Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vitamin K-antagonists are recommended for the prevention of stroke in patients with chronic atrial fibrillation, recent myocardial infarction or prostatic heart valves. Anticoagulant therapy is seldom prescribed, however, presumably for fear of haemorrhagic sequelae. The risk of bleeding during anticoagulant therapy has been evaluated in 10 recent studies of warfarin treatment for the prevention of arterial thromboembolism. The mean annual incidences of fatal and major bleeding was 0.5 percent and 1.6 percent, respectively, as compared with the placebo figures of 0.1 percent and 0.6 percent, respectively. In 3 studies where the effect of aspirin has been evaluated the mean annual incidence of fatal and major bleeding was 0.2 percent and 0.8 percent, respectively. The figures for warfarin therapy where lower than those reported from older studies. The reasons for the reduction in incidence may be less intensive anticoagulant treatment than formerly, improved laboratory control by the introduction of the International Normalized Ratio, and careful pretreatment evaluation of patients selected for clinical trials.
 ...
PMID:[Bleeding complications in oral anticoagulant treatment]. 772 54

Older individuals contribute heavily to the percentage of deaths due to myocardial infarction (MI) and stroke. The incidence of venous thromboembolism (VTE) is highest in subjects > 65 years. Prospective intervention trials involving groups of clinically comparable subjects > or = 60 allow the following statements to be made with regard to the use of antithrombotic drugs in the elderly. Antiplatelet agents. To prevent recurrence of ischaemic stroke and MI in stable/unstable angina, MI, TIA/stroke or peripheral arterial disease, aspirin is the drug of choice. Clopidogrel is more effective than aspirin in this respect. Heparin. For the treatment of acute deep venous thrombosis (DVT) and pulmonary embolism (PE), intravenous standard heparin or subcutaneous standard heparin are effective (aPTT 1.5-2.0 times baseline values). As the risk of bleeding increases with age, low-molecular-weight heparins (LMWH) are preferable in the elderly. For the prophylaxis of VTE in general surgery in subjects at low-moderate risk, low-dose heparin or low doses of LMWH are effective. In subjects at high risk, adjusted-dose heparin plus physical devices or high-dose LMWH are recommended. The combination of heparin and aspirin is the standard treatment for unstable angina and non-Q wave MI. LMWH are as active as standard heparin in this indication. Vitamin K antagonists. For the chronic treatment of VTE, warfarin is also the treatment of choice (INR 2.0-3.0) in the elderly, though lower doses are needed due to their hypersensitivity to oral anticoagulants. For the prevention of thromboembolic stroke in patients > 75 with atrial fibrillation, warfarin is the drug of choice. Patients aged 65-75 may receive warfarin or aspirin. Thrombolytic agents. Thrombolytic agents are not recommended for treating DVT in the elderly because of their limited risk/benefit ratio and should be confined to massive PE. In the absence of contraindications, thrombolysis for MI may be considered in the elderly.
 ...
PMID:Antithrombotic drugs for older subjects. Guidelines formulated jointly by the Italian Societies of Haemostasis and Thrombosis (SISET) and of Gerontology and Geriatrics (SIGG). 1138 24

Vitamin K-inhibiting anticoagulants, especially warfarin, have become standard treatment for reducing the incidence of strokes and systemic emboli in patients with nonvalvular atrial fibrillation (NVAF). The randomized controlled trials that form the scientific basis for the efficacy of anticoagulants in prophylaxis of embolic events show small but statistically significant benefit with warfarin and other vitamin K inhibitors. The generalizability of these randomized trials to clinical practice is highly questionable because of the low percentage of NVAF patients from the participating institutions that entered the trials, the relatively young age of the patients, and the superior anticoagulation monitoring compared with that in general practice. Indirect comparisons of warfarin with aspirin by looking at separate meta-analyses of placebo-controlled randomized trials give potentially biased results. The meta-analyses of trials directly comparing warfarin with aspirin have diametrically opposing conclusions. In contrast to observational studies of general medical practice, randomized trials significantly underestimate the bleeding risks of warfarin. Anticoagulants for stroke prophylaxis for NVAF cause about 17,000 major bleeds in the United States per year, of which about 4000 are fatal. In 5 randomized trials with follow-up periods of 1.3-2.3 years, 10% to 38% of patients permanently discontinued anticoagulants. The 2-year average follow up of patients in the randomized trials is too short to predict the long-term impact of anticoagulation on the natural history of NVAF. Aspirin should be preferred over anticoagulants in prophylaxis against cardiogenic embolism in NVAF patients.
 ...
PMID:Anticoagulants for nonvalvular atrial fibrillation (NVAF)--drug review. 1282 65

