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

Antiplatelet medications are an important part of the therapy of cerebrovascular diseases. Oral agents such as aspirin have an established role in the secondary prevention of stroke. An aspirin and dipyridamole combination has recently been approved. Ticlopidine has been proven to be more effective than aspirin, but its potentially serious side effect profile makes long-term use hazardous. Clopidogrel has been demonstrated to be both more effective than and at least as safe as aspirin. The combination of clopidogrel plus aspirin represents the likely future therapy for high-risk patients. The role of oral antiplatelet therapy in the acute treatment of stroke is beginning to be clarified. Aspirin treatment appears to be strongly indicated. Intravenous antiplatelet therapy with glycoprotein IIb/IIIa inhibitors for acute stroke and as an adjunct to carotid artery stenting appears promising.
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PMID:Update on clinical trials of antiplatelet therapy for cerebrovascular diseases. 1109 81

Atherothrombosis is the major underlying cause of acute coronary syndromes, ischemic stroke, and peripheral artery disease, and thus is the leading cause of death and disability in Western countries. Platelet inhibitors play a major role in preventing these ischemic complications. There is strong evidence from the Antiplatelet Trialists' Collaboration meta-analysis that aspirin reduces the combined risk of stroke, myocardial infarction (MI), or vascular death in atherosclerotic patients. The Ticlopidine Aspirin Stroke Study (TASS) compared aspirin and ticlopidine in the secondary prevention of high-risk patients after ischemic stroke and demonstrated a significant advantage for ticlopidine over aspirin. In peripheral arterial disease, the Swedish Ticlopidine Multicentre Study (STIMS) showed that ticlopidine was very effective against placebo. Intravenous antiplatelet agents, such as abciximab, tirofiban, and eptifibitide were also proven effective in acute coronary syndromes and unstable angina. In the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) trial, clopidogrel was compared with aspirin in patients with symptomatic atherothrombosis regardless of the initial localization of the ischemic event (coronary, cerebral, or peripheral). The efficacy of clopidogrel based on the first occurrence of ischemic stroke, MI, or vascular death showed a relative risk reduction of 8.7% over and above the 25% reduction currently accepted with aspirin (p < 0.05). The greatest benefit of clopidogrel was in the reduction of fatal and nonfatal MI in the most severe groups of patients, providing a 19% relative risk reduction (p = 0.008). The recent disappointing results obtained with oral glycoprotein IIb/IIIa receptor blocking agents may emphasize the need for other antiplatelet combination therapy, such as aspirin-clopidogrel, in coronary disease, stents, stroke, and possibly atherothrombosis in high-risk patients.
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PMID:Value of antiplatelet therapy in preventing thrombotic events in generalized vascular disease. 1112 82

Stroke represents the third common cause of death and hospitalization. However, there are yet no drugs that have reliable effects on acute stroke in Japan. Therefore, the development of new drugs that can support patients is required. There are various candidate drugs for acute stroke such as antithrombotic agents, anticoagulants, thrombolytic agents, neuroprotectants, and so on. Recently clinical trials suggest that aspirin may improve outcome, although these studies demonstrated a modest benefit of aspirin. Abciximab (ReoPro) is a human/mouse monoclonal antibody directed against the platelet receptor glycoprotein IIb/IIIa. It appears to be safe and might improve functional outcome. The large randomized trails were started to test the hypothesis that thrombolysis by an intravenous administration of a recombinant tissue type plasminogen activator (rtPA) could restore cerebral blood flow and improve patient outcome in acute ischemic stroke. These results can support the use of intravenous rtPA for stroke treatment within 3 h after onset, but not beyond 3 h. Development of an effective neuroprotective agent for the treatment of acute stroke remains problematic. Antioxidants, MCI-186 and ebselen, have finished phase III of clinical trials in Japan and were effective. We hope that efficacious drugs for acute stroke can be used for patients.
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PMID:[The development of new drugs for acute stroke]. 1118 6

