Thrombolysis for acute stroke

Thrombolysis for acute stroke is effective if administered according to the approved protocol. Since the initial report of success in 1995, a number of subsequent reports confirmed the safety and efficacy of this treatment. There is no particular subgroup of patients at increased likelihood of benefit or hemorrhage that can be identified at baseline. Unlike many expensive therapies, thrombolysis for acute stroke saves the health care system considerable long-term costs. The search for even safer and more effective thrombolytics continues.     

Recent trials of antithrombotics in the management of patients with acute coronary syndromes

Conclusions This is an exciting time to practice acute care cardiology as the tools of molecular biology are being used to discover multiple new therapies that affect the thrombotic system and may offer real benefit to patients. Correspondingly, the tools of information technology offer the real possibility that these new therapies can be rapidly and definitively studied in large outcome trials. Continued biologic discovery, coupled with reliable clinical trials methodology should allow clinicians to offer patients and society therapies with proven benefits and understood risks.     

Optimum control of blood glucose for prevention and treatment of ischemic and hemorrhagic stroke

Opinion statement  Stroke is the most common cause of disability and a major cause of mortality. Each year, more than 500,000 Americans sustain a stroke. Reperfusion and antithrombotic therapies are still of limited benefit, hence increasing interest has been focused on therapeutic approaches that prevent and/or modulate infarct evolution. Hyperglycemia in acute stroke has a poor prognosis and is associated with significant morbidity and mortality. However, it remains unclear whether intensive lowering of blood glucose levels in the hyperacute and acute phases of stroke improves clinical outcomes. Experimental data suggest that elevated blood glucose may contribute to infarct expansion directly through a number of maladaptive metabolic pathways and that treatment with insulin may attenuate these adverse effects. Despite some controversy surrounding the optimal level of blood glucose control, much of the evidence to date supports rigorous blood glucose control and comprehensive cardiovascular risk factor management to prevent stroke in patients with diabetes. The current recommendation is to aim for strict control of blood pressure, glucose, and lipids along with lifestyle modification to improve cardiovascular health. However, there remains a distinct paucity of information concerning secondary stroke prevention. To date, the overwhelming evidence suggests that aggressive glucose management should be the standard of care in all patients with stroke and hyperglycemia. This article presents an overview of the recommendations for the optimum control of blood glucose for prevention and treatment of ischemic and hemorrhagic stroke.     

Prim?r- und Sekund?rpr?vention des Schlaganfalls

Despite considerable advances in acute stroke therapy, stroke prevention remains the most promising approach for reducing the burden of stroke. A healthy lifestyle and the treatment of cardiometabolic risk factors are the cornerstones of both primary and secondary stroke prevention. Due to a proportionately higher risk of bleeding complications, platelet inhibitors are not recommended for primary stroke prevention. Platelet inhibitors are effective in the secondary prevention of stroke with acetyl salicylic acid (ASS) and clopidogrel showing the most consistent data. New oral anticoagulants are slightly more effective than coumarin and significantly reduce the risk of intracranial hemorrhage. They offer the opportunity to bring more patients with atrial fibrillation at risk for stroke into anticoagulation particularly those on ASS therapy. Surgery for patients with asymptomatic carotid artery stenosis should be viewed critically with respect to an only marginal benefit and improvement in medical therapies. Carotid endarterectomy remains the gold standard for patients with symptomatic carotid stenosis because of an increased procedural stroke risk with carotid stenting. Patients with symptomatic intracranial stenosis or cryptogenic stroke and a patent foramen ovale should receive only medical treatment.     

Acute Coronary Syndrome in the Patient with Diabetes: Is the Management Different?