Anticoagulation with antivitamin K (AVK) is very effective for primary and secondary prevention of thromboembolic events. However, questions persist about the risks and management of over-anticoagulation. For reversal of excessive anticoagulation by warfarin, AVK withdrawal, oral or parenteral vitamin K administration, prothrombin complex or fresh frozen plasma may be used, depending on the excess of anticoagulation, the existence and site of active bleeding, patient characteristics and the indication for AVK. In over-anticoagulated patients, vitamin K aims at rapid lowering of the international normalized ratio (INR) into a safe range to reduce the risk of major bleeding and therefore improving patient outcome without exposing the patient to the risk of thromboembolism due to overcorrection, resistance to AVK, or an allergic reaction to the medication. The risk of bleeding increases dramatically when the INR exceeds 4.0-6.0, although the absolute risk of bleeding remains fairly low, <5.5 per 1000 per day. Patient characteristics, including advanced age, treated hypertension, history of stroke, and concomitant use of various drugs, affect the risk of bleeding. The absolute risk of thromboembolism associated with overcorrection appears to be in the same range as the risk of bleeding due to over-anticoagulation. The use of vitamin K in patients with warfarin over-anticoagulation lowers excessively elevated INR faster than withholding warfarin alone; however, it has not been clearly demonstrated that vitamin K treatment does, in fact, lower the risk of major hemorrhage. As vitamin K administration via the intravenous route may be complicated by anaphylactoid reactions, and via the subcutaneous route by cutaneous reactions, oral administration is preferred. A dose of 1-2.5mg of oral phytomenadione (vitamin K(1)), reduces the range of INR from 5.0-9.0 to 2.0-5.0 within 24-48 hours, and for an INR >10.0, a dose of 5mg may be more appropriate. Overcorrection of the INR or resistance to warfarin is unlikely if the above doses of vitamin K are used. Vitamin K is less effective for over-anticoagulation after treatment with acenocoumarol or phenprocoumon than after treatment with warfarin.
 ...
PMID:The use of vitamin K in patients on anticoagulant therapy: a practical guide. 1496 65

Anticoagulation therapy with unfractionated heparin, low-molecular-weight heparins and oral vitamin K antagonists is currently the mainstay of treatment and prevention of thromboembolic disorders (such as deep vein thrombosis, pulmonary embolism and stroke prevention in patients with atrial fibrillation). Although these therapies have proven benefits, they also have important limitations that result in their underuse in routine clinical practice. Consequently, many patients identified by guidelines as requiring anticoagulant therapy receive no or inadequate treatment. Heparins require parenteral administration and pose the risk of heparin-induced thrombocytopenia. Vitamin K antagonists have a narrow separation of antithrombotic and haemorrhagic effects and numerous food and drug-drug interactions, and require frequent coagulation monitoring and dose adjustment to ensure effective antithrombotic protection while minimizing the risk of bleeding complications. In response to these limitations, several new anticoagulants have recently been developed, including selective factor Xa inhibitors such as fondaparinux and ximelagatran, the first oral agent in the new class of direct thrombin inhibitors and the first new oral anticoagulant for almost 60 years. Ximelagatran possesses many of the properties of an ideal agent for anticoagulation therapy. With its oral formulation, consistent and predictable pharmacological profile and no coagulation monitoring, ximelagatran has the potential to increase the use and duration of anticoagulation treatment in thromboembolic disorders and to reduce the burden associated with long-term management.
 ...
PMID:Current issues in anticoagulation. 1581 98

Atrial fibrillation is the most common sustained cardiac arrhythmia and the most frequently encountered cause of embolic stroke. Vitamin K antagonists (such as warfarin) have represented the cornerstone of anticoagulation practice for the last 60 years. Although highly effective in preventing thromboembolic events among patients with atrial fibrillation, warfarin therapy is limited by a multitude of potential problems. Hence, warfarin is significantly underused in clinical practice, with only half of warfarin-treated patients actually achieving therapeutic anticoagulation in routine clinical practice. Consequently, there is an overwhelming need for an alternative oral anticoagulant for patients with atrial fibrillation that is safer, more practical and effective. Ximelagatran (Exanta, AstraZeneca) is a novel oral direct thrombin inhibitor that is rapidly converted to the active compound melagatran after oral absorption. It has a low potential for drug interactions, anticoagulation monitoring is not required, and it is administered at a fixed twice-daily dose. The Stroke Prevention using the ORal Thrombin Inhibitor in patients with nonvalvular atrial Fibrillation (SPORTIF) III and V trials have together demonstrated the noninferiority of ximelagatran relative to warfarin for the prevention of stroke and embolic events in atrial fibrillation. Unfortunately, initial optimism has been tempered by serious concerns over its safety data in view of its propensity to cause elevation in liver enzymes.
 ...
PMID:Ximelagatran for stroke prevention in atrial fibrillation. 1607 67

