Efficacy In Stroke Prevention Research Articles

Advances in Health Policy 2007

Notable advances have been made in stroke policy and outcomes research over the past year. Policy-relevant gray and published research is included in this review. The advances selected are organized under 3 areas: stroke policy and related evidence, predictive modeling, and quality improvement. ### The Role of Evidence in Stroke Policy Investments Different types of evidence are required at each stage in the development and implementation of large scale stroke strategies. The role of evidence was examined in the development of the Ontario Stroke System (a $30 million per year health policy initiative to improve stroke care in Ontario, Canada). Researchers identified key stages in the implementation process and the various types of evidence mobilized at each stage.1 The value of this research for stroke knowledge translation and policy is that evidence can be systematically organized and shared strategically to achieve policy commitments. ### Strategies for Improving Stroke Care The Helsingborg Declaration 2006 on European Stroke Strategies2 is a consensus document with substantial potential for influencing stroke policy in Europe. The Declaration states that by 2015 all persons in Europe with stroke should have access to a continuum of care in the acute phase including rehabilitation and secondary prevention. Clear goals for improving outcomes, the means to achieve them, and evaluation are outlined. The document also calls for a system to be established to incorporate new research into stroke care. In Canada, work continues on implementing the Canadian Stroke Strategy. The Canadian Stroke Network, a national center of excellence, has been a major contributor in developing research and knowledge translation toward improved policy and care.3 The policy challenge for Canada is that health is a provincial responsibility with substantially different health resources and commitments to stroke in each province. During 2007, several gains were made. For example, the Alberta Provincial Stroke Strategy was developed and a commitment of $1.1 million CDN was …

Intracranial arterial stenting for symptomatic stenoses: a Latin American experience

Background The proportionally higher incidence of intracranial atherosclerosis among Asian and black patients and a greater proclivity for intracranial artery stenosis in the Hispanic population merit drawing attention to a Latin American experience with intracranial arterial stenting. Methods This is a retrospective analysis of an observational study of 33 intracranial lesions (each >50% stenosis) in 32 patients treated by intracranial angioplasty in 6 Latin American centers over a 3-year period. The investigation used a unique device, a balloon-expandable stent (Lekton Motion stent system, now Pharos, Biotronik, AG, Bülach, Switzerland). Results The treated patients ranged in age from 30 to 81 years (mean, 59.3 years; SD, 12 years), including 24 male and 8 female patients (sex ratio, 4:1). Two were Asians, 4 were blacks, and the rest were white Hispanic. Our mean follow-up is of 10.2 months (SD, 7.84 months), with a mortality rate of 9.4% (3/32), a nonfatal complication rate of 6.2%, and a stroke rate (rate of recurrence) of 0%. The mean pretreatment stenosis of 68.75% (SD, 14%) was reduced to a residual of 5.16% (SD, 16%) ( P = .000; 95% confidence interval, 56.8%-70.3%). A control angiogram was performed in 82% of patients, and in that case, the restenosis 50% or greater was of 8.7% during the follow-up period. Conclusion The treatment of intracranial stenosis with the Lekton Motion stent (Pharos) is feasible with a high technical success rate. Restenosis as well as the rate of new neurologic events during follow-up suggests some efficacy of stroke prevention by using the latest-generation, highly trackable, balloon-expandable stents.

Strokes attributable to underuse of warfarin and antiplatelets

Despite their proven efficacy in stroke prevention, warfarin and antiplatelets remain underused. We determined the frequency of ischemic strokes attributable to underuse of warfarin and antiplatelets for stroke prevention in a Danish community. We included all patients with ischemic stroke in a Copenhagen community with 302,000 inhabitants admitted to the hospital between September 1999 and May 2000 (n = 426). Patients who did not receive warfarin or antiplatelet medication even though they were at known risk for cardiovascular disease before the incident stroke were identified; they had known atrial fibrillation, prior myocardial infarction, angina, or prior stroke transient ischemic attack (TIA). Sufficient information on cardiovascular risk factors before stroke was available in 404 patients. A total of 54 patients had atrial fibrillation known before the stroke. Of these, 16 had not received warfarin or antiplatelets on admission, 27 had not received warfarin but had received antiplatelets, and 11 had received warfarin. Assuming that warfarin and antiplatelets reduces the risk of stroke by 66% and 25%, respectively, it was calculated that between 6 and 12 of these strokes with atrial fibrillation could have been prevented if warfarin or antiplatelets had been given before stroke. A total of 147 patients had known stroke/TIA and/or myocardial infarction/angina before stroke (41 patients had not received antiplatelets on admission). If antiplatelet therapy had been given before stroke, 10 of these strokes could have been prevented. Our findings indicate that underuse of warfarin and antiplatelets is still of considerable magnitude and attributable to 4% to 5% (16 to 22 out of 404) of the ischemic strokes in a Danish urban community.

