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

The secondary prevention of ischemic stroke is aided by the use of antiplatelet therapy, and the predominant current choices are aspirin, aspirin plus extended-release dipyridamole, and clopidogrel. The potential utility of combining platelet antiaggregants with different mechanisms of action proved successful with aspirin plus extended-release dipyridamole, and this approach has been explored with the combination of clopidogrel and aspirin. In the Management of Atherothrombosis With Clopidogrel in High-Risk Patients trial, this combination was compared with clopidogrel alone for secondary prevention in patients with transient ischemic attack and stroke in a high-risk population with a high prevalence of other vascular risk factors. A nonsignificant trend for a reduction of the combined endpoint of ischemic stroke, myocardial infarction, vascular death, and rehospitalization was observed in the combination therapy group (P = .24). The frequency of serious, life-threatening bleeding adverse effects was almost doubled in the combination arm. Neurologists need to be aware of these results and avoid the use of clopidogrel plus aspirin in patients with stroke or transient ischemic attack until evidence that the combination is safe in this population is provided. Neurologists faced with patients who have had a stroke or transient ischemic attack and are receiving this combination of antiplatelet agents after coronary stenting should inform their cardiology colleagues of the reported bleeding risk, and they should encourage the use of the combination for as short a time period as possible after such coronary intervention.
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PMID:Results of the management of atherothrombosis with clopidogrel in high-risk patients trial: implications for the neurologist. 1640 33

Although the mechanisms of action by which aspirin, clopidogrel and dipyridamole inhibit platelets are well characterised, their effects on soluble modulators of thrombosis, inflammation, and endothelial function have yet to assessed systematically. In this investigation aspirin (A), clopidogrel (C), and dipyridamole (D) were administered singly and in combination (A, C, D, AC, AD, CD, ACD) in random order for 2 weeks (without washout) to 11 healthy subjects and 11 patients with previous ischaemic stroke. At the end of each treatment period plasma cyclic guanosine monophosphate (cGMP), monocyte chemoattractant pertide-1 (MCP-1), nitric oxide metabolites (NO(x)), plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor (vWf); and serum C-reactive protein (CRP) and platelet derived growth factor (PDGF); were measured blinded to treatment. Dipyridamole reduced plasma vWf levels (%) in both volunteers, -10.0 (4.95), and patients, -10.11 (4.34) (p < 0.05). Dipyridamole also lowered CRP (mg/l) in patients, -0.96 (0.47), but not volunteers. Clopidogrel reduced PAI-1 (ng/ml) in volunteers, -5.30 (2.20) (p < 0.05), and patients, -3.61 (2.75) (non-significant trend). Aspirin lowered PDGF (ng/ml) in volunteers, -3.46 (1.55), but not patients. Triple antiplatelet therapy was superior to dual and mono therapy in reducing vWf levels. In conclusion, antiplatelet agents have non-platelet-related effects on soluble modulators of thrombosis, inflammation, and endothelial function. In particular, dipyridamole reduces plasma vWf and clopidogrel lowers plasma PAI-1 levels. These effects may explain, in part, their roles in preventing atherothrombogenesis.
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PMID:Effect of aspirin, clopidogrel and dipyridamole on soluble markers of vascular function in normal volunteers and patients with prior ischaemic stroke. 1642 Oct 11

Clopidogrel is an antiplatelet drug that has been shown in several trials to reduce clinical events such as cardiovascular death, stroke, and myocardial infarction when compared to aspirin in a broad range of patients with atherosclerotic vascular disease. Clopidogrel has also been shown to reduce the same events by 20% when added to aspirin in patients with unstable angina and also in patients undergoing coronary artery stenting. Despite this information being available for 5 to 10 years, guideline recommendations, and the knowledge that 5% of patients have major allergy to aspirin, New Zealand patients have only been able to receive funded clopidogrel for a short period, typically 3 weeks, after coronary artery stenting. We believe this is an example where New Zealanders have been denied treatments, despite a strong evidence-base, by PHARMAC's actions of delaying the funding of new drugs. We need to have a better process whereby New Zealanders can rapidly access new treatments.
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PMID:PHARMAC and lack of funding for clopidogrel. 1649 86

