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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antithrombotic therapy plays a central role in secondary prevention after ischemic stroke and transient ischemic attack. The choice among warfarin, aspirin, and other antiplatelet agents, however, depends on the cause of stroke and other individual patient characteristics. The use of warfarin anticoagulation in patients with atrial fibrillation and ischemic stroke has demonstrated robust reductions in risk of recurrent events, comparable with those achieved in primary prevention. Warfarin may also be recommended for patients with other high-risk cardioembolic sources of stroke. The role of warfarin in noncardioembolic ischemic stroke is more controversial. The Warfarin Aspirin Recurrent Stroke Study found no evidence of superiority of warfarin over aspirin in stroke patients overall, nor in any major stroke subtype, including those patients with patent foramen ovale. In post-hoc analyses, there was some evidence of benefit with warfarin in patients with cryptogenic stroke without hypertension. Risks of major bleeding did not differ significantly between warfarin and aspirin groups. For most patients with noncardioembolic strokes, therefore, antiplatelet therapy is the preferred option, although clinician experience still dictates practice in individual situations. Newer antiplatelet agents, and the combination of novel agents with aspirin, are also finding a role in stroke prevention as clinical trial data become available.
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PMID:The role of warfarin and aspirin in secondary prevention of stroke. 1475 59

For over two decades, valuable insights have been accumulated from epidemiologic studies and randomized trials about the risks for and prevention of AF-related stroke. AF substantially raises the risk of stroke, most likely through an atrio-embolic mechanism. Warfarin and other members of its class of oral anticoagulants targeted at an INR of 2.5 can abrogate the risk of stroke attributable to AF effectively and fairly safely. High-quality management of anticoagulation can be achieved in usual clinical care. These insights have important implications for the care of individual patients and more generally for public health. Future research is needed to specify the risk of stroke and hemorrhage among patients with AF better, particularly among older individuals, to optimize use of antithrombotic agents, and to define the role of recently developed antithrombotic drugs and invasive nondrug approaches.
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PMID:Anticoagulation for atrial fibrillation. 1499 47

Dissection of the carotid artery in the neck is a relatively common condition. Most dissections are spontaneous, likely related to activities that cause sudden stretch of the pharyngeal portion of the carotid artery. Many patients do not develop brain ischemia but have a triad of neck and head pain, Horner's syndrome, and pulsatile tinnitus. Others present with transient or persistent brain ischemia. Strokes are due to the embolization of thrombus material from the lumen of the dissected artery to the intracranial arteries, most often the middle cerebral artery. Although there have been no randomized therapeutic trials in patients with carotid artery dissection, experience shows that standard anticoagulants in the form of heparin followed by Coumadin (Du Pont Pharma, Wilmington, DE) are effective in preventing further artery-to-artery emboli.
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PMID:Carotid Artery Dissection. 1509 17

Atrial fibrillation (AF) is a common arrhythmia that significantly increases the risk of stroke by the formation and embolism of left-atrial appendage thrombi. This risk can be substantially reduced with antithrombotic therapies such as aspirin or warfarin. Those with the highest risk receive the most benefit from adjusted-dose warfarin compared with aspirin or low-dose warfarin. Because of its efficacy in reducing strokes, adjusted-dose warfarin has been shown to be cost-effective in several different settings, but mostly for AF patients with at least 1 additional risk factor. Warfarin must be adjusted to international normalized ratios (INRs) within the target range of 2.0 to 3.0 to minimize the risk--as well as the cost--of stroke and bleeding. Subtherapeutic INR values occur commonly, but the consequences are increased risk of stroke and therefore increased costs. Of the several strategies available for managing anticoagulation, the key element to controlling costs is avoiding out-of-range values.
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PMID:Pharmacoeconomics of atrial fibrillation and stroke prevention. 1515 48

