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

Antiplatelet drugs protect against myocardial infarction, stroke, cardiovascular death and other serious vascular events in patients with a history of previous vascular events or known risk factors for cardiovascular disease. Aspirin reduces the risk of serious vascular events in patients at high risk of such an event by about a quarter and is recommended as the first-line antiplatelet drug. Clopidogrel reduces the risk of serious vascular events among high-risk patients by about 10% compared with aspirin. It is as safe as aspirin, but much more expensive. It is an appropriate alternative to aspirin for long-term secondary prevention in patients who cannot tolerate aspirin, have experienced a recurrent vascular event while taking aspirin, or are at very high risk of a vascular event (>/= 20% per year). Addition of clopidogrel to aspirin reduces the risk of serious vascular events among patients with non-ST-segment elevation acute coronary syndromes by 20%, and patients undergoing percutaneous coronary intervention by 30%, compared with aspirin alone. Addition of a glycoprotein IIb/IIIa receptor antagonist to aspirin reduces the risk of vascular events among patients with non-ST-segment elevation acute coronary syndromes by 10% and among patients undergoing percutaneous coronary intervention by 30%, compared with aspirin alone; it appears to provide incremental benefit in patients also treated with clopidogrel. Addition of dipyridamole to aspirin seems to be more effective than aspirin alone for preventing recurrent stroke, but its overall effect in preventing serious vascular events in patients with ischaemic stroke and transient ischaemic attack has not been determined.
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PMID:Antiplatelet drugs. 1276 6

Acute manifestations of atherosclerosis, e.g. myocardial infarction and ischaemic stroke, are among the most common causes of death in the western part of the world. Rupture of an atherosclerotic plaque results in activation, adhesion and aggregation of platelets. Antithrombotic treatment has shown to reduce mortality and morbidity and is used in both primary and secondary prevention. The thienopyridine Clopidogrel specifically and irreversibly inhibits the binding of ADP to platelet surface ADP-receptors, thereby inhibiting platelet activation and aggregation. In this publication the pharmacological background and clinical documentation for the use of Clopidogrel both as monotherapy and in combination with Acetylicsalisylic acid are reviewed.
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PMID:[Clopidogrel: background information and use in clinical practice]. 1277 93

Platelets play a key role in the development of ischemic complications in the arterial circulation. Antiplatelet therapy has proven effective in the treatment and prevention of ischemic events. Numerous clinical studies have confirmed the therapeutic efficacy of aspirin to such a point that this antiplatelet agent has become the gold standard in clinical practice. Clopidogrel is a thienopyridine compound that inhibits platelet aggregation by selectively binding to adenylate cyclase-coupled ADP receptors. Results of a large, double-blind, randomized study (CAPRIE) confirm that administration of clopidogrel to patients with atherosclerotic vascular disease is more effective than aspirin in reducing the combined risk of ischemic stroke, myocardial infarction or vascular death. The present article highlights the importance of activation of platelets through ADP receptors and reviews the pharmacology and clinical studies of clopidogrel, a selective inhibitor of these mechanisms.
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PMID:Clopidogrel: a selective inhibitor of platelet ADP receptors. 1287 16

Stroke is one of the leading causes of death and debilitation. Several million stroke survivors are alive throughout the world today. Prevention of recurrent stroke is of major importance to stroke survivors. Several pharmacological agents are currently available for use in secondary stroke prevention.Clopidogrel, the combination of immediate-release aspirin and extended-release dipyridamole and aspirin alone are the most widely recommended agents for use in the secondary prevention of strokes. Clopidogrel has shown superiority over aspirin in the combined endpoints of stroke, death and myocardial infarction. The immediate-release aspirin/extended-release dipyridamole combination has shown superiority to aspirin alone in the secondary prevention of stroke. Dipyridamole has been studied as an antiplatelet agent for several decades. Early trials to prove its efficacy compared with aspirin were not favourable, and patients often experienced many adverse effects. Researchers began developing an extended-release formulation in an effort to maintain therapeutic blood concentrations with less frequent daily administration and better adverse effect profile. Pharmacokinetic analysis of this new product showed it to have a more consistent and reproducible absorption compared with immediate-release dipyridamole. The rate of absorption of extended-release dipyridamole is considerably slower than that of immediate-release dipyridamole, while similar plasma concentrations are maintained to optimise antiplatelet efficacy. This allows extended-release dipyridamole to be administered twice daily rather than four times daily.A large-scale randomised trial was conducted with extended-release dipyridamole 200mg in combination with immediate-release aspirin 25mg given twice daily. The combination product showed a greater efficacy at preventing a recurring stroke then either agent administered alone. Indirect comparisons with clopidogrel show that the combination of immediate-release aspirin/extended-release dipyridamole may be more effective than clopidogrel at preventing a recurring stroke.
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PMID:Clinical pharmacokinetics of antiplatelet agents used in the secondary prevention of stroke. 1288 64

