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

Clopidogrel is a thienopyridine that irreversibly inhibits platelet aggregation by selectively binding to adenylate cyclase-coupled ADP receptors on the platelet surface. In animal models, clopidogrel reduced the formation of both arterial and venous thrombi. After oral administration, clopidogrel is rapidly absorbed and undergoes metabolic activation in the liver. The principal circulating metabolite is SR 26334, an inactive carboxylic acid derivative. The active metabolite is not yet known. Findings of a large, well controlled study of clopidogrel versus aspirin in patients with atherosclerotic vascular disease (CAPRIE study) indicate that clopidogrel has superior efficacy in terms of prevention of ischaemic stroke, myocardial infarction and vascular death. Clopidogrel-treated patients experienced less frequent gastrointestinal upset, abnormal liver function and gastrointestinal haemorrhage than patients who received aspirin, but more frequent rash and diarrhoea. Neutropenia and thrombocytopenia occurred rarely and at similar rates in both groups.
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PMID:Clopidogrel. 2642 34

Following cerebral ischaemia a recurrent stroke must be avoided in most patients by means of antithrombotic agents. Based on the results reviewed here of new therapy studies, we discuss the presently available antithrombotic treatment options for prophylaxis in ischaemic stroke. TASS (Ticlopidine Aspirin Stroke Study) and CATS (Canadian American Ticlopidine Study) are two multicentre studies investigating the effect of ticlopidine, a new antiplatelet agent of the thienopyridine family, compared to acetylsalicylic acid (ASA) respectively placebo, in the secondary prophylaxis of ischaemic stroke. A significant relative risk reduction of ticlopidine against ASA (21%) and against placebo (28.1%) was shown. CAPRIE (Clopidogrel vs. Aspirin in Patients with Risk of Ischemic Events) evaluated clopidogrel and ASA in the secondary prophylaxe of stroke, myocardial infarction and peripheral vascular occlusive disease. Clopidogrel has been shown to be as effective as ticlopidine compared to ASA in the secondary prevention of vascular disease but had the advantage of a far less severe side effect profile as ticlopidine. ESPS 2 (2nd European Stroke Prevention Study) compared dipyridamole and ASA alone and in combination against placebo in stroke prevention. The combination of agents showed a 24.4% relative risk reduction to suffer ischaemic stroke as opposed to placebo. The ranking of heparin and heparinoids in the secondary prevention of ischaemic stroke has not been completely established but seems to diminish according to recently published data from three major trials. The American TOAST study (Trial of Org 10172 in Acute Stroke Treatment) failed to prove any advantage of intravenous Orgaran compared to placebo. In IST (International Stroke Trial) and CAST (Chinese Acute Stroke Trial) the benefits of heparin are invalidated by a higher bleeding rate of patients on intravenous heparin therapy. Furthermore, the results of IST have to be judged critically because of significant methodical inadequacies. When applying antithrombotic agents, therapeutic effect and presumed better outcome should be weighed against the risk of associated bleedings. The indication for an antithrombotic treatment should be reevaluated in regular control examinations and the possibility of a less aggressive treatment should be considered.
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PMID:[Antithrombotic therapy after cerebral ischemia]. 941 27

Arterial thrombosis frequently leads to death or disability from stroke, peripheral arterial disease, or myocardial infarction (MI). Treating the underlying causes of these diseases is the key to producing significant reduction in morbidity, mortality, and health care costs. Prevention of arterial thrombosis is the primary indication for antiplatelet therapy, and intense research has been conducted in the past decade to develop novel antiplatelet agents with favorable safety profiles. The results of the Antiplatelet Trialists' Collaboration, which definitively established the rationale for antiplatelet agents in the prevention of death, MI, and stroke, were an important stimulus for this research. This large meta-analysis combined data from 145 randomized trials and showed that antiplatelet therapy (most commonly aspirin, 75 to 325 mg/d) reduced the risk of vascular events, including nonfatal MI, nonfatal stroke, and vascular death, by 25% in patients at high risk for occlusive vascular disease. The limitations and adverse effects associated with traditional antiplatelet agents such as aspirin have prompted the search for newer antiplatelet agents. Clinical trials such as the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) study, which was the first study to evaluate aspirin and clopidogrel in patients with cerebrovascular, cardiac, and peripheral arterial disease, have established the importance of newer antiplatelet effects in the management of patients with diseases associated with atherosclerosis. The pathophysiology of atherosclerosis, the mechanisms of action of antiplatelet agents, and the results of these and other clinical trials that document the value of antiplatelet agents in atherosclerosis are reviewed in this paper.
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PMID:Antiplatelet therapy in atherosclerotic cardiovascular disease. 958 29

