Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A teaching hospital is working with the Victorian State Government and universities, integrating cost-effectiveness evidence into clinical practice guidelines (CPGs), protocols and pathways for respiratory and cardiology interventions. Acute myocardial infarction (AMI) findings are reported. Results will stimulate cost-effective practice and inform medical associations, federal and state governments and international organisations developing CPGs. Published CPGs by the American College of Cardiology/American Heart Foundation for AMI in 1999 are reviewed by a large interdisciplinary hospital-based committee given cost-effectiveness evidence. Levels of evidence criteria rating on methodological rigor for effectiveness and costs are applied. National Health and Medical Research Council (NHMRC) grades of recommendation criteria for combinations of relative effectiveness versus relative costs and cut-off points are used. Extrapolating results between countries was addressed by applying the OECD's health purchasing power parity series. Recommendations for revisions to United States guidelines and for local application are formulated. United States Guidelines require updating: Regarding angioplasty, percutaneous transluminal coronary angioplasty (PTCA) is cost-effective for men aged 60 years relative to recombinant tissue plasminogen activator (tPA), with additional cost per life year saved of 274 ecu. PTCA with discharge after 3 days is cost-effective in low-risk AMI. Regarding GP IIb/IIIa drugs, Abciximab during intervention incurred equal mean hospital costs for placebo, abciximab bolus, and abciximab bolus+infusion with incremental 6-month cost for the latter treatment costing 293 US dollars per patient. Agent recouped almost all initial therapy costs with significant benefits. Incremental cost of abciximab per event prevented is 3,258 US dollars. Tirofiban was compared to placebo after high-risk angioplasty for AMI or unstable angina. Tirofiban decreased the rate of hospital deaths, myocardial infarction, revascularisation at 2 days by 36% relative to placebo (8% vs. 12%) without increased cost. Clinical benefits were similar at 30 days. Tirofiban+heparin+aspirin was compared to heparin+aspirin. Tirofiban arm resulted in net savings of 33,418 ecu per 100 patients for the first 7 days of treatment. Regarding thrombolytics, tPA is more cost-effective than streptokinase. Incremental costs for each life saved when streptokinase is substituted by recombinant tissue plasminogen are 31%, 45%, 97% higher in Germany, Italy and the United States than in the United Kingdom. Regarding anticoagulants, enoxaparin is a promising alternative to unfractionated heparin for hospitalised patients with non-Q-wave myocardial infarction or unstable angina, saving 1,485 Canadian dollars per patient over 12 months with 10% reduction in 1 year risk of death, myocardial infarction or recurrent angina. Regarding antiarrhymics, the cost-effectiveness of no amiodarone, amiodarone for patients with depressed heart rate variability (DHRV), and amiodarone for patients with DHRV plus positive programmed ventricular stimulation (PPVS) for high-risk post-AMI was investigated. Amiodarone for DHRV+PPVS patients was dominated by a blend of the two alternatives. Compared to no amiodarone, the incremental cost-effectiveness of amiodarone for DHRV patients was 39,422 US dollars per quality adjusted life year gained. Amiodarone for DHRV is the most appropriate. Other CPG updates concern serum markers, for example, cardiac troponin I assay (c-Tnl), cost advantages of ad hoc angioplasty and secondary prevention through antioxidants and pravastatin. Australian costs are reported later in the paper.
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PMID:Integrating cost-effectiveness evidence into clinical practice guidelines in Australia for acute myocardial infarction. 1560 15

Acute ischemic stroke (AIS) is a common cause of morbidity and mortality worldwide. Thrombolytic therapy with tissue plasminogen activator, the only approved treatment for AIS, is received by less than 2% of patients. Moreover, there is a slight increase in hemorrhagic complications with thrombolysis. Therefore, there is a need for newer therapeutic modalities in AIS, which could be used in window periods beyond 3-6 h after stroke onset with fewer hemorrhagic complications. Glycoprotein IIb/IIIa inhibitors (GPI), after their initial success in patients with acute coronary syndromes, promised much in patients with AIS over the past decade or so. However, their exact role in patients with AIS, including the window periods and type of strokes, and the risk of symptomatic or asymptomatic hemorrhage are unclear at the moment. The current review focuses on the literature concerning the use of GPI in AIS and looks at the available evidence regarding their use. Abciximab thought to be safe and effective in initial case series and early trials, has not been shown to improve outcomes in AIS, and is associated with higher rates of hemorrhage. Tirofiban appears to be safe and effective in initial trials and there is a need to conduct further trials to establish its role in AIS.
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PMID:Platelet glycoprotein IIb/IIIa inhibitors in acute ischemic stroke. 1912 33

