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

Peripheral arterial disease (PAD) is associated with platelet hyperaggregability as well as an increase in morbidity and mortality from myocardial infarction and stroke. Enhanced platelet activation in PAD may substantially contribute to these adverse outcomes. A relative resistance to aspirin therapy has been reported in patients with PAD. Therefore, clopidogrel may be superior to aspirin in treatment of PAD. Furthermore, the aspirin + clopidogrel combination could be more effective than monotherapy but its risk-benefit ratio has yet to be evaluated. Clopidogrel is preferable to ticlopidine because of its safer profile and the convenience of once-daily administration. The glycoprotein (Gp) IIb/IIIa inhibitors may also find a place as short-term therapy after peripheral angioplasty. There is a need to consider the use of clopidogrel in patients who cannot tolerate aspirin. Patients who have an event while taking aspirin also present a problem. One possibility here is to substitute aspirin with clopidogrel or to add clopidogrel to the aspirin. Although these options are currently not evidence based in patients with PAD, there is emerging evidence showing that they are realistic choices.
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PMID:The role of platelets in peripheral arterial disease: therapeutic implications. 1197 62

In a large, randomized, placebo-controlled trial in centers that use a conservative approach to acute coronary syndromes, the antiplatelet drug clopidogrel (Plavix) decreased the rate of the combined end point of cardiovascular death, nonfatal myocardial infarction, or stroke by 20% in patients presenting with acute coronary syndromes without ST-segment elevation. The benefit was at the cost of an increase in bleeding, however. This strategy may need to be tailored in centers that use a more aggressive treatment strategy of early angiography and revascularization.
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PMID:The CURE trial: using clopidogrel in acute coronary syndromes without ST-segment elevation. 1202 81

In patients with transient ischemic attack (TIA) or ischemic stroke of noncardiac origin, antiplatelet drugs are able to decrease the risk of stroke by 11% to 15%, and decrease the risk of stroke, myocardial infarction (MI), and vascular death by 15% to 22%. Aspirin leads to a moderate but significant reduction of stroke, MI, and vascular death in patients with TIA and ischemic stroke. Low doses are as effective as high doses, but are better tolerated in terms of gastrointestinal side effects. The recommended aspirin dose, therefore, is between 50 and 325 mg. Bleeding complications are not dose-dependent, and also occur with the lowest doses. The combination of aspirin (25 mg twice daily) with slow-release dipyridamole (200 mg twice daily) is superior compared with aspirin alone for stroke prevention. Ticlopidine is effective in secondary stroke prevention in patients with TIA and stroke. For some end points, it is superior to aspirin. Due to its side-effect profile (neutropenia, thrombotic thrombocytopenic purpura ), ticlopidine should be given to patients who are intolerant of aspirin. Prospective trials have not indicated whether ticlopidine is suggested for patients who have recurrent cerebrovascular events while on aspirin. Clopidogrel has a better safety profile than ticlopidine. Although not investigated in patients with TIA, clopidogrel should also be effective in these patients assuming the same pathophysiology than in patients with stroke. Clopidogrel is second-line treatment in patients intolerant for aspirin, and first-line treatment for patients with stroke and peripheral arterial disease or MI. A frequent clinical problem is patients who are already on aspirin because of coronary heart disease or a prior cerebral ischemic event, and then suffer a first or recurrent TIA or stroke. No single clinical trial has investigated this problem. Therefore, recommendations are not evidence-based. Possible strategies include the following: continue aspirin, add dipyridamole, add clopidogrel, switch to ticlopidine or clopidogrel, or switch to anticoagulation with an International Normalized Ratio (INR) of 2.0 to 3.0. The combination of low-dose warfarin and aspirin was never studied in the secondary prevention of stroke. In patients with a cardiac source of embolism, anticoagulation is recommended with an INR of 2.0 to 3.0. At the present time, anticoagulation with an INR between 3.0 and 4.5 cannot be recommended for patients with noncardiac TIA or stroke. Anticoagulation with an INR between 3.0 and 4.5 carries a high bleeding risk. Whether anticoagulation with lower INR is safe and effective is not yet known. Treatment of vascular risk factors should also be performed in secondary stroke prevention.
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PMID:Antithrombotic Secondary Prevention After Stroke. 1219 15

