We think you have liked this presentation. If you wish to download it, please recommend it to your friends in any social system. Share buttons are a little bit lower. Thank you!
Presentation is loading. Please wait.
Published byPorter Bowdle
Modified about 1 year ago
© 2012 Direct One Communications, Inc. All rights reserved. 1 Anticoagulation Therapy: New Opportunities, New Challenges Suraj Kapa, MD Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania A REPORT FROM THE 2011 SCIENTIFIC SESSIONS OF THE AMERICAN HEART ASSOCIATION
© 2012 Direct One Communications, Inc. All rights reserved. 2 Indications for Oral Anticoagulation Multiple clinical trials and guideline statements support the use of long-term oral anticoagulation for stroke prevention in high-risk patients with atrial fibrillation (AF). 1–8 Long-term oral anticoagulation is also a mainstay in the management of patients with: » Mechanical heart valves » Deep venous thrombosis (DVT) » Pulmonary embolism
© 2012 Direct One Communications, Inc. All rights reserved. 3 Shortcomings of Warfarin Warfarin therapy requires control of patients’ prothrombin time or international normalized ratio (INR) within a narrow therapeutic range. Warfarin levels above the therapeutic range lead to an increased risk of life-threatening bleeding, and levels below the therapeutic range obviate any potential benefits from the drug. Ensuring maintenance of therapeutic INRs requires frequent blood testing. Multiple dietary and pharmacologic interactions may complicate the maintenance of a therapeutic INR. 9,10
© 2012 Direct One Communications, Inc. All rights reserved. 4 Thrombus Formation In AF, the tissue factor pathway is the primary target for preventing thrombus formation and stroke. 12–15 Thrombus formation involves tissue factor-bearing cells that come into contact with circulating coagulation factors. As factor VII comes into contact with tissue factor on these cells, an activated complex forms, which triggers factors IX and X. Factor Xa and factor Va then form prothrombinase complexes that activate prothrombin to thrombin, which, in turn, then stimulates factor VII and other components of the coagulation cascade.
© 2012 Direct One Communications, Inc. All rights reserved. 5 Coagulation Cascade Schematic diagram of the coagulation cascade along the tissue factor pathway and the targets of direct factor Xa and thrombin inhibitors. The vitamin K antagonist warfarin typically works on several calcium- dependent clotting factors, including factors II, VII, IX (not shown), and X.
© 2012 Direct One Communications, Inc. All rights reserved. 6 Targeting Specific Coagulation Factors Newer oral anticoagulants target specific points in the coagulation cascade: » Factor Xa inhibitors (eg, rivaroxaban, apixaban) target factor Xa, preventing the conversion of prothrombin to thrombin. » Direct thrombin inhibitors (eg, dabigatran, ximelagatran) target thrombin (factor IIa), blocking the conversion of fibrinogen to fibrin. The goal of novel oral anticoagulants is, in part, to offer more specific targeting and to afford more predictable responses than current anticoagulant therapies, such as warfarin, can offer.
© 2012 Direct One Communications, Inc. All rights reserved. 7 The Ideal Oral Anticoagulant Ideally, an oral anticoagulant would: Require no remote monitoring Have little interaction with food or other drugs Offer a good safety profile with regard to bleeding risk Have similar efficacy to warfarin in reducing thromboembolic events Reach therapeutic levels within several hours
© 2012 Direct One Communications, Inc. All rights reserved. 8 Warfarin When warfarin therapy is started, its anticoagulant effects may not be apparent for several days. The duration of action of a single dose is 2–5 days. The therapeutic effect of warfarin exists within a narrow therapeutic window as dictated by the INR. Considerable inter- and intraindividual dose variability may be affected by a wide range of physiologic (liver and thyroid function), genetic, and environmental (eg, diet, other drugs) factors. 9,10 Regular monitoring is required to avoid excessive or insufficient anticoagulation. 16
© 2012 Direct One Communications, Inc. All rights reserved. 9 Dabigatran Dabigatran etexilate is a direct thrombin inhibitor that is given at a fixed oral dose without the need for INR monitoring. 17,18 Because of potential P-glycoprotein (P-gp) interactions, its absorption may be decreased if dabigatran is taken with a proton pump inhibitor. 19 Excretion may be slowed in patients taking P-gp pump inhibitors such as quinidine, verapamil, or amiodarone, raising plasma levels of dabigatran. 19 The drug has a relatively short half-life (12–17 hours). Patients with acute or chronic renal failure may require reduced doses. 17,18
© 2012 Direct One Communications, Inc. All rights reserved. 10 Rivaroxaban and Apixaban Rivaroxaban and apixaban are direct factor Xa inhibitors. 20–23 The two drugs interact slightly differently with the S4 region of factor X. Both rivaroxaban and apixaban bind to the catalytic/active site of factor X and directly interfere with the coagulation cascade. They have predictable pharmacokinetics and allow for fixed oral dosing without the need for INR monitoring. Similar to dabigatran, the half-lives of rivaroxaban and apixaban are under 12 hours.