Stroke disease remains a national priority due to the high morbidity and mortality. Good clinical practice dictates that risk factors are identified and corrected. Various therapeutic regimens have been tested in trials of sufficient strength to give answers. In the second European Stroke Prevention Study (ESPSZ), low dose aspirin (50 mg/d), sustained release dipyridamole (200 mg/d) were shown to reduce recurrence of stroke and TIA. The combination was twice as effective. Also in the Clopidogrel/aspirin Prevention of Recurrence of Ischaemic Events (CAPRIE) trial clopidogrel was shown to be superior to aspirin. In clinical practice patients with stroke or TIA should be investigated rapidly, their risk factors corrected and appropriate drug regimens implemented.
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PMID:Secondary prevention of stroke--an update. 972 33

Ticlopidine and clopidogrel achieve antiplatelet effects by inhibiting the binding of adenosine 5'-disphosphate to its platelet receptor. Ticlopidine was first shown to decrease major events compared with placebo or aspirin in patients with stroke or recent transient ischemic attack. Randomized studies in patients undergoing coronary artery stenting have shown that ticlopidine reduces the risk for subacute stent thrombosis compared with warfarin-based regimens. Smaller studies have also shown this drug to have benefit during follow-up in patients with unstable angina, peripheral arterial disease, saphenous vein coronary bypass grafts, and diabetic retinopathy. Clopidogrel was recently approved by the U.S. Food and Drug Administration for the reduction of ischemic events in patients with recent myocardial infarction, stroke, or peripheral arterial disease (incidence, 5.32% per year compared with 5.83% per year for aspirin; P = 0.043) with no added risk for neutropenia. The combination of clopidogrel and aspirin, as well as the utility of clopidogrel in other patient populations and in stenting, requires further study. Ticlopidine and clopidogrel seem to have beneficial effects compared with aspirin (the current standard) in a broad range of patients. These observations highlight the importance of antiplatelet therapy in cardiovascular disease.
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PMID:The antiplatelet effects of ticlopidine and clopidogrel. 973 68

Platelets have assumed a role in the development of focal cerebral ischemia by virtue of their participation in thromboemboli that may initiate stroke symptoms. Platelets are one component of the blood-vascular axis responsible for preventing hemorrhage. Activated platelets initiate hemostatic plug formation and provide a scaffolding for coagulation activation. Platelets are activated by a number of stimuli, such as exposure of the vascular subendothelium, fibrin deposition, and abnormal surfaces, e.g., atheromata. A number of observations, including the appearance of platelet thrombi on atheromata in situ, indicate that platelet physiology is relevant to stroke. In addition, certain antiplatelet agents (e.g., aspirin) significantly reduce the incidence of ischemic stroke after initial transient ischemic attacks. Aspirin, the combination of aspirin and dipyridamole, and ticlopidine have all been shown to be useful in reducing the frequency of secondary stroke events. Clopidogrel has been shown to reduce the frequency of secondary vascular ischemic events when stroke, myocardial infarction, and peripheral arterial disease are considered together. Unfortunately, all antithrombotic agents carry a potential risk for inducing symptomatic intracerebral hemorrhage during ischemic stroke. The mechanism by which this may happen with antiplatelet agents has not yet been determined. As in other areas of stroke treatment, it is the balance between efficacy in reduction of symptomatic thrombotic events and the risk for hemorrhage that will define benefit.
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PMID:The role of platelets in ischemic stroke. 974 24

Aspirin's benefit in preventing vascular outcomes is well established. It reduces the relative risk for stroke, myocardial infarction, and vascular death by about 25% compared with placebo. Almost 10 years ago we learned that ticlopidine is more effective than aspirin (about 12% relative risk reduction for stroke or death). However, ticlopidine has important adverse effects. In 1996, the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial showed that clopidogrel, a new thienopyridine similar to ticlopidine, is also more effective than aspirin (by a similar amount) and is as safe as aspirin. Also in 1996, the European Stroke Prevention Study 2 (ESPS-2) showed that dipyridamole alone prevents stroke and that when combined with aspirin it is more effective, probably comparable to ticlopidine and clopidogrel. Dipyridamole combined with aspirin reduced the relative risk for stroke or death by about 13% compared with aspirin alone. Both clopidogrel and dipyridamole are safe but will cost more than aspirin. Aspirin also appears beneficial for acute stroke treatment. The Chinese Acute Stroke Trial (CAST) and the International Stroke Trial (IST) demonstrated that aspirin given at the time of an acute ischemic stroke reduces the risk for early death (about 5 less/1,000 treated), recurrence or death (about 10 less/1,000 treated), and dependence (about 5 less/1,000 treated). Overall, the benefits of aspirin in acute stroke treatment and stroke prevention are definite but modest. Combination therapy with antiplatelet agents that act through different mechanisms is a promising way to maximize the benefits of antiplatelet treatment.
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PMID:What have we learned from recent antiplatelet trials? 974 31

