Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Traditional anticoagulant drugs, including unfractionated heparin and warfarin, have several limitations. New anticoagulants have been developed that target a single coagulation factor and have predictable dose-response relationships. These include direct thrombin inhibitors and factor Xa inhibitors. Two parenteral direct thrombin inhibitors, lepirudin and argatroban, have FDA approval for the management of heparin-induced thrombocytopenia (HIT). Bivalirudin is a parenteral direct thrombin inhibitor that is licensed for patients undergoing percutaneous coronary interventions and for those with HIT who require percutaneous coronary interventions. Ximelagatran, an oral prodrug of the direct thrombin inhibitor melagatran, showed efficacy in the prevention and treatment of venous thromboembolism as well as stroke prevention in patients with atrial fibrillation. However, due to nonhematologic safety concerns, it did not receive FDA approval in the US. Fondaparinux is a synthetic pentasaccharide, which binds to antithrombin, thereby indirectly selectively inhibiting factor Xa. Fondaparinux demonstrated efficacy compared to low-molecular-weight heparin in randomized clinical trials and is FDA approved for the prevention and treatment of venous thromboembolism. The OASIS 5 trial in non-ST-segment elevation acute coronary syndromes recently demonstrated that the fondaparinux dose approved for prophylaxis of deep venous thrombosis is as efficacious with respect to ischemic outcomes as therapeutic doses of enoxaparin; fondaparinux, however, was associated with a substantial reduction in major bleeding at 9 days and mortality at 1 and 6 months. A number of oral direct factor Xa inhibitors as well as other oral direct thrombin inhibitors are in clinical development for the prevention and treatment of thrombosis; the current status of these anticoagulants is reviewed along with the challenges faced in designing pivotal clinical trials of these agents in comparison to existing anticoagulants.
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PMID:New anticoagulants. 1712 98

Fondaparinux is the first selective inhibitor of the coagulation factor Xa which is commercially avaliable for clinical use. It has been approved for the prevention of venous thromboembolism in patients undergoing orthopedic surgery and for the initial therapy of venous thromboembolism. In randomized clinical trials the value of fondaparinux in the treatment of ST-elevation myocardial infarction (STEMI) has been investigated. The PENTALYSE study showed that fondaparinux was at least as effective and safe as unfractionated heparin in 333 patients with STEMI undergoing fibrinolysis with t-PA. In the recent large OASIS-6 trial with 12,092 patients the treatment with 2.5 mg fondaparinux daily significantly reduced death and reinfarctions until day 30 compared with guideline recommended usual care and compared with unfractionated heparin (9.7% vs 11.2%, p = 0.008) without increasing major bleedings (1.0% vs 1.3%, p = 0.13). This advantage was predominantly seen in the subgroups of patients with fibrinolysis and without early reperfusion therapy. However, in the subgroup of primary percutaneous coronary interventions (PCIs) no clinical benefit of fondaparinux was found, but there were more catheter thrombosis and acute thrombotic complications. In summary, fondaparinux is a new antithrombin that is an efficient, safe, and easy to use in treatment for STEMI patients, particularly those not undergoing primary PCI.
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PMID:Management of acute coronary syndromes with fondaparinux. 1770 40

This review updates the latest developments concerning new anticoagulants. It describes potential targets in the coagulation pathway: inhibition of the initiation of coagulation, factor Xa and thrombin inhibitors. The focus is laid on substances in late development that already passed the phase II trial for venous thromboembolism (VTE)-prevention as "proof of concept". In the group of factor Xa inhibitors, the indirect inhibitor Fondaparinux has got approval for the indications prevention and therapy of VTE and acute coronary syndromes (OASIS 5 and 6). Rivaroxaban is the first direct factor Xa inhibitor that was admitted for approval in the indication VTE-prevention. The first trial of the program RECORD 1-4 was finished, trials for the indications therapy of VTE (EINSTEIN) and stroke prevention in atrial fibrillation (ROCKET AF) are in phase III. The use in acute coronary symptoms is - like apixaban - evaluated in phase II. The ADOPT trial with apixaban for VTE-prevention, as well as the BOTTICELLI trial for atrial fibrillation, have reached phase III. After the withdrawal of Ximelagatran, Dabigatran is the most developed direct thrombin inhibitor, being extensively studied in the comprehensive phase- III-program REVOLUTION and in approval for the indication VTE-prevention.
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PMID:[New anticoagulants]. 1827 58