Atrial fibrillation (AF) is now regarded as the arrhythmia for which patients are hospitalized the most frequently, an arrhythmia that is responsible for significant morbidity and mortality. Of particular importance is that the arrhythmia is associated with a significant incidence of thromboembolism which may induce disabling and incapacitating strokes, sometimes fatal. In the past, it was thought that in patients with AF restoration and maintenance of sinus rhythm prevent the development of strokes, a presumption that has not been vindicated by controlled clinical trials. On the other hand, over many decades, it has been established that appropriate anticoagulation especially with warfarin can reduce stroke rate in nonvalvular AF by about 70%, and mortality by 26%. Aspirin reduces stroke rate by 26%, mortality by about 10%. Thus, in AF oral anticoagulants have become the focal point of therapy for the prevention of strokes and the safety and efficacy of such a therapy has been established by controlled clinical trials; moreover, the subsets of patients with AF in whom anticoagulation is mandatory have been defined on the basis of defined risk factors. Warfarin is now the anticoagulant of choice although its limitations are considerable in terms of drug-drug interactions, narrow range of therapeutic index requiring strict monitoring of intensity of anticoagulation, among other limitations which influence compliance of therapy with the agent. In this review, the continuing role of warfarin in the prevention of stroke in patients with AF is discussed as a background for the development of newer anticoagulants. The issue is of particular importance in the older patients, in whom the development of safer antithrombotic therapies remain a major challenge. In this context, the potential role of the direct thrombin inhibitors hold promise for the future and the evolving data on leading compounds of this class which may be competitive with warfarin are discussed.
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PMID:Antithrombotic therapies for stroke prevention in atrial fibrillation. 1519 94

We report a patient with essential thrombocythemia (ET) who developed progressive occlusive cerebrovascular disease accompanied by ischemic events. A 40-year-old woman presented with an ischemic stroke in the territory of the left middle cerebral artery (MCA). Diagnostic work-up disclosed a moderate stenosis of the left carotid siphon and a mildly increased platelet count. Due to aspirin intolerance warfarin was administered. Twelve months later, ischemic strokes in the left MCA territory recurred. A left internal carotid artery occlusion at the origin was diagnosed. Bone marrow biopsy showed an increased number of megakaryocytes. Warfarin was replaced by clopidogrel. Cerebral artery obstructions remained unchanged during the next 3 years (six follow-up examinations); no further ischemic events occurred during that period, while mild thrombocytosis persisted. ET may be associated with progressive obstructions of large cerebral arteries; in our case, clopidogrel was effective in preventing recurrence of ischemic events.
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PMID:Progressive occlusive disease of large cerebral arteries and ischemic events in a patient with essential thrombocythemia. 1538 83

Traditional anticoagulants employed in the treatment of thrombosis include the injectable heparins and oral warfarin. Though effective, these traditional agents are fraught with limitations in their ease of use in the clinical setting. Warfarin, for example, has many pharmacokinetic properties and food-and-drug interactions that result in unpredictable patient response and the need for expensive and time-consuming monitoring of coagulation status. Ximelagatran is a novel, promising, orally active, direct thrombin inhibitor currently in development that, for the first time in 50 years, offers a potential alternative to the mainstay oral agent "warfarin." Advantages of ximelagatran over warfarin include predictable pharmacokinetics and pharmacodynamics, a broad therapeutic window, no routine anticoagulant monitoring, no clinically significant drug interactions, and fixed-dose administration. Ximelagatran has been evaluated for thromboprophylaxis following orthopedic surgery, acute treatment and secondary prevention of venous thrombosis, stroke prevention in atrial fibrillation, and acute coronary syndromes. Results of clinical trials suggest that ximelagatran is equally or more efficacious than warfarin and/or low-molecular-weight heparin therapy without increasing rates of minor or major bleeding. Although postmarketing surveillance will provide the final test of this drug, the future looks promising for addition of a new anticoagulant with the potential to provide excellent efficacy, predictable response, and reduced adverse effects. Pending regulatory approval, ximelagatran may help overcome barriers to appropriate anticoagulant therapy, thereby decreasing morbidity and mortality associated with thrombotic diseases.
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PMID:New blood thinner offers first potential alternative in 50 years: ximelagatran. 1552 58

