Optimal duration of anticoagulation in patients with venous thromboembolism

Size: px
Start display at page:

Download "Optimal duration of anticoagulation in patients with venous thromboembolism"

Transcription

1 Review Article Indian J Med Res 134, July 2011, pp Optimal duration of anticoagulation in patients with venous thromboembolism Paolo Prandoni, Chiara Piovella, Luca Spiezia, Fabio Dalla Valle & Raffaele Pesavento Department of Cardiothoracic & Vascular Sciences, Clinica Medica II & Thromboembolism Unit, University of Padua, Italy Received April 18, 2011 The risk of recurrent venous thromboembolism (VTE) approaches 40 per cent of all patients after 10 yr of follow up. This risk is higher in patients with permanent risk factors of thrombosis such as active cancer, prolonged immobilization from medical diseases, and antiphospholipid syndrome; in carriers of several thrombophilic abnormalities, including deficiencies of natural anticoagulants; and in patients with unprovoked presentation. Patients with permanent risk factors of thrombosis should receive indefinite anticoagulation, consisting of subtherapeutic doses of low molecular weight heparin in cancer patients, and oral anticoagulants in all other conditions. Patients whose VTE is triggered by major surgery or trauma should be offered three months of anticoagulation. Patients with unprovoked VTE, including carriers of thrombophilia, and those whose thrombotic event is associated with minor risk factors (such as hormonal treatment, minor injuries, long travel) should receive at least three months of anticoagulation. The decision as to go on or discontinue anticoagulation after this period should be individually tailored and balanced against the haemorrhagic risk. Post-baseline variables, such as the D-dimer determination and the ultrasound assessment of residual thrombosis can help identify those patients in whom anticoagulation can be safely discontinued. As a few emerging anti-xa and anti-iia compounds seem to induce fewer haemorrhagic complications than conventional anticoagulation, while preserving at least the same effectiveness, these have the potential to open new scenarios for decisions regarding the duration of anticoagulation in patients with VTE. Key words Anticoagulation - deep venous thrombosis - pulmonary embolism - thrombophilia - venous thromboembolism Introduction After discontinuing anticoagulation a substantial proportion of patients with deep venous thrombosis (DVT) and/or pulmonary embolism (PE) will develop recurrent venous thromboembolic (VTE) events. According to the findings from prospective cohort studies conducted at our Institution 1,2 and elsewhere 2-7, recurrent events are expected to develop in up to 40 per cent of all patients, this figure being considerably higher in patients with unprovoked than in those with provoked VTE, provided that factors accounting for the first episode are transitory. Risk factors of recurrent thromboembolism 1. Persistent acquired risk factors After stopping anticoagulation patients with active cancer, especially those with metastatic malignancy and those undergoing chemotherapy, 15

2 16 INDIAN J MED RES, july 2011 carry a particularly high risk of recurrent VTE 8, and so do patients with chronic medical diseases requiring prolonged immobilization 9,10. Although there is no conclusive evidence coming from randomized clinical trials, all such patient should be treated with long-term anticoagulation unless they have contraindications. According to the results of recent randomized clinical trials, low molecular weight heparins (LMWH) in full doses for the first month followed by approximately 75 per cent of the initial dosage for another 5 month period has the potential to halve the rate of recurrent events while not increasing the haemorrhagic risk 11. Conventional oral anticoagulants still represent the treatment of choice in medical conditions other than neoplastic diseases 12. Indefinite treatment should also be considered in patients with multiple (especially if unprovoked) VTE episodes 13, the insertion of a permanent vena caval filter (whenever anticoagulation is not contraindicated) 14 and the antiphospholipid antibody syndrome 15. Whether these subjects require anticoagulation regimens that are more intense than usual has long been debated. Based on the results of recent randomized studies 16,17, the latest international guidelines recommend also for these patients the adoption of conventional regimens Transient risk factors Patients whose thrombosis is provoked by a major reversible risk factor, such as surgery or major trauma, have a low risk of recurrence, whereas this risk becomes higher when thrombosis is provoked by a minor reversible risk factor, such as minor leg trauma, estrogen therapy, pregnancy or puerperium, or prolonged air travel 5. Accordingly, patients with major transient risk factors, such as major trauma or surgery, should be given 12 wk of anticoagulation 12,18. This period can be halved in those patients in whom DVT is confined to the calf vein system 3,19. In patients with minor transient risk factors, such as minor trauma, long air travel, hormonal therapy, a longer duration may be considered according to each individual case, after carefully considering the haemorrhagic risk and patients preferences 12. When a thrombotic episode arises during pregnancy, it should be managed with LMWHs in full doses for at least three months, bearing in mind that the treatment should not be discontinued before the end of pregnancy, and should always be extended to cover the first six weeks after delivery Unprovoked VTE After discontinuing anticoagulation, patients with the first episode of unprovoked VTE have a risk of recurrences that approaches 50 per cent of all such patients after 8-10 yr 1,2. This figure will not change after prolonging anticoagulation up to 6 or 12 months 19, Patients presenting with a first episode of unprovoked VTE should be offered at least 3 months of oral anticoagulant therapy, targeting an (INR) between 2,0 and The decision as to go on or discontinue anticoagulation after this period should be individually tailored and balanced against the haemorrhagic risk 12. Indeed, the annual incidence of major bleeding from long-term anticoagulation is per cent, and the case-fatality rate of an episode of major bleeding is considerably higher that that of an episode of recurrent VTE Whether low-dose warfarin, that is a dose that produces a targeted INR between 1.5 and 2.0, may offer a suitable option for patients requiring longer periods of anticoagulation has long been debated 26,27. We believe that conventional warfarin regimen should be regarded as the first choice. However, a low-intensity regimen can be considered in particular situations depending on individual judgment, for example, in patients reputed to be at a higher haemorrhagic risk. Several post-baseline parameters have the potential to identify subgroups of patients with unprovoked VTE in whom anticoagulation can be safely discontinued. In a few cohort studies, the ultrasound persistence of residual thrombosis after an episode of proximal DVT was found to be an independent risk factor for recurrent thromboembolism 28,29. In subsequent randomized clinical trials and systematic reviews of available studies it has been shown that adjusting the duration of anticoagulation according to the persistence of residual thrombosis reduces the risk of recurrent VTE by 40 per cent Following the demonstration that a marker of a thrombotic tendency (D-dimer) can be helpful in the risk stratification, and thus ultimately therapeutic guidance, of individual patients with DVT 6,33-35, a randomized clinical trial showed that in patients who are left without anticoagulation as a consequence of a negative D-dimer assessed one month after warfarin discontinuation the rate of recurrent events is only slightly higher than in patients with positive D-dimer who continue anticoagulation 36. In addition, repeating D-dimer testing after anticoagulation suspension has the potential to identify a number of individuals in

3 PRANDONI et al: ANTICOAGULATION IN PATIENTS WITH VTE 17 whom D-dimer reverts to be positive and are, therefore, candidate to resume anticoagulation in order to prevent VTE recurrences 37. Another post-baseline factor potentially associated with an increased risk of recurrent VTE is the early development of post-thrombotic manifestations 38. In this regard, an example of how useful a few post-baseline parameters can be, alone or in combination with baseline variables, for the identification of patients at low risk of recurrent VTE, has recently been offered by the prospective study by Rodger et al 39. Indeed, women with unprovoked VTE and none or 1 of a number of parameters (early post-thrombotic manifestations, D-dimer positivity at time of discontinuing anticoagulation, obesity, and age older than 65) were found to exhibit a considerably lower risk of recurrent VTE than the remaining patients. An interesting prediction model for the development of recurrent VTE has recently been published by a group of Austrian investigators, which enables identification of the recurrence risk based on the combination of two baseline factors (sex and type of clinical presentation) and one post-baseline factor (D-dimer) 40. This observation is interesting, but requires confirmation in settings other than that where the model has been developed. 4. Inherited thrombophilia While inherited thrombophilia does not increase the risk of recurrent thromboembolism while on warfarin 41, whether and to which extent carriers of inherited thrombophilia exhibit a higher risk of recurrent VTE after discontinuing anticoagulation is controversial. It is generally accepted, although not conclusively demonstrated, that carriers of antithrombin (AT), protein C and S 42, carriers of hyperhomocysteinemia 43 and carriers of increased levels of factor VIII or IX 44-46, have a recurrence risk that is higher than that of control subjects. Whether carriers factor V Leiden or prothrombin G20210A variant - including homozygous carriers and carriers of double heterozygosity have a higher risk of recurrence as well is controversial, as there are data in favour and against this association 47,48. Discrepancies among studies may be related to different selection of inception cohort, length of follow up, initial treatment of the acute thrombotic disorder, duration of treatment, and changes in general management of thrombotic patients. As a consequence, whether detection of these abnormalities, which are highly prevalent in western countries, has the potential to identify a subgroup of patients who might benefit from the adoption of individually adjusted prevention strategies following their first thrombotic episode, is virtually unknown. Recent studies suggest that prolonging anticoagulation for one year following the qualifying episode of VTE has the potential to reduce the risk of recurrent events in comparison to conventional 3-month anticoagulation 49,50. According to the results of a controlled, randomized clinical trial, homocysteine lowering by B-vitamin supplementation does not help prevent recurrent venous thrombosis Other factors Following the observation that males exhibit a higher recurrence risk than females 52, a few metaanalyses of several studies confirmed the somewhat unexpected association between male sex and recurrent VTE 53,54. Whether this finding is accounted for by sexspecific risk factors at time of first venous thrombosis is controversial Patients with a first symptomatic unprovoked DVT are at higher risk of recurrent VTE than patients with a first unprovoked PE 2,57. In addition, patients with clinically symptomatic PE have consistently been found to be at a higher risk of recurrent PE than those with DVT alone. These findings have recently been confirmed by a patient-level meta-analysis 58. Old age, which has long been regarded as a risk factor of venous thrombosis, has recently been identified as a predictive factor of recurrent VTE 59. Thus, the common practice of administering old patients lower regimens or shorter periods of anticoagulation because of the fear of haemorrhagic complications should be reconsidered 60. Likewise, excess body weight was recently found to be a powerful and independent risk factor of recurrent VTE 61. Obese patients should therefore, be carefully educated, as decrease in body weight is likely to play a key role in reducing the risk of recurrent events. Finally, it has recently been reported that a number of simple laboratory tests, such as the activated partial thromboplastin time and global coagulation assays measuring thrombin generation can help identify patients at a lower or higher risk of recurrent VTE These observations show potential, but need confirmation.