Atrial fibrillation (AF), the most commonly encountered cardiac rhythm disorder, affects approximately 1% of the general population and is associated with serious complications, most notably ischemic stroke. AF-associated stroke occurs at an annual rate of 4.5%. Anticoagulation therapy with warfarin has been demonstrated in randomized controlled trials to reduce the risk for AF-related stroke by two thirds, but warfarin therapy is markedly underused in clinical practice because of its narrow therapeutic window and its implications on quality of life. This article reviews the present knowledge and potential future research avenues for the role of antiplatelet therapy in AF as an alternative to anticoagulation with warfarin for prevention of AF-associated stroke. Antiplatelet therapy recently has been shown to be protective against thrombotic events related to blood stasis. There is ample evidence from experimental and clinical studies that a combination of different antiplatelet agents may increase antithrombotic efficacy compared to monotherapy. Accordingly, a series of randomized controlled trials (ACTIVE [Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events]) has been designed to vigorously examine the role of combined antithrombotic therapy for prevention of vascular events, including stroke in high-risk AF patients. The ACTIVE program began patient enrollment in spring 2003.
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PMID:Combined antiplatelet therapy in atrial fibrillation: review of the literature and future avenues. 1295 May 21

Life style modification has been shown to reduce stroke risk. In patients with risk factors several drugs have proven their efficacy. The most effective medications are antihypertensives, antidiabetics, statins and antithrombotics. In the prevention of recurrent stroke in patients with a noncardioembolic ischemic stroke antiplatelet agents are used. Aspirin or a combination aspirin/dipyridamol are the first-line agents. Clopidogrel is recommended for patients with aspirin intolerance, several risk factors or recurrent cerebrovascular events. Warfarin has demonstrated efficacy in stroke prevention in patients with cardioembolic stroke, cerebral venous thrombosis and antiphospholipid antibody syndrome. Other, less well established indications for warfarin in the secondary prevention of stroke are: symptomatic intracranial artery stenosis; large aortic atheroma and extracranial carotid or vertebral artery dissection.
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PMID:[Stroke prevention]. 1457 20

Antiplatelet drugs have an established place in the prevention of vascular events in a variety of clinical conditions, such as myocardial infarction, stroke and cardiovascular death. Both European and American guidelines recommend the use of antiplatelet drugs in patients with established coronary heart disease and other atherosclerotic disease. In high-risk patients, such as those with post-acute myocardial infarction (AMI), ischaemic stroke or transient ischaemic attack, and in patients with stable or unstable angina, peripheral arterial occlusive disease or atrial fibrillation, antiplatelet treatment may reduce the risk of a serious cardiovascular event by approximately 25%, including reduction of non-fatal myocardial infarction by 1/6, non-fatal stroke by 1/4 and cardiovascular death by 1/6. Some data indicate that antiplatelet drugs may also have a role in primary prevention. In people who are aged over 65 years, or have hypertension, hypercholesterolaemia, diabetes, obesity or familial history of myocardial infarction at young age, aspirin may reduce both cardiovascular deaths and total cardiovascular events. Aspirin has been studied and used most extensively. It may exert its beneficial effect not only by acting on platelets, but also by other mechanisms, such as preventing thromboxane A2 (TXA2)-induced vasoconstriction or reducing inflammation. Indeed, experimental data show that low-dose aspirin may suppress vascular inflammation and thereby increase the stability of atherosclerotic plaque. Moreover, in human studies, aspirin seems to be most effective in those with elevated C-reactive protein levels. Vascular events, however, do occur despite aspirin administration. This may be due to platelet activation by pathways not blocked by aspirin, intake of drugs that interfere with aspirin effect or aspirin resistance. In the CAPRIE (Clopidogrel vs. Aspirin in Patients at Risk of Ischaemic Events) study, long-term clopidogrel administered to patients with atherosclerotic vascular disease was more effective than aspirin in reducing the combined risk of ischaemic stroke, myocardial infarction or vascular death. In the setting of coronary stenting, a double regimen including aspirin and ticlopidine or clopidogrel has proved more effective in the prevention of in-stent thrombosis than aspirin alone. Chronic oral administration of the inhibitors of platelet membrane receptor GP IIb/IIIa has been largely disappointing.
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PMID:Role of antiplatelet drugs in the prevention of cardiovascular events. 1459 62