Carotid Plaque Pathology

To determine the relationship between ulceration, thrombus, and calcification of carotid artery atherosclerotic plaques and symptoms of ipsilateral or contralateral stroke. We compared microscopic plaque morphology from patients with and without stroke symptoms ipsilateral or contralateral to the plaque. Plaques were characterized for ulceration, thrombus, and calcification. We analyzed plaques from 241 subjects: 170 patients enrolled in the Asymptomatic Carotid Atherosclerosis Study (ACAS) and 71 patients enrolled in the North American Symptomatic Carotid Endarterectomy Trial (NASCET); 128 subjects had no history of stroke symptoms, 80 subjects had ipsilateral symptoms, and 33 had contralateral symptoms. Plaque ulceration was more common in plaques taken from symptomatic patients than those without symptoms (36% versus 14%; P<0.001); frequency of ulceration was similar for plaques associated with ipsilateral (34%) and contralateral (42%) symptoms. Thrombus was most common in plaques taken from patients with both ipsilateral symptoms and ulceration. The extent of calcification was unassociated with stroke symptoms. Carotid plaque ulceration and thrombosis are more prevalent in symptomatic patients. Ulceration is more common in symptomatic patients regardless of side of carotid symptoms, whereas thrombus is associated with ipsilateral symptoms and plaque ulceration. Preoperative identification of carotid ulceration and thrombus should lead to greater efficacy of stroke prevention by carotid endarterectomy.

Recent trials in atrial fibrillation: lessons learned beyond rate and rhythm

Atrial fibrillation (AF) is a common disorder, responsible for the majority of hospitalizations due to arrhythmias. It is well established that AF predisposes patients to the development of thrombi and a markedly increased risk of ischaemic stroke. The prevalence of AF increases dramatically with age, and, as the overall population ages, AF will become an increasingly important cause of morbidity and mortality. Numerous prospective randomized studies have shown that oral anticoagulation is an effective means for primary stroke prevention (risk reduction [RR] 62%) as well as secondary RR. Aspirin is also effective but to a lesser degree than oral anticoagulation. In a meta-analysis of six clinical trials, aspirin reduced the risk of stroke by approximately 20%. The risk reduction with aspirin just achieved statistical significance and there was considerable variability in the effects of aspirin in the individual trials, with only one of the six trials demonstrating a statistically significant reduction in the risk of stroke with aspirin. The balance between efficacy for stroke prevention and safety with regards to bleeding complications is best achieved at a target international normalized ratio of 2.0–3.0. This has been confirmed by several prospective studies and retrospective analyses. Trials evaluating rate control versus rhythm control strategies in AF have reinforced the need for continued anticoagulation. The AFFIRM (Atrial Fibrillation Follow-up of Rhythm Control Management) and RACE (Rate Control Versus Electrical Cardioversion) trials have demonstrated a high rate of stroke even in ‘rhythm-controlled’ patients and have given the medical community reason to reconsider the cessation of anticoagulation in cardioverted patients. However, ultimately, the fear of bleeding complications, specifically intracranial haemorrhage, has resulted in the underuse of anticoagulation despite its proven efficacy. The recent American College of Cardiology/American Heart Association/European Society of Cardiology guidelines for the management of AF recommend an individualized approach based on the estimated risk for stroke and bleeding during anticoagulation. Newer agents with more predictable anticoagulation, and thus expected improvement of the risk/benefit ratio, may not only help clinicians meet the guideline recommendations but also expand the number of patients eligible for highly effective stroke-preventive treatment.