This study was conducted to evaluate the feasibility, safety, and acute results of percutaneous excimer laser coronary angioplasty (ELCA) in acute coronary syndromes. Fifty-nine patients were treated with ELCA (308 nm), including 33 patients with unstable angina pectoris (UAP) (35 vessels with 39 lesions) and 26 patients with acute myocardial infarction (AMI) (26 vessels with 29 lesions). In each patient the target lesion had a complex morphology. Overall, 71% of the patients had contraindications for pharmacologic thrombolytic agents or glycoprotein IIb/IIIa receptor antagonists. All patients received adjunct balloon dilation followed by stent implantation in 88% of patients with AMI versus 76% of patients with UAP (p = NS). Quantitative angiography was performed at an independent core laboratory; 86% laser success and 100% procedural success was achieved in the AMI group versus 87% laser success and 97% procedural success in the UAP group (p = NS). In the AMI group, the minimal luminal diameter increased from 0.77 +/- 0.56 to 1.44 +/- 0.47 mm after lasing to a final 2.65 +/- 0.47 mm versus 0.77 +/- 0.38 to 1.35 +/- 0.4 mm after lasing to 2.66 +/- 0.5 mm final in the UAP group. A prelaser percent stenosis of 76 +/- 17% for the AMI group versus 70 +/- 16% for the UAP group (p = NS) was decreased after lasing to 52 +/- 16% for the AMI group versus 51 +/- 14% for the UAP group (p = NS) and to a final stenosis of 15 +/- 17% for the AMI group versus 12 +/- 15% for the UAP group (p = NS). A 96% laser-induced reduction of thrombus burden area was achieved in the AMI group versus 97% in the UAP group (p = NS). Preprocedure Thrombolysis In Myocardial Infarction flow of 1.3 +/- 0.9 in the AMI group versus 2.3 +/- 1.2 for the UAP group (p = 0.01) increased to a final flow of 3.0 +/- 0 for the AMI group versus 3.0 +/- 0 for the UAP group (p = NS). There were no deaths, cerebrovascular accident, emergency bypass surgery, acute closure, major perforation or major dissection, distal embolization, or bleeding complications in either group. One patient with AMI had localized perforation (caused by guidewire) without sequelae and 1 patient with UAP had an abnormal increase in creatine kinase levels. All 59 patients survived the laser procedure, improved clinically, and were discharged. Thus, early experience in patients with acute coronary syndromes suggest that percutaneous ELCA is feasible and safe.
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PMID:Effectiveness of excimer laser coronary angioplasty in acute myocardial infarction or in unstable angina pectoris. 1127 39

The elderly, particularly those over 80, are the fastest growing component of the population. Coronary artery disease accounts for 44% of all deaths in the elderly. Age is also one of the strongest predictors of mortality from acute myocardial infarction (AMI) and in those that survive, long term outcome is worse. In part, the poor inhospital mortality is due to difficulty in diagnosis, but is also likely to be caused by the widespread reluctance to use reperfusion therapy to treat the elderly. Reperfusion therapy has been shown to be equally effective in the elderly, despite an overall increased mortality. The results of randomized trials comparing thrombolysis to angioplasty show an advantage of primary angioplasty over thrombolysis. In the Global Use of Strategies to Open Occluded coronary Arteries in Acute Coronary Syndromes (GUSTO) IIb trial, the advantage was noted in all age groups, including the elderly. The Primary Angioplasty in Myocardial Infarction (PAMI) trial supports these findings. The trials also suggest that the risks are lower with angioplasty than thrombolysis, with a significant lower risk of stroke. Today, with improved outcomes using stents and glycoprotein IIb/IIIa agents, the advantages of primary angioplasty may be even greater than those reported in prior trials. The available data strongly support the use of primary angioplasty in the elderly as an effective reperfusion therapy and, due to improved safety and greater efficacy, should be the preferred treatment in the elderly. (c)1999 by CVRR, Inc.
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PMID:Is Primary Angioplasty the Best Treatment for AMI in the Elderly? 1141 24