The Penumbra Stroke System (PSS) was cleared for use in patients with ischemic stroke by the FDA in January 2008. We describe our experience of using this new system in acute large vessel occlusive disease following thrombolysis. Fifteen consecutive patients (mean age 60 years) suffering from acute ischemic stroke were treated with the PSS after intravenous or intra-arterial standard treatment with tissue plasminogen activator (n = 14) or ReoPro (n = 1). All patients presented with TIMI 3 before use of the PSS. Carotid stenting (n = 3) and intracranial balloon angioplasty or stenting (n = 2) were performed if indicated. Neurological evaluation was performed using the NIHSS score and the mRS score. Initial median NIHSS score in 12 patients with occlusions in the anterior circulation was 15; three patients with basilar artery occlusion presented with coma. Median symptom to procedure start time was 151 min. In the anterior circulation, 9 of the 12 target vessels were recanalised successfully (TIMI 2 and 3). The rate of patients with independent clinical outcome (mRS </= 2) was 42%. One patient died 5 days after unsuccessful treatment, one after 28 days and one after 85 days owing to heart attack. Basilar artery occlusions could be recanalised in all cases to TIMI 3. The clinical result after 90 days was mRS 4 in two cases and mRS 5 in one case. Symptomatic haemorrhage did not occur. The PSS can safely be used for recanalisation in patients with acute ischemic stroke due to large vessel occlusion, who have already received thrombolysis treatment. The recanalisation rate was 80%. Symptomatic haemorrhage did not occur. Randomized trials may demonstrate that endovascular mechanical thrombectomy improves patient outcome.
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PMID:Penumbra Stroke System as an "add-on" for the treatment of large vessel occlusive disease following thrombolysis: first results. 1935 Feb 48

The effects of gel-filtered platelets on euglobulin clot lysis time (ECLT) were analyzed to elucidate the possible role of platelets in thrombolysis. Gel-filtered platelet-supplemented ECLT (plt-ECLT) was significantly shorter than ECLT without platelets (regular ECLT). Abciximab, anti-glycoprotein IIb/IIIa (GPIIb/IIIa) antibody, and cytochalasin B nullified the enhancement of ECLT by platelets, and increased plt-ECLT beyond regular ECLT. When gel-filtered platelets were used after disruption, ECLT was not shortened but rather became longer than regular ECLT, probably due to natural fibrinolysis inhibitors released from platelets. Therefore, for platelets to enhance fibrinolysis, intact cell structure and cytoskeletal reorganization after thrombin stimulation is required. Various GPIIb/IIIa antagonists prolonged plt-ECLT. The concentrations of GPIIb/IIIa antagonists required to prolong plt-ECLT, were varied. Interestingly, the effects of these antagonists were independent of their ability to inhibit thrombin-induced platelet aggregation, but dependent on their ability to induce clot retraction. T-250, a GPIIb/IIIa antagonist, had the smallest effect on plt-ECLT. These drugs do not affect regular ECLT or tissue plasminogen activator (tPA)-catalyzed Glu-plasminogen activation in the presence of thrombin-activated platelets. Although their overall effect on thrombolysis is inhibitory, platelets could promote fibrinolysis through a GPIIb/IIIa-dependent mechanism.
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PMID:Enhancement of fibrinolysis by gel-filtered platelets and its quenching by cytochalasin B and GPIIb/IIIa antagonists. 1990 11

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

Abciximab is a glycoprotein IIb/IIIa receptor antagonist that functions to prevent platelet aggregation, thus reducing thrombus initiation and propagation. It has been widely used during percutaneous endovascular interventions, such as aneurysm coil embolization, angioplasty, atherectomy, and stent placement, as both a preventative and a salvage therapy. The use of abciximab in cardiac and neurosurgical procedures has been associated with a reduced incidence of ischemic complications and a decreased need for repeated intervention. In these settings, abciximab has been delivered transarterially via a microcatheter or infused intravenously for systemic administration. The authors describe novel in situ delivery of abciximab as an agent to dissolve "white clots," which are composed primarily of platelets, during an intracranial superficial temporal artery to middle cerebral artery bypass in a 28-year-old woman with severe intracranial occlusive disease. Abciximab was able to resolve multiple platelet-based clots after unsuccessful attempts with conventional clot dispersal techniques, such as heparinized saline, tissue plasminogen activator, mechanical passage of a wire through the vessel lumen, and multiple takedowns and re-anastomosis. After abciximab was administered, patency was demonstrated intraoperatively using indocyanine green dye and confirmed postoperatively at 1 and 10 months via CT angiography. The in situ use of abciximab as an agent to disperse a thrombus during intracranial bypass surgery is novel and has not previously been described in the literature, and serves as an additional tool during intracranial vessel bypass surgery.
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PMID:In situ administration of abciximab for thrombus resolution during intracranial bypass surgery: case report. 2935 Jun 5