Unfractionated heparin, low-molecular-weight heparins and vitamin K antagonists are established antithrombotic agents, but all have a number of limitations. Unfractionated heparin requires parenteral administration, has a short half-life and variable dose-response relationship. Low molecular weight heparins are more effective than low-fixed-dose unfractionated heparin in the prevention of postoperative venous thromboembolism in high-risk surgical patients but they still require subcutaneous administration. Vitamin K antagonists have a narrow therapeutic window and require a careful laboratory monitoring to minimize the risk of bleeding or thrombosis. Direct thrombin inhibitors are selective inhibitors of this key enzyme. Direct thrombin inhibitors inactivate thrombin without requiring any plasma cofactor, inhibit both free and fibrin-bound thrombin, and do not appreciably bind to plasma proteins. Ximelagatran, the first oral direct thrombin inhibitor, is rapidly absorbed and converted to its active form melagatran, which can itself be administered subcutaneously. Ximelagatran has been evaluated in the prevention of venous thromboembolism after major orthopaedic surgery, in the treatment of venous thromboembolism, in the prevention of stroke in patients with atrial fibrillation and in the prevention of recurrence after acute coronary syndromes. In the European studies in major orthopaedic surgery ximelagatran was administered orally after one or two days of melagatran, given subcutaneously. This review will report on the mechanism of action and clinical pharmacology of direct antithrombin agents and on the results of the clinical trials performed with direct thrombin inhibitors in the prevention of venous thromboembolism after major orthopaedic surgery. Taken together, these results indicate that direct thrombin inhibitors, ximelagatran in particular, have the potential to be a valid alternative to low molecular weight heparins and oral anticoagulants in the prevention of venous thromboembolism after major orthopaedic surgery.
 ...
PMID:Direct thrombin inhibitors for the prevention of venous thromboembolism after major orthopaedic surgery. 1630 19

Shortcomings of the existing anticoagulants, vitamin K antagonists and heparins, have led to the development of newer anticoagulant therapies. In particular, Vitamin K antagonists' slow onset of action, numerous drug interactions, narrow therapeutic window and need for frequent monitoring make it the most obvious target for replacement. Targeting specific coagulation enzymes or steps in the coagulation pathway, new anticoagulants have been or are under evaluation in clinical trials for a number of clinical indications, namely the prevention and treatment of venous thromboembolism, the prevention of ischemic stroke in patients with atrial fibrillation, and in acute coronary syndromes. Following a brief review of pharmacological aspects, this article will summarize the results of Phase III clinical trials evaluating the novel anticoagulants fondaparinux, ximelagatran and idraparinux. At present, most attention is directed at developing an oral anticoagulant to replace vitamin K antagonists for prevention of systemic thromboembolism. A number of newer agents are in both early and advanced stages of investigation.
 ...
PMID:Clinical trials of new anticoagulants. 1663 60

Atrial fibrillation is the most common sustained rhythm disturbance and its prevalence is increasing worldwide due to the progressive aging of the population. Current guidelines clearly depict the gold standard management of acute symptomatic atrial fibrillation but the best-long term approach for first or recurrent atrial fibrillation is still debated with regard to quality of life, risk of new hospitalizations, and possible disabling complications, such as thromboembolic stroke, major bleeds and death. Some authors propose that regaining sinus rhythm in all cases, thus re-establishing a physiologic cardiac function not requiring a prolonged antithrombotic therapy, avoids the threat of intracranial or extracranial haemorrhages due to Vitamin K antagonists or aspirin. On the contrary, advocates of a rate control approach with an accurate antithrombotic prophylaxis propose that such a strategy may avoid the risk of cardiovascular and non cardiovascular side effects related to antiarrhythmic drugs. This review aims to explore the state of our knowledge in order to summarize evidences and issues that need to be furthermore clarified.
 ...
PMID:Rate-control or rhythm-control: where do we stand? 1694 79

The objective of this study was to evaluate the safety and efficacy of low-intensity warfarin treatment plus aspirin during the first 6 months after surgery in patients undergoing heart valve substitution with mechanical prostheses. Vitamin K antagonists (VKA) are able to reduce but not eliminate thrombosis and systemic embolism in patients with mechanical heart valves. The intensity of treatment and additional use of aspirin in these patients is still controversial. Consecutive patients undergoing aortic or mitral valve replacement (or a combination of the two) with mechanical prostheses were invited to participate in the study. After stratifying for site of prosthesis, patients were randomized to receive low intensity VKA treatment (target INR 2.5) plus aspirin (100 mg/day) for the first six months (Group A) or standard-intensity (INR target 3.7) VKA treatment (Group B). Mean follow-up was 1.5 years. Principal outcome events were systemic embolism, major bleeding, and vascular death. A total of 94 patients in Group A and 104 in Group B were randomized and followed up for 144 and 163 patient years, respectively. There were 5 (5%) events in Group A (4 major bleeding events and 1 vascular death) and 4 (4%) in group B (2 major bleeding events and 2 ischemic stroke). All the events except 1 occurred within the first 6 months after surgery. Cumulative incidence of primary outcome events was 5.8% (95% CI 0.9 to 10.7) in Group A and 4.3% (95% CI 0.2 to 8.4) in Group B (p=0.6). Low-intensity treatment plus aspirin during the first six months after surgery appears to be as effective and safe as moderate-high-intensity anticoagulation.
 ...
PMID:Low-intensity oral anticoagulant plus low-dose aspirin during the first six months versus standard-intensity oral anticoagulant therapy after mechanical heart valve replacement: a pilot study of low-intensity warfarin and aspirin in cardiac prostheses (LIWACAP). 1763 86


1 2 3 4 5 6 7 8 9 10 Next >>