4 18 INDIAN J MED RES, july 2011 Recurrent VTE in the fertile age Women who had their first episode in fertile age are at a higher risk of experiencing recurrent thromboembolism when they are given hormonal treatment or become pregnant. This risk is particularly high in women in whom the first episode had been triggered by hormonal compounds or had developed during pregnancy Accordingly, hormonal treatment should be strongly discouraged in women with previous VTE. Whenever hormonal treatment is reputed to be necessary, the contemporary administration of oral anticoagulants should be considered. Postpartum anticoagulation is recommended in all women with previous VTE 70. While the systematical adoption of compression elastic stockings is recommended in all women with previous VTE throughout pregnancy, antenatal thromboprophylaxis with LMWH should be offered whenever the previous episode was unprovoked or was pregnancy- or estrogen-related, in carriers of thrombophilia, if there is a family history of thrombosis, if there are additional risk factors (such as obesity), and in women with multiple previous VTE episodes 70. New perspectives for the long-term treatment of patients with VTE Finally, new categories of oral antithrombotic drugs are emerging, which have the potential to simplify the long-term treatment of patients with VTE by obviating the need for periodic laboratory monitoring, while being associated with a favourable benefit-to-risk ratio. They include compounds that inhibit factor Xa, such as rivaroxaban, and compounds that inhibit thrombin, such as dabigatran etexilate. Recently, the results of the Recover 71 and those of the Einstein 72 randomized clinical trials, dealing with the initial and long-term treatment of VTE patients with dabigatran etexilate and rivaroxaban, respectively, have been reported. In the former study, the administration of dabigatran etexilate at the dose of 150 mg twice daily for 6 months in patients with acute VTE was found to be as effective as warfarin in patients who had all been treated with heparins or fondaparinux for the initial 7 to 10 days, and was associated with a statistically significant reduction in the incidence of major or clinically relevant bleeding complications 71. In the latter, the administration of rivaroxaban from the beginning at the dose of 15 mg twice daily for three weeks followed by 20 mg once daily for 3 to 12 months in patients with acute DVT was found to be at least as effective and safe as conventional enoxaparin-warfarin treatment 72. Of interest, rivaroxaban was found to be significantly more effective than comparators for the achievement of the combined end-point recurrent VTE plus major bleeding. In addition, prolonging rivaroxaban at the dose of 20 mg once daily for an additional 6 to 12- month period in patients who had received at least three months of rivaroxaban or warfarin achieved an 82 per cent reduction in the risk of recurrent events over placebo while being associated with less than 1 per cent of major bleeding complications 72. References 1. Prandoni P, Lensing AWA, Cogo A, Cuppini S, Villalta S, Carta M, et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 1996; 125 : Prandoni P, Noventa F, Ghirarduzzi A, Pengo V, Bernardi E, Pesavento R, et al. The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1626 patients. Haematologica 2007; 91 : Schulman S, Rhedin AS, Lindmarker P, Carlsson A, Lärfars G, Nicol P, et al, and the Duration of Anticoagulation Trial Study Group. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. N Engl J Med 1995; 332 : Hansson PO, Sorbo J, Eriksson H. Recurrent venous thromboembolism after deep vein thrombosis. Incidence and risk factors. Arch Intern Med 2000; 1260 : Baglin T, Luddington R, Brown K, Baglin C. Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. Lancet 2003; 362 : Palareti G, Legnani C. Cosmi B, Valdré L, Lunghi B, Bernardi F, et al. Predictive value of D-Dimer test for recurrent venous thromboembolism after anticoagulation withdrawal in subjects with a previous idioipathic event and in carriers of congenital thrombophilia. Circulation 2003; 108 : Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR. Thrombophilia, clinical factors, and recurrent venous thrombotic events. JAMA 2005; 293 : Prandoni P, Falanga A, Piccioli A. Cancer and venous thromboembolism. Lancet Oncol 2005; 6 : Kearon C. Long-term management of patients after venous thromboembolism. Circulation 2004; 110 (Suppl 1) : Prandoni P, Villalta S, Tormene D, Spiezia L, Pesavento R. Immobilization resulting from chronic medical diseases: a new risk factor for recurrent venous thromboembolism in anticoagulated patients. J Thromb Haemost 2007; 5 : Lee AY, Levine MN, Baker RI, Levine MN, Baker RI, Bowden C, et al, for the Randomized Comparison of Low-Molecular- Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003; 349 :