Clopidogrel, in combination wih aspirin, is currently the drug of choice to prevent thrombosis after coronary stent implantation. Currently, clopidogrel is administered to the vast majority of patients without any assessment of platelet inhibition. Response variability and resistance, however, definitely occur to clopidogrel treatment. Preliminary data support the hypothesis that patients with reactive or clopidogrel nonresponsive platelets are at risk for thrombotic events. However, the magnitude of the clinical effect remains unknown and relationship between nonresponsiveness and risk of clinical events is under-investigated. Several important questions that must be answered are: A) What is the relation of clopidogrel resistance and high platelet reactivity to the occurrence of stent thrombosis, recurrent myocardial infarction, stroke and death?; B) Is there a threshold of platelet reactivity that correlates with the onset of thrombotic risk?; and C) What is the cost of administering clopidogrel to non-responsive patients? Finally, our understanding of the clinical relevance of drug resistance and high platelet reactivity should be facilitated by the use of validated point-of-service devices. The mechanisms of the response variability to clopidogrel remain incompletely defined. The contribution of intra- and extracellular pathways are under investigation.
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PMID:Clopidogrel resistance: implications for coronary stenting. 1661 Nov 10

Atherothrombosis is the most common cause of an acute ischemic event. Antiplatelet agents form the cornerstone of atherothrombosis prevention. The purpose of this article is to review the use of antiplatelet agents in patients that are at particularly high risk of atherothrombotic events. To undertake this review, we searched the literature to identify key studies on the use of antiplatelet agents in this group of patients. Antiplatelet agents, such as aspirin and clopidogrel, play a fundamental role in the treatment and management of secondary thrombotic events. The routine use of aspirin is recommended, as it has been shown to reduce the risk of thrombotic events by approximately 25%. Additional benefit has been demonstrated with clopidogrel, both as a monotherapy and in combination with aspirin. In the CAPRIE trial, 19,185 patients with atherosclerotic vascular disease were randomized to receive clopidogrel (75 mg/day) or aspirin (325 mg/day) for a mean duration of follow-up of 1.91 years. Clopidogrel provided an additional 8.7% relative risk reduction in the primary composite endpoint of ischemic stroke, myocardial infraction or vascular death compared with aspirin. In the CURE trial, the addition of clopidogrel to background aspirin was associated with a 20% relative risk reduction in a composite of death from cardiovascular causes, nonfatal myocardial infarction or stroke compared with aspirin alone. In patients undergoing PCI as part of the PCI-CURE substudy, clopidogrel was associated with a 30% relative reduction in the incidence of cardiovascular events in the first 30 days after intervention compared with aspirin. The benefits of antiplatelet therapy continue to be investigated. Whether dual antiplatelet therapy is superior to aspirin monotherapy for high-risk primary prevention is unknown. The ongoing CHARISMA trial aims to determine the relative efficacies of aspirin monotherapy and aspirin/clopidogrel combination therapy in a broad range of high-risk patient populations. In addition, the REACH registry, a worldwide survey of symptomatic and high-risk patients, has been set up to provide vital epidemiological information regarding the risks of atherothrombosis in order to contribute to the development of better preventive strategies and management regimens for at-risk patients.
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PMID:Antiplatelet therapy in populations at high risk of atherothrombosis. 1739 57

The long-awaited results of the Management of Atherothrombosis with Clopidogrel in High-Risk Patients with Recent Transient Ischemic Attack (MATCH) study, a large-scale trial undertaken to evaluate the safety and efficacy of clopidogrel + aspirin for secondary prevention of stroke, have been published. The efficacy of any antiplatelet therapy, including aspirin, is modest when it is used as monotherapy, and combination therapy with 2 antiplatelet agents has shown promise in reducing the risk for secondary stroke in patients who have had a previous transient ischemic attack (TIA) or ischemic stroke. However, unlike the Second European Stroke Prevention Study (ESPS-2), which demonstrated a significant reduction in risk for secondary stroke with aspirin + extended-release dipyridamole versus aspirin alone the results of the MATCH trial indicated that the reduction in risk achieved by adding aspirin to clopidogrel is not significantly greater than that achieved with clopidogrel alone. Furthermore, a significant increase in life-threatening bleeding complications was associated with the combination of clopidogrel + aspirin. Given these findings, clopidogrel + aspirin cannot be recommended at this time for the secondary prevention of stroke in patients who have had a previous ischemic stroke or TIA.
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PMID:MATCH results: implications for the internist. 1675 Sep 67