© 2012 Direct One Communications, Inc. All rights reserved. 11 Models of Care: Warfarin Therapy Routine medical care, wherein a physician or office staff manage warfarin dosing based on INRs obtained from blood draws in a laboratory or via a point-of-care device in the clinic. Anticoagulation clinics managed by dedicated healthcare professionals that have systematic policies to manage and dose patients, using either point-of-care or laboratory-based INRs. 25–27 Patients using a point-of-care monitor at home to measure their INRs and then reporting back to the personnel in a clinic to alter the dose. 28,29
© 2012 Direct One Communications, Inc. All rights reserved. 12 Switching to Newer Oral Anticoagulants Advantages: » Fixed oral dosing » No need to monitor prothrombin time or INR » Fewer drug interactions » No dietary restrictions Disadvantages: » Lack of validated tests to assay their anticoagulant effect 30 » No antidote readily available to halt bleeding » More difficult to assess patient compliance » Lack of data on long-term adverse effects beyond bleeding » Absence of head-to-head comparisons between novel oral anticoagulants
© 2012 Direct One Communications, Inc. All rights reserved. 13 Other Issues with Newer Anticoagulants Peaks and troughs in anticoagulation levels may result from their relatively shorter half-lives, compared with warfarin. The dosing of these drugs is fixed, so there is no easy way to measure their therapeutic effects using specific blood tests. Additional monitoring of liver and renal function may be needed to ensure that dose adjustments or switching of agents is not required. There is little to educate patients about beyond compliance.
© 2012 Direct One Communications, Inc. All rights reserved. 14 Comparison of Oral Anticoagulants
© 2012 Direct One Communications, Inc. All rights reserved. 15 Anticoagulant Therapy and Stroke Patients with AF-related stroke have a 1.8-fold increase in mortality when compared with those who experience a stroke unrelated to AF, possibly because AF-related strokes tend to be larger in size and more often lead to hemorrhagic transformation. 2,31,32 Although patients with AF and at least two additional risk factors for stroke benefit from warfarin therapy, many patients and their physicians resist using warfarin because of concerns related to INR monitoring, the risk of falls, and the potential for bleeding and intracranial hemorrhage.
© 2012 Direct One Communications, Inc. All rights reserved. 16 INR Variability in AF Patients Randomized clinical trials comparing dabigatran, apixaban, and rivaroxaban with warfarin have shown a strong trend toward the superiority of these novel oral anticoagulants in preventing stroke and in reducing the rate of intracranial hemorrhage. 33–36 However, data from systematic overviews suggest that patients on warfarin maintain a therapeutic INR only 63% of the time at best, with even worse results being observed in community practices. 37 The importance of maintaining a minimum INR of 2.0 to obtain effective stroke prevention during warfarin therapy has been well documented. 38–41
© 2012 Direct One Communications, Inc. All rights reserved. 17 INR Variability in AF Patients Analyses of data from the ROCKET AF, RE-LY, and ARISTOTLE studies have shown no significant difference in stroke outcomes between patients given a novel oral anticoagulant and those using warfarin. 33–36,42 However, RE-LY data showed that 50% of patients using warfarin who had a therapeutic INR at least 67% of the time had a composite event rate of 5.48, which was lower than the event rates among patients using dabigatran, whereas patients who were in the therapeutic range less than 54% of the time had an event rate of 12.32, which was much worse than the event rate in patients taking dabigatran. 42
© 2012 Direct One Communications, Inc. All rights reserved. 18 INR Variability in AF Patients In the SPORTIF trial, 25% of patients who had the greatest percentage of time in the therapeutic INR range had the lowest event rates; however, patients who were in the therapeutic range less than 60% of the time had much higher event rates. 43,44 In the ATRIA study, there was an 8-fold increase in ischemic events with any reduction in the INR 4.0, there was a 12-fold increase in intracranial hemorrhage. 45
© 2012 Direct One Communications, Inc. All rights reserved. 19 Self-Monitoring of INR Levels Self-testing may provide a better way to maintain INR levels within a narrow therapeutic window. Results from the THINRS trial suggested beneficial trends in mortality, major bleeding, and stroke when patients performed self-testing, rather than relying on specific clinics for monitoring and managing their anticoagulation therapy. 46–48 Similarly, in the STOARM2 trial, INR management improved with automated self-monitoring, with INR values 5 seen in only 0.47% of patients. 49
© 2012 Direct One Communications, Inc. All rights reserved. 20 Self-Monitoring of INR Levels Other studies have suggested that anticoagulation clinics run by clinical pharmacists may reduce major events, hospitalizations, and emergency visits by 60%–80%, when compared with usual clinic-based management of warfarin, and that weekly INR self- testing and self-management may reduce major events by as much as 70% and mortality by as much as 61%. 28,29,46–51 Thus, some contend that the primary issue is to fix how we are managing patients using warfarin rather than to switch patients to another agent.
