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

The incidence of thrombosis as a complication of invasive surgery, in cancer patients, as a cause or complication of stroke, acute myocardial infarction (AMI), thrombolysis, unstable angina (UA) or angioplasty is substantial. To better serve this patient population in the prevention and prophylaxis of thrombosis, new types of anticoagulant drugs are under development by the pharmaceutical industry. The goal of these efforts are orally-active anticoagulants with specificity and pharmacokinetic properties that could translate into better control of anticoagulation and thrombosis and less bleading liability compared to the currently used anticoagulants: heparin, the low molecular weight heparins and warfarin. Various approaches for which there is a great deal of activity include: tissue factor/Factor VIIa inhibitors, Factor Xa inhibitors, thrombin inhibitors, glycoprotein IIb/IIIa antagonists. There is also interest in Factor IXa inhibitors, thrombin receptor antagonists and inhibitors of plasminogen activator inhibitor-1.
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PMID:Future therapies for the prevention and treatment of venous and arterial thrombosis. 1599 61

Stroke is 1 of the most devastating complications associated with percutaneous coronary intervention. The present study used the combined 2000 to 2001 New York State Angioplasty Registry to compare the clinical characteristics and in-hospital outcomes of patients with and without stroke after percutaneous coronary intervention. Of the 76,903 patients who underwent angioplasty, 140 (0.18%) experienced stroke. Multivariate regression analysis revealed age, glycoprotein IIb/IIIa inhibitor use, acute myocardial infarction or congestive heart failure on admission, history of carotid disease, chronic renal disease, and placement of an intra-aortic balloon pump as independent predictors for stroke complicating percutaneous coronary intervention.
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PMID:Neurological complications following percutaneous coronary interventions (a report from the 2000-2001 New York State Angioplasty Registry). 1625 91

Thrombolysis with intravenous alteplase is the only validated and approved treatment for acute ischaemic stroke. It is currently licensed for use within 3 h of stroke onset. This treatment improves functional outcome without increasing mortality, although it can initially cause a devastating intracerebral haemorrhage. Risk factors for this complication have been identified and postmarketing studies have shown an acceptable safety profile when the guidelines for drug prescription and administration are rigorously applied. Intravenous alteplase is weakly effective in recanalising major intracranial artery occlusions and more potent strategies of reperfusion are needed. Ongoing clinical trials are evaluating alteplase combined with transcranial ultrasound and intravenous microbubbles, alteplase at reduced doses combined with intravenous glycoprotein IIb/IIIa inhibitors and intravenous alteplase at a reduced dose followed by intra-arterial recanalisation.
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PMID:Intravenous alteplase for acute ischaemic stroke. 1631 8

Tirofiban is one of three glycoprotein IIb/IIIa receptor antagonists approved by the US FDA, beside abciximab and eptifibatide. The approval of tirofiban covers conservative treatment of myocardial infarction and unstable angina, as well as percutaneous coronary intervention, for which treatment with tirofiban is recommended in moderate-to-high-risk patients. The efficacy of glycoprotein IIb/IIIa antagonists in myocardial infarction indicated that these agents may also be helpful in the treatment of acute ischaemic stroke. Although experimental data are lacking, observational studies are promising. In recent years, increasing effort in studying glycoprotein IIb/IIIa antagonists has been made, mostly for treatment with abciximab. However, there is one Phase II trial that investigated treatment with tirofiban.
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PMID:Tirofiban for the treatment of ischaemic stroke. 1637 Sep 24

Platelets are believed to play a part in all stages of the pathogenesis of ischemic stroke, from the initial formation of the atherosclerotic plaque, through plaque destabilization to the development of neuronal cell death. A process common to all of these pathogenic changes is the ability of the activated platelet to adhere to the site of disease. In addition, the release of the membrane vesicles from platelets enhances many of these processes. Therefore, an understanding of platelet adhesion and platelet microparticle release can aid the development toward the treatment and prevention of stroke. There has been much research into interventions that can reduce platelet activation in atherosclerosis and stroke. The benefits of nonpharmacologic interventions in stroke, such as diet and lifestyle modification, may in part be mediated by their effects on platelet activation. In addition, the antiplatelet drug aspirin has been shown to be useful in both the treatment of acute stroke and the secondary prevention of atherothrombosis. Other antiplatelet agents, such as the glycoprotein IIb/IIIa inhibitors and triflusal, are currently being evaluated for the treatment of acute atherothrombotic stroke.
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PMID:Platelet microparticles and platelet adhesion: therapeutic implications for the prevention and treatment of stroke. 1663 45

Aspirin, dipyridamole, cilostazol, thienopyridines and glycoprotein IIb/IIIa inhibitors represent the classical examples of the established antiplatelet agents commonly used for the secondary prevention in patients after vascular events. Obviously, the era of expanding antiplatelet regimens and indications may require new agents as the substitutes, or additions to the available strategies. However, recent results of the majority of antiplatelet trials strongly suggest boarder line advantages in clinical outcomes, and higher associated bleeding risks with the novel antiplatelet agents or/and regimens. Moreover, unexpected failures, such as lack of efficacy of clopidogrel and aspirin combination for ischaemic stroke prevention (MATCH), or use of the same antiplatelet regimen for the primary vascular prevention (CHARISMA) raise legitimate concerns that the concept 'the more the better' may not be valid. Broad use of statins, angiotensin receptor blockers and selective serotonin reuptake inhibitors may be in part responsible for the lack of impressive results with the antiplatelet therapy because each of these drug classes per se inhibits platelets. In this review, we discuss the available evidence and potential clinical significance of these findings.
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PMID:Platelet inhibition beyond conventional antiplatelet agents: expanding role of angiotensin receptor blockers, statins and selective serotonin reuptake inhibitors. 1689 41

