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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aims Abciximab has previously been shown to enhance thrombolysis and improve myocardial perfusion when combined with reduced doses of alteplase. The purpose of the reteplase phase of TIMI 14 was to evaluate the effects of abciximab when used in combination with a reduced dose of reteplase for ST-elevation myocardial infarction. Methods and Results Patients (n=299) with ST-elevation myocardial infarction were treated with aspirin and randomized to a control arm with standard dose reteplase (10+10 U given 30 min apart) or abciximab (bolus of 0.25 mg. kg(-1)and 12-h infusion of 0.125 microg. kg(-1). min(-1)) in combination with reduced doses of reteplase (5+5 U or 10+5 U). Control patients received standard weight-adjusted heparin (bolus of 70 U. kg(-1); infusion of 15 U. kg(-1). h(-1)), while each of the combination arms with abciximab and reduced dose reteplase received either low dose heparin (bolus of 60 U. kg(-1); infusion of 7 U. kg(-1). h(-1)) or very low dose heparin (bolus of 30 U. kg(-1); infusion of 4 U. kg(-1). h(-1)). The rate of TIMI 3 flow at 90 min was 70% for patients treated with 10+10 U of reteplase alone (n=87), 73% for those treated with 5+5 U of reteplase with abciximab (n=88), and 77% for those treated with 10+5 U of reteplase with abciximab (n=75). Complete (>/=70%) ST resolution at 90 min was seen in 56% of patients receiving a reduced dose of reteplase in combination with abciximab compared with 48% of patients receiving reteplase alone. Conclusions Reduced doses of reteplase when administered in combination with abciximab were associated with higher TIMI 3 flow rates than reported previously for reduced doses of reteplase without abciximab and were at least as high as for full dose reteplase alone
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PMID:Combination reperfusion therapy with abciximab and reduced dose reteplase: results from TIMI 14. The Thrombolysis in Myocardial Infarction (TIMI) 14 Investigators. 1107 95

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

The only drug approved by the US FDA for use in patients with acute ischemic stroke is the thrombolytic, alteplase. Whereas alteplase rapidly restores blood flow, the drug has to be administered within 6 hours after symptom onset and is associated with an increased incidence of intracerebral hemorrhage (ICH). Moreover, transient and permanent re-occlusions associated with increased mortality continue to occur after thrombolysis with alteplase. Platelets are believed to play a pivotal role in the pathogenesis of atherothrombosis and the binding of the platelet glycoprotein (GP) IIb/IIIa receptor to fibrinogen is the final common pathway leading to platelet aggregation and thrombus formation. Antiplatelet agents such as platelet GP IIb/IIIa receptor antagonists have been studied in numerous multicenter, randomized clinical trials in patients with acute coronary symptoms (ACS). The intravenous GP IIb/IIIa receptor antagonists abciximab, eptifibatide and tirofiban are approved by the FDA for use in patients with ACS, and intravenous tirofiban is also approved for use during coronary intervention. Oral GP IIb/IIIa receptor antagonists such as lotrafiban, xemilofiban, sibrafiban and orbofiban have failed to provide myocardial protection in patients with ACS. Compared with ACS, few trials have evaluated the efficacy and tolerability of platelet GP IIb/IIIa receptor antagonists in patients with cerebrovascular syndromes. Agents such as SM-20302, TP201, ME3277, murine 7E3 F(ab')(2 )and SDZ-GPI 562 have been reported to preserve microvascular patency in different animal models of acute ischemic stroke and they may have neuroprotective properties. Platelet GP IIb/IIIa receptor antagonists may be suitable as a single therapeutic or as an adjunct therapeutic to thrombolysis with alteplase for the treatment of stroke. Platelet GP IIb/IIIa receptor antagonists may enhance the efficacy of thrombolytics and reduce potentially fatal adverse effects such as ICH. Preliminary results from the Abciximab in Emergent Stroke Treatment Trial (AbESTT) indicate that abciximab, administered as a bolus dose 0.25 mg/kg followed by 12-hour infusion, was associated with significant improvement in clinical rating scores and no significant increase in bleeding episodes in patients with acute stroke. The tolerability of argatroban in patients with acute stroke is currently being assessed in the multicenter Argatroban in Ischemic Stroke (ARGIS-1) trial.
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PMID:Therapeutic potential of platelet glycoprotein IIb/IIIa receptor antagonists in the management of ischemic stroke. 1472 35

