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

Using patients with polycythemia vera (PV) as an experimental model, we evaluated the impact of clot retraction (CR) and architecture of the clot on fibrinolysis. We studied the kinetics of clot retraction and the fibrinolysis rate in whole blood from 48 PV patients and 48 healthy controls. Measurements were performed before and after isovolemic eryhrocytapheresis (ECP). CR was measured by optical method. Clot lysis time (CLT) and maximum clot firmness (MCF) were measured by thromboelastometry in recalcified blood supplemented with t-PA and tissue factor. Compared with healthy controls, CR rate in PV patients was higher (0.0219 vs. 0.0138; p<0.001), the clot volume smaller and MCF elevated (64 vs. 58 mm). CR rate correlated with platelet count (r=0.546; p=0.001) but not with erythrocyte concentration (r=0.192; p>0.3). Compared with healthy controls, CLT in PV patients was significantly prolonged (158 min vs. 71 min). Fibrinolysis rate inversely correlated with CR rate (r=-0.566; p<0.001); MCF (r=-0.704; p<0.001) and platelet count (r=-0.461; p<0.001). As judged by confocal microscope, in comparison to healthy controls, clots formed in blood from PV patients demonstrated booth a distinctly higher degree of crosslinking and possessed thinner fibers. Altered CR, MCF and fibrinolysis speeds were not normalized following the ECP procedure. Tirofiban (a blocker of platelet GPIIb/IIIa receptors), unlike aspirin, normalized abnormal CR and fibrinolysis in blood from PV patients. Collectively, our data indicate that in PV patients, abnormal CR may result in formation of thrombi that are more resistant to fibrinolysis. ECP and aspirin failed to normalize platelet-related fibrinolysis resistance.
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PMID:Platelet-related fibrinolysis resistance in patients suffering from PV. Impact of clot retraction and isovolemic erythrocytapheresis. 2482 95

The aim of the present study was to assess the use of tirofiban injections for rescue therapy following artery reocclusion due to intra-luminal thrombosis during endovascular thrombectomy in patients with acute ischemic stroke (AIS). A total of seven cases of patients treated with adjunctive tirofiban injections following failed endovascular thrombectomy due to instant intra-luminal thrombosis were retrospectively assessed. A Solitaire stent was used as the primary thrombectomy device in all patients. Tirofiban was injected intra-arterially via a temporarily deployed Solitaire stent with continuous intravenous infusion for the subsequent 24 h; half of the conventionally recommended dose was employed. Outcome measures included angiographic reperfusion (mTICI), symptomatic intracranial hemorrhage, mortality and functional independence at 90 days (modified Rankin Scale, 0-2). Six patients had occlusions in the middle cerebral artery and one patient had occlusions in the basilar artery. Of the seven patients, five exhibited successful reperfusion (mTICI 2b-3) and achieved functional independence following 90 days. Reperfusion failed in the remaining two patients, who succumbed within 90 days of therapy. No intracranial or extracranial hemorrhage cases were identified. The results of the present study suggest that tirofiban facilitates reperfusion and ameliorates long-term prognosis in patients with AIS undergoing endovascular thrombectomy, and may be safe for those receiving intravenous tissue plasminogen activator therapy.
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PMID:Tirofiban facilitates the reperfusion process during endovascular thrombectomy in ICAS. 2891 83