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

Clopidogrel (Plavix-Sanofi Winthrop/Bristol-Myers Squibb) and [symbol: see text] ticlopidine (Ticlid-Sanofi Winthrop) are inhibitors of platelet function and are promoted as potential alternatives to aspirin. Clopidogrel is licensed for the secondary prevention of vascular events in patients with established atherosclerotic disease. The manufacturer claims that clopidogrel is "significantly more effective at reducing myocardial infarction, stroke and vascular death" compared to aspirin. Ticlopidine is licensed as an alternative to aspirin for secondary prevention of stroke and coronary complications in patients with intermittent claudication. However, in the UK, ticlopidine is more commonly used with aspirin to prevent complications following insertion of coronary stents during angioplasty. We consider whether the claims for clopidogrel and the current use of ticlopidine are justified.
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PMID:Clopidogrel and [symbol: see text] ticlopidine--improvements on aspirin? 1069 86

Clopidogrel is launched in Belgium by Sanofi-Synthelabo and Bristol-Myers Squibb under the trade name of Plavix. It is a potent and irreversible ADP receptor antagonist that proved to be more effective than aspirin as antiplatelet agent in the multicentre, randomised double-blind CAPRIE study. It is indicated, at a dosage of 75 mg/day, for the reduction of atherosclerotic events including myocardial infarction, ischaemic stroke and vascular death in patients with atherosclerosis manifested by recent stroke, myocardial infarction or established peripheral vascular disease. Furthermore, recent studies demonstrated that the combination of clopidogrel with aspirin is more effective than aspirin alone and better tolerated than the combination ticlopidine-aspirin for the prevention of atherothrombosis after placement of intravascular stents. Ongoing trials are evaluating the efficacy and safety of such clopidogrel-aspirin combination after acute ischaemic coronary events or in patients at very high risk of stroke. Thus the indications of clopidogrel may become even larger in a next future.
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PMID:[Pharmacy clinics. Medication of the month. Clopidogrel (Plavix)]. 1133 92

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

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

Clopidogrel bisulfate (hereafter, clopidogrel), a selective inhibitor of ADP-induced platelet aggregation, is approved for the reduction of atherothrombotic events in patients with ST-segment elevation myocardial infarction (STEMI). In COMMIT/CCS-2, a well designed trial in 45,852 adult patients with STEMI, relative to aspirin alone, clopidogrel 75 mg/day plus aspirin treatment significantly reduced the risk of both coprimary endpoints: the composite endpoint of reinfarction, stroke, or death from any cause and the risk of death from any cause. Based on the findings of this trial, treating 1000 patients for approximately 2 weeks with clopidogrel is associated with nine fewer patient deaths, reinfarctions, or strokes during treatment. In CLARITY-TIMI 28, a well designed supportive study in 3491 adult patients with STEMI, clopidogrel plus aspirin reduced the odds that a composite primary endpoint event of an occluded infarct-related artery, recurrent myocardial infarction, or death from any cause would occur versus aspirin plus placebo. Clopidogrel treatment was generally well tolerated in these clinical trials, with no significant between-group difference in the rate of major bleeding in either trial. Experience in other patient populations (e.g. those with recent myocardial infarction, recent ischemic stroke, or established peripheral arterial disease) has shown that longer-term (< or =3 years) clopidogrel monotherapy is generally well tolerated.
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PMID:Clopidogrel bisulfate: in ST-segment elevation myocardial infarction. 1719 34

Clopidogrel (Plavix), Iscover) selectively and irreversibly inhibits adenosine diphosphate (ADP)-induced platelet aggregation. Long-term administration of clopidogrel was associated with a modest but statistically significant advantage over aspirin in reducing adverse cardiovascular outcomes in patients with established cardiovascular disease in the CAPRIE trial. In other large well designed multicentre trials, such as CURE, COMMIT and CLARITY-TIMI 28, the addition of clopidogrel to aspirin therapy improved outcomes in patients with acute coronary syndromes. However, some issues regarding the use of clopidogrel remain unresolved, such as the optimal loading dose in patients undergoing percutaneous coronary interventions (PCI) and the optimal treatment duration following drug-eluting intracoronary stent placement. Results of several large randomised trials, therefore, have established clopidogrel as an effective and well tolerated antiplatelet agent for the secondary prevention of ischaemic events in patients with various cardiovascular conditions, including those with ischaemic stroke or acute coronary syndromes. In addition, treatment guidelines from the US and Europe acknowledge the importance of clopidogrel in contemporary cardiovascular medicine.
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PMID:Clopidogrel: a review of its use in the prevention of thrombosis. 1735 22