Fondaparinux sodium (Arixtra) is a synthetic, sulfated pentasaccharide, selective factor Xa inhibitor that is indicated in Europe for preventing thrombus formation in patients with acute coronary syndromes (ACS; the focus of this review), including those with ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), or unstable angina.The large (n = 20,078), well designed OASIS-5 trial showed that subcutaneous fondaparinux 2.5 mg/day for <or=8 days was noninferior to subcutaneous enoxaparin 1 mg/kg twice daily (once daily in those with renal dysfunction) in reducing death or ischemic events at 9 days and the efficacy was maintained for up to 6 months (study end) in patients with unstable angina or NSTEMI. During this time, major bleeding occurred in fewer fondaparinux than enoxaparin recipients, resulting in a benefit: risk balance favoring fondaparinux. The incidence of death or reinfarction at 30 days was significantly lower in recipients of subcutaneous fondaparinux 2.5 mg/day than in those who received usual care (including unfractionated heparin [UFH] treatment as indicated) in patients with STEMI in the large (n > 12,000) OASIS-6 trial. There were no differences in the incidence of major bleeding between these groups, resulting in a benefit : risk balance favoring fondaparinux. The specificity and selectivity of fondaparinux, combined with its long half-life and 100% bioavailability, allows once-daily anticoagulation without the need for monitoring activated clotting time. Subcutaneous fondaparinux was noninferior to enoxaparin treatment in patients with unstable angina or NSTEMI, and was more effective than usual care in those with STEMI. Fondaparinux has a favorable tolerability profile, particularly with regard to the risk of major bleeding, and limited data suggest that it is more cost effective than enoxaparin in the short term. Thus, overall, clinical evidence suggests that fondaparinux has a valuable place in the treatment of patients with ACS.
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PMID:Fondaparinux sodium: a review of its use in the management of acute coronary syndromes. 1842 94

Fondaparinux sodium (Arixtra) is a synthetic, sulfated pentasaccharide, selective factor Xa inhibitor that is indicated in Europe for preventing thrombus formation in patients with acute coronary syndromes (ACS; the focus of this review), including those with ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), or unstable angina. The large (n = 20,078), well designed OASIS-5 trial showed that subcutaneous fondaparinux 2.5 mg/day for < or =8 days was noninferior to subcutaneous enoxaparin 1 mg/kg twice daily (once daily in those with renal dysfunction) in reducing death or ischemic events at 9 days and the efficacy was maintained for up to 6 months (study end) in patients with unstable angina or NSTEMI. During this time, major bleeding occurred in fewer fondaparinux than enoxaparin recipients, resulting in a benefit : risk balance favoring fondaparinux. The incidence of death or reinfarction at 30 days was significantly lower in recipients of subcutaneous fondaparinux 2.5 mg/day than in those who received usual care (including unfractionated heparin treatment as indicated) in patients with STEMI in the large (n > 12,000) OASIS-6 trial. There were no differences in the incidence of major bleeding between these groups, resulting in a benefit : risk balance favoring fondaparinux. The specificity and selectivity of fondaparinux, combined with its long half-life and 100% bioavailability, allows once-daily anticoagulation without the need for monitoring activated clotting time. Subcutaneous fondaparinux was noninferior to enoxaparin treatment in patients with unstable angina or NSTEMI, and was more effective than usual care in those with STEMI. Fondaparinux has a favorable tolerability profile, particularly with regard to the risk of major bleeding, and limited data suggest that it is more cost effective than enoxaparin in the short term. Thus, overall, clinical evidence suggests that fondaparinux has a valuable place in the treatment of patients with ACS.
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PMID:Spotlight on fondaparinux sodium in acute coronary syndromes. 1899 58