5 PRANDONI et al: ANTICOAGULATION IN PATIENTS WITH VTE Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133 (6 Suppl) : 454S-545S. 13. Schulman S, Granqvist S, Holmstrom M, Carlsson A, Lindmarker P, Nicol P, et al, and the Duration of Anticoagulation Trial Study Group. The duration of oral anticoagulant therapy after a second episode of venous thromboembolism. N Engl J Med 1997; 336 : Decousus H, Leizorovicz A, Parent F, Page Y, Tardy B, Girard P, et al. A clinical trial of vena cava filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. N Engl J Med 1998; 338 : Schulman S, Svenungsson E, Granqvist S. Anticardiolipin antibodies predict early recurrence of thromboembolism and death among patients with venous thromboembolism following anticoagulant therapy. Am J Med 1998; 104 : Crowther MA, Ginsberg JS, Julian J, Denburg J, Hirsh J, Douketis J, et al. A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Engl J Med 2003; 349 : Finazzi G, Marchioli R, Brancaccio V, Schinco P, Wisloff F, Musial J, et al. A randomized clinical trial of high-intensity warfarin vs. conventional antithrombotic therapy for the prevention of recurrent thrombosis in patients with the antiphospholipid syndrome. J Thromb Haemost 2005; 3 : Kearon C, Ginsberg JS, Anderson DR, Kovacs MJ, Wells P, Julian JA, et al. Comparison of 1 month with 3 months of anticoagulation for a first episode of venous thromboembolism associated with a transient risk factor. J Thromb Haemost 2004; 2 : Pinede L, Ninet J, Duhaut P, Chabaud S, Demolombe-Rague S, Durieu I, et al. Investigators of the Durée Optimale du Traitement AntiVitamines K (DOTAVK) Study. Comparison of 3 and 6 months of oral anticoagulant therapy after a first episode of proximal deep vein thrombosis or pulmonary embolism and comparison of 6 and 12 weeks of therapy after isolated calf deep vein thrombosis. Circulation 2001; 103 : Kearon C, Gent M, Hirsh J, Weitz J, Kovacs MJ, Anderson DR, et al. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N Engl J Med 1999; 340 : Agnelli G, Prandoni P, Santamaria MG, Bagatella P, Iorio A, Bazzan M, et al. Warfarin Optimal Duration Italian Trial Investigators. Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis. N Engl J Med 2001; 345 : Agnelli G, Prandoni P, Becattini C, Silingardi M, Taliani MR, Miccio M, et al. Warfarin Optimal Duration Italian Trial Investigators. Extended oral anticoagulant therapy after a first episode of pulmonary embolism. Ann Intern Med 2003; 139 : Douketis JD, Shu Gu C, Schulman S, Ghirarduzzi A, Pengo V, Prandoni P. The risk for fatal pulmonary embolism after discontinuing anticoagulant therapy for venous thromboembolism. Ann Intern Med 2007; 147 : Linkins LA, Choi PT, Douketis JD. Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism. A meta-analysis. Ann Intern Med 2003; 139 : Carrier M, Le Gal G, Wells PS, Rodger MA. Systematic review: case-fatality rates of recurrent venous thromboembolism and major bleeding events among patients treated for venous thromboembolism. Ann Intern Med 2010; 152 : Ridker PM, Goldhaber SZ, Danielson E, Rosenberg Y, Eby CS, Deitcher SR, et al. PREVENT Investigators. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med 2003; 348 : Kearon C, Ginsberg JS, Kovacs MJ, Anderson DR, Wells P, Julian JA, et al. Extended Low-Intensity Anticoagulation for Thrombo-Embolism Investigators. Comparison of lowintensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med 2003; 349 : Prandoni P, Lensing AW, Prins MH, Bernardi E, Marchiori A, Bagatella P, et al. Residual venous thrombosis as a predictive factor of recurrent venous thromboembolism. Ann Intern Med 2002; 137 : Piovella F, Crippa L, Barone M, Viganò D Angelo S, Serafini S, Galli L, et al. Normalization rates of compression ultrasonography in patients with a first episode of deep vein thrombosis of the lower limbs: association with recurrence and new thrombosis. Haematologica 2002; 87 : Prandoni P, Prins MH, Lensing AW, Ghirarduzzi A, Ageno W, Imberti D, et al. AESOPUS Investigators. Residual thrombosis on ultrasonography to guide the duration of anticoagulation in patients with deep venous thrombosis: a randomized trial. Ann Intern Med 2009; 150 : Siragusa S, Malato A, Anastasio R, Cigna V, Milio G, Amato C, et al. Residual vein thrombosis to establish duration of anticoagulation after a first episode of deep vein thrombosis: the DACUS study. Blood 2008; 112 : Tan M, Mos ICM, Klok FA, Huisman MV. Residual venous thrombosis as predictive factor for recurrent venous thromboembolim in patients with proximal deep vein thrombosis: a sytematic review. Br J Haematol; 2011; 1111 : Palareti G, Legnani C, Cosmi B, Guazzaloca G, Pancani C, Coccheri S. Risk of venous thromboembolism recurrence: high negative predictive value of D-dimer performed after oral anticoagulation is stopped. Thromb Haemost 2002; 87 : Eichinger S, Minar E, Bialonczyk C, Hirschl M, Quehenberger P, Schneider B, et al. D-dimer levels and risk of recurrent venous thromboembolism. JAMA 2003; 290 : Verhovsek M, Douketis JD, Yi Q, Shrivastava S, Tait RC, Baglin T, et al. Systematic review: D-dimer to predict recurrent disease after stopping anticoagulant therapy for unprovoked venous thromboembolism. Ann Intern Med 2008; 149 : Palareti G, Cosmi B, Legnani C, Tosetto A, Brusi C, Iorio A, et al. PROLONG Investigators. D-dimer testing to determine the duration of anticoagulation therapy. N Engl J Med 2006; 355 :

6 20 INDIAN J MED RES, july Cosmi B, Legnani C, Tosetto A, Pengo V, Ghirarduzzi A, Testa S, et al. PROLONG Investigators (on behalf of Italian Federation of Anticoagulation Clinics). Usefulness of repeated D-dimer testing after stopping anticoagulation for a first episode of unprovoked venous thromboembolism: the PROLONG II prospective study. Blood 2010; 115 : Stain M, Schönauer V, Minar E, Bialonczyk C, Hirschl M, Weltermann A, et al. The post-thrombotic syndrome: risk factors and impact on the course of thrombotic disease. J Thromb Haemost 2005; 3 : Rodger MA, Kahn SR, Wells PS, Anderson DA, Chagnon I, Le Gal G, et al. Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy. CMAJ 2008; 179 : Eichinger S, Heinze G, Jandeck LM, Kyrle PA. Risk assessment of recurrence in patients with unprovoked deep vein thrombosis or pulmonary embolism. The Vienna Prediction Model. Circulation 2010; 121 : Kearon C, Julian JA, Kovacs MJ, Anderson DR, Wells P, Mackinnon B, et al. ELATE Investigators. Influence of thrombophilia on risk of recurrent venous thromboembolism while on warfarin: Results from a randomized trial. Blood 2008; 112 : De Stefano V, Simioni P, Rossi E, Tormene D, Za T, Pagnan A, et al. The risk of recurrent venous thromboembolism in patients with inherited deficiency of natural anticoagulants antithrombin, protein C and protein S. Haematologica 2006; 91 : Eichinger S, Stümpflen A, Hirschl M, Bialonczyk C, Herkner K, Stain M, et al. Hyperhomocysteinemia is a risk factor of recurrent venous thromboembolism. Thromb Haemost 1998; 80 : Kyrle PA, Minar E, Hirschl M, Bialonczyk C, Stain M, Schneider B, et al. High plasma levels of factor VIII and the risk of recurrent venous thromboembolism. N Engl J Med 2000; 343 : Eischer L, Gartner V, Schulman S, Kyrle PA, Eichinger S. 6 versus 30 months anticoagulation for recurrent venous thrombosis in patients with high factor VIII. Ann Hematol 2008; 88 : Weltermann A, Eichinger S, Bialonczyk C, Minar E, Hirschl M, Quehenberger P, et al. The risks of recurrent venous thromboembolism among patients with high factor IX levels. J Thromb Haemost 2003; 1 : Segal JB, Brotman DJ, Necochea AJ, Emadi A, Samal L, Wilson LM, et al. Predictive value of factor V Leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation: a systematic review. JAMA 2009; 301 : Lijfering WM, Middeldorp S, Veeger NJ, Hamulyák K, Prins MH, Büller HR, et al. Risk of recurrent venous thrombosis in homozygous carriers and double heterozygous carriers of factor V Leiden and prothrombin G20210A. Circulation 2010; 121 : Taliani MR, Becattini C, Agnelli G, Prandoni P, Moia M, Bazzan M, et al. Warfarin Optimal Duration Italian Trial (WODIT) Investigators. Duration of anticoagulant treatment and recurrence of venous thromboembolism in patients with and without thrombophilic abnormalities. Thromb Haemost 2009; 101 : Prandoni P, Tormene D, Spiezia L, Pesavento R, Simioni P. Duration of anticoagulation and risk of recurrent thromboembolism in carriers of factor V Leiden or prothrombin mutation. J Thromb Haemost 2008; 6 : den Heijer M, Willems HP, Blom HJ, Gerrits WB, Cattaneo M, Eichinger S, et al. Homocysteine lowering by B vitamins and the secondary prevention of deep-vein thrombosis and pulmonary embolism. A randomized, placebo-controlled, double blind trial. Blood 2007; 109 : Eichinger S, Weltermann A, Minar E, Stain M, Schönauer V, Schneider B, et al. Symptomatic pulmonary embolism and the risk of recurrent venous thromboembolism. Arch Intern Med 2004; 164 : McRae S, Tran H, Schulman S, Ginsberg J, Kearon C. Effect of patient s sex on risk of recurrent venous thromboembolism: a meta-analysis. Lancet 2006; 368 : Douketis J, Tosetto A, Marcucci M, Baglin T, Cosmi B, Cushman M, et al. Risk of recurrence after venous thromboembolism in men and women: patient level metaanalysis: BMJ 2011; 342 : d Lijfering WM, Veeger NJ, Middeldorp S, Hamulyák K, Prins MH, Büller HR, et al. A lower risk of recurrent venous thrombosis in women compared to men is explained by sexspecific risk factors at time of first venous thrombosis in thrombophilic families. Blood 2009; 114 : Le Gal G, Kovacs MJ, Carrier M, Do K, Kahn SR, Wells PS, et al. Risk of recurrent venous thromboembolism after a first oestrogen-associated episode. Data from the REVERSE cohort study. Thromb Haemost 2010; 104 : Kovacs MJ, Kahn SR, Wells PS, Anderson DA, Chagnon I, LE Gal G, et al. Patients with a first symptomatic unprovoked DVT are at higher risk of recurrent VTE than patients with a first unprovoked PE. J Thromb Haemost 2010; 8 : Baglin T, Douketis J, Tosetto A, Marcucci M, Cushman M, Kyrle P, et al. Does the clinical presentation and extent of venous thrombosis predict likelihood and type of recurrence? A patient level meta-analysis. J Thromb Haemost 2010; 8 : Eischer L, Eichinger S, Kyrle PA. Age at first venous thromboembolism and risk of recurrence: a prospective cohort study. Medicine (Baltimore) 2009; 88 : López-Jiménez L, Montero M, González-Fajardo JA, Arcelus JI, Suárez C, Lobo JL, et al. RIETE Investigators. Venous thromboembolism in very elderly patients: findings from a prospective registry. Haematologica 2006; 91 : Eichinger S, Hron G, Bialonczyk C, Hirschl M, Minar E, Wagner O, et al, Overweight obesity, and the risk of recurrent venous thromboembolism. Arch Intern Med 2008; 68 : Grand maison A, Bates SM, Johnston M, McRae S, Ginsberg JS. ProC Global : A functional screening test that predicts recurrent venous thromboembolism. Thromb Haemost 2005; 93 : Hron G, Kollars M, Binder BR, Eichinger S, Kyrle PA. Identification of patients at low risk for recurrent venous thromboembolism by measuring thrombin generation. JAMA 2006; 296 :