An epidemiological needs assessment of carotid endarterectomy in an English health region. Is the need being met?

Objective: To compare the level of provision of carotid endarterectomy (an intervention of proved efficacy for prevention of stroke in patients with symptomatic high grade carotid artery stenosis) with estimates...

虚血性脳血管障害の病態と治療

Recently it has been proved that carotid endarterectomy (CEA) is effective for the prevention of major stroke for the patients with symptomatic severe carotid stenotic lesion. However, the efficacy of extracranial-intracranial arterial bypass (EC-IC bypass surgery) for the patients with cerebrovascular occlusive lesion is still controversial. Several cooperative trials to clarify the surgical efficacy of stroke prevention and improvement of brain function had been unsuccessfully attempted. Despite this situation, a considerable number of neurosurgeons still believe bypass surgery should play some role in the treatment of cerebral ischemia.In this paper, we review the pathophysiology of cerebral ischemia, and discuss how to surgically treat it.

The stroke prevention in atrial fibrillation III study: Rationale, design, and patient features

Clinical trials have consistently shown warfarin's high degree of efficacy for stroke prevention in patients with nonvalvular atrial fibrillation (AF). However, aspirin therapy may be sufficient for large subgroups of low-risk AF patients. In addition, many elderly AF patients cannot receive or sustain adjusted-dose warfarin because of bleeding (minor and major), drug interactions, and other disutility. For such patients, a safer and easier to administer anticoagulation regimen is desirable. The Stroke Prevention in Atrial Fibrillation (SPAF) III Study has two components, based on stratification of patients as high-risk or low-risk for thromboembolism. In high-risk patients, adjusted-dose warfarin (INR 2.0 to 3.0) is compared with low-intensity, fixed-dose warfarin (INR 1.2 to 1.5 initial dose adjustment) plus aspirin (325 mg/d) in a randomized trial. Patients categorized as low-risk all receive aspirin 325 mg/d and are followed-up to assess the reliability and durability of the risk stratification scheme. Medications are administered open-label. Primary events (ischemic strokes and systemic emboli) are assessed by a local neurologist and verified by an Events Committee, neither having knowledge of assigned treatment. Transesophageal echocardiography is obtained at entry, when possible. High-risk criteria for the 1,044 patients in the randomized trial (mean age,=72 years) are impaired left ventricular function (45%), systolic blood pressure >160 mm Hg (32%), prior thromboembolism (38%), and female gender over age 75 years (24%). The mean INR is 2.4 for adjusted-dose and 1.3 for fixed-dose warfarin, with mean daily doses of 3.9 mg and 2.1 mg, respectively. Compared with high-risk patients, those categorized as low-risk (n=892) are younger (mean age, 67 years; P<.001), with lower mean systolic blood pressures, (P<.001), and less ischemic heart disease (P<.001), but similar diastolic blood pressures. Given the large variation in stroke rate among AF patients, blanket recommendations for antithrombotic prophylaxis of all AF patients are not optimal. Patient age, gender, left ventricular function, and systolic blood pressure may be useful markers of the inherent thromboembolic risk and may influence selection of antithrombotic therapy to prevent stroke in AF patients.

Cerebrovascular, neuronal, and behavioral effects of long-term Ca2+ channel blockade in aging normotensive and hypertensive rat strains.