Diabetic patients who present with an acute coronary syndrome (ACS) have a particularly adverse prognosis, largely contributed by increased platelet reactivity and higher burden of disease severity. Diabetic patients with ACS derive a greater benefit from established therapies, particularly platelet-inhibiting therapies, including clopidogrel pretreatment, and glycoprotein IIb/IIIa inhibitor use. Recent data show intense ADP-P2Y12 platelet receptor inhibition with prasugrel is of particular clinical value in the diabetic patient with ACS, without excessive bleeding. Diabetic patients with ACS also benefit more from aggressive revascularization strategies. Recent data show the benefit of drug-eluting stents in the setting of primary percutaneous coronary intervention for ST-segment elevation myocardial infarction in decreasing target vessel revascularization up to 2 years, particularly in patients at highest risk for restenosis with bare metal stents (likely diabetic patients). This review summarizes the data supporting the key pharmacologic and revascularization management strategies to guide the clinician in taking care of diabetic patients who present with an ACS event.     

Which novel agents for acute myeloid leukemia are likely to change practice?

There has been little progress in drug development in acute myeloid leukemia (AML) in the recent past. This recently changed with the approval of several therapies for patients with this disease and prompts one to consider which therapies may change practice for patients with AML. To change practice, a therapy must be adopted as a standard of care intervention based on its efficacy and safety profile and must endure as the accepted treatment for a particular indication for a significant period of time. Here I attempt to determine which therapies, approved or in development, may change practice in the field of AML.     

Differences in stroke care practices between regional and metropolitan hospitals

BACKGROUND: A recent audit of stroke care in major Australian metropolitan teaching hospitals showed considerable variation in care practices and uptake of evidence-based therapies. We could find no published data on stroke care practices in regional Australia. AIM: To compare acute stroke care practices at four regional hospitals with a metropolitan teaching hospital with a stroke unit. METHODS: The hospital medical records of 30 consecutive patients at each hospital (total 150 patients), with a discharge diagnosis of stroke, were retrospectively audited to identify differences in stroke care practices, including the use of investigations, acute interventions, and secondary prevention strategies, between the regional and metropolitan, and between smaller (less than 150 stroke admissions annually) and larger (more than 250 admissions annually) hospitals. RESULTS: Patients treated at regional or smaller hospitals were less likely to have a computed tomography head scan within 24 h of admission, carotid duplex, echocardiography, estimations of lipids and glucose, a swallow assessment, involvement of allied health professionals or be prescribed prophylaxis against deep vein thrombosis, compared to patients treated at metropolitan or larger hospitals. CONCLUSIONS: Significant differences in stroke care practices exist between regional/smaller and metropolitan/larger hospitals. Strategies designed to minimize variation in care practices, such as evidence-based care pathways, should be explored.     

Acute stroke and transient ischaemic attack management – time to act fast

Stroke is Australia's second single greatest killer with 53 000 new events each year at a rate of 1 every 10 min. Stroke services should be organized to enable people to access proven therapies, such as stroke unit care and thrombolysis, to reduce the impact of stroke. Timely, efficient and coordinated care from ambulance services, emergency services and stroke services will maximize recovery and prevent costly complications and subsequent strokes. Efficient management of patients with transient ischaemic attack can produce significant reductions in subsequent stroke events and risk stratification using the ABCD2 tool can aid management decisions. Evidence for acute stroke care continues to evolve and it is crucial that health professionals are aware of, and implement, best practice clinical guidelines for stroke care.     

Cerebrovascular complications of fibromuscular dysplasia

Opinion statement Patients with cerebral ischemia or hemorrhage due to fibromuscular dysplasia (FMD) should be admitted to a monitored hospital bed and receive supportive stroke care. Based on our personal clinical experience, we recommend antiplatelet agents for future stroke prevention in patients with symptomatic FMD. In patients with watershed stroke due to hemodynamically significant FMD, our opinion is that hypertensive, hypervolemic therapy should be initiated immediately. Additionally, we suggest that potential revascularization therapies, such as intraoperative or primary percutaneous angioplasty, should be discussed.     

