Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034065 (pulmonary embolism)
 14,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In recent years, new opportunities have emerged that have the potential to change rapidly the therapeutic scenario of patients with acute venous thromboembolism (VTE). Selected patients with deep vein thrombosis (DVT) can be treated effectively and safely at home with fixed doses of low molecular weight heparins. The prompt administration of compression elastic stockings in addition to anticoagulant drugs in patients with acute DVT has the potential to halve the rate of late postthrombotic sequelae. The long-term use of low molecular weight heparins is likely to be more effective than oral anticoagulants for the secondary prevention of VTE in patients with advanced malignancy. Patients with pulmonary embolism and right ventricular dysfunction might benefit from the early administration of thrombolytic drugs in combination with heparin to a greater extent than from heparin alone. Despite an impressive amount of clinical information on the proper duration of oral anticoagulants in patients with unprovoked VTE, the optimal long-term treatment of these patients remains undefined. Finally, new categories of drugs are emerging that have the potential to replace conventional anticoagulants in the near future. They include compounds that inhibit factor Xa or thrombin.
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PMID:New strategies for the treatment of acute venous thromboembolism. 1717 91

Although only part of the entire treatment regimen, antithrombotic therapy represents a large portion of the total costs associated with acute coronary syndromes (ACS) treatment. Unfractionated heparin (UFH), the mainstay of antithrombotic therapy, carries the risk of bleeding and associated interventions, and must be closely monitored. UFH therapy also has an increased risk of heparin-induced thrombocytopenia (HIT) and osteoporosis. These drawbacks prompted the development of newer antithrombotic agents, particularly low molecular weight heparins (LMWH) and factor Xa inhibitors. LMWH have several clinical advantages over UFH and has been demonstrated to be more effective than UFH in ACS. Because UFH is inexpensive, newer therapies need to demonstrate economic attractiveness over UFH. In addition to acquisition costs, it is important to consider the cost of all key components throughout the continuum of care. Health economic analyses show that the clinical advantages of the LMWH enoxaparin are also likely to result in net cost-saving benefits, due to reductions in diagnostic catheterization, percutaneous transluminal coronary angioplasty, and intensive care unit length of stay. Fondaparinux, an indirect inhibitor of factor Xa, does not require routine monitoring or multiple daily dosing, and is unlikely to interact with HIT antibodies. Large randomized clinical trials have shown that fondaparinux is at least as safe and efficacious as enoxaparin or UFH in the prevention of venous thromboembolism (VTE) and treatment of deep vein thrombosis or pulmonary embolism. Data from 2 recently published trials are similarly indicating noninferiority of fondaparinux in ACS patients. Health economic analysis of fondaparinux treatment is currently limited to VTE scenarios but point to a cost benefit associated with fondaparinux compared with enoxaparin.
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PMID:Easing the economic burden of acute coronary syndromes: cost-effectiveness of emerging therapies. 1720 89

Rivaroxaban (BAY 59-7939) is an oral, direct factor Xa inhibitor in clinical development for the prevention and treatment of venous thromboembolism (VTE). This analysis of pooled results from two phase II studies of rivaroxaban for VTE prevention after major orthopaedic surgery aimed to strengthen the conclusions of the individual studies. One study was conducted in patients undergoing total hip replacement (THR; N = 722), and one in patients undergoing total knee replacement (TKR; N = 621). In both studies, patients were randomized, doubleblind, to oral, twice-daily (bid) rivaroxaban beginning after surgery, or subcutaneous enoxaparin (40 mg once daily beginning before THR, and 30 mg bid beginning after TKR). Treatment continued until mandatory bilateral venography was performed 5-9 days after surgery. Total VTE (deep vein thrombosis, pulmonary embolism, and all-cause mortality) occurred in 16.1-24.4% of per-protocol patients receiving rivaroxaban 5-60 mg, and 27.8% receiving enoxaparin (n = 914). There was a flat dose response relationship between rivaroxaban and total VTE (p = 0.39). Major bleeding (safety population, n = 1,317) increased dose-dependently with rivaroxaban (p < 0.001), occurring in 0.9%, 1.3%, 2.1%, 3.9%, and 7.0% of patients receiving rivaroxaban total daily doses of 5, 10, 20, 40, and 60 mg, respectively, versus 1.7% of patients receiving enoxaparin. No routine coagulation monitoring was performed, and there were no significant differences between dose response relationships with rivaroxaban after THR and TKR. Overall, rivaroxaban total daily doses of 5-20 mg had the most favorable balance of efficacy and safety, relative to enoxaparin, for the prevention of VTE after major orthopaedic surgery.
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PMID:Rivaroxaban for thromboprophylaxis after orthopaedic surgery: pooled analysis of two studies. 1754 94