Aspirin (acetylsalicylic acid) is the most widely studied and prescribed antiplatelet drug for patients at high risk of vascular disease. It affects a single pathway in the platelet activation process and provides incomplete protection against cardiovascular events. Adenosine diphosphate receptor antagonists, by blocking an alternate pathway of platelet activation, are slightly more effective than aspirin in reducing serious vascular events in patients at high risk, with similar results for the subset of transient ischaemic attack/ischaemic stroke patients. Clopidogrel is an effective and safe alternative in patients who do not tolerate aspirin, in diabetics, in hypercholesterolaemic patients, or in those with a previous history of cardiac surgery. Moreover, antiplatelet combination therapy using agents with different mechanisms of action is an attractive preventive approach. In this way, dipyridamole combined with aspirin is being tested in the European/Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) in cerebrovascular disease patients. Clinical and preclinical studies have demonstrated that therapy with clopidogrel and aspirin provides synergistic antiplatelet effects. The Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) and PCI-CURE trials demonstrate the benefit of this combination therapy in patients who suffer from unstable angina or non-Q-wave myocardial infarction treated or not by percutaneous coronary intervention. The relative risk reduction in ischaemic events in long-term use was 20%. This antiplatelet regimen was safe and well tolerated. Currently, this therapeutic option is tested in individuals with ischaemic stroke in the Management of Atherothrombosis with Clopidogrel in High-Risk Patients with Recent Transient Ischaemic Attacks or Ischaemic Stroke (MATCH) Trial.
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PMID:Antiplatelet drugs in ischemic stroke prevention: from monotherapy to combined treatment. 1469 84

Clopidogrel is a selective inhibitor of ADP-induced platelet aggregation. A large, multicenter, randomized study in 12 562 patients with acute coronary syndromes without ST-segment elevation demonstrated that treatment with clopidogrel (loading dose of 300 mg followed by once daily treatment with 75 mg) in addition to standard therapy including aspirin (75 to 325 mg/day) significantly reduced the risk of the combined endpoint of cardiovascular death, myocardial infarction or stroke compared with treatment with standard therapy. Furthermore, the composite risk of these outcomes or refractory ischemia was also significantly reduced in patients treated with clopidogrel plus aspirin. The effects of clopidogrel were independent of background treatment with cardiovascular medications and/or interventions. The risk of severe ischemia, recurrent angina or heart failure was also significantly reduced in patients receiving clopidogrel plus aspirin. There was also a significant reduction in the need for coronary revascularization during the initial period of hospitalization. In patients undergoing percutaneous coronary intervention (PCI), the relative risk of the combined endpoint of cardiovascular death, myocardial infarction or urgent target-vessel revascularization within 30 days of the intervention was significantly reduced. Moreover, the relative risk of the single endpoint of myocardial infarction within 30 days of PCI was significantly in favor of clopidogrel-treated patients. Hemorrhagic events (both major and minor) were significantly more frequent in patients with acute coronary syndromes receiving treatment with clopidogrel plus aspirin than in patients treated with aspirin alone. This was largely attributable to an increased incidence in the rate of gastrointestinal hemorrhage and bleeding at the site of arterial puncture. However, there was no difference between the two groups in the incidence of bleeding episodes that were considered to be life-threatening.
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PMID:Clopidogrel: potential in the prevention of cardiovascular events in patients with acute coronary syndromes. 1472 5

Dual antiplatelet therapy that inhibits more than one pathway of platelet activation is appealing and biologically rational. The CURE study evaluated the efficacy and safety of clopidogrel on top of acetylsalicylic acid (ASA) versus standard therapy (including ASA) in over 12,000 patients with unstable angina or non-ST-segment elevation myocardial infarction (MI). Clopidogrel in combination with ASA reduced the relative risk of the combined atherothrombotic endpoint of cardiovascular death, MI or stroke by 20% (95% CI 0.72-0.90; p < 0.001) and the absolute risk of this composite endpoint by 2.1%. While the study was not powered or designed to demonstrate a reduction in stroke, there was a 14% reduction in stroke risk (p > 0.05). Dual antiplatelet therapy was associated with an acceptable 1% increase in the incidence of major bleeding events (p = 0.001). PCI-CURE, a prespecified substudy of patients who underwent percutaneous coronary intervention (PCI) during CURE, confirmed the early and sustained benefits of clopidogrel therapy seen in the overall CURE study. CREDO was a randomized, double-blind, placebo-controlled trial in more than 2,100 patients that evaluated the continuation of clopidogrel on top of standard therapy including ASA for 12 months after PCI, and the benefit of a preprocedural clopidogrel loading dose. The long-term results at 1 year showed that there was a 27% reduction in the risk of stroke, MI or death with long-term clopidogrel therapy (p = 0.02). There was a consistent benefit of extended clopidogrel therapy for each component of the composite endpoint, with a 25.1% relative risk reduction for all-cause stroke. In patients who received clopidogrel > or =6 h before PCI, there was a 39% reduction in the risk of death, MI or urgent target-vessel revascularization at 28 days (p = 0.051). These data suggest important implications in the future for the use of an early loading dose of clopidogrel in patients undergoing carotid stenting and, if proven in current or future trials, the use of a loading dose followed by long-term continuation of clopidogrel in other high-risk atherothrombotic patients such as those with transient ischaemic attack or ischaemic stroke.
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PMID:Recent clinical trial results with antiplatelet therapy: implications in stroke prevention. 1473 Feb 52


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