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Oral Anticoagulants (oral + anticoagulant)
Kinds of Oral Anticoagulants Terms modified by Oral Anticoagulants Selected AbstractsThe Use of Oral Anticoagulants (Warfarin) in Older PeopleJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 8 2002American Geriatrics Society guideline abstracted from Chest 2001;S119. First page of article [source] Long-term Management of an Implantable Left Ventricular Assist Device Using Low Molecular Weight Heparin and Antiplatelet Therapy: A Possible Alternative to Oral AnticoagulantsARTIFICIAL ORGANS, Issue 5 2007Bart Meuris Abstract:, Between January 2004 and December 2005, out of 14 patients with decompensated heart failure who were treated with an INCOR left ventricular assist device (Berlin Heart AG, Berlin, Germany), 10 patients were kept on a long-term regime of low molecular weight heparin (LMWH) and antiplatelet therapy. The treatment objective was bridge-to-transplantation. All patients received LMWH in therapeutic doses according to body weight, in combination with daily aspirin 160 mg, clopidogrel 75 mg, and three times dipyridamole 75 mg. Effectiveness of the low molecular weight regime was monitored through measurement of antifactor Xa activity (base and peak levels). Antiplatelet therapy was monitored through weekly platelet function tests. Within this group of 10 patients, six patients successfully received transplants and four patients died, the latest death after 405 days of INCOR support. Causes of death were sepsis, intestinal hemorrhage, acute right ventricular failure, and one major stroke. Long-term management of INCOR assist devices using a combination of LMWH and antiplatelet therapy is feasible. This treatment strategy can serve as an alternative to oral anticoagulants. [source] Factor Xa or thrombin: is factor Xa a better target?JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2007J. ANSELL Summary., Existing vitamin K antagonists (VKAs) have drawbacks that limit their effectiveness, safety, and overall frequency of use. Oral anticoagulants in development with targeted action against individual coagulation factors, specifically direct factor (F) Xa and IIa inhibitors, appear to have pharmacokinetic and pharmacodynamic properties that overcome the limitations of the VKAs. Based on the theory of how coagulation factors interact, on the results of in vitro studies, and on clinical outcomes, there is accumulating evidence that FXa may represent a better target for inhibition than FIIa. This is based on an understanding of the amplified nature of coagulation factor interactions and fibrin formation, the need for smaller doses of an anticoagulant to block coagulation progression earlier in the sequence of reactions, the evidence for incomplete suppression of thrombin generation with direct thrombin inhibitors, evidence for rebound hypercoagulability with thrombin inhibitors, and clinical results with the indirect, parenteral, FXa inhibitor (fondaparinux), as well as early phase II results of new oral Xa and IIa inhibitors compared with enoxaparin. The latter studies, although not comparative, provide some evidence for the effectiveness and safety of Xa inhibitors at a range of doses not seen with the direct IIa inhibitors. [source] Oral anticoagulants and the risk of osteoporotic fractures among elderly,,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 5 2004Danielle Pilon MD Abstract Purpose Coumadin-based oral anticoagulants are associated with a decrease in bone mass density, but their role in fracture risk is equivocal. Because the use of oral anticoagulants is prevalent among the elderly, as is the risk and morbidity of osteoporotic fractures, the association between osteoporotic fractures and oral anticoagulants needs to be clarified. Method We conducted a case-control study on a 10% random sample of subjects aged 70 years and older enrolled in the Quebec universal health insurance plan between 1992 and 1994. Incident cases of a first osteoporotic fracture were identified by International Classification of Diseases, Ninth Revision codes. Exposure was defined as one or more prescriptions of oral anticoagulants dispensed before the osteoporotic fracture. Ten controls for each case, matched by age and date of osteoporotic fracture, were identified. Results Among 1523 cases, 48 (3.2%) were ever exposed to oral anticoagulants; among 15,205 controls, 461 (3.0%) were ever exposed (crude odds ratio: 1.0: 95% confidence interval: 0.7,1.5). These negative results persisted after adjusting for potential confounding variables and stratifying exposure into cumulative dose and treatment duration. Conclusions Coumadin-based oral anticoagulants are not significantly associated with osteoporotic fractures among the elderly, providing reassurance for elderly patients on long-term oral anticoagulants. Copyright © 2003 John Wiley & Sons, Ltd. [source] Appraisal of current vitamin K dosing algorithms for the reversal of over-anticoagulation with warfarin: the need for a more tailored dosing regimenEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2006Elizabeth A. Sconce Abstract:, Warfarin is the most commonly prescribed oral anticoagulant in the UK for the treatment and prevention of thromboembolic disorders. Vitamin K administration is an effective way of reversing excessive anticoagulation. Over-anticoagulated patients present with a wide range of international normalized ratio (INR) values and may respond differently to a fixed dose of vitamin K. Current dosing algorithms for vitamin K administration in the non-urgent treatment of over-anticoagulation do not take this variability in response into account. Consequently, over a third of over-anticoagulated patients still remain outside their target INR 24 h after treatment. Such patients are therefore prone to either haemorrhage (if the patient is still over-anticoagulated) or thromboembolism (if the INR reversal is over-corrected). A number of factors such as patient age, body weight, co-morbidity, frailty, warfarin daily dose and CYP2C9 and VKORC1 polymorphism could affect response to vitamin K and thus the rate and extent of INR reversal. There is a need for a more individualized approach to the reversal of over-anticoagulation in asymptomatic or mildly haemorrhagic patients in order to improve the safety of warfarin therapy. [source] Ultrasound screening for asymptomatic deep vein thrombosis after major orthopaedic surgery: the VENUS studyJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 7 2007S. M. SCHELLONG Summary.,Background:,Venography is currently used to assess the incidence of deep vein thrombosis (DVT) in dose-finding and confirmatory trials of new antithrombotic agents. Centrally adjudicated, complete compression ultrasound (CCUS) could be a non-invasive alternative to venography. Objectives:,A substudy of two, similarly designed, phase IIb trials of a novel, oral anticoagulant for the prevention of venous thromboembolism after elective hip or knee arthroplasty was undertaken to validate CCUS against venography. Patients/Methods:,Patients received study drugs until mandatory, bilateral venography was performed 7 ± 2 days after surgery. CCUS was performed within 24 h after venography by sonographers blinded to the venography result. Sonographers were trained and certified for the standardized examination and documentation procedure. Venograms and sonograms were adjudicated centrally at different sites by two independent readers; discrepancies between readers were resolved by consensus. Results:,A total of 1104 matching pairs of evaluable venograms and sonograms were obtained from the participants of the two trials (n = 1435): 19% of venograms and 20% of sonograms were not evaluable. The observed frequency of any DVT was 18.9% with venography and 11.5% with CCUS. Sensitivity of CCUS compared with venography was 31.1% for any DVT (95% confidence interval 23.4, 38.9), 21.0% (2.7, 39.4) for proximal DVT, and 30.8% (23.1, 38.6) for distal DVT. The figures for specificity were 93.0% (91.0, 95.1), 98.7% (98.0, 99.5), and 93.3% (91.5, 95.3), respectively. Conclusions:,Based on these results, centrally adjudicated CCUS will be unable to replace venography for DVT screening early after major orthopaedic surgery in studies evaluating anticoagulant drugs. [source] Clinical outcomes with unfractionated heparin or low-molecular-weight heparin as bridging therapy in patients on long-term oral anticoagulants: the REGIMEN registry,JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 6 2006A. C. SPYROPOULOS Summary.,Background: Patients who receive long-term oral anticoagulant (OAC) therapy often require interruption of OAC for an elective surgical or an invasive procedure. Heparin bridging therapy has been used in these situations, although the optimal method has not been established. No large prospective studies have compared unfractionated heparin (UFH) with low-molecular-weight heparin (LMWH) for the perioperative management of patients at risk of thromboembolism requiring temporary interruption of long-term OAC therapy. Patients/methods: This multicenter, observational, prospective registry conducted in North America enrolled 901 eligible patients on long-term OAC who required heparin bridging therapy for an elective surgical or invasive procedure. Practice patterns and clinical outcomes were compared between patients who received either UFH alone (n = 180) or LMWH alone (n = 721). Results: Overall, the majority of patients (74.5%) requiring heparin bridging therapy had arterial indications for OAC. LMWH, in mostly twice-daily treatment doses, represented approximately 80% of the study population. LMWH-bridged patients had significantly fewer arterial indications for OAC, a lower mean Charlson comorbidity score, and were less likely to undergo major or cardiothoracic surgery, receive intraprocedural anticoagulants or thrombolytics, or receive general anesthesia than UFH-bridged patients (all P < 0.05). The LMWH group had significantly more bridging therapy completed in an outpatient setting or with a < 24-h hospital stay vs. the UFH group (63.6% vs. 6.1%, P < 0.001). In the LMWH and UFH groups, similar rates of overall adverse events (16.2% vs. 17.1%, respectively, P = 0.81), major composite adverse events (arterial/venous thromboembolism, major bleed, and death; 4.2% vs. 7.9%, respectively, P = 0.07) and major bleeds (3.3% vs. 5.5%, respectively, P = 0.25) were observed. The thromboembolic event rates were 2.4% for UFH and 0.9% for LMWH. Logistic regression analysis revealed that for postoperative heparin use a Charlson comorbidity score > 1 was an independent predictor of a major bleed and that vascular, general, and major surgery were associated with non-significant trends towards an increased risk of major bleed. Conclusions: Treatment-dose LMWH, mostly in the outpatient setting, is used substantially more often than UFH as bridging therapy in patients with predominately arterial indications for OAC. Overall adverse events, including thromboembolism and bleeding, are similar for patients treated with LMWH or UFH. Postoperative heparin bridging should be used with caution in patients with multiple comorbidities and those undergoing vascular, general, and major surgery. These findings need to be confirmed using large randomized trials for specific patient groups undergoing specific procedures. [source] Latest news and product developmentsPRESCRIBER, Issue 21 2008Article first published online: 2 DEC 200 Osteoporosis guideline A new guideline on the management of osteoporosis in men over 50 and post-menopausal women has been published by the National Osteoporosis Guideline Group (www.shef.ac.uk/NOGG), a group of organisations representing health professionals and patients, with funding from several pharmaceutical companies. The guideline recommends using the FRAX tool (www.shef.ac.uk/FRAX) to assess the 10-year fracture risk in individuals with risk factors to facilitate targeting DXA scans to measure bone mineral density. Patients who have already sustained a fragility fracture should be treated without risk assessment. Treatment recommendations are similar to those published in draft NICE guidance on primary and secondary prevention, selecting alendronate as the drug of first choice for most patients. Efalizumab efficacy A multicentred postapproval trial has demonstrated long-term efficacy and a favourable safety profile for efalizumab (Raptiva) in moderate to severe chronic plaque psoriasis. The CONTROL II study, presented in September at the 17th EADV congress in Paris, was conducted at 170 sites in 18 European countries and involved 1255 patients who had failed to respond to traditional systemic therapies. In this non-blinded study, 68 per cent of participants achieved the primary efficacy end-point and showed improvement within the first 12 weeks; control was maintained in responding patients who continued treatment. Adverse effects were graded as mild or moderate and similar to those reported in earlier studies. There was no evidence of an increase in malignancies or infections. New oral anticoagulant Rivaroxaban (Xarelto), an oral factor Xa inhibitor, has been introduced for the prevention of venous thrombo-embolism in patients undergoing elective hip or knee replacement