Atherothrombosis involves the mutually interactive dual mechanistic processes of atherosclerotic plaque progression and thrombus formation. In the setting of acute plaque rupture, resultant thrombus formation precipitates acute ischemic events such as acute coronary syndromes (ACS), stroke, and transient ischemic attack. Peripheral arterial disease is also a manifestation of atherothrombotic disease, and occurs both acutely and as a result of underlying disease progression. Atherothrombotic disease is highly prevalent and imposes a substantial burden on the community. For example, coronary artery disease was the single greatest cause of mortality among men and women in the US and accounted for an estimated US dollars 142.1 billion in health costs in 2005. Activated platelets are the prime mediators of arterial thrombus formation. This review discusses the evidence supporting the use of oral antiplatelet agents with other risk prevention strategies in the long-term secondary prevention of atherothrombotic disease. The most widely used oral antiplatelet agent is aspirin (acetylsalicylic acid), and both aspirin and clopidogrel have proven roles in the management of atherothrombotic disease. Clopidogrel should also be used in combination with aspirin in patients with non-ST-segment elevation ACS and those undergoing percutaneous coronary intervention. Recent data suggest that clopidogrel may have a significant role, with or without fibrinolytic therapy, in the immediate management of ST-segment elevation ACS.
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PMID:The role of oral antiplatelet agents in atherothrombotic disease. 1678 Mar 88

Alternative antiplatelet therapy for stroke prevention is indicated for patients who experience transient ischemic attacks (TIAs) while on aspirin therapy (strength of recommendation [SOR]: A, based on 1 meta-analysis and 1 randomized controlled trial). The combination of aspirin and extended-release dipyridamole reduces the risk of stroke following a TIA (SOR: A). Thieno-pyridines (eg, clopidogrel and ticlopidine) are an alternative for patients at high risk for a cardioembolic event. Ticlopidine reduces the risk of stroke following TIA, specifically showing benefit for patients previously on aspirin (SOR: A). Clopidogrel has not shown significant reduction in reoccurrence of stroke and has not been studied for patients with a previous TIA. Aspirin and a thieno-pyridine do not provide significant additional reduction in secondary strokes (SOR: A).
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PMID:Clinical inquiries. What is the best management for patients who have a TIA while on aspirin therapy? 1682 51

Clopidogrel has become a mainstay in the management of acute coronary syndrome patients over the past decade, as well as an essential component of percutaneous coronary intervention (PCI) pharmacotherapy. Until recently, no prospective study has evaluated the effectiveness of clopidogrel in the setting of an ST-segment elevation myocardial infarction (STEMI). The majority of patients presenting with STEMI receive thrombolytic therapy (aspirin, heparin and a fibrinolytic agent) although many do not achieve or maintain adequate reperfusion of the infarct-related artery. The CLARITY (Clopidogrel as Adjunctive Reperfusion Therapy) study and the PCI-CLARITY substudy were designed to address whether a beneficial effect of clopidogrel, including a loading dose, would be attained among STEMI patients who were being treated with thrombolytic therapy and undergoing coronary angiography during the index hospitalisation. A total of 3491 patients who presented within 12 h after the onset of STEMI were randomly assigned to receive clopidogrel (300-mg loading dose followed by 75 mg daily) or placebo. Patients were scheduled to undergo coronary angiography after 48 h, and those who underwent PCI during the index hospitalisation formed the basis of PCI-CLARITY. This PCI cohort was followed for the combined end point of cardiovascular death, recurrent myocardial infarction and stroke for 30 days.
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PMID:Clopidogrel in ST-elevation myocardial infarction patients undergoing percutaneous coronary intervention. 1687 70

Atrial fibrillation is associated with substantial morbidity and mortality. Pooled data from trials comparing antithrombotic treatment with placebo have shown that warfarin reduces the risk of stroke by 62%, and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin is superior to aspirin in preventing strokes, with a relative risk reduction of 36%. Ximelagatran, an oral direct thrombin inhibitor, was found to be as efficient as vitamin K antagonist drugs in the prevention of embolic events, but has been recently withdrawn because of abnormal liver function tests. The ACTIVE-W (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) study has demonstrated that warfarin is superior to platelet therapy (clopidogrel plus aspirin) in the prevention af embolic events. Idraparinux, a Factor Xa inhibitor, is being evaluated in patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs hold promise in atrial fibrillation through cardiac remodelling. Preliminary studies suggest that statins could interfere with the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for the exclusion of left atrial appendage are under investigation in high-risk patients.
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PMID:Optimising stroke prevention in non-valvular atrial fibrillation. 1702 Apr 34


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