© 2012 Direct One Communications, Inc. All rights reserved. 21 Cost-Effectiveness Cost-effectiveness analyses of newer anticoagulants in preventing stroke in patients with AF are limited. At a cost of $7–$9/day (two capsules), dabigatran use may cost an estimated $10,000 per year of life saved. 52–54 However, this analysis does not consider direct comparisons against the cost of maintaining patients on warfarin under current models of care. Further studies are needed to better analyze the relative cost-effectiveness of warfarin versus that of any of the newer oral anticoagulants and also to consider the cost of improving INR management.
© 2012 Direct One Communications, Inc. All rights reserved. 22 Potential of Newer Oral Anticoagulants A shorter half-life with rapid offset and potential attendant clotting risk The need for a reversal agent in cases of acute bleeding or at the time of emergent procedures The lack of laboratory monitoring to evaluate patient adherence Newer anticoagulant agents have issues 55 not shared with warfarin, including: These newer agents are easy to use, and AF patients can benefit from lower stroke risk without needing repeated blood tests for INR monitoring, so the potential benefits are obvious.
© 2012 Direct One Communications, Inc. All rights reserved. 23 Anticoagulant Therapy and DVT The same concerns related to INR monitoring, the narrow therapeutic window of warfarin, and the wide variety of dietary and pharmacologic interactions with warfarin still exist in treating patients with DVT. One key difference in these patients is that the goal is treating an existing problem rather than preventing a potential one. 56,57 However, the decision to treat as an outpatient versus as an inpatient is more difficult, because the time to reach an effective therapeutic range on warfarin varies from 2 to 5 days.
© 2012 Direct One Communications, Inc. All rights reserved. 24 Rivaroxaban vs Warfarin in DVT In both the EINSTEIN DVT trial, which compared rivaroxaban with warfarin, and in an extension of the EINSTEIN trial, which examined the prevention of recurrent venous thromboembolism with rivaroxaban, a nonsignificant decrease in mortality was noted with rivaroxaban therapy. 58,59 The study population excluded use of interacting medications (strong CYP3A4 inhibitors and inducers) and patients with significantly elevated liver function tests or renal impairment. Warfarin-treated patients were within the therapeutic INR range less than 60% of the time.
© 2012 Direct One Communications, Inc. All rights reserved. 25 Dabigatran vs Warfarin in DVT In the RE-COVER trial, dabigatran was noninferior to warfarin in treating acute DVT. 60 The study population excluded patients if they had recent unstable cardiovascular disease, baseline liver function test results that were more than twice the upper limit of normal, or significant renal impairment. As in the EINSTEIN DVT trial and similar clinical trials in AF, warfarin-treated patients were within the therapeutic INR range less than 60% of the time.