Anticoagulants are the mainstay of treatment of venous thromboembolic and acute coronary events. Improvements of new over established anticoagulants are targeted to achieve more favorable pharmacokinetics, minimal hemorrhagic side effects, a predictable dose response that obviates the need for coagulation monitoring, and more appropriate dose selection for the indication of interest. New parenteral anticoagulants are free of the complications of HIT, can be selected so that they are safe in patients with impaired renal or hepatic function, and can be administered once daily without the need for coagulation monitoring. Drug development has been focused on two key targets: factor Xa and factor IIa (thrombin). Fondaparinux is the first selective inhibitor of the coagulation factor Xa which is commercially available for clinical use. It has been approved for the prevention of venous thromboembolism in patients undergoing orthopedic surgery, abdominal surgery and for the initial therapy of deep venous thrombosis and venous thromboembolism. Fondaparinux sodium injection has been accepted for priority review by the United States Food and Drug Administration based on positive results from two pivotal, Phase III trials (OASIS 5 and 6) that evaluated its role in the treatment of a broad spectrum of patients with acute coronary syndromes (ACS). In this article, we review the available literature that provides evidence for the efficacy of fondaprinux in management of thromboembolic disease as well as acute coronary syndromes.
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PMID:Update on fondaparinux: role in management of thromboembolic and acute coronary events. 2018 52

Fondaparinux (Arixtra) is an anticoagulant that selectively inhibits activated factor X, thereby interrupting the blood coagulation cascade. In OASIS-5, a large pivotal trial in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), subcutaneous fondaparinux 2.5 mg once daily was noninferior to subcutaneous enoxaparin 1 mg/kg twice daily (both agents were administered over a mean of about 5 days in combination with antiplatelet therapy) in reducing death or ischaemic events at 9 days, and the efficacy was maintained for up to 6 months (study end). However, fondaparinux was associated with a significantly lower rate of bleeding than enoxaparin in the first 9 days, and at 3 and 6 months. This lower rate of bleeding led to lower long-term mortality and morbidity with fondaparinux than with enoxaparin. In modelled cost-utility analyses conducted from a healthcare payer perspective in Spain, France and the US with a lifetime horizon, fondaparinux once daily was predicted to be cost effective relative to enoxaparin twice daily with regard to the incremental cost per QALY gained. In Spain and the US, fondaparinux dominated enoxaparin (i.e. was less costly and more effective) and, in the French analysis, the incremental cost per QALY gained with fondaparinux versus enoxaparin was well within recommended thresholds. Results of short-term (6-month) cost analyses in the US and France also favoured fondaparinux over enoxaparin. Sensitivity analyses demonstrated that base-case conclusions were robust over a range of parameter estimates and assumptions, including plausible variations in baseline risk of a cardiac event or baseline risk of bleeding. In conclusion, in patients with NSTE-ACS receiving antiplatelet therapy, fondaparinux was cost effective relative to enoxaparin in cost-utility analyses in Europe and the US. This cost advantage primarily reflects the lower rate of bleeding with fondaparinux than with enoxaparin and the lower rate of mortality and morbidity over the long term.
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PMID:Fondaparinux: a pharmacoeconomic review of its use in the management of non-ST-segment elevation acute coronary syndrome. 2061 58

Antithrombotic therapy is the cornerstone of management of patients with acute coronary syndromes. Its role has become increasingly important with the widespread use of percutaneous revascularization, particularly after stent implantation. In this context, use of dual antiplatelet therapy is mandatory, combining aspirin with thienopyridines, mostly clopidogrel. As well as antiplatelets, anticoagulants are also required in patients with acute myocardial infarction up to the time of percutaneous intervention and stent implantation. Following the tremendous success of clopidogrel and enoxaparin over the last decade, new antithrombotic agents have been introduced, of which fondaparinux and prasugrel are examples, with both advantages and disadvantages compared to older drugs. The last European Congress in Barcelona in 2009 was particularly rich in this area as the results of three major clinical trials were presented, all with significant implications for clinical practice: the PLATO study testing the first reversible antiplatelet drug acting via the P2Y12 platelet receptor; the CURRENT-OASIS 7 study testing higher doses of aspirin and clopidogrel; and the SEPIA-ACS1 TIMI 42 trial launching the new parenteral anticoagulant otamixaban, a factor Xa inhibitor. These three trials are briefly reviewed in the current paper, highlighting the characteristics that may lead to new recommendations and the implications for daily clinical practice.
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PMID:Recent research on antithrombotics. News on the treatment of patients with acute coronary syndromes. 2086 7