Balancing benefit against risk in the choice of therapy for coronary artery disease. Lesson from prospective, randomized, clinical trials of percutaneous coronary intervention and coronary artery bypass graft surgery

The ageing world population faces a coming pandemic of high-risk coronary artery disease (CAD). Patients with CAD have 3 therapeutic options, which are based on objective clinical outcome: medical therapy and risk factor modification (Medicine), and 2 forms of revascularization, coronary artery bypass graft surgery (CABG), and percutaneous coronary intervention (PCI). More than 50 large (>100 patients), multicenter, prospective, randomized clinical trials (RCT) have compared these treatment options in terms of clinical benefits and patient risks. The randomized trials which demonstrated hard outcome (survival, myocardial infarction, stroke) benefits from statins, angiotensin-converting enzyme inhibition and thienopyridines have all been completed subsequent to the publication of most Medicine versus revascularization trials. These medical therapies, plus aspirin, beta-blockers, and risk factor modification, should be made available to patients regardless of the decision to revascularize, or the decision by what means (CABG or PCI). This review integrates the information from these trials, comparing the clinical benefits against the risks inherent in the 3 therapeutic options. The results of our review show that: trials of medicine versus revascularization (either CABG or PCI) support the revascularization paradox, in that the patients at highest risk of adverse outcome, from myocardial ischemia, have a hard outcome benefit (survival, MI, or stroke) from revascularization. This paradox, first seen in the Medicine versus CABG trials of the 1970s, is evident in the trials comparing fibrinolysis and other medicines, with primary PCI for ST-elevation myocardial infarction (MI). The paradox is evident in the conservative versus invasive strategy trials of non-ST-elevation MI and unstable angina, where the benefit of revascularization occurs only in high-risk subsets. The paradox often results in sicker patients, who have more to gain from revascularization, being denied it because of the elevated perception of risk (comparable to a reperfusion paradox in ST-elevation MI, where patients most likely to benefit from thrombolytics are denied them because of the perception of risk). Trials that compared medicine with revascularization for the treatment of acute MI support the use of PCI as the preferred early stabilization strategy (90% of all PAMI trial patients). The majority of the PCI versus CABG trials enrolled populations that were at relatively low risk for ischemic clinical events. These trials demonstrated few hard outcome (survival, MI, or stroke) differences between CABG and PCI. On the basis of the results obtained the following conclusions may be drawn: medicines are the primary options for stable, low-risk CAD, and should be given to all CAD patients. Medically refractory is a useful high-risk marker of potential benefit from revascularization. CABG continues to be the complete revascularization option for patients with multivessel, multi-lesion CAD, in part because of its application to chronic occlusions. PCI is the acute stabilization method of choice for patients with on-going ischemia and acute MI, especially among patients with hemodynamic compromise, and/or major comorbidity.     

Sugar and Stroke: Cerebrovascular Disease and Blood Glucose Control

In this review we will discuss the cerebrovascular consequences of dysglycemia and current evidence for therapy, making reference to recent work in the fields of neuropathology, epidemiology, and relevant clinical trial data. Prospective observational and clinical trial data show a clear association between diabetes mellitus and vascular disease, which extends to cerebrovascular disease. The benefits of intervention to lower blood glucose in terms of microvascular health are well established but benefit on macrovascular, especially cerebrovascular, health has been less apparent. Recent large‐scale trials and metaanalyses have helped us to better define the role of glycemic control in macrovascular disease. Although few studies of glycemic therapy have used cerebrovascular disease as a primary endpoint, stroke‐specific data can be derived. Associations between blood glucose and outcome are also apparent for acute stroke. A period of hyperglycemia is common, with elevated blood glucose in the periinfarct period consistently linked with poor outcome in patients with and without diabetes. The mechanisms that underlie this deleterious effect of dysglycemia on ischemic neuronal tissue remain to be established, although in vitro research, functional imaging, and animal work have provided clues. While prompt correction of hyperglycemia can be achieved, trials of acute insulin administration in stroke and other critical care populations have been equivocal. Diabetes mellitus and hyperglycemia per se are associated with poor cerebrovascular health, both in terms of stroke risk and outcome thereafter. Interventions to control blood sugar are available but evidence of cerebrovascular efficacy are lacking. In diabetes, glycemic control should be part of a global approach to vascular risk while in acute stroke, theoretical data suggest intervention to lower markedly elevated blood glucose may be of benefit, especially if thrombolysis is administered. Trials have been underpowered to demonstrate treatment effect and any intervention must be balanced against risk of hypoglycemia.     