The role of aspirin in the secondary prevention of ischaemic events is being challenged. CAPRIE, a blinded multicenter randomized trial of over 19,000 patients followed for 1-3 years, assessed the effect of clopidogrel in the secondary prevention of major vascular events. Patients with a recent myocardial infarction, stroke or peripheral arterial disease were randomized to treatment with clopidogrel or aspirin. Clopidogrel was associated with a statistically significant, overall 8.7%, relative reduction in the risk of ischaemic events, but the direction and size of the effect was not homogeneous with respect to three predefined clinical subgroups. Clopidogrel may be slightly better in preventing major ischaemic events in high-risk patients, but the results of CAPRIE suggest that there is room for doubt. It remains to be seen whether treatment with clopidogrel is cost-effective compared with aspirin. However, aspirin may still be of value in the early treatment of acute stroke. IST was a 20,000 patient, randomized, open-label study of aspirin plus heparin or neither in patients with acute ischaemic stroke that should be treated in 48 hours. There was a small but statistically nonsignificant reduction in mortality and disability at 6 months for patients allocated to early treatment with aspirin compared with those who were scheduled to avoid aspirin in the first 2 weeks after the stroke. Similar results were seen in CAST, a double-blind trial of aspirin vs. placebo in patients with suspected ischaemic stroke treated within 48 hours. A meta-analysis of the results of IST, CAST and MAST-I showed a statistically significant effect of early aspirin treatment. The role of aspirin in the treatment of acute stroke within 48 hours appears to be established.
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PMID:The results of CAPRIE, IST and CAST. Clopidogrel vs. Aspirin in Patients at Risk of Ischaemic Events. International Stroke Trial. Chinese Acute Stroke Trial. 978 32

The mechanisms of action of currently available and newer antiplatelet agents and evidence of the efficacy of antiplatelet agents for primary and secondary prevention of coronary artery disease are reviewed. Available data do not support the widespread use of aspirin for primary prevention of cardiovascular disease. Patients over the age of 50 years with at least one additional risk factor for coronary artery disease may benefit, although possibly at an increased risk of hemorrhagic stroke. Aspirin is recommended for secondary prevention of vascular disease in patients with stable or unstable angina, clinical or laboratory evidence of coronary artery disease, history of myocardial infarction, or history of stroke or transient ischemic attack. There are no data supporting a role for dipyridamole for primary or secondary prevention of ischemic heart disease. Abciximab has been shown to reduce the risk of cardiovascular complications at 30 days after percutaneous transluminal coronary angioplasty in patients with refractory unstable angina. Studies with other glycoprotein IIb/IIIa-receptor antagonists, including eptifibatide, tirofiban, and lamifiban, have yielded promising results. Ticlopidine may be used for secondary prevention of cardiovascular disease in patients with unstable angina who are allergic to or intolerant of aspirin. Clopidogrel has been shown to be safe and effective for secondary prevention of vascular events. Aspirin has a role in secondary prevention of coronary artery disease; among patients who are allergic to or intolerant of aspirin, ticlopidine has a role in patients with unstable angina and clopidogrel has a potential role in patients with ischemic heart or vascular disease.
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PMID:Antiplatelet therapy in coronary artery disease: review and update of efficacy studies. 978 97

Effective antiplatelet drugs--aspirin, ticlopidine, dipyridamole, and clopidogrel--are reviewed. Aspirin has remained the pharmacologic foundation of stroke prevention, primarily because of its low cost. It has been shown to provide a 22% relative risk reduction of stroke in high-risk patients. Its principal adverse effect is gastrotoxicity. Ticlopidine has been widely used in patients with a high risk of stroke who are sensitive to aspirin or in whom aspirin has failed. It has been associated with a median reduction in adenosine diphosphate-induced platelet aggregation of 70% in about 8-11 days. Ticlopidine has been shown to be superior to aspirin at three years in preventing stroke. The principal adverse effects are diarrhea and rash; there has been a 2.4% occurrence of neutropenia. In a trial comparing aspirin, dipyridamole, and a combination of the two, the risk of stroke was 18% lower with aspirin, 16% lower with dipyridamole, and 37% lower with combination therapy compared with placebo. The adverse-effect profile of dipyridamole has proven to be less problematic than that of aspirin or ticlopidine. In a trial comparing clopidogrel with aspirin, patients receiving clopidogrel had an annual 5.32% risk of ischemic stroke, myocardial infarction, or vascular death compared with 5.83% for patients receiving aspirin. Clopidogrel has been associated with a small occurrence of rash and diarrhea, and gastrointestinal intolerance and hemorrhage were less frequent with clopidogrel than with aspirin. Both aspirin and clopidogrel are associated with a low occurrence of neutropenia. Aspirin, ticlopidine, dipyridamole, and clopidogrel have earned a role in stroke prevention; the different adverse-effect profiles of the drugs will influence the choice of agent.
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PMID:Clinical considerations in selecting antiplatelet therapy in cerebrovascular disease. 978 98


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