© 2012 Direct One Communications, Inc. All rights reserved. 26 Choosing an Oral Anticoagulant for DVT Ability to keep the patient on warfarin within therapeutic INR levels Costs of individual agents Unknown long-term risks related to novel anticoagulants Lack of clarity regarding efficacy in patients with significant liver or renal impairment Considerations related to the choice of an initial oral anticoagulant for patients with acute DVT are similar to those used for patients with AF, namely, the:
© 2012 Direct One Communications, Inc. All rights reserved. 27 Laboratory Monitoring Although dabigatran can raise the INR, activated partial thromboplastin time (aPTT), and thrombin time, the degree of elevation has not been clearly associated with its therapeutic effect. 61 The ecarin clotting time (ECT)—in which a known quantity of ecarin is added to the patient’s plasma and the time to clotting is evaluated—has been suggested for monitoring the anticoagulant activity of dabigatran. 61 ECT is notably unaffected by heparin or warfarin. 61 Recently developed chromogenic dabigatran assays may permit monitoring serum dabigatran levels. 61
© 2012 Direct One Communications, Inc. All rights reserved. 28 Laboratory Monitoring Similarly, an anti-factor Xa level may be used to evaluate the therapeutic effects of rivaroxaban or apixaban. 61 These assays are not as quickly obtained or as widely available as is the INR. Furthermore, therapeutic ranges for these laboratory tests remain to be determined.
© 2012 Direct One Communications, Inc. All rights reserved. 29 Managing Bleeding Complications There is some evidence that the anticoagulant actions of dabigatran and rivaroxaban may be reversible. 62–65 Preclinical studies suggest that both recombinant factor VIIa and prothrombin complex concentrate (PCC) can reverse the effects of dabigatran and rivaroxaban on bleeding time and aPTT. Injection of PCC immediately reversed the anticoagulant activity of rivaroxaban in 12 healthy human volunteers but had no effect on dabigatran- induced increases in aPTT, ECT, or thrombin time. 62 How these blood products might function in actual emergent clinical situations is unknown.
© 2012 Direct One Communications, Inc. All rights reserved. 30 Conclusions Although the introduction of rivaroxaban, apixaban, and dabigatran has the potential to revolutionize the day-to-day care of patients who require oral anticoagulation therapy, the best use of these drugs ultimately may need to be determined on a patient- by-patient and center-by-center basis. The efficacy of individual centers in managing INRs, the ability to safely maintain a therapeutic INR range in individual patients on warfarin, and the current lack of a clear methodology for monitoring or reversing the anticoagulant effects of these new agents all must be taken into account when a patient is switched from warfarin to them.
© 2012 Direct One Communications, Inc. All rights reserved. 31 Conclusions The new era of anticoagulant therapy has resulted in a milieu of studies and evolving guidelines to help refine the optimum use of these novel agents as more convenient and possibly safer therapeutic alternatives to warfarin. Future studies to examine the cost-effectiveness of these agents and their impact on individual patients and systems-based care, as well as head-to-head comparisons of novel oral anticoagulants, will be the key to understanding how these novel agents may enter the current lexicon of anticoagulation.
© 2012 Direct One Communications, Inc. All rights reserved. 32 References 1.Wann LS, Curtis AB, January CT, et al ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (updating the 2006 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011;123:104– Fuster V, Ryden LE, Cannom DS, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to revise the 2001 guidelines for the management of patients with atrial fibrillation). Circulation. 2006;114:e257–e The Boston Area Anticoagulation Trial for AF Investigators. The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic AF. N Engl J Med. 1990;323:1505– Stroke Prevention in Atrial Fibrillation Investigators. Stroke Prevention in AF Study: final results. Circulation. 1991;84:527– EAFT (European Atrial Fibrillation Trial) Study Group. Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke. Lancet. 1993;342:1255– Petersen P, Boysen G, Godtfredsen J, et al. Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation: the Copenhagen AFASAK study. Lancet. 1989;1:175– Ezekowitz MD, Bridgers SL, James KE, et al. Warfarin in the prevention of stroke associated with nonrheumatic AF. Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators. N Engl J Med. 1992;327:1406– Connolly SJ, Laupacis A, Gent M, et al. Canadian Atrial Fibrillation Anticoagulation (CAFA) study. J Am Coll Cardiol. 1991;18:349– McMillin GA, Vazquez SR, Pendleton RC. Current challenges in personalizing warfarin therapy. Expert Rev Clin Pharmacol. 2011;4:349–362.