Since the introduction of Aspirin in the 1950s many substances have been introduced with an antiplatelet effect. Only few have been proved to be superior to aspirin in some clinical settings. Ticlopidin and its biochemical analog clopidogrel block the ADP-induced platelet aggregation. Clopidogrel having a better profile in terms of adverse events has been established over ticlopidin. It can be used for secondary prevention in patients with stroke, myocardial infarction or peripheral arterial disease instead of aspirin, certainly in cases with aspirin intolerance or with relapsing cardiovascular event under treatment with aspirin. For a general substitution of aspirin through clopidogrel hard evidence is still lacking. The combination aspirin + clopidogrel has been proved superior to aspirin in the treatment of patients with unstable angina or myocardial infarction without ST-segment elevation. For an extension of this indication to other clinical entities further evidence is needed. GPIIb/IIIa blockers are a well established treatment modality in patients undergoing coronary catheter interventions. Oral GPIIb/IIIa blockers, probably because of their pharmacokinetic profile, have proved to be insufficient in protecting from cardiovascular events compared to aspirin. Practical aspects concerning use of the newer antiplatelet agents during pregnancy, preoperatively and in spinal anesthesia are discussed.
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PMID:[New antiaggregants and their importance for the practitioner]. 1263 74

Aspirin is the drug of choice in most patients with acute stroke, if thrombolysis is contraindicated. Heparin is only used in acute stroke due to cerebral venous thrombosis, extracranial carotid or vertebral artery dissection and cardiac emboli with high risk of recurrence. In the prevention of recurrent stroke in patients with a noncardioembolic ischemic stroke antiplatelet agents are used. Aspirin is the first-line agent. Clopidogrel or a combination aspirin/dipyridamol are recommended for patients with several risk factors or recurrent cerebrovascular events. Warfarin has demonstrated a clear efficacy in stroke prevention in patients with atrial fibrillation, cerebral venous thrombosis and antiphospholipid antibody syndrome. Other, less well established possible indications for warfarin in the secondary prevention of stroke are symptomatic intracranial artery stenosis, large aortic atheroma, extracranial carotid or vertebral artery dissection and patent foramen ovale.
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PMID:[Anticoagulation and antiaggregation in neurological patients]. 1263 76

Peripheral vascular occlusive disease (PAOD) is frequently seen in patients suffering from coronary heart or cerebrovascular disease and is, considered as a prognostic predictor for the morbidity and mortality of this patient group. Thus, secondary antithrombotic and antiplatelet prophylaxis in these patients is not limited to achievement of long-term patency of the revascularized or recanalized arterial segment, but plays as well a pivotal role for the prevention of myocardial infarction and stroke. Generally, claudicants as well as patients undergoing percutaneous transluminal angioplasty (PTA), supragenicular femoro-popliteal artificial bypass surgery, aortofemoral, iliaco-femoral unilateral bypass, or aortobifemoral Y-graft implantation with unimpaired arterial outflow are treated life-long with low dose acetylsalicylic acid (ASA) 75-250 mg. On the other hand, those undergoing axillo-femoral, femoro-femoral crossover, aorto-profundal or femoro-popliteal infragenicular and femoro-distal venous bypass surgery should be treated with vitamin K antagonists. The role of Clopidogrel in secondary prevention after peripheral revascularization and recanalization still needs to be defined.
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PMID:[Anticoagulation and antiaggregation in patients with peripheral arterial occlusive diseases]. 1263 77

Platelets play a central role in both the short- and long-term manifestations of atherothrombosis. In acute coronary syndrome (ACS), there is a steep rise in cardiovascular events early, followed by an incremental rise in cardiovascular events over the long term. This long-term event rate is related to persistent platelet activation and thrombin generation. There is therefore a need to optimize both short- and long-term oral antiplatelet and antithrombotic strategies. The benefits of aspirin therapy, when administered early and continued over the long term, were demonstrated in several early randomized trials. The Antithrombotic Trialists' Collaboration found a 46% reduction in vascular events with antiplatelet therapy (mostly aspirin). However, despite treatment with aspirin and proven therapies, recurrent events remain high. The adenosine diphosphate receptor antagonists, ticlopidine and clopidogrel, inhibit the early steps of platelet activation, degranulation, and release of prothrombotic and inflammatory mediators, while also preventing activation of the glycoprotein IIb/IIIa receptor. The Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial demonstrated the benefits of aspirin plus clopidogrel in reducing major cardiovascular events (cardiovascular death, myocardial infarction [MI], and stroke reduced by 20%, p = 0.00009) in a broad range of patients with ACS when administered early and continued over the long term. The benefits emerge very rapidly after a 300 mg loading dose. For the large number of patients undergoing percutaneous coronary intervention in the CURE trial, there was a substantial risk reduction with clopidogrel pretreatment followed by long-term therapy (p < 0.002). This benefit was present, regardless of whether intervention was performed early or late. The significant benefits of aspirin and clopidogrel persist for the combined efficacy-safety end point of cardiovascular death, MI, stroke, or life-threatening bleeding when clopidogrel is started early, combined with aspirin and other standard therapies, and continued for up to one year.
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PMID:Short- and long-term oral antiplatelet therapy in acute coronary syndromes and percutaneous coronary intervention. 1264 45