7 PRANDONI et al: ANTICOAGULATION IN PATIENTS WITH VTE Hron G, Eichinger S, Weltermann A, Quehenberger P, Halbmayer WM, Kyrle PA. Prediction of recurrent venous thromboembolism by the activated partial thromboplastin time. J Thromb Haemost 2006; 4 : Besser M, Baglin C, Luddington R, van Hylckama Vlieg A, Baglin TJ. High rate of unprovoked recurrent venous thrombosis is associated with high thrombin-generating potential in a prospective cohort study. J Thromb Haemost 2008; 6 : Hoibraaten E, Qvigstad E, Arnesen H, Larsen S, Wickstrom E, Sandset PM. Increased risk of recurrent venous thromboembolism during hormone replacement therapy-- results of the randomized, double-blind, placebo-controlled estrogen in venous thromboembolism trial. Thromb Haemost 2000; 84 : Pabinger I, Grafenhofer H, Kaider A, Kyrle PA, Quehenberger P, Mannhalter C, et al. Risk of pregnancy-associated recurrent venous thromboembolism in women with a history of venous thrombosis. J Thromb Haemost 2005; 3 : De Stefano V, Martinelli I, Rossi E, Battaglioli T, Za T, Mannuccio Mannucci P, et al. The risk of recurrent venous thromboembolism in pregnancy and puerperium without antithrombotic prophylaxis. Br J Haematol 2006; 135 : White RH, Chan WS, Zhou H, Ginsberg JS. Recurrent venous thromboembolism after pregnancy-associated versus unprovoked thromboembolism. Thromb Haemost 2008; 100 : Bates SM, Greer IA, Pabinger I, Sofaer S, Hirsh H. Venous thromboembolism, thrombophilia, antithrombotic therapy, and pregnancy. American College of Chest Physicians Evidence- Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133 (6 Suppl); S. 71. Schulman S, Kearon C, Kakkar AK, Mismetti P, Schellong S, Eriksson H, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 2009; 361 : The Einstein Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363 : Reprint requests: Dr Paolo Prandoni, Department of Cardiothoracic & Vascular Sciences, Thromboembolism Unit, University of Padua, Via Giustiniani 2, Padua, Italy

Paul G. Lee. 2 ND YEAR RESEARCH ELECTIVE RESIDENT S JOURNAL Volume III, 1998-1999. A. Objective

Paul G. Lee. 2 ND YEAR RESEARCH ELECTIVE RESIDENT S JOURNAL Volume III, 1998-1999. A. Objective A comparison of six months of anticoagulation with extended anticoagulation for a first episode of venous thromboembolism in patients with thrombophilia Paul G. Lee A. Objective a. To evaluate the risk

More information

Thrombophilia. Steven R. Lentz, M.D. Ph.D. Carver College of Medicine The University of Iowa May 2003

Thrombophilia. Steven R. Lentz, M.D. Ph.D. Carver College of Medicine The University of Iowa May 2003 Thrombophilia Steven R. Lentz, M.D. Ph.D. Carver College of Medicine The University of Iowa May 2003 Thrombophilia Hereditary and acquired risk factors for thrombosis Venous thromboembolism Arterial thromboembolism

More information

To provide an evidenced-based approach to treatment of patients presenting with deep vein thrombosis.

To provide an evidenced-based approach to treatment of patients presenting with deep vein thrombosis. DEEP VEIN THROMBOSIS: TREATMENT TARGET AUDIENCE: All Canadian health care professionals. OBJECTIVE: To provide an evidenced-based approach to treatment of patients presenting with deep vein thrombosis.

More information

Long-Term Anticoagulant Therapy: Clinical Decision and Therapeutic Strategies. Kenneth A. Bauer, MD Harvard Medical School Boston, MA USA

Long-Term Anticoagulant Therapy: Clinical Decision and Therapeutic Strategies. Kenneth A. Bauer, MD Harvard Medical School Boston, MA USA Long-Term Anticoagulant Therapy: Clinical Decision and Therapeutic Strategies Kenneth A. Bauer, MD Harvard Medical School Boston, MA USA Risk Factors for VTE (Clinical) Transient/Provoked/Secondary Surgery

More information

Thrombosis and Hemostasis

Thrombosis and Hemostasis Thrombosis and Hemostasis Wendy Lim, MD, MSc, FRCPC Associate Professor, Department of Medicine McMaster University, Hamilton, ON Overview To review the important developments in venous thromboembolism

More information

Vittorio Pengo M.D. (CV as of April 2014)

Vittorio Pengo M.D. (CV as of April 2014) Vittorio Pengo M.D. (CV as of April 2014) Professor of Cardiovascular Medicine, Department of Cardiac Thoracic and Vascular Sciences, and Director of Thrombosis Center, University of Padova School of Medicine,

More information

Venous Thromboembolic Treatment Guidelines

Venous Thromboembolic Treatment Guidelines Venous Thromboembolic Treatment Guidelines About the NYU Venous Thromboembolic Center (VTEC) The center s mission is to deliver advanced screening, detection, care, and management services for patients

More information

DATE: 06 May 2013 CONTEXT AND POLICY ISSUES

DATE: 06 May 2013 CONTEXT AND POLICY ISSUES TITLE: Low Molecular Weight Heparins versus New Oral Anticoagulants for Long-Term Thrombosis Prophylaxis and Long-Term Treatment of DVT and PE: A Review of the Clinical and Cost-Effectiveness DATE: 06

More information

What is the appropriate duration of treatment for VTE? Any advances in predicting recurrence?

What is the appropriate duration of treatment for VTE? Any advances in predicting recurrence? What is the appropriate duration of treatment for VTE? Any advances in predicting recurrence? Beverley Hunt Thrombosis & Haemostasis, King s College Guy s & St Thomas Trust Medical Director of Lifeblood:

More information

What Does Pregnancy Have to Do With Blood Clots in a Woman s Legs?

What Does Pregnancy Have to Do With Blood Clots in a Woman s Legs? Patient s Guide to Prevention of Blood Clots During Pregnancy: Use of Blood-Thinning A Patient s Guide to Prevention of Blood Clots During Pregnancy: Use of Blood-Thinning Drugs to Prevent Abnormal Blood

More information

New Oral Anticoagulants

New Oral Anticoagulants New Oral Anticoagulants Tracy Minichiello, MD Associate Professor of Medicine Chief, San FranciscoVA Anticoagulation and Thrombosis Service Ansell, J. Hematology Copyright 2010 American Society of Hematology.

More information

DVT/PE Management with Rivaroxaban (Xarelto)

DVT/PE Management with Rivaroxaban (Xarelto) DVT/PE Management with Rivaroxaban (Xarelto) Rivaroxaban is FDA approved for the acute treatment of DVT and PE and reduction in risk of recurrence of DVT and PE. FDA approved indications: Non valvular

More information

APSR RESPIRATORY UPDATES

APSR RESPIRATORY UPDATES APSR RESPIRATORY UPDATES Volume 6, Issue 1 Newsletter Date: January 2014 APSR EDUCATION PUBLICATION Inside this issue: Venous thromboembolism Pulmonary embolism and deep vein thrombosis. 2 Outpatient versus

More information

Prior Authorization Guideline

Prior Authorization Guideline Guideline Guideline Name Formulary Xarelto (rivaroxaban) UnitedHealthcare Community & State Approval Date 0/0/203 Revision Date 8//204 Technician Note: CPS Approval Date: /5/20; CPS Revision Date: 8/20/204

More information

UHS CLINICAL CARE COLLABORATION: Outpatient & Inpatient

UHS CLINICAL CARE COLLABORATION: Outpatient & Inpatient Guidelines for Anticoagulation Initiation and Management Y2014 UHS CLINICAL CARE COLLABORATION: Outpatient & Inpatient Topic Page Number MEDICATION FLOW AND PATIENT FLOW... 2 AND 3 PARENTERAL ANTICOAGULANTS...