© 2012 Direct One Communications, Inc. All rights reserved. 33 References 10.White PJ. Patient factors that influence warfarin dose response. J Pharm Pract. 2010;23:194– Lader E, Martin N, Cohen G, et al. Warfarin therapeutic monitoring: is 70% time in the therapeutic range the best we can do? J Clin Pharm Ther Dec 16. Epub ahead of print. 12.Davie EW, Fujikawa K, Kisiel W. The coagulation cascade: initiation, maintenance, and regulation. Biochemistry. 1991;30:10363– Davie EW. Biochemical and molecular aspects of the coagulation cascade. Thromb Haemost. 1995;74:1–6. 14.McVey JH. Tissue factor pathway. Best Pract Res Clin Haematol. 1999;12:361– Nakamura Y, Nakamura K, Fukushima-Kusano K, et al. Tissue factor expression in atrial endothelia associated with nonvalvular atrial fibrillation: possible involvement in intracardiac thrombogenesis. Thromb Res. 2003;111:137– Hirsh J, Dalen JE, Anderson DR, et al. Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest. 1998;114:445S–469S. 17.Redondo S, Martinez MP, Ramajo M, et al. Pharmacological basis and clinical evidence of dabigatran therapy. J Hematol Oncol. 2011;4: Hankey GJ, Eikelboom JW. Dabigatran etexilate: a new oral thrombin inhibitor. Circulation. 2011;123:1436– Liesenfeld KH, Lehr T, Dansirikul C, et al. Population pharmacokinetic analysis of the oral thrombin inhibitor dabigatran etexilate in patients with non-valvular atrial fibrillation from the RE-LY trial. J Thromb Haemost. 2011;9:2168– Perzborn E, Roehrig S, Straub A, et al. Rivaroxaban: a new oral factor Xa inhibitor. Arterioscler Thromb Vasc Biol. 2010;30:376– Laux V, Perzborn E, Kubitza D, Misselwitz F. Preclinical and clinical characteristics of rivaroxaban: a novel, oral direct factor Xa inhibitor. Semin Thromb Hemost. 2007;33:515–523.
© 2012 Direct One Communications, Inc. All rights reserved. 34 References 22.Raghavan N, Frost CE, Yu Z, et al. Apixaban metabolism and pharmacokinetics after oral administration to humans. Drug Metab Dispos. 2009;37:74– He K, Luettgen JM, Zhang D, et al. Preclinical pharmacokinetics and pharmacodynamics of apixaban, a potent and selective factor Xa inhibitor. Eur J Drug Metab Pharmacokinet. 2011;36:129– Potpara TS, Lip GY. New anticoagulation drugs for atrial fibrillation. Clin Pharmacol Ther. 2011;90:502– Nutescu EA, Bathija S, Sharp LK, et al. Anticoagulation patient self-monitoring in the United States: considerations for clinical practice adoption. Pharmacotherapy. 2011;31:1161– MacGregor SH, Hamley JG, Dunbar JA, et al. Evaluation of a primary care anticoagulant clinic managed by a pharmacist. BMJ. 1996;312: Edgeworth A, Coles EC. An evaluation of near-patient testing of anticoagulant control in general practice. Int J Health Care Qual Assur. 2010;23:410– Gardiner C, Longair I, Pescott MA, et al. Self-monitoring of oral anticoagulation: does it work outside trial conditions. J Clin Path. 2009;62:168– Perera R, Heneghan C, Fitzmaurice D. Individual patient meta-analysis of self-monitoring of an oral anticoagulation protocol. J Heart Valve Dis. 2008;17:233– Lindhoff-Last E, Samama MM, Ortel TL, et al. Assays for measuring rivaroxaban: their suitability and limitations. Ther Drug Monit. 2010;32:673– Wolf PA, Mitchell JB, Baker CS, et al. Impact of atrial fibrillation on mortality, stroke, and medical costs. Arch Intern Med. 1998;158:229– Lin HJ, Wolf PA, Kelly-Hayes M, et al. Stroke severity in atrial fibrillation: the Framingham Study. Stroke. 1996;27:1760– Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–1151.