Venous thromboembolism (VTE), encompassing both deep vein thrombosis (DVT) and pulmonary embolism, remains a common and costly condition that is associated with significant morbidity and mortality. Treatment options for initial management of DVT include unfractionated heparin (UFH), low-molecular-weight heparins (LMWHs), and fondaparinux, which is the first of a new class of pentasaccharide antithrombotic agents with anti-factor Xa activity. LMWHs are an important tool in DVT management, offering advantages over UFH such as ease of dosing, lack of need for coagulation monitoring, and reduced risk for heparin-induced thrombocytopenia (HIT). Fondaparinux is also characterized by a simple dosing regimen, no need for coagulation monitoring, and potentially a lower risk of HIT compared with LMWH. In a recent clinical trial of DVT management, efficacy and bleeding rates with fondaparinux appeared similar to those observed with LMWH. In contrast to LMWH, fondaparinux is generally given as a fixed dose across a range of patient weights rather than calculated per individual patient weight. Given the increasing economic burden of VTE, particularly due to its increased rate among the elderly, pharmacoeconomic analyses have become a particularly useful tool to aid in selecting among similarly effective and safe agents for VTE treatment. A recent cost-effective analysis demonstrated that fondaparinux use offers an attractive economic alternative to other agents for initial DVT therapy that could yield cost savings without compromising clinical outcomes or patient safety.
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PMID:The pharmacoeconomics of deep vein thrombosis treatment. 1791 58

Anticoagulant therapy is the cornerstone of treatment of venous thromboembolism (VTE). Such treatment is divided into 2 stages: Rapid initial anticoagulation is given to minimize the risk of thrombus extension and fatal pulmonary embolism, whereas extended anticoagulation is aimed at preventing recurrent VTE, thereby reducing the risk of postphlebitic syndrome. With currently available drugs, immediate anticoagulation can only be achieved with parenteral agents, such as heparin, low-molecular-weight heparin, or fondaparinux. Extended treatment usually involves the administration of vitamin K antagonists, such as warfarin. Emerging anticoagulants have the potential to streamline VTE treatment. These agents include idraparinux, a long-acting synthetic pentasaccharide that is given subcutaneously on a once-weekly basis, and new oral anticoagulants that target thrombin or factor Xa. This article (1) reviews the pharmacology of these agents, (2) outlines their potential strengths and weaknesses, (3) describes the results of clinical trials with these new drugs, and (4) identifies the evolving role of new anticoagulants in the management of VTE.
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PMID:New anticoagulants for treatment of venous thromboembolism. 1829 93

Heparin-induced thrombocytopenia (HIT) is a prothrombotic drug reaction caused by platelet-activating antibodies that recognize multimolecular complexes of platelet factor 4 (PF4) bound to heparin. HIT is an intense hypercoagulability state (increased thrombin generation in vivo) that is complicated more often by venous thromboembolism (deep vein thrombosis, pulmonary embolism) than by arterial thrombosis. HIT is a risk factor for coumarin-induced microthrombosis, particularly affecting acral regions of limbs with deep vein thrombosis (venous limb gangrene). Coumarins (e.g., warfarin) are therefore contraindicated during the acute (thrombocytopenic) phase of HIT. Venous thromboembolism can occur early during an episode of HIT, sometimes even before HIT-associated platelet count declines become clear. Recognition of HIT may be facilitated through the use of a clinical scoring system, the 4Ts ( Thrombocytopenia, Thrombosis, Timing, and o Ther explanations). Anti-PF4/polyanion enzyme-immunoassays (EIAs) and washed platelet activation assays readily detect HIT antibodies, and thus have high diagnostic sensitivity; however, only the platelet activation assays have high diagnostic specificity, suggesting that HIT is likely to be overdiagnosed in settings where EIAs are used exclusively for diagnosis. Treatment of HIT emphasizes substitution of heparin with an alternative nonheparin anticoagulant, such as a direct thrombin inhibitor (lepirudin, argatroban), or an indirect (antithrombin-mediated) inhibitor of factor Xa (danaparoid, fondaparinux?).
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PMID:The approach to heparin-induced thrombocytopenia. 1830 88

The increasing incidence of patients who develop acute coronary syndrome (ACS) stresses the importance of effective initial treatment to reduce morbidity and mortality. The recommended initial therapeutic regimen for patients with ACS includes both anticoagulants and antiplatelet agents to prevent excessive coronary thrombosis, stroke, and further coronary events. Most commonly, unfractionated heparin (UFH) is used for initial antithrombotic treatment of ACS, despite limited published evidence regarding effectiveness and safety (bleeding complications). Therefore, this treatment regimen is primarily based upon expert opinion rather than evidence-based medicine. Studies addressing the dilemma of effectiveness and increased risk of bleeding when using UFH and low molecular weight heparin (LMWH) in patients with ACS showed superior clinical outcome in patients treated with LMWH. Nevertheless, the concurrent increased risk of bleeding while using anticoagulants is a severe problem and negatively impacts upon clinical outcome. Furthermore, non-hemorrhagic side effects of heparin such as heparin-induced thrombocytopenia (HIT), and skin reactions at the site of subcutaneous injection are reduced but not abolished by replacing UFH with LMWH. The limitations of UFH and LWMH as outlined above provided the impetus for the development of a pentasaccharide, called fondaparinux, which inhibits factor Xa selectively. Fondaparinux has been shown to be as effective as enoxaparin in the prevention of thrombosis in patients undergoing orthopedic surgery and showed similar results compared to enoxaparin or UFH in patients with deep-vein-thrombosis or pulmonary embolism. Recently, a large clinical study addressed the dilemma of the effectiveness and adverse effects of anticoagulation in ACS by comparing fondaparinux and LMWH such as enoxaparin in patients with unstable angina or non ST-segment elevation myocardial infarction (NSTEMI).
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PMID:Factor Xa inactivation in acute coronary syndrome. 1847 65