More information

INTRODUCTION Thrombophilia deep vein thrombosis DVT pulmonary embolism PE inherited thrombophilia

INTRODUCTION Thrombophilia deep vein thrombosis DVT pulmonary embolism PE inherited thrombophilia INTRODUCTION Thrombophilia (Hypercoagulability) is a condition in which a person forms blood clots more than normal. Blood clots may occur in the arms or legs (e.g., deep vein thrombosis DVT), the lungs

More information

ABOUT XARELTO CLINICAL STUDIES

ABOUT XARELTO CLINICAL STUDIES ABOUT XARELTO CLINICAL STUDIES FAST FACTS Xarelto (rivaroxaban) is a novel, oral direct Factor Xa inhibitor. On September 30, 2008, the European Commission granted marketing approval for Xarelto for the

More information

Thrombin generation and recurrent venous thromboembolism

Thrombin generation and recurrent venous thromboembolism Thrombin generation and recurrent venous thromboembolism T. Zhu, W. Ye, F. Dali Ali, L. Carcaillon, V. Remones, M. Alhenc Gelas, P. Gaussem, P.Y. Scarabin, J. Emmerich INSERM U765, University Paris Descartes,

More information

INTRODUCTION Thrombophilia deep vein thrombosis DVT pulmonary embolism PE inherited thrombophilia

INTRODUCTION Thrombophilia deep vein thrombosis DVT pulmonary embolism PE inherited thrombophilia INTRODUCTION Thrombophilia (Hypercoagulability) is a condition in which a person forms blood clots more than normal. Blood clots may occur in the arms or legs (e.g., deep vein thrombosis DVT), the lungs

More information

Review. Deep-vein thrombosis (DVT) has an estimated annual incidence. Diagnosis and treatment of deep-vein thrombosis. Abstract.

Review. Deep-vein thrombosis (DVT) has an estimated annual incidence. Diagnosis and treatment of deep-vein thrombosis. Abstract. Diagnosis and treatment of deep-vein thrombosis Dimitrios Scarvelis, Philip S. Wells DOI:0.503/cmaj.060366 Abstract Deep-vein thrombosis (DVT) is a common condition that can lead to complications such

More information

rivaroxaban 15mg and 20mg film-coated tablets (Xarelto ) SMC No. (852/13) Bayer plc

rivaroxaban 15mg and 20mg film-coated tablets (Xarelto ) SMC No. (852/13) Bayer plc rivaroxaban 15mg and 20mg film-coated tablets (Xarelto ) SMC No. (852/13) Bayer plc 08 February 2013 The Scottish Medicines Consortium (SMC) has completed its assessment of the above product and advises

More information

Recent advances in the management of venous thromboembolism

Recent advances in the management of venous thromboembolism VOLUME 45ㆍ NUMBER 1ㆍ MARCH 2010 THE KOREAN JOURNAL OF HEMATOLOGY REVIEW ARTICLE Recent advances in the management of venous thromboembolism Walter Ageno Research Center on Thromboembolic Diseases and Antithrombotic

More information

Backgrounder. Current anticoagulant therapies

Backgrounder. Current anticoagulant therapies Backgrounder Bayer AG Investor Relations 51368 Leverkusen Germany www.investor.bayer.com Current anticoagulant therapies Anticoagulant drugs have significantly reduced the risk of thromboembolic events

More information

USE AND INTERPRETATION OF LABORATORY COAGULATION TESTS IN PATIENTS WHO ARE RECEIVING A NEW ORAL ANTICOAGULANT (DABIGATRAN, RIVAROXABAN, APIXABAN)

USE AND INTERPRETATION OF LABORATORY COAGULATION TESTS IN PATIENTS WHO ARE RECEIVING A NEW ORAL ANTICOAGULANT (DABIGATRAN, RIVAROXABAN, APIXABAN) USE AND INTERPRETATION OF LABORATORY COAGULATION TESTS IN PATIENTS WHO ARE RECEIVING A NEW ORAL ANTICOAGULANT (DABIGATRAN, RIVAROXABAN, APIXABAN) TARGET AUDIENCE: All Canadian health care professionals:

More information

Acute behandeling van longembolie. Peter Verhamme. Bloedings- en Vaatziekten UZ Leuven. Research support and/or honoraria:

Acute behandeling van longembolie. Peter Verhamme. Bloedings- en Vaatziekten UZ Leuven. Research support and/or honoraria: Acute behandeling van longembolie Peter Verhamme Bloedings- en Vaatziekten UZ Leuven Disclosures Research support and/or honoraria: Bayer, Boehringer-Ingelheim, Daiichi-Sankyo, Pfizer, BMS, Sanofi, Leo-pharma

More information

Disclosure. New Agents for Treatment of DVT. Prevalence of DVT VTE. Normal Hemostasis 7/17/2015. Mark Oliver, MD, RVT, RPVI,FSVU

Disclosure. New Agents for Treatment of DVT. Prevalence of DVT VTE. Normal Hemostasis 7/17/2015. Mark Oliver, MD, RVT, RPVI,FSVU New Agents for Treatment of DVT Disclosure PI Adopt and Amplify trials Mark Oliver, MD, RVT, RPVI,FSVU BMS and Pfizer Speaker VTE Venous Thromboembolism Recognized DVT s New : 170,000 Recurrent : 90,000

More information

Dabigatran etexilate for the treatment and secondary prevention of deep vein thrombosis and/or pulmonary embolism ERRATUM

Dabigatran etexilate for the treatment and secondary prevention of deep vein thrombosis and/or pulmonary embolism ERRATUM Dabigatran etexilate for the treatment and secondary prevention of deep vein thrombosis and/or pulmonary embolism ERRATUM This report was commissioned by the NIHR HTA Programme as project number 12/78

More information

Venous Disease: The Who, How, When and Why. Jacoby Stieler ARNP-C Iowa Heart Vein Center

Venous Disease: The Who, How, When and Why. Jacoby Stieler ARNP-C Iowa Heart Vein Center Venous Disease: The Who, How, When and Why Jacoby Stieler ARNP-C Iowa Heart Vein Center Objectives Patients to refer to the vein center Office procedures commonly performed in the vein center at Iowa Heart

More information

Gruppo di lavoro: Malattie Tromboemboliche

Gruppo di lavoro: Malattie Tromboemboliche Gruppo di lavoro: Malattie Tromboemboliche 2381 Soluble Recombinant Thrombomodulin Ameliorates Hematological Malignancy-Induced Disseminated Intravascular Coagulation More Promptly Than Conventional Anticoagulant

More information

Pulmonary embolism. Pulmonary embolismbookmark this page

Pulmonary embolism. Pulmonary embolismbookmark this page Pulmonary embolism Essence of this ArticlePulmonary embolism (PE) occurs when a part of a thrombus, usually dislodged from a deep vein thrombosis (DVT), passes into the pulmonary circulation, occluding

More information

DVT and Pulmonary Embolism: Part II. Treatment and Prevention

DVT and Pulmonary Embolism: Part II. Treatment and Prevention PRACTICAL THERAPEUTICS DVT and Pulmonary Embolism: Part II. Treatment and Prevention DINO W. RAMZI, M.D., C.M., and KENNETH V. LEEPER, M.D. Emory University School of Medicine, Atlanta, Georgia Treatment

More information

Anticoagulant therapy

Anticoagulant therapy Anticoagulation: The risks Anticoagulant therapy 1990 2002: 600 incidents reported 120 resulted in death of patient 92 deaths related to warfarin usage 28 reports related to heparin usage Incidents in

More information

The annual incidence of venous

The annual incidence of venous Recurrent Venous Thromboembolism NICHOLAS J. GALIOTO, MD; DANA L. DANLEY, MD; and RYAN J. VAN MAANEN, DO Broadlawns Medical Center, Des Moines, Iowa A previous venous thromboembolism is the most important

More information

New Anticoagulants for the Treatment of Thromboembolism With a little subplot on superficial thrombophlebitis. Mark Crowther

New Anticoagulants for the Treatment of Thromboembolism With a little subplot on superficial thrombophlebitis. Mark Crowther New Anticoagulants for the Treatment of Thromboembolism With a little subplot on superficial thrombophlebitis Mark Crowther 1 Disclosures Advisory Boards in last 24 months Pfizer, Alexion, Bayer, CSL Behring,

More information

Anticoagulation at the end of life. Rhona Maclean Rhona.maclean@sth.nhs.uk

Anticoagulation at the end of life. Rhona Maclean Rhona.maclean@sth.nhs.uk Anticoagulation at the end of life Rhona Maclean Rhona.maclean@sth.nhs.uk Content Anticoagulant Therapies Indications for anticoagulation Venous thromboembolism (VTE) Atrial Fibrillation Mechnical Heart

More information

Direct Oral Anticoagulants for Acute Venous Thromboembolism: Closing the Circle?