surgery. Compared with the low molecular weight heparin enoxaparin (Clexane), rivaroxaban has been shown to reduce the risk of venous thrombosis by 70 per cent after hip replacement and by 49 per cent after knee replacement; the risk of bleeding was similar. At the recommended dose of 10mg once daily, prophylaxis after hip surgery lasts five weeks and costs £157; prophylaxis after knee surgery lasts two weeks and costs £63. New products UCB Pharma has introduced lacosamide (Vimpat) as adjunctive treatment of partial-onset epilepsy with or without secondary generalisation in patients aged 16 and over. A month's treatment at the recommended maintenance dose of 100-200mg twice daily costs approximately £73-£140. A new non-nucleoside reverse transcriptase inhibitor (NNRI) is available for the treatment of HIV-1 infection in combination with a boosted protease inhibitor (PI) and other antiretrovirals in treatment-experienced adults. Etravirine (Intelence) costs approximately £320 for one month's treatment at the recommended dose of 200mg twice daily. Voltarol Pain-Eze (diclofenac) 12.5mg tablets are now available without prescription; a pack of 18 tablets costs £5.99. Atypicals and EPS risk Atypical antipsychotics are not associated with a significantly lower risk of extra-pyramidal symptoms than first-generation agents such as perphenazine (Fentazin), a new analysis of the CATIE study has shown (Br J Psychiatry 2008;193:279,88). CATIE was a large trial comparing the efficacy and safety of antipsychotics in the treatment of schizophrenia in which perphenazine was a representative first-generation agent (Am J Psychiatry 2006;163:611,22). This analysis found no differences in the risk of parkinsonism, dystonia, akathisia or tardive dyskinesia between perphenazine and the newer antipsychotics; use of antiparkinsonian medication was higher with risperidone and lower with quetiapine (Seroquel). Mental health website A new website offering information about mental illnesses and drug treatment has been launched by the United Kingdom Psychiatric Pharmacy Group (UKPPG), the College of Mental Health Pharmacists (CMHP), the Pharmaceutical Schizo-phrenia Initiative (PSI) and the National Institute for Mental Health in England (NIMHE). www.choiceandmedication.org.uk includes information about 17 mental illnesses and a large number of drug treatments. It offers links to other sites offering information and downloadable leaflets, help to identify the local mental health trust and downloadable charts comparing treatments for each indication. [source] Latest news and product developmentsPRESCRIBER, Issue 6 2008Article first published online: 24 APR 200 Government responds to NICE report The Government has published its response to the Health Select Committee's report into NICE, broadly arguing that the Committee's recommendations are either already being dealt with or are not appropriate. The Committee recommended appraisals for all new drugs, shorter, rapid appraisals to coincide with their launch, and improved mechanisms for setting drug prices. The Government says its negotiations on the PPRS preclude a detailed response but suggests a rapid system may not be transparent or legally robust. It is exploring how high-cost drugs can be brought within the payment-by-results tariff. While defending NICE's reliance on QALYs, the Government accepts the need to explore how wider economic factors can be considered. As for the threshold cost per QALY by which NICE defines cost effectiveness, it says this is being validated scientifically and NICE will continue to determine the threshold. More topically, the Committee criticised the quality of clinical trial data available to NICE. The Government sees no need to compel pharmaceutical companies to disclose information and says NICE is already becoming more involved with research programmes. All clinical trials must be registered (confidentially) with the EU and the Government believes mandatory registration in the UK would be ineffective and illegal. Prescription charge up again from April The Government has raised the prescription charge by 25p to £7.10 per item with effect from 1 April. Prescription prepayment certificates will cost £27.85 for three months and £102.50 for 12 months. The increase, below the annual rate of inflation for the 10th successive year, will be levied on the 12 per cent of prescriptions that are liable for the charge: 5 per cent via prepayment certificates and 7 per cent from other prescriptions. The charge will generate £435 million in England in 2008/09; this excludes money from prescriptions written by dispensing doctors, which is retained by the PCT. Following criticism of the charge by the Health Select Committee, the Government says it has reviewed the charge and is now consulting on ,cost-neutral' options. MHRA safety update The MHRA warns of possible dose errors associated with Boots Medisure Domiciliary Dosage System in its latest issue of Drug Safety Update (2008;1:issue 8). One case has been reported in which incomplete sealing allowed tablets to mix between compartments. No other cases are known and the MHRA says no harm was reported but the risk is serious. The system should be carefully sealed and inspected visually and physically. The MHRA reaffirms its plans to reclassify all pseudoephedrine and ephedrine products to prescription-only status in 2009 if the new restrictions on sales do not reduce misuse. Other topics in this month's Update include revised indications for oral ketoconazole (Nizoral), restricting its use to selected conditions unresponsive to topical therapy; reformulation of the injectable antibiotic Tazocin (piperacillin plus tazobactum); the risk of peripheral neuropathy associated with pegylated interferon and telbivudine (Sebivo) in the treatment of hepatitis B; and serious adverse events associated with modafinil (Provigil). First oral anticoagulant since warfarin In January this year the EMEA issued a positive opinion to recommend marketing authorisation of the oral, fixed-dose, direct thrombin inhibitor dabigatran etexilate (Pradaxa) for the primary prevention of venous thromboembolism (VTE) in adult patients that have undergone elective knee or hip replacement surgery. Marketing authorisation for the EU (including the UK) is expected from the European Commission in the next few weeks, making dabigatran the first oral anticoagulant since warfarin was introduced in 1954. Dabigatran etexilate has been shown to be as safe and effective as enoxaparin (Clexane) with a similar adverse event profile in the noninferiority phase III RENOVATE (Lancet 2007;370: 949-56) and RE-MODEL (J Throm Haemost 