To discuss new features that were published during the past few years on diagnosis and treatment of venous thromboembolism (VTE). Progress has been made in assessing clinical probability of pulmonary embolism (PE), in addressing the particular aspects of PE diagnosis in the elderly, in evaluating the diagnostic performance of single- and multi-detector row helical computed tomography (hCT), and in looking at the role of D-dimer measurement and lower limb venous compression ultrasonography in the diagnostic work-up of PE. New therapeutic options have also been proposed. Diagnosing VTE depends upon several, mainly non-invasive diagnostic tools that must be used sequentially, depending on the clinical situation and the local expertise. In the vast majority of patients, a noninvasive work-up is feasible and the diagnostic algorithms are becoming simpler. We focused on new developments of clinical probability assessment, PE in the elderly, potential new uses of D-dimer measurement, advent of multidetector row helical computed tomography and utility of ultrasonography to detect deep vein thrombosis in PE suspected patients. Treatment of acute venous thromboembolism consists of parenteral administration of heparin (usually low-molecular-weight heparin or, more recently, fondaparinux) overlapped and followed by oral vitamin K antagonists that will be administered for a certain period of time (usually 3 to 12 months), depending upon the estimated risks of recurrence and bleeding in each individual patient. Contemporary features include the controversial possibility of reducing the intensity of oral anticoagulant treatment (INR 1.5-2) after an initial full-intensity treatment (INR 2-3) period of 3 to 12 months, and the emergence of new anticoagulant drugs such as direct oral synthetic inhibitors of thrombin or factor Xa.
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PMID:Venous thromboembolism: contemporary diagnostic and therapeutic aspects. 1869 May 88

Weight adapted low molecular weight heparin (LMWH) treatment is recommended as initial anticoagulant therapy of deep vein thrombosis, pulmonary embolism, in patients with myocardial ischemia or when oral anticoagulation (OAC) must be interrupted peri- operatively. Traditionally unfractioned heparin (UFH) was used as standard short acting anticoagulant, with the therapy monitored by frequent laboratory testing. Currently LMWH have broadly replaced UFH as first- choice anticoagulant due to more preferable pharmacokinetics and a better safety profile. Therapeutic anticoagulation with LMWH can be achieved by subcutaneous weight adapted application and measurement of anti-factor Xa- activity (anti-Xa) has been established as gold standard for LMWH- monitoring. However, since almost all LMWH dosing regimens have been developed empirically without laboratory monitoring, there is still a debate ongoing about the usefulness and impact of anti-Xa-testing. Data are lacking that prove a clear correlation between obtained levels of anti-Xa and the patients' clinical outcome. Newer methods have been developed aiming to determine a broader spectrum of LMWH depending anticoagulant activity. Even though there are some promising preliminary results, these alternative methods are not ready for routine clinical use yet. Nevertheless, current guidelines advise determination of anti-Xa in special patient populations with markedly altered LMWH metabolism or to exclude residual LMWH- activity before surgery at very high risk of bleeding. The aim of this article is to review critically the usefulness of anti- Xa guidance of LMWH- therapy and to give new perspectives on upcoming methods of LMWH- monitoring.
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PMID:Monitoring therapeutic anticoagulation with low molecular weight heparins: is it useful or misleading? 1885 41

Management of venous thromboembolism disease could be improved by new drugs with lower risk of bleeding and without the need of regular monitoring of anticoagulant effect. In this way, idraparinux, anti-Xa inhibitor, has been compared to conventional therapy (coumarins) for the treatment of deep vein thrombosis and pulmonary embolism. Is it worth to treat patients more than six months? This has been evaluated in an interesting study. Prophylaxis after hip replacement surgery is indicated to reduce the risk of venous thromboembolism, new drugs are under investigation. Dabigatran etexilate, a direct thrombin inhibitor, has been shown as effective as enoxaparin in reducing the risk of venous thromboembolism after total hip replacement surgery. In 2007, new european guidelines for non-STsegment elevation acute coronary syndromes have been published. Two new antithrombotic drugs, bivalirudin and fondaparinux, are now part of the different possible choices according to specific considerations. New factor Xa and factor IIa inhibitors are under investigation and are compared to heparin in PCI for NSTE-ACS. Fondaparinux and more recently otamixaban have given interesting results. These new recommendations have not yet taken into account new data published in 2007. What will be the positioning of prasugrel, a new thienopyridine, after the results of theTRITON trial? In patients with SCA treated by PCI, prasugrel reduced the ischemic events, while increasing major bleedings. In 2007, numerous publications and meta-analyses on drug-eluting stents (DES) have been published and tempered the fear about a possible increase in mortality with the use of DES.
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PMID:[What's new on antithrombotics?]. 1895 Jul 43


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