Direct Oral Anticoagulants for Acute Venous Thromboembolism: Closing the Circle? Direct Oral Anticoagulants for Acute Venous Thromboembolism: Closing the Circle? Running title: Verhamme et al.; DOACs for acute venous thromboembolism Peter Verhamme, MD, PhD 1 ; Henri Bounameaux, MD

More information

indications November 2 nd, 2012 Dalhousie University

indications November 2 nd, 2012 Dalhousie University + New oral anticoagulants: A review of current indications November 2 nd, 2012 Dr. Sudeep Shivakumar, Hematology Dalhousie University + Objectives es To review indications for anticoagulation To discuss

More information

Provided by the American Venous Forum: veinforum.org

Provided by the American Venous Forum: veinforum.org CHAPTER 3 CLOTTING DISORDERS Original authors: Edith A. Nutescu, Jessica B. Michaud, Joseph A. Caprini, Louis W. Biegler, and Robert R. McCormick Abstracted by Kellie R. Brown Introduction The normal balance

More information

New Oral Anticoagulants. How safe are they outside the trials?

New Oral Anticoagulants. How safe are they outside the trials? New Oral Anticoagulants How safe are they outside the trials? Objectives The need for anticoagulant therapy Indications for anticoagulation Traditional anticoagulant therapies Properties of new oral anticoagulants

More information

Traveller s Thrombosis. Dr. Peter Verhamme Vascular Medicine and Haemostasis UZ Leuven

Traveller s Thrombosis. Dr. Peter Verhamme Vascular Medicine and Haemostasis UZ Leuven Traveller s Thrombosis Dr. Peter Verhamme Vascular Medicine and Haemostasis UZ Leuven Case 1: To thromboprophylaxe or not Women, aged 49, BMI 29, Combined Oral Contraceptives. Family history of provoked

More information

Anticoagulation Initiation,Monitoring and Titration. Ng Heng Joo Department of Haematology Singapore General Hospital

Anticoagulation Initiation,Monitoring and Titration. Ng Heng Joo Department of Haematology Singapore General Hospital Anticoagulation Initiation,Monitoring and Titration Ng Heng Joo Department of Haematology Singapore General Hospital The 3 I s on the Anticoagulated Patient Indication? Intensity? Indefinite? Indications

More information

National Guidance and New Protocols

National Guidance and New Protocols National Guidance and New Protocols Dr Jane Strong Consultant Haematologist DVT clinical lead Acute VTE chair DAWN AC Twentieth User Group Meeting 8 th October 2012 DVT patient pathway Assessment Diagnosis

More information

The use of rivaroxaban in patients with antiphospholipid syndrome: A series of 12 cases

The use of rivaroxaban in patients with antiphospholipid syndrome: A series of 12 cases ÔØ Å ÒÙ Ö ÔØ The use of rivaroxaban in patients with antiphospholipid syndrome: A series of 12 cases Maksim Son, Ewa Wypasek, Magdalena Celinska-Lowenhoff, Anetta Undas PII: S0049-3848(15)00048-1 DOI:

More information

National Guidance and New Protocols

National Guidance and New Protocols National Guidance and New Protocols Dr Jane Strong Consultant Haematologist DVT clinical lead Acute VTE chair DAWN AC Twentieth User Group Meeting 8 th October 2012 Autumn dawn Restless geese take flight

More information

Top 10 Thrombosis and Anticoagulation Highlights from ASH 2014

Top 10 Thrombosis and Anticoagulation Highlights from ASH 2014 Top 10 Thrombosis and Anticoagulation Highlights from ASH 2014 Stephan Moll, MD UNC School of Medicine, Chapel Hill, NC 1. New Anticoagulant Factor XI lowering drug NEJM publication Dec 7 th (late- breaking

More information

rivaroxaban 15 and 20mg film-coated tablets (Xarelto ) SMC No. (755/12) Bayer PLC

rivaroxaban 15 and 20mg film-coated tablets (Xarelto ) SMC No. (755/12) Bayer PLC rivaroxaban 15 and 20mg film-coated tablets (Xarelto ) SMC No. (755/12) Bayer PLC 13 January 2012 The Scottish Medicines Consortium (SMC) has completed its assessment of the above product and advises NHS

More information

Outpatient Treatment of Deep Vein Thrombosis with Low Molecular Weight Heparin (LMWH) Clinical Practice Guideline August 2013

Outpatient Treatment of Deep Vein Thrombosis with Low Molecular Weight Heparin (LMWH) Clinical Practice Guideline August 2013 Outpatient Treatment of Deep Vein Thrombosis with Low Molecular Weight Heparin (LMWH) Clinical Practice Guideline August 2013 General Principles: There is compelling data in the medical literature to support

More information

Bayer Initiates Rivaroxaban Phase III Study to Support Dose Selection According to Individual Benefit-Risk Profile in Long- Term VTE Prevention

Bayer Initiates Rivaroxaban Phase III Study to Support Dose Selection According to Individual Benefit-Risk Profile in Long- Term VTE Prevention Investor News Not intended for U.S. and UK Media Bayer AG Investor Relations 51368 Leverkusen Germany www.investor.bayer.com Long-term prevention of venous blood clots (VTE): Bayer Initiates Rivaroxaban

More information

6/19/2012. Update on Venous Thromboembolism Prophylaxis. Disclosure. Learning Objectives. No conflicts of interest to declare

6/19/2012. Update on Venous Thromboembolism Prophylaxis. Disclosure. Learning Objectives. No conflicts of interest to declare Update on Venous Thromboembolism Prophylaxis Disclosure No conflicts of interest to declare Learning Objectives After completion of this presentation, participants should be able to: Define venous thromboembolism,

More information

New Oral Anticoagulants. July 2012

New Oral Anticoagulants. July 2012 New Oral Anticoagulants July 2012 Objectives Review coagulation cascade and previous treatment options for anticoagulation Understand points of interaction within coagulation cascade and new oral agents

More information

Friday April 8 th 2016

Friday April 8 th 2016 Preliminary Scientific Program - ICTHIC April 8-10, 2016 Friday April 8 th 2016 9,00-11,00 am Industry sponsored session 11,00-11,15 am Congress Opening: A Falanga, FR Rickles, B Brenner 11,15-1,30 pm

More information

Venous Thromboembolism: Long Term Anticoagulation. Dan Johnson, Pharm.D.

Venous Thromboembolism: Long Term Anticoagulation. Dan Johnson, Pharm.D. Venous Thromboembolism: Long Term Anticoagulation Dan Johnson, Pharm.D. Disclosures No financial relationships with products discussed Off-label use of drug therapy always discussed Objectives Review clinical

More information

4/9/2015. Risk Stratify Our Patients. Stroke Risk in AF: CHADS2 Scoring system JAMA 2001; 285: 2864-71

4/9/2015. Risk Stratify Our Patients. Stroke Risk in AF: CHADS2 Scoring system JAMA 2001; 285: 2864-71 Anticoagulation in the 21 st Century Adam Karpman, D.O. Saint Francis Medical Center/Oklahoma State University Medical Center Disclosures: None Atrial Fibrillation Most common arrhythmia in clinical practice.

More information

PERI-OPERATIVE MANAGEMENT OF PATIENTS WHO ARE RECEIVING A NEW ORAL ANTICOAGULANT (DABIGATRAN, RIVAROXABAN,

PERI-OPERATIVE MANAGEMENT OF PATIENTS WHO ARE RECEIVING A NEW ORAL ANTICOAGULANT (DABIGATRAN, RIVAROXABAN, PERI-OPERATIVE MANAGEMENT OF PATIENTS WHO ARE RECEIVING A NEW ORAL ANTICOAGULANT (DABIGATRAN, RIVAROXABAN, APIXABAN) TARGET AUDIENCE: All Canadian health care professionals, including primary care physicians,

More information

Randomized, double-blind, parallel-group, multicenter, doubledummy

Randomized, double-blind, parallel-group, multicenter, doubledummy ABOUT RECORD STUDIES FAST FACTS RECORD is a global program of four trials in more than 12,500 patients, comparing Xarelto (rivaroxaban) and enoxaparin in the prevention of venous thromboembolism (VTE)

More information

Thrombose associée au cancer. Prévention et traitement. Guy Meyer Université Paris Descartes Hopital Europeen Georges Pompidou, Paris, France

Thrombose associée au cancer. Prévention et traitement. Guy Meyer Université Paris Descartes Hopital Europeen Georges Pompidou, Paris, France Thrombose associée au cancer Prévention et traitement Guy Meyer Université Paris Descartes Hopital Europeen Georges Pompidou, Paris, France Conflits d intérêt G Meyer Investigateur: Bayer, Daichi-Sankyo,

More information

Low Molecular Weight Heparin. All Wales Medicines Strategy Group (AWMSG) Recommendations and advice

Low Molecular Weight Heparin. All Wales Medicines Strategy Group (AWMSG) Recommendations and advice Low Molecular Weight Heparin All Wales Medicines Strategy Group (AWMSG) Recommendations and advice Starting Point Low Molecular Weight Heparin (LMWH): Inhibits factor Xa and factor IIa (thrombin) Small

More information

Clive Kearon, Susan R. Kahn, Giancarlo Agnelli, Samuel Goldhaber, Gary E. Raskob and Anthony J. Comerota. DOI 10.1378/chest.