2007;5:217885) trials, which investigated the efficacy and safety of dabigatran compared to enoxaparin in reducing the risk of VTE after total hip and knee surgery respectively. Dabigatran has the practical advantage over low-molecular-weight heparin of oral postoperative administration and no risk of heparin-induced thrombocytopenia and, unlike warfarin, does not require monitoring or dose titration. Risk scale predicts anticholinergic effects US investigators have developed a scale for predicting the risk of anticholinergic side-effects from older patients' medicines (Arch Intern Med 2008;168: 508-13). The scale assigns a score from 1 (low) to 3 (high) for the risk of anticholinergic effects such as dry mouth, constipation and dizziness associated with commonly prescribed medicines. Checking the scale retrospectively in older patients in residential care, a higher score was associated with a 30 per cent increased risk of side-effects after adjustment for age and number of medicines. When this was repeated prospectively in a primary-care cohort, the increased risk was 90 per cent. HRT cancer risk persists The latest analysis of the Women's Health Initiative (WHI) trial of HRT shows that the small increase in the risk of cancer persists for up to three years after stopping treatment (J Am Med Assoc 2008;299:1036-45). WHI was stopped after 5.6 years' follow-up when it became clear the risks of HRT outweighed its benefits. This follow-up after a further three years (mean 2.4) involved 15 730 women. The annual risk of cardiovascular events was similar for HRT (1.97 per cent) and placebo (1.91 per cent). Cancers were more common among women who had taken HRT (1.56 vs 1.26 per cent), in particular breast cancer (0.42 vs 0.33 per cent). All-cause mortality was higher, but not statistically significantly so, with HRT (1.20 vs 1.06 per cent). Tight glycaemic control may increase falls Maintaining HbA1C at or below 6 per cent with insulin is associated with an increased risk of falls, a US study suggests (Diabetes Care 2008;31:391-6). The Health, Aging and Composition study involved 446 older people with type 2 diabetes (mean age 74) followed up for approximately five years. The incidence of falls ranged from 22 to 30 per cent annually. Comparing subgroups with HbA1C of ,6 per cent and >8 per cent, an increased risk of falls was associated with insulin use (odds ratio 4.4) but not oral hypoglycaemic drugs. Copyright © 2008 Wiley Interface Ltd [source] From heparins to factor Xa inhibitors and beyondEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2005S. Alban Abstract Despite some disadvantages, unfractionated heparin (UFH) and oral anticoagulants have been the only anticoagulants for prophylaxis and therapy of thromboembolic disorders for several decades. Based on the increasing knowledge of the structure and pharmacology of heparin, low molecular weight heparins (LMWH) have been developed in the 1980s. Compared to UFH, their advantages are mainly based on their reduced nonspecific binding to proteins and cells resulting in improved pharmacokinetics. In 1991, LMWH were declared as the most efficient prophylaxis in high-risk patients. Although the use of LMWH is increasing and they are today also applied for therapy and in other indications like acute coronary syndrome, they are considered not optimal concerning efficacy and safety. With the approval of fondaparinux for the prevention of venous thromboembolic disease in high-risk orthopedic patients, there might be a paradigm shift in the field of anticoagulants. Fondaparinux, a synthetic, chemically defined pentasaccharide, is the first selective inhibitor of factor Xa. By its highly specific binding to antithrombin, it selectively inhibits factor Xa and consequently prevents thrombin generation. In contrast to UFH and LMWH, it does not bind to any other cells and other proteins than antithrombin. This leads to a favourable linear pharmacokinetic profile, allowing once-daily subcutaneous application of a fixed dose without monitoring in thromboembolism prophylaxis. In addition to the evaluation of fondaparinux for further indications, chemical modifications of this pentasaccharide such as the long-acting idraparinux are currently under investigation. [source] Severity of cerebral white matter lesions and infarcts in patients with transient or moderately disabling cerebral ischaemia: reproducibility of grading by neurologistsEUROPEAN JOURNAL OF NEUROLOGY, Issue 8 2006E. L. L. M. De Schryver Diffuse or multifocal ischaemic white matter lesions increase the risk of intracranial haemorrhage in patients using oral anticoagulants for secondary prevention after cerebral ischaemia of arterial origin. We studied whether neurologists could reliably assess the presence of these white matter abnormalities. As part of the European/Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT), the severity of white matter lesions and presence of ischaemic lesions were twice assessed in a consensus meeting of three neurologists (from a pool of nine) as absent, moderate or severe, in a sample of 126 randomly selected CT or MRI scans. The neurologists were not aware of the duplicate grading. The degree of agreement between the first and second observation was calculated with kappa statistics. The kappa value for agreement between the first and second assessment of white matter lesions was 0.58 (95% CI 0.40,0.76). The kappa value for the presence of clinically relevant and/or irrelevant ischaemic lesions was 0.68 (95% CI 0.58,0.78). Clinicians can assess the presence of white matter lesions with sufficient reliability. Such assessment may prevent unnecessary risk with oral anticoagulation in secondary prevention after cerebral ischaemia of arterial origin, of which the efficacy is currently being assessed in ESPRIT. [source] Frequency of cytochrome P450 2C9 allelic variants in the Chinese and French populationsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2003Jue Quin Yang Abstract Cytochrome P450 2C9 (CYP2C9) is a polymorphic enzyme responsible for the metabolism of different drugs with low therapeutic index such as oral anticoagulants. CYP2C9*2 and CYP2C9*3 are two single nucleotide polymorphic allelic variants. The frequency of these alleles in different ethnic populations is extremely variable. In this study, we compared the frequencies of CYP2C9 allelic variants among 394 Chinese living in Shanghai to 151 French Caucasians living in Paris. The allelic frequencies of CYP2C9 variants of the Chinese and the French subjects were 0.963, 0.001, 0.036 and 0.77, 0.15, 0.08 for CYP2C9*1, CYP2C9*2, CYP2C9*3, respectively. Chinese CYP2C9*3 allelic frequency