The intravenous glycoprotein IIb/IIIa antagonists abciximab, tirofiban and eptifibatide are well accepted for the therapy of patients with unstable angina and/or as concomitant medication during coronary interventions. Despite the fact that these drugs are not used in all patients presenting with unstable angina during coronary interventions, the scientific evidence is overwhelming including the substantial reduction in mortality 3 years after utilisation of abciximab for coronary interventions in patients with unstable angina. In addition to these two indications, intravenous glycoprotein IIb/IIIa antagonists are currently being investigated for use in patients undergoing carotid artery interventions, peripheral arterial interventions and stroke, as well as adjunct therapy in patients undergoing fibrinolytic therapy during acute myocardial infarction. In contrast, the large trials being performed in patients with unstable angina and following coronary interventions using oral glycoprotein IIb/IIIa antagonists have been very disappointing. There were only minor therapeutic effects detectable, resulting in a slight reduction in ischemic cardiac events in some investigations, however, in all studies, there was a slight trend towards an increased mortality in the glycoprotein IIb/IIIa receptor-antagonist-treated group of patients. In meta-analysis, an approximately 35% relative increase in mortality has been calculated for patients being treated long term with the oral glycoprotein antagonists. The reason for this therapeutic failure is still unknown, however, the limited bioavailability of these drugs, together with our still very limited knowledge about the regulation of the platelet fibrinogen receptor, may be partially responsible for this therapeutic failure. Other compounds with improved pharmacokinetic properties are currently in clinical development.
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PMID:Oral glycoprotein IIb/IIa antagonists for unstable angina--is there still a chance for the oral substances? 1156 79

The pivotal role of the platelets in the genesis of acute coronary syndromes emphasises the importance of an early and sustained antiplatelet therapy. The CURE trial shows that clopidogrel in addition to aspirin achieves this double goal, with a 20% relative risk reduction in the primary composite endpoint of cardiovascular death, myocardial infarction or stroke in the first 30 days. The benefits are apparent as early as the first 24 hours of starting the treatment. There is also a consistent benefit of clopidogrel across all groups, including both high-risk and low-risk patients, which overrides an excess of 6 out of a thousand cases treated per year of bleeds, which require transfusion. Several clinical implications of the CURE trial are analyzed: the kind of patients who benefit more on clopidogrel, how long should treatment with clopidogrel continue, cost-benefit consideration, the impact of the findings on the benefit of the use of clopidogrel, on the use of glycoprotein IIb/IIIa receptor antagonists, clopidogrel pretreatment and long term therapy in patients undergoing percutaneous coronary intervention and bleeding risk with surgery.
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PMID:[Clopidogrel in acute coronary syndromes with non-ST elevation. Clinical implications of the CURE trial]. 1197 14

Pharmacological therapy for acute nonhaemorrhagic stroke has become a reality over the last 5 years. Mechanistically, both thrombolytic (tissue plasminogen activator and urokinase) and antiplatelet (aspirin) monotherapy have demonstrated efficacy. However, unintended actions limit the extent of clinical improvement in each circumstance. For example, in addition to excess bleeding, tissue plasminogen activator therapy has been associated with complement activation, neuronal toxicity and laminin degradation, while aspirin may reduce nitric oxide synthase activity and cerebral blood flow. Attention is now directed toward improving the therapeutic index for each class of agents. Generally, while thrombolytic therapy is focused on developing agents with greater fibrin specificity and safety (that is, a reduction in intracranial haemorrhage rate), the development of antiplatelet agents is primarily focused on achieving greater potency. The latter is being investigated by combining agents with different mechanisms (aspirin and dipyridamole, aspirin and clopidogrel) as well as agents designed to block the glycoprotein IIb/IIIa receptor, the final common pathway for platelet aggregation. Thus, combination therapy using both thrombolytic and antiplatelet agents will further attempt to improve the therapeutic index by increasing potency and improving the safety profile. Anecdotal case studies support the merits of this approach and are consistent with the data reported for myocardial ischaemia and interventional strategies. It is anticipated that drug therapy directed at both thrombolytic and antiplatelet targets will ultimately result in a widened therapeutic window that will allow acute stroke therapy to be administrated to a much greater number of patients than is currently possible.
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PMID:Combining antiplatelet and thrombolytic therapies for stroke. 1193 43