Some recent clinical trials have concluded the following: Patients who need noncardiac surgery and who are at risk of major cardiac events should not undergo revascularization with the aim of achieving a better perioperative outcome. They should have an office evaluation only and be prescribed a beta-blocker, if indicated. Except for unusual, high-risk cases, patients at risk of stroke due to atherosclerotic carotid artery stenosis should undergo carotid endarterectomy rather than carotid stenting. Because the technology is still developing, however, carotid stenting may still be appropriate as part of a clinical trial. Although drug-eluting coronary stents reduce the risk of restenosis in the short-term, they pose a small but significant risk of in-stent thrombosis. Clopidogrel (Plavix) should be prescribed for at least a year following drug-eluting stent placement, and perhaps indefinitely. Patients with known coronary heart disease have better outcomes if they receive aggressive statin therapy (eg, atorvastatin [Lipitor] 80 mg/day) to lower their serum levels of low-density lipoprotein cholesterol to less than 70 mg/dL.
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PMID:Cardiovascular medicine update 2007: perioperative risk, carotid angioplasty, drug-eluting stents, stronger statins. 1768 27

The Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) study (N Engl J Med 2006; 354:1706-1717, J Am Coil Cardiol 2007; 49:1982-1988) assessed the effect of dual antiplatelet therapy with clopidogrel (Plavix) and aspirin in patients at risk of atherothrombotic events. At a median of 28 months, the rate of the primary efficacy end point (a composite of myocardial infarction, stroke, and death from cardiovascular causes) was not significantly lower in the group receiving clopidogrel plus aspirin than in the group receiving placebo plus aspirin. However, one subgroup may have derived some benefit from the combination: those at higher risk owing to a history of myocardial infarction, ischemic stroke, or symptomatic peripheral arterial disease.
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PMID:Interpreting the CHARISMA study. What is the role of dual antiplatelet therapy with clopidogrel and aspirin? 1849 35

Myocardial infarction and stroke are caused by blood clots forming over a ruptured or denuded atherosclerotic plaque (atherothrombosis). Production of prostaglandin E(2) (PGE(2)) by an inflamed plaque exacerbates atherothrombosis and may limit the effectiveness of current therapeutics. Platelets express multiple G-protein coupled receptors, including receptors for ADP and PGE(2). ADP can mobilize Ca(2+) and through the P(2)Y(12) receptor can inhibit cAMP production, causing platelet activation and aggregation. Clopidogrel (Plavix), a selective P(2)Y(12) antagonist, prevents platelets from clotting but thereby increases the risk of severe or fatal bleeding. The platelet EP(3) receptor for PGE(2), like the P(2)Y(12) receptor, also inhibits cAMP synthesis. However, unlike ADP, facilitation of platelet aggregation via the PGE(2)/EP(3) pathway is dependent on co-agonists that can mobilize Ca(2+). We used a ligand-based design strategy to develop peri-substituted bicylic acylsulfonamides as potent and selective EP(3) antagonists. We show that DG-041, a selective EP(3) antagonist, inhibits PGE(2) facilitation of platelet aggregation in vitro and ex vivo. PGE(2) can resensitize platelets to agonist even when the P(2)Y(12) receptor has been blocked by clopidogrel, and this can be inhibited by DG-041. Unlike clopidogrel, DG-041 does not affect bleeding time in rats, nor is bleeding time further increased when DG-041 is co-administered with clopidogrel. This indicates that EP(3) antagonists potentially have a superior safety profile compared to P(2)Y(12) antagonists and represent a novel class of antiplatelet agents.
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PMID:Antagonists of the EP3 receptor for prostaglandin E2 are novel antiplatelet agents that do not prolong bleeding. 1919 56

Clopidogrel (Plavix) is a potent platelet inhibitor that has been demonstrated to be significantly more effective than aspirin for the prevention of atherothrombotic events in patients with established atherosclerotic disease in the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) study. Furthermore, the benefit of clopidogrel compared with placebo in patients with acute coronary syndromes, as well as those undergoing percutaneous coronary intervention receiving a standard therapy including aspirin, has been largely demonstrated by the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE), Clopidogrel for the Reduction of Events During Observation (CREDO), CLopidogrel as Adjunctive ReperfusIon TherapY-Thrombolysis In Myocardial Infarction (CLARITY-TIMI)28, and Clopidogrel and Metoprolol in Myocardial Infarction Trial/Secon Chinese Cardiac Study (COMMIT/CCS-2) trials. However, in the Management of Atherothrombosis with Clopidogrel in High-risk patients with recent transient ischemic attack or ischemic stroke (MATCH) trial, there was no clinical benefit of adding aspirin versus placebo to a standard therapy of clopidogrel in patients with cerebrovascular disease. The implications of these findings, as well as future perspectives from upcoming trials, shall be discussed herein.
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PMID:Clopidogrel: cardiologists' panacea or neurologists' headache? 1980 96


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