was twice as lower as the French subjects, but three times higher than Korean (0.036 vs. 0.011). The CYP2C9*2 allele could be detected in only one Chinese subject, whereas it represented the major allelic variant in French Caucasians. The low frequency of the CYP2C9*2 and CYP2C9*3 allelic variants in Chinese subjects does not justify their detection in clinical practice, unlike French Caucasians. [source] Managing oral anticoagulation therapy: improving clinical outcomes.JOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 6 2008A review Summary Many physicians are reluctant to prescribe oral anticoagulation therapy (OAT) because of the fear of haemorrhagic complications. Changes in patient health, lifestyle or diet and other drugs can alter the effectiveness of oral anticoagulants. These potential interferences, added to the fact that each individual has a different reaction to these drugs, requires that therapy is monitored regularly. This article aims to review those strategies which help to achieve optimal anticoagulation control and improve the outcomes of OAT. Relevant articles were identified through a search of MEDLINE and included publications reporting on intensity of anticoagulation, the initiation of therapy and the role of pharmacogenetics, the transition from primary to secondary care, management by specialized clinics using decision support software and home-testing. Implementation of these strategies would increase the use of oral anticoagulants by physicians and offers the potential to improve patient safety and reduce adverse events. [source] Contemporary management of pulmonary embolism: the answers to ten questionsJOURNAL OF INTERNAL MEDICINE, Issue 3 2010H. Bounameaux Abstract., Bounameaux H (Division of Angiology and Hemostasis, Department of Internal Medicine, University Hospitals of Geneva and Faculty of Medicine, Geneva, Switzerland). Contemporary management of pulmonary embolism: the answers to ten questions (Review). J Intern Med 2010; 268: 218,231. Pulmonary embolism (PE) cannot be diagnosed solely on a clinical basis, because of the lack of sensitivity and specificity of clinical signs and symptoms. Pulmonary angiography is invasive and resource demanding. Because the prevalence of PE is relatively low (20% or less) amongst individuals who are clinically suspected of having the disease, submitting all of them to imaging (multi-detector CT angiography or ventilation/perfusion lung scintigraphy) would not be cost-effective. Therefore, diagnostic algorithms have been developed that include clinical probability assessment and D-dimer measurement to select the patients who require noninvasive imaging. Once the diagnosis is suspected or confirmed, therapy must be started to avoid potentially fatal recurrence. Treatment starts for an initial 3-month period with a 5-day course of parenteral unfractionated or low-molecular-weight heparin or fondaparinux overlapping with and followed by oral vitamin K antagonists monitored to maintain an international normalized ratio of 2,3. This initial period of 3 months may then be followed by a long-term secondary prevention period in patients who experience an idiopathic thromboembolic event and are at low risk of bleeding. New oral anticoagulants that do require patient monitoring and might exhibit a more favourable benefit,risk balance are currently under extensive clinical testing and might change the situation in the near future. A critical appraisal of the contemporary management of suspected PE is given in this overview with the discussion of 10 practical questions. [source] Observance of Antiplatelet Therapy after Stent Implantation in Patients under Chronic Oral Anticoagulant TreatmentJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 3 2008JOSÉ VALENCIA M.D., Ph.D. Purpose: Patients undergoing coronary stenting must take dual antiplatelet therapy during a variable period. The combination of chronic oral anticoagulants (COA) with antiplatelet therapy has been related to an increased risk of hemorrhage. The aim of this study was to evaluate the level of the antiplatelet therapy observance in those patients and the incidence of adverse events after 1 year. Methods: Patients with prior COA treatment with coronary lesions suitable for stenting were included. Clinical assessment was performed on admission, with follow-up at 1, 6, and 12 months. Antiplatelet and COA treatment, adverse cardiac events, and hemorrhagic episodes were registered. Results: A total of 70 patients were included. Mean age was 70.5 ± 8.7 years. The most common cause of COA was atrial fibrillation. Conventional stents were used in 40% and drug-eluting stents (DES) in 60%. Treatment at discharge was: ASA + clopidogrel + COA 64.2%, ASA + clopidogrel 25.4%, COA + clopidogrel 7.5%, and COA + ASA 3%. Observance of antiplatelet and COA therapy at 1-6-12 month follow-up after conventional stent was: COA 73.1-70.8-69.6%; ASA 92.3-75.4-65.2%; clopidogrel 92.3-62.5-43.5%. In patients receiving DES, it was: COA 76.9-78.9-80.6%, ASA 79.5-65.8-55.7%, and clopidogrel 94.9-84.2-61.1%. Dual antiplatelet therapy in patients with DES over these periods was taken in 79.5-51.4-27.8%, respectively. The incidence of adverse events was minor bleeding 11.4%, major bleeding 8.6%, myocardial infarction 4.3%, stent thrombosis 1.4%, and death 12.8%. Conclusions: There is a great variability in the treatment prescribed at discharge. Low observance with dual antiplatelet therapy has been detected in these patients, particularly after DES implantation, and they present a very high rate of complications in the follow-up. [source] Percutaneous Left and Right Heart Catheterization in Fully Anticoagulated Patients Utilizing the Radial Artery and Forearm Vein: A Two-Center ExperienceJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 3 2006TED S. N. LO M.R.C.P. Background: Stopping oral anticoagulants prior to cardiac catheterization is associated with an increased risk of thromboembolism. Performing the procedures via the femoral artery and vein without interruption of anticoagulation is associated with a high rate of major access site complications. The transradial technique for left heart catheterization is safe in fully anticoagulated patients but few data are available on the percutaneous right and left heart catheterization utilizing a combination of the radial artery and antecubital vein in this group of patients. Methods: We report our experience in 28 consecutive patients that underwent left and right heart catheterizations via this percutaneous arm approach without interruption of anticoagulation. These were compared to 31 consecutive non-anticoagulated