Transcranial "diagnostic" ultrasound (US) has been shown to accelerate thrombolysis related to recombinant tissue-type plasminogen activator (rt-PA). In this in vitro study, we evaluated the potential of US to increase clot dissolution mediated by Abciximab (Abc) compared to rt-PA. The effect of 1.8-MHz pulsed wave (PW) Doppler US on dissolution of whole venous blood clots (WBC) and platelet-rich clots (PRC) treated with Abc and rt-PA was investigated in an in vitro model. Clot dissolution was measured by weight loss. Abc-related WBC dissolution was enhanced by additional US, but the effect was not any more detectable when the US was attenuated by a human temporal bone (US-tb). In PRC there was no additional effect of US on the Abc-related clot lysis. Rt-PA-related clot dissolution was increased by US in WBC and PRC as well, however, US-tb was only effective in WBC. The effect of insonation on WBC dissolution treated with the combination of Abc plus rt-PA was lower compared with those treated with rt-PA. In this in vitro experiment, the additional effect of "diagnostic" US in combination with Abc was only present in WBC and less strong than with rt-PA. The results do not support the use of Abc for sonothrombolysis targeting both, fibrin-rich and platelet-rich clots. In contrast, US when combined with rt-PA increases dissolution in both, WBC and PRC as well.
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PMID:Sonothrombolysis is effective with recombinant tissue-type plasminogen activator, but not with Abciximab. Results from an in vitro study with whole blood clots and platelet-rich clots. 1996 61

About 80% of strokes are ischaemic. Approximately 12% of patients die within 3 months following stroke, and another 20% are institutionalised or become highly dependent. In early 2013, what is the harm-benefit balance of antithrombotic treatments used in the acute phase of ischaemic stroke? To answer this question, we reviewed the available data using the standard Prescrire methodology. Clinical trials of aspirin in the acute phase of ischaemic stroke consist mainly of two randomised trials including a total of 40 541 patients. After 1 to 6 months, 13 deaths or sequelae resulting in dependence are prevented when 1000 patients are treated with aspirin during the acute phase. Aspirin increases the risk of symptomatic intracranial haemorrhage when it is introduced less than 24 hours after treatment with alteplase. Abciximab, an injectable antiplatelet agent, showed no tangible clinical benefit in 5 randomised placebo-controlled trials in a total of 1275 patients. Clopidogrel and prasugrel, two other antiplatelet agents, have not been evaluated in this setting. However, in case of allergy to aspirin, clopidogrel is a useful alternative in other situations associated with a risk of arterial ischaemia. In a randomised trial including 458 patients, cilostazol and aspirin were similarly effective after 3 months of follow-up, but cilostazol caused cardiac arrhythmias. Ticlopidine has too many adverse effects to consider it a useful drug. Anticoagulant therapy during the acute phase of stroke has an unfavourable harm-benefit balance, including in patients with stroke secondary to cardiac embolism. Low-molecular-weight heparin reduces the risk of pulmonary embolism but has no impact on overall mortality. The aim of thrombolysis is to unclog the affected artery. Intravenous alteplase administration is the best-assessed thrombolytic method. Twelve randomised trials have compared intravenous thrombolysis with alteplase versus no thrombolytic therapy in 7012 patients. Among patients treated within 3 hours after stroke onset, 41% survived without sequelae after alteplase administration, versus 32% in the absence of thrombolysis; alteplase had no statistically significant impact on mortality at the end of follow-up. Efficacy appeared to be similar in patients over 80 years old.The harm-benefit balance may also be favourable when thrombolysis is started more than 3 hours after stroke onset, but when it is initiated more than 4.5 hours after stroke onset, it increases mortality. Four randomised trials showed that intra-arterial thrombolysis with urokinase or pro-urokinase had a beneficial effect, versus no thrombolysis, in a total of 356 patients. In a randomised trial including 362 patients, intra-arterial thrombolysis did not have a better harm-benefit balance than intravenous thrombolysis. Among the various physical and mechanical methods used to remove or dissolve clots, the best-evaluated is ultrasound plus intravenous alteplase thrombolysis; initial results with this procedure warrant further clinical trials. Rapid intervention and patient selection are both crucial in optimising the harm-benefit balance of intravenous alteplase thrombolysis. This treatment should only be used when management begins within the first hours following stroke symptom onset, and when there are no risk factors for bleeding, especially intracranial bleeding. For other patients, aspirin is the only antithrombotic drug known to reduce, albeit only slightly, the risk of death and sequelae following ischaemic stroke.
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PMID:Antithrombotic drugs and ischaemic stroke. 2442 42