Clive Kearon, Susan R. Kahn, Giancarlo Agnelli, Samuel Goldhaber, Gary E. Raskob and Anthony J. Comerota. DOI 10.1378/chest. Antithrombotic Therapy for Venous Thromboembolic Disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Clive Kearon, Susan R. Kahn, Giancarlo Agnelli,

More information

Heritable Thrombophilia and Pregnancy Associated Thrombosis

Heritable Thrombophilia and Pregnancy Associated Thrombosis Heritable Thrombophilia and Pregnancy Associated Thrombosis Meyer Michel SAMAMA, Jacqueline CONARD, V. MATHIEUX, Grigoris T. GEROTZIAFAS, Marie Hélène HORELLOU, Ismail ELALAMY Service d Hématologie Biologique

More information

Committee Approval Date: September 12, 2014 Next Review Date: September 2015

Committee Approval Date: September 12, 2014 Next Review Date: September 2015 Medication Policy Manual Policy No: dru361 Topic: Pradaxa, dabigatran Date of Origin: September 12, 2014 Committee Approval Date: September 12, 2014 Next Review Date: September 2015 Effective Date: November

More information

NnEeWw DdEeVvEeLlOoPpMmEeNnTtSs IiıNn OoRrAaLl AaNnTtIiıCcOoAaGgUuLlAaTtIiıOoNn AaNnDd RrEeVvEeRrSsAaLl

NnEeWw DdEeVvEeLlOoPpMmEeNnTtSs IiıNn OoRrAaLl AaNnTtIiıCcOoAaGgUuLlAaTtIiıOoNn AaNnDd RrEeVvEeRrSsAaLl NnEeWw DdEeVvEeLlOoPpMmEeNnTtSs IiıNn OoRrAaLl AaNnTtIiıCcOoAaGgUuLlAaTtIiıOoNn AaNnDd RrEeVvEeRrSsAaLl Mikele Wissing, RN June 2014 Introduction until recently, was the unrivaled medication for treatment

More information

DISCLAIMER ARTHROPLASTY SOCIETY VTE INFORMATION

DISCLAIMER ARTHROPLASTY SOCIETY VTE INFORMATION DISCLAIMER ARTHROPLASTY SOCIETY VTE INFORMATION Venous thromboembolism is the most common complication after total hip and total knee arthroplasty. In recent times members of the Australian Orthopaedic

More information

Eliquis. Policy. covered: Eliquis is. indicated to. reduce the. therapy. Eliquis is. superior to. of 32 to. Eliquis is AMPLIFY. nonfatal. physicians.

Eliquis. Policy. covered: Eliquis is. indicated to. reduce the. therapy. Eliquis is. superior to. of 32 to. Eliquis is AMPLIFY. nonfatal. physicians. Eliquis (apixaban) Policy Number: 5.01.573 Origination: 06/2014 Last Review: 07/2015 Next Review: 07/2016 Policy BCBSKC will provide coverage for Eliquis when it is determined to be medically necessary

More information

CHEST Antithrombotic Therapy and Prevention of Thrombosis, 9 th ed Sarah Meyer, PharmD November 9, 2012

CHEST Antithrombotic Therapy and Prevention of Thrombosis, 9 th ed Sarah Meyer, PharmD November 9, 2012 CHEST Antithrombotic Therapy and Prevention of Thrombosis, 9 th ed Sarah Meyer, PharmD November 9, 2012 1. CHEST has made a few changes 1 a. For patients sufficiently healthy to be treated as outpatients,

More information

Clinical Study Synopsis

Clinical Study Synopsis Clinical Study Synopsis This Clinical Study Synopsis is provided for patients and healthcare professionals to increase the transparency of Bayer's clinical research. This document is not intended to replace

More information

What I m Going to Tell You

What I m Going to Tell You Can we Avoid DVT and PE? What is the Role of Prophylaxis? Steven Fein, M.D., MPH What I m Going to Tell You Identifying who is at risk for DVT/PE Preventing DVT/PE in post-op ortho patients Preventing

More information

New Anticoagulants: When and Why Should I Use Them? Disclosures

New Anticoagulants: When and Why Should I Use Them? Disclosures Winship Cancer Institute of Emory University New Anticoagulants: When and Why Should I Use Them? Christine L. Kempton, MD, MSc Associate Professor of Pediatrics and Hematology and Medical Oncology Hemophilia

More information

Rivaroxaban A new oral anti-thrombotic Dr. Hisham Aboul-Enein Professor of Cardiology Benha University 12/1/2012

Rivaroxaban A new oral anti-thrombotic Dr. Hisham Aboul-Enein Professor of Cardiology Benha University 12/1/2012 Rivaroxaban A new oral anti-thrombotic Dr. Hisham Aboul-Enein Professor of Cardiology Benha University 12/1/2012 Agenda Ideal anticoagulant. Drawbacks of warfarin. Rivaroxaban in clinical trails. Present

More information

CDEC FINAL RECOMMENDATION

CDEC FINAL RECOMMENDATION CDEC FINAL RECOMMENDATION RIVAROXABAN (Xarelto Bayer Inc.) New Indication: Pulmonary Embolism Note: The Canadian Drug Expert Committee (CDEC) previously reviewed rivaroxaban for the treatment of deep vein

More information

Kevin Saunders MD CCFP Rivergrove Medical Clinic Wellness Institute @ SOGH April 17 2013

Kevin Saunders MD CCFP Rivergrove Medical Clinic Wellness Institute @ SOGH April 17 2013 Kevin Saunders MD CCFP Rivergrove Medical Clinic Wellness Institute @ SOGH April 17 2013 Family physician with Rivergrove Medical Clinic Practice in the north end since 1985 Medical Director of the Wellness

More information

The novel anticoagulants: entering a new era

The novel anticoagulants: entering a new era Review article Peer reviewed article SWISS MED WKLY 2009;139(5 6):60 64 www.smw.ch 60 The novel anticoagulants: entering a new era Henri Bounameaux Division of Angiology and Haemostasis, Department of

More information

NHS FORTH VALLEY RIVAROXABAN AS TREATMENT FOR DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM IN ADULTS

NHS FORTH VALLEY RIVAROXABAN AS TREATMENT FOR DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM IN ADULTS NHS FORTH VALLEY RIVAROXABAN AS TREATMENT FOR DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM IN ADULTS Date of First Issue 01/12/ 2012 Approved 15/11/2012 Current Issue Date 29/10/2014 Review Date 29/10/2016

More information

2. Background This indication of rivaroxaban had not previously been considered by the PBAC.

2. Background This indication of rivaroxaban had not previously been considered by the PBAC. PUBLIC SUMMARY DOCUMENT Product: Rivaroxaban, tablets, 15mg and 20mg, Xarelto Sponsor: Bayer Australia Ltd Date of PBAC Consideration: March 2013 1. Purpose of Application The application requested the

More information

Position Statement: The Use of VTED Prophylaxis in Foot and Ankle Surgery

Position Statement: The Use of VTED Prophylaxis in Foot and Ankle Surgery Position Statement: The Use of VTED Prophylaxis in Foot and Ankle Surgery Position Statement There is currently insufficient data for the (AOFAS) to recommend for or against routine VTED prophylaxis for

More information

About the RECORD Clinical Trial Program

About the RECORD Clinical Trial Program About the RECORD Clinical Trial Program Fast facts RECORD was a global program of four trials in more than 12,500 patients, comparing Xarelto (rivaroxaban) and enoxaparin in the prevention of venous thromboembolism

More information

CLINICAL PRACTICE GUIDELINE: MOBILITY WITH A DEEP VEIN THROMBOSIS (DVT) Page 1 of 10

CLINICAL PRACTICE GUIDELINE: MOBILITY WITH A DEEP VEIN THROMBOSIS (DVT) Page 1 of 10 Page 1 of 10 1.0 FOCUS: Mobilization with a Deep Vein Thrombosis (DVT). The purpose of this clinical practice guideline (CPG) is to ensure that new knowledge is integrated across Fraser Health and to standardize