patients that underwent the procedure via a conventional femoral artery and vein approach. Results: Arterial and venous accesses were achieved and complete angiographic and hemodynamic data obtained in all patients. There were no access site complications in the anticoagulated patients despite an International normalized ratio (INR) of 2.5 ± 0.5. Procedural duration was longer in the anticoagulated group of patients, but fluoroscopy time and patient radiation dose were similar in both groups. Conclusion: Our experience suggests that left and right heart catheterization can be safely performed in most fully anticoagulated patients using this technique with a low bleeding and thromboembolic risk and no increase in radiation exposure. [source] Can oral vitamin K before elective surgery substitute for preoperative heparin bridging in patients on vitamin K antagonists?JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 3 2010A. STEIB See also Douketis JD, Spyropoulos AC. Vitamin K to reverse the anticoagulant effect of vitamin K antagonists: can you teach an old dog new tricks? This issue, pp 496,8. Summary.,Background: After a vitamin K antagonist (VKA) overdose, 1,2 mg of oral vitamin K can lower the International Normalized Ratio (INR) to the therapeutic range. Objective: To establish whether oral vitamin K can substitute for heparin bridging and decrease the INR to , 1.5 before elective surgery. Methods: Patients on long-term VKAs were randomized either to heparin bridging after the last VKA dose on day , 5 before surgery (group H) or to VKA treatment until day , 2, followed by 1 mg of oral vitamin K on the day before surgery (group K). Blood clotting variables were assessed on days ,5/,2, 1 and 0, and postoperatively. If the target INR was not achieved 2 h before incision, surgery was deferred or performed after injection of prothrombin complex concentrate (PCC). Results: In 30 of 94 included patients, baseline INR was outside the chosen range (18, INR < 2; 12, INR > 3.5), leaving 34 eligible patients in group H and 30 in group K. The groups were balanced in terms of body mass index, VKA treatment duration and indication, scheduled surgery, preoperative and postoperative hemoglobin, and blood loss. The INR was significantly higher in group K on days , 1 and 0 than in group H. An INR , 1.5 was not achieved in 20 group K patients (66%). Surgery was postponed or performed after PCC injection in 12 of these 20 patients. Conclusions: Oral vitamin K (1 mg) cannot substitute for heparin bridging before surgery. In addition, one-third of patients on VKAs were exposed to a risk of bleeding (overdose) or thrombosis (underdose), thus highlighting the need for new oral anticoagulants. [source] Bridging therapy in patients on long-term oral anticoagulants who require surgery: the Prospective Peri-operative Enoxaparin Cohort Trial (PROSPECT)JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 11 2007A. S. DUNN Summary., Background:, The peri-operative management of patients on oral anticoagulants (OACs) is a common clinical problem. Our aim was to determine the incidence of major bleeding during peri-operative administration of treatment-dose enoxaparin and the impact of the extensiveness of the procedure on the risk of bleeding. Methods:, We performed a prospective cohort study of 260 patients at 24 North American sites on OACs for atrial fibrillation or a history of deep vein thrombosis (DVT) requiring invasive or surgical procedures whose treating physician felt that bridging therapy was required. Warfarin was withheld, and once-daily s.c. enoxaparin (1.5 mg kg,1) was given peri-operatively. Patients were followed for 28 days after OAC was therapeutic. Results:, Major bleeding was observed in nine of 260 patients (3.5%, 95% CI: 1.6,6.5). The bleeding risk varied markedly by extensiveness of procedure: the incidence of major bleeding for invasive procedures, minor surgery and major surgery was 0.7% (95% CI: 0.02,3.7), 0% (95% CI: 0,5.0), and 20.0% (95% CI: 9.1,35.7), respectively. There were five thromboembolic events in total (1.9%, 95% CI: 0.6,4.4). There were four arterial events (2.3%, 95% CI: 0.6,5.7) in 176 patients with atrial fibrillation, and one venous event (1.0%, 95% CI: 0.03,5.7) in 96 patients with prior DVT. Conclusions:, Bridging therapy with once-daily therapeutic-dose enoxaparin administered primarily in an outpatient setting has a low incidence of major bleeding for patients undergoing invasive procedures and minor surgery. Further studies are needed to optimize the bridging strategy for patients undergoing major surgery. [source] Clinical outcomes with unfractionated heparin or low-molecular-weight heparin as bridging therapy in patients on long-term oral anticoagulants: the REGIMEN registry,JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 6 2006A. C. SPYROPOULOS Summary.,Background: Patients who receive long-term oral anticoagulant (OAC) therapy often require interruption of OAC for an elective surgical or an invasive procedure. Heparin bridging therapy has been used in these situations, although the optimal method has not been established. No large prospective studies have compared unfractionated heparin (UFH) with low-molecular-weight heparin (LMWH) for the perioperative management of patients at risk of thromboembolism requiring temporary interruption of long-term OAC therapy. Patients/methods: This multicenter, observational, prospective registry conducted in North America enrolled 901 eligible patients on long-term OAC who required heparin bridging therapy for an elective surgical or invasive procedure. Practice patterns and clinical outcomes were compared between patients who received either UFH alone (n = 180) or LMWH alone (n = 721). Results: Overall, the majority of patients (74.5%) requiring heparin bridging therapy had arterial indications for OAC. LMWH, in mostly twice-daily treatment doses, represented approximately 80% of the study population. LMWH-bridged patients had significantly fewer arterial indications for OAC, a lower mean Charlson comorbidity score, and were less likely to undergo major or cardiothoracic surgery, receive intraprocedural anticoagulants or thrombolytics, or receive general anesthesia than UFH-bridged patients (all P < 0.05). The LMWH group had significantly more bridging therapy completed in an outpatient setting or with a < 24-h hospital stay vs. the UFH group (63.6% vs. 6.1%, P < 0.001). In the LMWH and UFH groups, similar rates of overall adverse events (16.2% vs. 17.1%, respectively, P = 0.81), major composite adverse events (arterial/venous thromboembolism, major bleed, and death; 4.2% vs. 7.9%, respectively, P = 0.07) and major bleeds (3.3% vs. 5.5%, respectively, P = 0.25) were observed. The thromboembolic event rates were 2.4% for UFH and 0.9% for LMWH. Logistic regression analysis revealed that for postoperative heparin use a Charlson comorbidity score > 1 was an independent predictor of a major bleed and that vascular, general, and major surgery were associated with non-significant trends towards an increased risk of major bleed. Conclusions: Treatment-dose LMWH, mostly in the outpatient setting, is used substantially more often than UFH as bridging therapy in patients with predominately arterial indications for OAC. Overall adverse events, including thromboembolism and bleeding, are similar for patients treated with LMWH or UFH. Postoperative heparin bridging should be used with caution in patients with multiple comorbidities and those undergoing vascular, general, and major surgery. These findings need to be confirmed using large randomized trials for specific patient groups undergoing specific procedures. [source] Incidence of cancer after a first episode of idiopathic venous thromboembolism treated with 3 months or 1 year of oral anticoagulationJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2003M. R. Taliani Summary.,Background:,A prolonged treatment with oral anticoagulants has been claimed to reduce the incidence of newly diagnosed cancer in the long-term follow-up of patients with venous thromboembolism. Objectives:,In a multicenter prospective study we assessed the incidence of newly diagnosed clinically overt cancer in patients with a first episode of idiopathic venous thromboembolism (VTE) treated with oral anticoagulants for 3 months or 1 year. Patients and methods:,Consecutive patients with an idiopathic venous thromboembolism who had completed 3 months of oral anticoagulant therapy without having a recurrence, bleeding or newly diagnosed cancer were randomized to discontinue oral anticoagulant therapy or to continue it for nine additional months. Idiopathic venous thromboembolism was defined as thrombosis occurring in the absence of known cancer, known thrombophilia, or temporary risk factors for venous thromboembolism. All patients were followed up for at least 1 year after randomization. Results:,A total of 429 patients, 265 patients with DVT and 164 with PE, were followed up for an average of 43.7 months after randomization. A newly diagnosed cancer occurred in 32 patients (7.5%), 13 (6.2%) of the 210 patients treated for 3 months and 19 (8.7%) of the 219 patients treated for 1 year (RR = 0.71, 95% confidence interval 0.36,1.41). Conclusions:,The incidence of newly diagnosed clinically overt cancer is not reduced in patients with idiopathic venous thromboembolism treated with 1-year anticoagulant treatment compared with patients treated for 3 months. [source] US4 Pharmacotherapy complicating dental surgeryORAL DISEASES, Issue 2006Boras Planning dental treatments for patients taking antithrombotic can be difficult for the general dental practitioner, particularly when surgical interventions are needed. The drugs employed in the long-term treatment of such patients include platelet aggregation inhibitors and oral anticoagulants. Platelet aggregation inhibitors do not represent a contraindication to oral surgery. The activity of oral anticoagulants can be affected by many substances, for this reason it is necessary to monitor by INR the patients taking those drugs. When INR is within therapeutic limits for the more common conditions, most of the oral surgery interventions do not need any special precaution. Evidence indicates that suspending antithrombotic drugs is not indicate, as complications following a thrombotic accident are more frequent and serious than bleedings following oral surgery. It is well known that systemic corticosteroid therapy due to the effect on adrenal suppression can interfere with dental surgical procedures. However, that is largely dependent on the type and dose of corticosteroid that patient is currently taking, or has been taking in the last 12 months and on the type and extent of surgical procedure which is to be performed. Surgical management of dental patients with history of systemic corticosteroid therapy is proposed from the existing literature. [source] Novel oral anticoagulants and diet: The potential for interaction,AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2009Farhad Kamali No abstract is available for this article. [source] Oral anticoagulants and the risk of osteoporotic fractures among elderly,,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 5 2004Danielle Pilon MD Abstract Purpose Coumadin-based oral anticoagulants are associated with a decrease in bone mass density, but their role in fracture risk is equivocal. Because the use of oral anticoagulants is prevalent among the elderly, as is the risk and morbidity of osteoporotic fractures, the association between osteoporotic fractures and oral anticoagulants needs to be clarified. Method We conducted a case-control study on a 10% random sample of subjects aged 70 years and older enrolled in the Quebec universal health insurance plan between 1992 and 1994. Incident cases of a first osteoporotic fracture were identified by International Classification of Diseases, Ninth Revision codes. Exposure was defined as one or more prescriptions of oral anticoagulants dispensed before the osteoporotic fracture. Ten controls for each case, matched by age and date of osteoporotic fracture, were identified. Results Among 1523 cases, 48 (3.2%) were ever exposed to oral anticoagulants; among 15,205 controls, 461 (3.0%) were ever exposed (crude odds ratio: 1.0: 95% confidence interval: 0.7,1.5). These negative results persisted after adjusting for potential confounding variables and stratifying exposure into cumulative dose and treatment duration. Conclusions Coumadin-based oral anticoagulants are not significantly associated with osteoporotic fractures among the elderly, providing reassurance for elderly patients on long-term oral anticoagulants. Copyright © 2003 John Wiley & Sons, Ltd. [source] Underutilization of gastroprotective measures in patients receiving nonsteroidal antiinflammatory drugsARTHRITIS & RHEUMATISM, Issue 8 2002Walter Smalley Objective To determine the frequency of use of recommended gastroprotective strategies in a cohort of patients receiving recurrent treatment with nonsteroidal antiinflammatory drugs (NSAIDs). Methods A cross-sectional study was performed using administrative data from the Tennessee Medicaid (TennCare) program. The study population consisted of 76,765 recurrent recipients of NSAIDs (NSAID users), comprising 24% of the 319,402 