Our understanding of the pathogenesis of congestive heart failure (CHF) has improved remarkably in recent years. However, despite better knowledge and novel pharmaceutical strategies, this disease is still one of the most brutal killers in the Western world. The pathophysiology of CHF is complex, and much of our comprehension revolves strictly around the neurohormonal and mechanical mechanisms involved. It has been suggested that CHF is associated with altered hemostasis, but whether a prothrombotic state contributes to the pathogenesis and progression of the disease is still not well known. The purpose of this review article is to discuss our current knowledge of platelet activation in patients with CHF and the potential role of antiplatelet agents in preventing these hemostatic abnormalities. Clopidogrel is an established medication that reduces the incidence of stroke, myocardial ischemia, or vascular death. It is currently the drug of choice in the prophylaxis of subacute stent thrombosis and postischemic stroke treatment. Promising results of the most resent trials (Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events [CAPRIE] and Clopidogrel in Unstable angina to prevent Recurrent Events [CURE]) may expand future indications of this ADP receptor antagonist for prevention of thrombotic complications in the CHF population. Currently conducted clinical trials (Warfarin and Antiplatelet Therapy in Chronic Heart Failure [WATCH] and Plavix Use for Treatment of Congestive Heart Failure [PLUTO-CHF] should clarify the role of clopidogrel in these patients.
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PMID:Platelet activation in patients with congestive heart failure: do we have enough evidence to consider clopidogrel? 1266 Jun 60

The Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) study investigated the use of clopidogrel in the treatment of acute coronary syndromes. Clopidogrel treatment led to an impressive 20% relative risk reduction in the composite outcome measure of vascular death, myocardial infarction, and stroke. Increased bleeding and greater requirements for blood transfusions were seen with clopidogrel. The addition of clopidogrel to aspirin represents a major advance in the treatment of acute coronary syndromes.
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PMID:The Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) study: to what extent should the results be generalizable? 1267 54

Antiplatelet drugs have been shown to prevent a range of atherothrombotic events, including transient ischaemic attack (TIA) and ischaemic stroke. Clopidogrel and ticlopidine are adenosine diphosphate (ADP)-receptor antagonists that inhibit ADP-induced fibrinogen binding to platelets, a necessary step in the platelet aggregation process. The Antithrombotic Trialists' Collaboration recently published a major meta-analysis that assessed the effect of antiplatelet therapy in patients with various manifestations of atherosclerosis. In total, this analysis included 135,000 patients in comparisons of antiplatelet agents versus control and 77,000 patients in comparisons of different antiplatelet regimens. This meta-analysis found that overall, antiplatelet therapy reduces the combined odds of stroke, myocardial infarction (MI) or vascular death by 22%, and that antiplatelet agents reduce the odds of a non-fatal stroke by 25% over a wide range of patients with or without a history of cerebrovascular disease. In the CAPRIE trial of clopidogrel versus acetylsalicylic acid (ASA), there was a 10% odds reduction for stroke, MI or vascular death in favour of clopidogrel (p = 0.03). In a meta-analysis performed by the Cochrane Stroke Group, ADP-receptor antagonist therapy significantly reduced the odds of a serious vascular event (stroke, MI or vascular death) by 9% (2p = 0.01) and of any stroke by 12%. The safety/tolerability profile of clopidogrel was superior to that of ticlopidine, and at least as good as that of ASA. In CURE, a long-term benefit was observed with the use of clopidogrel on top of standard therapy (including ASA in all patients), with a 20% relative risk reduction for the primary endpoint of cardiovascular death, MI or stroke (p < 0.001) in patients with unstable angina and non-Q-wave MI. A consistent benefit was seen across all patient subgroups, including patients with a previous history of stroke. More recently, CREDO has demonstrated the incremental benefit of prolonged use of clopidogrel on top of ASA in patients undergoing elective PCI, with a 27% reduction in the combined risk of death, MI or stroke after 12 months of therapy (p = 0.02) and a 25% reduction in stroke over the same time period. The MATCH trial is currently being conducted to test the hypothesis that long-term administration of clopidogrel on top of ASA is superior to clopidogrel alone for the reduction of major ischaemic events in patients with recent TIA or ischaemic stroke who are at high risk of atherothrombotic recurrence. Further trials of clopidogrel on top of standard therapy (including ASA) are planned in neurology; these include SPS3, in patients with small subcortical strokes, and ATARI, in patients who have recently recovered from a TIA.
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PMID:Evidence with antiplatelet therapy and ADP-receptor antagonists. 1269 15


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