Thrombolytic therapy with rtPA increases the risk of hemorrhagic transformation (HT) after cerebral ischemia. We employed contrast enhancement MRI with Gd-DTPA to detect HT in a rat model of embolic stroke treated with rtPA and a glycoprotein IIb/IIIa receptor antagonist, 7E3 F(ab')2, at 4 h after embolic stroke. Male Wistar rats were subjected to embolic stroke and treated with the combination of rtPA and 7E3 F(ab')2 (n=12) or with saline (n=10) at 4 h after onset of stroke. MRI studies were performed immediately and at 24 h after embolization using a 7-T system. Histological measurements were obtained at 48 h. With Gd-DTPA, T1WI images and permeability related MRI parameters (the blood-to-brain transfer constant, Ki, and the distribution volume of mobile protons, Vp) of 15 out of 18 animals showed hyperintensity regions in gross or microscopic HT areas at 24 h, confirmed histologically at 48 h post stroke. Contrast enhancement MRI detected six of seven (86%) animals with gross HT and nine of eleven (82%) animals with microscopic HT at 24 h after ischemia. Two of eighteen animals with HT, had MRI indices of hemorrhage at 3 h post stroke. However, compared to HT data measured histologically at 48 h in embolic stroke rats, the enhanced areas by Gd-DTPA at 24 h were larger, and the patterns (time, intensity and region) did not directly correlate to the subtypes of HT, i.e., gross or microscopic hemorrhage. Contrast enhancement MRI using Gd-DTPA provides a method to detect gross and microscopic HT after stroke in rats.
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PMID:Detection of BBB disruption and hemorrhage by Gd-DTPA enhanced MRI after embolic stroke in rat. 1695 Feb 36

Ischemic stroke is a leading cause of death and disability in the Western world. At present, intravenous administration of tissue plasminogen activator within 3 h of symptom onset is the only proven effective treatment to re-establish cerebral blood flow in the case of acute vessel occlusion. Unfortunately, few patients presenting with acute ischemic stroke qualify for intravenous tissue plasminogen activator therapy. The focus of current research is, therefore, to find new treatment options by which to obtain early reperfusion, and to extend the therapeutic window for intervention beyond 3 h. The purpose of this Review is to provide an integrated view of the current state of reperfusion therapy in patients with acute stroke, including pharmacologic agents and the methods of delivery. The focus will be on intravenous and intra-arterial use of plasminogen activators in acute supratentorial infarction. Other therapies, such as antiplatelet agents (i.e. glycoprotein IIb/IIIa inhibitors), and anticoagulant drugs will be discussed briefly.
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PMID:Therapy for early reperfusion after stroke. 1712 98

Suppressing platelet activation improves efficacy of thrombolytic therapy for stroke and acute myocardial infarction. Combination treatment with recombinant tissue plasminogen activator (r-tPA) and glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitor that binds with high affinity to platelets may therefore improve the efficacy of thrombolytic therapy. The effect of platelet GPIIb/IIIa antagonists and/or r-tPA on the dynamics of platelet/fibrin clot formation, strength, and lysis was determined using thrombelastography in human blood under thrombin or tissue factor stimulation. The study utilized platelet GPIIb/IIIa antagonists with high affinity and slow off-rate (Class I) from resting and activated platelets in comparison with Class II antagonists (lower affinity and fast off-rate from platelet GPIIb/IIIa receptors). The combination of the active form of roxifiban (XV459; Class I) or the active form of orbofiban (Class II) with a subeffective concentration of r-tPA resulted in a synergistic effect in clot lysis with roxifiban active form XV459 but not with that of orbofiban at therapeutically achievable concentrations that inhibit human platelet aggregation. These data indicate differential enhanced thrombolysis of low levels of r-tPA with high-affinity Class I but not with low-affinity Class II GPIIb/IIIa antagonists in the absence of anticoagulants.
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PMID:In-vitro efficacy of different platelet glycoprotein IIb/IIIa antagonists and thrombolytics on platelet/fibrin-mediated clot dynamics in human whole blood using thrombelastography. 1717 28

Adverse cardiovascular events are the consequence of a molecular chain reaction at the site of vulnerable plaques. Key players are platelets and coagulation factors that are activated following plaque rupture and often cause arterial obstruction. Thrombin, a plasma serine protease, plays a role in hemostasis of coagulation as well as in thrombosis and cell growth, leading to restenosis and atherosclerosis. Interesting and promising new molecules, the direct thrombin inhibitors, have been shown to be as effective as the combination of glycoprotein IIb-IIIa inhibitors and heparin for the prevention of arterial thrombosis. Until recently, direct thrombin inhibitors could be applied only parenterally; therefore, therapy was limited to hospitalized patients. As a result of recent drug development, orally active direct thrombin inhibitors are now available and have been evaluated for the long-term treatment of venous thrombosis and arterial fibrillation. Due to their specific pharmacodynamic characteristics by binding directly to thrombin--and thus inhibiting platelet aggregation and fibrin generation--these novel drugs may also have therapeutic potential for the treatment of atherothrombotic disease and its complications such as myocardial infarction, stroke or limb ischemia.
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PMID:Therapeutical potential of direct thrombin inhibitors for atherosclerotic vascular disease. 1746 31


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