More information

Hypercoagulable States

Hypercoagulable States Hypercoagulable States Daniel A. Forman, DO daniel.forman@readinghealth.org 610 509 5067 April 26, 2014 Risk Factors for Venous Thromboembolism (VTE) Hereditary thrombophilias How long to treat Newer agents

More information

ACUTE DVT MANAGEMENT Richard J. DeMasi, MD April 26, 2014

ACUTE DVT MANAGEMENT Richard J. DeMasi, MD April 26, 2014 ACUTE DVT MANAGEMENT Richard J. DeMasi, MD April 26, 2014 Thromboembolism epidemiology 5 million DVT s 900,000 PE s 290,000 fatalities Heit J. Blood. 2005;106:910. 10 VTE events Since this talk began DVT

More information

Out with the Old and in with the New? Target Specific Anticoagulants for Atrial Fibrillation

Out with the Old and in with the New? Target Specific Anticoagulants for Atrial Fibrillation Out with the Old and in with the New? Target Specific Anticoagulants for Atrial Fibrillation Goal Statement Pharmacists and technicians will gain knowledge in the use of target specific oral anticoagulants

More information

Breadth of indications matters One drug for multiple indications

Breadth of indications matters One drug for multiple indications Breadth of indications matters One drug for multiple indications Sylvia Haas, MD, PhD Formerly of the Technical University of Munich Munich, Germany Disclosures: Sylvia Haas 1 Novel oral anticoagulants:

More information

Antithrombotic therapy

Antithrombotic therapy Orthogeriatrics Clinical Summary Document Antithrombotic therapy Topics Preexisting anticoagulation and timing of surgery Reversal of anticoagulation Perioperative thromboprophylaxis When should we be

More information

EXTENDED PROPHYLAXIS OF VENOUS THROMBOEMBOLISM IN MAJOR SURGERY. 1) Postoperative venous thromboembolism: a continuing problem after discharge?

EXTENDED PROPHYLAXIS OF VENOUS THROMBOEMBOLISM IN MAJOR SURGERY. 1) Postoperative venous thromboembolism: a continuing problem after discharge? 1 EXTENDED PROPHYLAXIS OF VENOUS THROMBOEMBOLISM IN MAJOR SURGERY 1) Postoperative venous thromboembolism: a continuing problem after discharge? Studies from the late 80 s and early 90 s pointed to the

More information

New Oral Anticoagulants: Topic Brief

New Oral Anticoagulants: Topic Brief New Oral Anticoagulants: Topic Brief June 9, 2015 High-Level Research Question In patients with nonvalvular atrial fibrillation (AF) or venous thromboembolic disease, or who have undergone surgery for

More information

PROFESSOR OF MEDICINE TEMPLE UNIVERSITY SCHOOL OF MEDICINE

PROFESSOR OF MEDICINE TEMPLE UNIVERSITY SCHOOL OF MEDICINE PRACTICAL APPROACH TO TREATMENT OF DVT JOSE MISSRI, M.D. PROFESSOR OF MEDICINE CHIEF OF CARDIOLOGY TEMPLE UNIVERSITY SCHOOL OF MEDICINE DVT/PE: Magnitude of the Problem Death 60,000 300,00 Pulmonary Hypertension

More information

Review of Non-VKA Oral AntiCoagulants (NOACs) and their use in Great Britain

Review of Non-VKA Oral AntiCoagulants (NOACs) and their use in Great Britain Review of Non-VKA Oral AntiCoagulants (NOACs) and their use in Great Britain Dr Alexander (Ander) Cohen Guy s and St Thomas Hospitals, King s College London, UK Pavia Spring Meeting 13 June 2014 Overview

More information

Venous Thrombo-Embolism (VTE) Therapy current challenges & opportunities

Venous Thrombo-Embolism (VTE) Therapy current challenges & opportunities Venous Thrombo-Embolism (VTE) Therapy current challenges & opportunities Asher Winder M.D. Director, Department of Hematology Wolfson Medical Center כנס האיגוד הישראלי לפרמקולוגיה קלינית 2012 04-May-2012

More information

Post-ISTH review: Thrombosis-I New Oral Anticoagulants 臺 大 醫 院 內 科 部 血 液 科 周 聖 傑 醫 師

Post-ISTH review: Thrombosis-I New Oral Anticoagulants 臺 大 醫 院 內 科 部 血 液 科 周 聖 傑 醫 師 Post-ISTH review: Thrombosis-I New Oral Anticoagulants 臺 大 醫 院 內 科 部 血 液 科 周 聖 傑 醫 師 The antithrombotic efficacy is limited but the risk of bleeding is indefinite Fuster V et al. Circulation 2011;123:e269-e367

More information

New anticoagulants: Monitoring or not Monitoring? Not Monitoring

New anticoagulants: Monitoring or not Monitoring? Not Monitoring The 2 nd World Congress on CONTROVERSIES IN HEMATOLOGY (COHEM) Barcelona, Spain September 6 8, 2012 New anticoagulants: Monitoring or not Monitoring? Not Monitoring Anna Falanga, MD Immunohematology and

More information

MANAGEMENT OF ACUTE DEEP VEIN THROMBOSIS UPDATE? Mr Chew Loon Guan Head Dept of General & Vascular Surgery Serdang Hospital

MANAGEMENT OF ACUTE DEEP VEIN THROMBOSIS UPDATE? Mr Chew Loon Guan Head Dept of General & Vascular Surgery Serdang Hospital MANAGEMENT OF ACUTE DEEP VEIN THROMBOSIS UPDATE? Mr Chew Loon Guan Head Dept of General & Vascular Surgery Serdang Hospital Caveat The following deep vein thrombosis is in regards to the lower extremity

More information

Medication Policy Manual. Topic: Eliquis, apixaban Date of Origin: July 12, 2013. Committee Approval Date: July 11, 2014 Next Review Date: July 2015

Medication Policy Manual. Topic: Eliquis, apixaban Date of Origin: July 12, 2013. Committee Approval Date: July 11, 2014 Next Review Date: July 2015 Medication Policy Manual Policy No: dru313 Topic: Eliquis, apixaban Date of Origin: July 12, 2013 Committee Approval Date: July 11, 2014 Next Review Date: July 2015 Effective Date: August 1, 2014 IMPORTANT

More information

Review Article The Efficacy and Safety of Rivaroxaban for Venous Thromboembolism Prophylaxis after Total Hip and Total Knee Arthroplasty

Review Article The Efficacy and Safety of Rivaroxaban for Venous Thromboembolism Prophylaxis after Total Hip and Total Knee Arthroplasty Thrombosis Volume 2013, Article ID 762310, 5 pages http://dx.doi.org/10.1155/2013/762310 Review Article The Efficacy and Safety of Rivaroxaban for Venous Thromboembolism Prophylaxis after Total Hip and

More information

Clinical Study Synopsis

Clinical Study Synopsis Clinical Study Synopsis This Clinical Study Synopsis is provided for patients and healthcare professionals to increase the transparency of Bayer's clinical research. This document is not intended to replace

More information

Enoxaparin for long term anticoagulation in patients unsuitable for oral anticoagulants

Enoxaparin for long term anticoagulation in patients unsuitable for oral anticoagulants Enoxaparin for long term anticoagulation in patients unsuitable for oral anticoagulants Traffic light classification- Amber 2 Information sheet for Primary Care Prescribers Relevant Licensed Indications

More information

Pulmonary Embolism Treatment Update

Pulmonary Embolism Treatment Update UC SF Pulmonary Embolism Treatment Update Jeffrey Tabas, MD Professor UCSF School of Medicine Emergency Department San Francisco General Hospital sf g h Disclosure No Financial Relationships to Disclose

More information

Heparin Induced Thrombocytopenia

Heparin Induced Thrombocytopenia Heparin Induced Thrombocytopenia Ann-Marie Liberman B.Sc.Phm., ACPR Clinical Pharmacist, Cardiac Surgery Clinical Trials Pharmacist Royal Columbian Hospital Fraser Health Disclosure Participated in research

More information

Lupus anticoagulant Pocket card

Lupus anticoagulant Pocket card Lupus anticoagulant Pocket card Issue number 5 2012 Antiphospholipid Syndrome 1 The antiphospholipid syndrome (APS) is diagnosed in patients with recurrent thromboembolic events and /or pregnancy loss

More information

Treatment of Deep-Vein Thrombosis

Treatment of Deep-Vein Thrombosis The new england journal of medicine clinical practice Treatment of Deep-Vein Thrombosis Shannon M. Bates, M.D.C.M., and Jeffrey S. Ginsberg, M.D. This Journal feature begins with a case vignette highlighting

More information