The pathogenesis of essential hypertension is not fully understood, but most of the cardiovascular, metabolic, neurogenic, and humoral abnormalities are explained by dysfunctions in the control of intracellular Ca2+ concentrations in the cells of the vascular wall. Most theories of disturbed calcium regulation focus on the calcium concentration within vascular smooth muscle cells. The implications of hypertension for the increased calcium content of aging arteries seem to be clear, but were only studied in the peripheral circulation; hypertension prominently augments the aging-related accumulation of calcium in the vessel wall. Although the contribution of calcium overload in hypertensive cerebrovascular damage is well documented, it is not clear yet if hypertension per se is the main cause of hypertension-associated calcium-dependent cerebral damage. Thus far, the hypotensive effects of most calcium antagonists were extensively described, and their efficacy in stroke prevention was proven. Earlier studies indicated that chronic administration of nimodipine revealed a protective effect in the occurrence of strokes in SHR-SP rats, yielding a decreased mortality rate. Because nimodipine did not lower the extremely high blood pressure of these animals, the mechanisms behind such nimodipine-induced stroke prevention may be attributed to a direct cerebrovascular and/or neuronal action of nimodipine. Hypertension is generally considered a vascular pathologic condition, and most research has been directed towards the influences of hypertension on large peripheral arteries such as the aorta and coronary artery. The influence of the CNS on the regulation of cardiovascular system and blood pressure regulation was described in detail, and the role of the CNS in hypertension also was the subject of study. The increased risk of stroke in hypertensive subjects generated numerous studies on the precise nature of compromised cerebrovascular functioning under hypertensive conditions. Few data are available on Ca2+ alterations in cerebral neurons during hypertension. Honda et al. demonstrated that voltage-dependent Ca2+ uptake was higher in cortical synaptosomes from SHR than form normotensive animals and suggested that an important alteration in Ca2+ channel characteristics may occur in SHR brain synaptosomes. Although the density of L-type calcium channels was shown to be higher in the hippocampus of SHR rats, others reported that the number of L-type calcium channels was significantly lower in the brain of SHR rats than WKY normotensive controls. The latter data suggest that hypertension may be associated with similar alterations in neuronal calcium homeostasis as demonstrated for aging in normotensive subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

Surgical Management of Carotid Artery Atherosclerotic Disease*

Cerebrovascular disease remains an important cause of disability and death in the geriatric population. This paper reviews the current state of knowledge with respect to the pathogenesis and medical and surgical treatment of carotid atherosclerosis. The majority of strokes are probably due to embolization from an ulcerated atherosclerotic plaque at the carotid bifurcation rather than from ischemia produced by global reduction in cerebral blood flow related to obstruction of the carotid arteries. Ultrasonography is an appropriate screening examination, but most vascular surgeons consider contrast angiography to be essential in the preoperative evaluation. Large clinical trials have evaluated the efficacy of stroke prevention by carotid endarterectomy in symptomatic patients. The North American Symptomatic Carotid Endarterectomy Trial clearly demonstrated a benefit of surgery in stroke prevention as compared with optimal medical therapy after only 18 months of follow-up. The European Carotid Surgery Trial and a VA Cooperative Study produced similar conclusions. Much less information is available concerning the patient with carotid atherosclerosis who has no cerebral symptoms. No convincing evidence that surgery is beneficial has yet been demonstrated, but a large multicenter clinical trial (Asymptomatic Carotid Atherosclerosis Study) remains in progress.

Prophylaxis and treatment of stroke. The state of the art in 1993.

The most significant impact on cerebral infarction comes from the primary prevention of the processes that lead to stroke in at-risk individuals prior to the development of symptoms. Antithrombotic therapy with warfarin or aspirin significantly reduces thromboembolic risk in non-valvular atrial fibrillation. The failure of primary preventive measures and the progression of disease is heralded by the development of cerebral or retinal ischaemic events; the majority of clinical trials investigating stroke prevention have targeted the secondary prevention of stroke in patients with ischaemic symptoms. A 25% risk reduction has been demonstrated with antiplatelet therapy. This was typically aspirin 1000 to 1300 mg/day, but more recently even lower doses have been beneficial, with lower rates of minor and major bleeding. Ticlopidine has demonstrated efficacy in the secondary prevention of stroke after transient ischaemic attacks and completed stroke, with a 2% risk of significant neutropenia. The benefits of carotid endarterectomy have been demonstrated in patients with symptomatic internal carotid artery stenosis involving 70 to 99% of the arterial diameter. Surgery is not indicated in patients with less than 30% internal carotid artery stenosis; 30 to 69% continues to be studied. When primary and secondary preventive measures have failed, strategies directed at managing acute focal cerebral ischaemia include re-establishing cerebral blood flow and limiting ischaemic neuronal injury. Advances in basic research that have identified components of the ischaemic cascade have been translated clinically into numerous clinical trials, each targeted to one or sometimes two steps in the hope of improving neuronal salvage.(ABSTRACT TRUNCATED AT 250 WORDS)