and their intentions for communicating equipoise to patients. Appointments in which these clinicians presented the RCT to trial-eligible patients were audio-recorded (n = 105). The appointments were analysed using thematic and content analysis approaches to identify practices that supported or challenged equipoise communication. A sample of appointments was independently coded by three researchers to optimise reliability in reported findings. Clinicians and patients provided full written consent to be interviewed and have appointments audio-recorded. Interviews revealed that clinicians’ sense of equipoise varied: although all were uncertain about which trial treatment was optimal, they expressed different levels of uncertainty, ranging from complete ambivalence to clear beliefs that one treatment was superior. Irrespective of their personal views, all clinicians intended to set their personal biases aside to convey trial treatments neutrally to patients (in accordance with existing evidence). However, equipoise was omitted or compromised in 48/105 (46%) of the recorded appointments. Three commonly recurring practices compromised equipoise communication across the RCTs, irrespective of clinical context. First, equipoise was overridden by clinicians offering treatment recommendations when patients appeared unsure how to proceed or when they asked for the clinician’s expert advice. Second, clinicians contradicted equipoise by presenting imbalanced descriptions of trial treatments that conflicted with scientific information stated in the RCT protocols. Third, equipoise was undermined by clinicians disclosing their personal opinions or predictions about trial outcomes, based on their intuition and experience. These broad practices were particularly demonstrated by clinicians who had indicated in interviews that they held less balanced views about trial treatments. A limitation of the study was that clinicians volunteering to take part in the research might have had a particular interest in improving their communication skills. However, the frequency of occurrence of equipoise issues across the RCTs suggests that the findings are likely to be reflective of clinical recruiters’ practices more widely. Conclusions Communicating equipoise is a challenging process that is easily disrupted. Clinicians’ personal views about trial treatments encroached on their ability to convey equipoise to patients. Clinicians should be encouraged to reflect on personal biases and be mindful of the common ways in which these can arise in their discussions with patients. Common pitfalls that recurred irrespective of RCT context indicate opportunities for specific training in communication skills that would be broadly applicable to a wide clinical audience.

Thrombolysis for Stroke

The results of the National Institute of Neurological Disorders and Stroke (NINDS) rtPA Stroke Study [1] provided clear evidence that tPA can be effective under specific circumstances. The European Cooperative Acute Stroke Study (ECASS) [2] provided additional signs that thrombolysis reduced morbidity but concern for increased hemorrhage-related mortality. Several other thrombolysis trials were stopped because of concerns about harmful effects. We asked several experts to offer their opinions on the role of thrombolysis in acute ischemic stroke in 1998. How are they dealing with this issue? Where should clinical trials go from here? We informed each contributor that we do not expect new data, detailed analyses or an authoritative review. Rather, we wanted their concise views on the subject. Their opinions follow. The term tPA is used throughout this paper to denote recombinant tissue plasminogen activator (rtPA, activase, alteplase). Also, ECASS is sometimes referred to as ECASS-I.

Controversies in neurology: asymptomatic carotid stenosis—intervention or just stick to medical therapy. The argument for carotid endarterectomy

Patients with a significant carotid stenosis are at an increased risk of suffering from a potentially fatal or disabling stroke. The current management strategies available to a patient with an asymptomatic carotid stenosis are either medical therapy alone, or in combination with either carotid endarterectomy, or carotid angioplasty and stenting. Medical therapy alone can reduce the incidence of stroke in general, but whether there is any reduction in stroke attributable to a significant carotid stenosis is less clear. Carotid endarterectomy, on the other hand, has been shown to reduce the incidence of ipsilateral ischaemic stroke in both symptomatic and asymptomatic patients, with the benefits extending into the long-term. Carotid angioplasty and stenting is a newer technique with the benefit of being minimally invasive. The results of trials comparing the technique to endarterectomy have had conflicting results, and the results of large multi-centre trials are awaited. Currently the safest strategy for a patient with a significant asymptomatic carotid stenosis consists of optimal medical therapy with carotid endarterectomy for those less than 75xa0years of age, who are suitable for surgery.