The Role of Hospitalists in the Acute Care of Stroke Patients

Stroke care has become progressively more complicated with advances in therapies necessitating timely intervention. There are multiple potential providers of stroke care, which traditionally has been the province of general neurologists and primary care physicians. These new players, be they vascular neurologists, neurohospitalists, internal medicine hospitalists, or neurocritical care physicians, at the bedside or at a distance, are poised to make a significant impact on our care of stroke patients. The collaborative model of care may be or become the most prevalent as physicians apply their distinct skill sets to the complex care of inpatients with cerebrovascular disease.     

Cerebrovascular complications of fibromuscular dysplasia

Opinion statement  Patients with cerebral ischemia or hemorrhage due to fibromuscular dysplasia (FMD) should be admitted to a monitored hospital bed and receive supportive stroke care. Based on our personal clinical experience, we recommend antiplatelet agents for future stroke prevention in patients with symptomatic FMD. In patients with watershed stroke due to hemodynamically significant FMD, our opinion is that hypertensive, hypervolemic therapy should be initiated immediately. Additionally, we suggest that potential revascularization therapies, such as intraoperative or primary percutaneous angioplasty, should be discussed.     

Stroke Treatment Using Intravenous and Intra-Arterial Tissue Plasminogen Activator

OPINION STATEMENT: Acute ischemic stroke is the most common cause of adult disability in the world and the third most common cause of death. Early restoration of perfusion to ischemic brain has been a highly successful strategy to decrease the disability associated with acute ischemic stroke. For acute stroke, intravenous (IV) tissue plasminogen activator (t-PA) is the only proven acute treatment that results in improved clinical outcomes. IV t-PA is indicated for ischemic stroke when administered within 4.5?h or less of symptom onset. This 4.5-hour treatment window represents a significant expansion from the previous 3-hour treatment window for therapy. Despite a longer time window, patients have the greatest chance for an improved outcome when treatment occurs as soon as possible from the time of symptom onset. The Emergency Department goal for treatment is a door to t-PA administration time of 60?min. In order to facilitate rapid evaluation and treatment, systems of care that streamline treatment should be developed at every institution that cares for acute ischemic stroke patients. For those with contraindications to t-PA and those outside the treatment window, catheter-directed intra-arterial (IA) t-PA administration or mechanical clot extraction is a potential means of restoring brain perfusion. These therapies should not preclude the use of IV t-PA when feasible and are frequently only available at tertiary care centers. Technological advances in IA devices for mechanical clot extraction make this a promising and growing area for advancing stroke therapy but remain under ongoing investigation to establish improved clinical outcomes.     

Management of acute ischemic stroke

The management of acute ischemic stroke aims to verify the clinical diagnosis, to start general supportive care and to enable decision-making about specific forms of therapy.The risk-benefit ratio is time-dependent for many therapeutic options; therefore time delays are a disadvantage within the rescue chain. The trained and multidisciplinary team of the stroke unit forms the backbone of acute management. In addition, technical infrastructure influences therapeutic options and cerebral imaging is the cornerstone.The following four therapies are evidence-based: treatment on a stroke unit, thrombolysis, early administration of acetylsalicylic acid (ASS) and hemicraniectomy in patients younger than 60 years with a so-called malignant infarction.This article describes the necessary diagnostic steps and the general and specific therapeutic options that comprise acute management within the first 48?h.     

Akutversorgung des isch?mischen Schlaganfalls

The management of acute ischemic stroke aims to verify the clinical diagnosis, to start general supportive care and to enable decision-making about specific forms of therapy. The risk-benefit ratio is time-dependent for many therapeutic options; therefore time delays are a disadvantage within the rescue chain. The trained and multidisciplinary team of the stroke unit forms the backbone of acute management. In addition, technical infrastructure influences therapeutic options and cerebral imaging is the cornerstone. The following four therapies are evidence-based: treatment on a stroke unit, thrombolysis, early administration of acetylsalicylic acid (ASS) and hemicraniectomy in patients younger than 60 years with a so-called malignant infarction. This article describes the necessary diagnostic steps and the general and specific therapeutic options that comprise acute management within the first 48?h.     