Inhibition of platelet aggregation with aspirin and anticoagulation with unfractionated heparin can be considered the gold standard treatment of patients with acute coronary syndromes. Replacement of unfractionated heparins by low-molecular weight heparins seem to further improve the cardiovascular risk. Additional treatment with glycoprotein IIb/IIIa receptor blockers led to a further reduction of the clinical event rate, especially in patients undergoing coronary interventions during an acute coronary syndrome (more than 30% relative risk reduction). However, the latter substances did only lead to marginal improvements in the setting of a conservative stabilization of patients with acute coronary syndrome (7% relative risk reduction). On the contrary, the initial treatment with clopidogrel in addition to aspirin and anticoagulation led to a 20% relative risk reduction for an endpoint of death, myocardial infarction and stroke in the CURE trial. The treatment with aspirin, clopidogrel (including loading-dose) for a treatment period of 3-12 months and anticoagulation for 2 days can be considered the new standard of treatment in patients with acute coronary syndromes (unstable angina, non-ST-segment elevation, myocardial infarction). Glycoprotein IIb/IIIa receptor blockers should be used especially during coronary interventions. Antianginal treatment should include nitrates and betablockers. A treatment with statins and ACE-inhibitors should be initiated in the early course of acute coronary syndrome for plaque stabilization.
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PMID:[Modern therapy in acute coronary syndrome]. 1197 80

Platelets play an important role in the pathophysiology of acute myocardial infarction, unstable angina, and ischemic stroke. The expression of the glycoprotein IIb/IIIa (alphaIIb/beta3 integrin) receptor on the surface of activated platelets constitutes the common pathway for platelet aggregation. Glycoprotein IIb/IIIa has low affinity for its soluble ligands (fibrinogen and von Willebrand factor) in resting platelets. In the setting of vascular injury, platelet activation occurs after binding of the glycoprotein Ib-IX-V receptor to von Willebrand factor in the extracellular matrix (at high shear rate) and binding of soluble agonists to specific platelet membrane receptors. The ensuing inside-out signaling increases several-fold the affinity and avidity of alphaIIb/beta3 for its ligands. High affinity ligand binding to alphaIIb/beta3 triggers outside-in signaling, causing microskeletal contraction and platelet retraction. The signaling pathways for inside-out and outside-in signaling are incompletely understood. Glycoprotein IIb/IIIa antagonists were developed under the premise that these agents would abrogate platelet aggregation while preserving platelet monolayer deposition at sites of injury. A number of parenteral and oral agents have been developed and evaluated in clinical trials. Three of them are approved in the United States and other countries: abciximab (ReoPro; the Fab fragment of a chimeric human-mouse antibody), eptifibatide (Integrelin; a cyclic heptapeptide), and tirofiban (Aggrastat; a tyrosine-derived nonpeptide molecule). The greatest clinical impact of these parenteral agents (used in conjunction with aspirin and heparin) has been in the prevention of ischemic complications after percutaneous coronary intervention. In contrast, oral agents have yielded disappointing results in the secondary prevention of acute coronary syndromes, and none of them are approved at present. Eptifibatide and tirofiban are specific for alphaIIb/beta3, whereas abciximab also exhibits cross-reactivity with the alphavbeta3 and alphaMbeta2 integrins. Although alphaIIb/beta3 is unique to platelets and megakaryocytes, alphavbeta3 is more widely distributed and mediates several functions, including endothelial cell migration, monocyte adhesion, angiogenesis, and inhibition of apoptosis. alphaMbeta2 mediates leukocyte-platelet interactions. In the percutaneous coronary intervention trials, abciximab has been more efficacious than the other parenteral agents, perhaps because of cross-reactivity with these other integrins, the pharmacodynamic profile of abciximab, or other effects. Other documented effects of abciximab include acute dethrombosis, reduction of thrombin generation, and improved flow in the coronary microcirculation after percutaneous coronary intervention. Abciximab is presently under evaluation in the treatment of acute ischemic stroke. Promising data have been obtained in experimental models of tumor angiogenesis and sickle cell anemia.
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PMID:Platelet glycoprotein IIb/IIIa antagonists: lessons learned from clinical trials and future directions. 1200 56


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