Non-rheumatic atrial fibrillation (NRAF) is one among the major public health problems, because it is associated with a high incidence of stroke or systemic thromboembolism. Warfarin significantly reduces cerebral/systemic events mainly in high-risk patients; unfortunately such drug is often as well under-used in eligible patients as under-dosed in treated patients. Traditional therapy with oral anticoagulants has several disadvatages: narrow therapeutic window, and often unpredictable dose-response so that frequent monitoring of the INR is required. It is therefore crucial that patients preferences and education be integrated into the decision-making process. Physicians often underprescribe oral anticoagulants since they perceive the risk of major bleeding as unacceptable because of some well known risk factors (e.g. previous bleedings, severe hypertension), and of qualms about drug interactions or alleged poor compliance. Therefore, the development of easy-to-use antithrombotic agents is still a challenge. New agents such as oral direct thrombin inhibitors are going to hold the promise for the next future. Ximelagatran is an orally active small molecule; being the first new oral anticoagulant used in large clinical trials. This molecule has many advantages in comparison to warfarin, such as the rapid onset/offset of action, the fixed oral dose, the no need of dose adjustment or of anticoagulation monitoring, as well the lack of food/alcohol intake interference as of drug interactions. The SPORTIF III and V trials have shown that ximelagatran is not inferior to warfarin in the prevention of strokes in patients with NRAF (both persistent and paroxysmal), but a side effect--consisting in the significant elevation of liver enzymes (> 3 times the upper limit of normal) in 6% of patients--was found. Further randomized trials are clearly needed, while current data suggest that ximelagatran will be able to represent a future viable therapeutic option for prevention of thromboembolism in patients with NRAF, offering huge advantages with respect to classic oral anticoagulants.
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PMID:[New perspectives for anticoagulation in non-rheumatic atrial fibrillation: oral antithrombins]. 1556 8

Warfarin therapy achieving an International Normalized Ratio between 2 and 3 has been shown to be effective in preventing stroke. However, warfarin administration is problematic because of its variable dose, interaction with numerous foods and drugs, narrow therapeutic range, need for chronic anticoagulation monitoring, and long onset and offset of action, which all contribute to the significant underuse of warfarin in patients with atrial fibrillation at risk for stroke despite clear indication for its use. This has led to new approaches. Studies with idraparinux (AMADEUS), a factor 10a inhibitor, and with aspirin and clopidogrel (ACTIVE), both platelet inhibitors, are on-going. Studies with ximelagatran (Stroke Prevention by Oral Thrombin Inhibition in Atrial Fibrillation [SPORTIF] trials III and V), an oral direct thrombin inhibitor, have been completed. They compared ximelagatran with warfarin in patients with nonvalvular atrial fibrillation at risk for stroke. The studies demonstrated that ximelagatran is not inferior to warfarin. Moreover, ximelagatran has rapid onset and offset of action, fixed oral dosing without the need for anticoagulation monitoring, low potential for food and drug interactions, and a therapeutic margin wider than that of warfarin. We anticipate further studies to demonstrate definitively that the small percentage of patients (0.5%) with elevation of both alanine aminotransferase (ALT) and bilirubin levels can be managed safely, thereby making ximelagatran a promising option for preventing thromboembolism in patients with atrial fibrillation at risk for stroke.
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PMID:New possibilities in anticoagulant management of atrial fibrillation. 1561 13

Venous thromboembolism, which is manifested as deep vein thrombosis (DVT) and pulmonary embolism (PE), represents a significant cause of death, disability, and discomfort. Two million people/year are affected by VTE, making it the third most common cardiovascular disease after coronary heart disease and stroke. The rationale for VTE prophylaxis stems from the clinically silent presentation of the disease and its prevalence among hospitalized patients. At greatest risk are patients undergoing major orthopedic surgery and those admitted to the intensive care unit with acute myocardial infarction, heart failure, ischemic stroke, respiratory disease, systemic infection, or other medical conditions that immobilize patients for 5 days or longer. Several anticoagulant regimens have been effective in reducing the risk of VTE after major orthopedic surgery. For patients undergoing total hip or knee replacement, treatment with adjusted-dose warfarin, low-molecular-weight heparins, or fondaparinux may be used. Warfarin, which has been around for more than 50 years, is the only oral anticoagulant available for VTE prophylaxis. Ximelagatran, a new low-molecular-weight oral prodrug of the direct thrombin inhibitor melagatran, has advantages over warfarin that may make it the drug of choice for prevention of VTE.
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PMID:The role of oral direct thrombin inhibitors in the prophylaxis of venous thromboembolism. 1562 37


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