Diabetes Mellitus and Acute Coronary Syndrome: Lessons From Randomized Clinical Trials

Diabetes mellitus is a major independent risk factor for acute coronary syndrome (ACS). In addition, diabetic patients with ACS suffer from increased mortality compared to their nondiabetic peers. Driven by multiple pathophysiological disturbances, such patients are predisposed to a proinflammatory, prothrombotic state, which may lead to plaque rupture. To counteract this more complex biology, several therapies and strategies have emerged, with some having unique preferential benefits in this population. Antiplatelet agents such as aspirin and clopidogrel have long been standard of care. Dose adjustment of these therapies remains the subject of continued research. Along with medical therapy, ACS diabetic patients preferentially benefit from primary percutaneous intervention compared to fibrinolysis. However, with advances in reperfusion techniques, the optimal strategy has yet to be determined. With these differences in ACS treatment responses, diabetic individuals may not just be a high-risk group, but may actually constitute a fundamentally different population, requiring dedicated clinical trials and individualized treatment regimens.     

Evolving role of revascularization in older adults with acute coronary syndrome

Revascularization following acute coronary syndrome reduces morbidity and, in some cases, improves survival. Revascularization is part of a care plan that must include optimal medical therapy for secondary prevention and also counseling to promote healthy behaviors. The use of revascularization and guideline-recommended therapies declines as patients age, which may be attributed, in part, to geriatric or “age-associated” vulnerability. Such common geriatric factors include functional decline, comorbid illness, heightened risks of adverse procedural complications or adverse drug reactions, and clinician-perceived decisions regarding risk versus benefit. Patient selection for invasive management must consider patient preferences and risks from age-related multimorbidity. In selected older adults for whom revascularization is favored, advances in percutaneous coronary practices have paralleled improvements in cardiac surgery, both of which are employed to treat older adults in the setting of acute ischemic heart disease.     

Elderly patients with acute coronary syndromes: higher risk and greater benefit from antiplatelet therapy and/or interventional therapies

Outcomes in elderly patients with acute coronary syndromes are worse than in younger patients, and disappointingly, some therapies, such as thrombolysis for ST elevation myocardial infarction, appear to have less relative benefit than in younger patients. However, in unstable angina and non-ST elevation myocardial infarction, the elderly appear to derive greater relative and absolute benefit from the newer more potent antithrombotic therapies. With the glycoprotein IIb/IIIa inhibitors, an equivalent relative benefit has been observed, which translated into a greater absolute benefit in older vs. younger patients. Similarly, when comparing clopidogrel plus aspirin to aspirin alone, there was a consistent 20% reduction in cardiovascular death, myocardial infarction, or stroke in both elderly and younger patients. An emerging area of focus, however, is that of the appropriate dose in the elderly. Because the elderly on average have worse renal function, many drugs will not be cleared as well, and thus higher plasma levels will exist, which can translate into higher bleeding complications. Future studies are evaluating downward dose-adjustment of new therapies in the elderly as a means of improving the efficacy/safety profile. Thus, in unstable angina and non-ST elevation myocardial infarction, elderly patients are at higher risk and appear to derive particular benefit from more aggressive antithrombotic and interventional therapies.     

Management of acute ischemic stroke.

Management of an acute ischemic stroke is multifaceted. Treatment in a specialized stroke unit reduces mortality and morbidity. Components of care include interventions to control or prevent medical or neurologic complications, rehabilitation, and initiations of therapies to forestall recurrent stroke. The key to modern treatment is the emergent administration of tissue plasminogen activator (rtPA). Thrombocyte treatment improves outcome when it is given within 3 hours of onset of stroke to carefully selected patients.