persons ages 50 years or older enrolled in the TennCare program from January 1999 through June 2000. Frequency of use of either of 2 recommended gastroprotective strategies, involving either traditional NSAIDs combined with recommended anti-ulcer cotherapy or use of a selective cyclooxygenase 2,inhibiting drug (coxib), was measured and categorized by risk for ulcer complication. Results Among this cohort of recurrent NSAID users, 16% received 1 of the 2 recommended gastroprotective therapies: 10% received traditional NSAIDs along with antiulcer drugs at the recommended doses and 6% received coxibs. Among those patients with ,2 risk factors for ulcer complications (age 75 years or older, peptic ulcer or gastrointestinal bleeding in the past year, or concurrent use of oral anticoagulants or corticosteroids), 30% received such gastroprotective therapy. Conclusion Use of recommended strategies to decrease ulcer complications in vulnerable populations is relatively uncommon. [source] Long-term Management of an Implantable Left Ventricular Assist Device Using Low Molecular Weight Heparin and Antiplatelet Therapy: A Possible Alternative to Oral AnticoagulantsARTIFICIAL ORGANS, Issue 5 2007Bart Meuris Abstract:, Between January 2004 and December 2005, out of 14 patients with decompensated heart failure who were treated with an INCOR left ventricular assist device (Berlin Heart AG, Berlin, Germany), 10 patients were kept on a long-term regime of low molecular weight heparin (LMWH) and antiplatelet therapy. The treatment objective was bridge-to-transplantation. All patients received LMWH in therapeutic doses according to body weight, in combination with daily aspirin 160 mg, clopidogrel 75 mg, and three times dipyridamole 75 mg. Effectiveness of the low molecular weight regime was monitored through measurement of antifactor Xa activity (base and peak levels). Antiplatelet therapy was monitored through weekly platelet function tests. Within this group of 10 patients, six patients successfully received transplants and four patients died, the latest death after 405 days of INCOR support. Causes of death were sepsis, intestinal hemorrhage, acute right ventricular failure, and one major stroke. Long-term management of INCOR assist devices using a combination of LMWH and antiplatelet therapy is feasible. This treatment strategy can serve as an alternative to oral anticoagulants. [source] Comedication related to comorbidities: a study in 1203 hospitalized patients with severe psoriasisBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2008S. Gerdes Summary Background, Psoriasis is a common dermatological disorder characterized by an immune-mediated chronic inflammation which is associated with a variety of other diseases commonly referred to as comorbidities. The treatments for these diseases may interfere with the course and the treatment of psoriasis. Little is known on the general drug intake of patients with psoriasis. Objectives, To gain more insight into the general drug intake of patients with severe psoriasis. A correlation of comedication to respective diseases could lead to a better knowledge of comorbidities. Methods, Data on demographics, comedication and comorbidities from 1203 patients with severe psoriasis in Germany were analysed. As a control group data from 7099 subjects from the German National Health Survey 1998 were used. Results, Patients with severe psoriasis are receiving significantly more different systemic drugs on average than the general population, with the most prominent difference in multidrug treatment. Drugs used in the treatment of arterial hypertension, diabetes mellitus and other diseases of the metabolic syndrome as well as oral anticoagulants and anticonvulsant agents showed the greatest differences. Special characteristics of antihypertensive drug treatments could be determined. Conclusions, The data obtained in this study provide the basis for an improved management of patients with psoriasis. Knowledge of existing comedication and comorbidities may lead to the ability to treat psoriasis and comorbidities at the same time more safely and to use possible synergistic effects. [source] The influence of polymorphisms of VKORC1 and CYP2C9 on major gastrointestinal bleeding risk in anticoagulated patientsBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2008Ramón Montes Summary The VKORC1 c.,1639G>A and CYP2C9 c.430C>T and c.1075A>C polymorphisms have been associated with increased sensitivity to oral anticoagulants. However, their role in gastrointestinal bleeding is unknown. We studied the risk of gastrointestinal bleeding associated with these polymorphisms, and how this risk was influenced by the anticoagulant dose and the use of common drugs. Eighty-nine patients with gastrointestinal bleeding during acenocoumarol therapy and 177 patients free of bleeding during acenocoumarol therapy were studied. None of the three polymorphisms constituted a serious gastrointestinal bleeding risk factor. However, patients bearing at least one of these polymorphisms were at high risk, when they simultaneously met one of the following conditions: a weekly dose of acenocoumarol higher than 15 mg [adjusted Odds Ratio (OR) (95% confidence interval (CI) = 4·19 (1·59,11·04)]; amiodarone use [adjusted OR (95% CI) = 9·97 (1·75,56·89)]; or aspirin use [adjusted OR (95% CI) = 8·97 (1·66,48·34)]. The consumption of statins was associated with a lower risk of gastrointestinal bleeding [adjusted OR = 0·50 (0·26,0·99)]. The risk of gastrointestinal bleeding during acenocoumarol therapy in carriers of any of the studied polymorphisms is severely increased with exposure to weekly doses of acenocoumarol higher than 15 mg or the use of amiodarone or aspirin. [source] Epidemiology of transient ischemic attack and ischemic stroke in patients with underlying cardiovascular diseaseCLINICAL CARDIOLOGY, Issue S2 2004M.P.H., Philip B. Gorelick M.D. Abstract It is estimated that 15 to 30% of ischemic strokes are cardioembolic in origin, and that atrial fibrillation, valvular heart disease, coronary artery disease, congestive heart failure, and myocardial infarction are significant risk factors for stroke, which underscores the importance for cardiologists to understand this condition. The high incidence and substantial cost of stroke justify aggressive treatment of stroke risk factors, especially in the elderly, diabetic, and black populations, and in patients who have had an initial stroke. Antiplatelet therapy and administration of oral anticoagulants have both been shown to have a substantial impact on stroke in specified populations at risk. [source] | |||||||||||||||||||||||||||||||