© 2012 Direct One Communications, Inc. All rights reserved. 35 References 34.Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883– Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981– Connolly SJ, Eikelboom J, Joyner C, et al. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011;364:806– Connolly SJ, Pogue J, Eikelboom J, et al. Benefit of oral anticoagulant over antiplatelet therapy in atrial fibrillation depends on the quality of international normalized ratio control achieved by centers and countries as measured by time in therapeutic range. Circulation. 2008;118:2029– Hart RG, Benavente O, McBride R, Pearce LA. Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis. Ann Intern Med. 1999;131:492– Hylek EM, Go AS, Chang Y, et al. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N Engl J Med. 2003;349:1019– Van Walraven C, Hart RG, Singer DE, et al. Oral anticoagulants vs aspirin in nonvalvular atrial fibrillation: an individual patient meta-analysis. JAMA. 2002;288:2441– Hylek EM, Skates SJ, Sheehan MA, Singer DE. An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation. N Engl J Med. 1996;335:540– Wallentin L, Yusuf S, Ezekowitz MD, et al. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet. 2010;376:975– Hylek EM, Frison L, Henault LE, Cupples A. Disparate stroke rates on warfarin among contemporaneous cohorts with atrial fibrillation: potential insights into risk from a comparative analysis of SPORTIF III versus SPORTIF V. Stroke. 2008;39:3009–3014.
© 2012 Direct One Communications, Inc. All rights reserved. 36 References 44.Amouyel P, Mismetti P, Langkilde LK, et al. INR variability in atrial fibrillation: a risk model for cerebrovascular events. Eur J Intern Med. 2009;20:63– Fang M, Go A, Chang Y, et al. Development of a new risk stratification scheme to predict warfarin- associated hemorrhage: the AnTicoagulation and Risk Factors in AF (ATRIA) study. Circulation. 2010;122:A Abstract. 46.Matchar DB, Jacobson AK, Edson RG, et al. The impact of patient self-testing of prothrombin time for managing anticoagulation: rationale and design of VA cooperative study #481—The Home INR Study (THINRS). J Thromb Thrombolysis. 2005;19:163– Dolor RJ, Ruybalid RL, Uyeda L, et al. An evaluation of patient self-testing competency of prothrombin time for managing anticoagulation: pre-randomization results of VA Cooperative Study #481—The Home INR Study (THINRS). J Thromb Thrombolysis. 2010;30:263– Matchar DB, Jacobson A, Dolor R, et al. Effect of home testing of international normalized ratio on clinical events. N Engl J Med. 2010;363:1608– Bussey HI. The future landscape of anticoagulation management. Pharmacotherapy. 2011;31:1151– Watzke HH, Forberg E, Svolba G, et al. A prospective controlled trial comparing weekly self-testing and self-dosing with the standard management of patients on stable oral anticoagulation. Thromb Haemost. 2000;83:661– Cromheecke ME, Levi M, Colly LP, et al. Oral anticoagulation self-management and management by a specialist anticoagulation clinic: a randomised cross-over comparison. Lancet. 2000;356:97– Banerjee A, Lane DA, Torp-Pedersen C, Lip GY. Net clinical benefit of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus no treatment in a “real world” atrial fibrillation population: a modelling analysis based on a nationwide cohort study. Thromb Haemost Dec 21. Epub ahead of print. 53.Pink J, Lane S, Pirmohamed M, Hughes DA. Dabigatran etexilate versus warfarin in management of non- valvular atrial fibrillation in UK context: quantitative benefit-harm and economic analyses. BMJ. 2011;343:d6333. Epub ahead of print.
© 2012 Direct One Communications, Inc. All rights reserved. 37 References 54.Freeman JV, Zhu RP, Owens DK, et al. Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in atrial fibrillation. Ann Intern Med. 2011;154:1– Eikelboom JW, Wallentin L, Connolly SJ, et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with AF: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation. 2011;31:2363– Jaff MR, McMurtry S, Archer SL, et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011;123:1788– Kearon C, Kahn SR, Agnelli G, et al. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). American College of Chest Physicians. Chest. 2008;133(suppl):454S–545S. 58.The Einstein Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363:2499– Romualdi E, Donadini MP, Ageno W. Oral rivaroxaban after symptomatic venous thromboembolism: the continued treatment study (EINSTEIN-Extension study). Expert Rev Cardiovasc Ther. 2011;9:841– Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361:2342– Favaloro EJ, Lippi G, Koutts J. Laboratory testing of anticoagulants: the present and future. Pathology. 2011;43:682– Eerenberg ES, Kamphuisen PW, Sijpkens MK, et al. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation. 2011;124:1573–1579.
© 2012 Direct One Communications, Inc. All rights reserved. 38 References 63.van Ryn J, Stangier J, Haertter S, et al. Dabigatran etexilate—a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost. 2010;103:1116– Battinelli EM. Reversal of new oral anticoagulants. Circulation. 2011;124:1508– Romualdi E, Rancan E, Siragusa S, Ageno W. Managing bleeding complications in patients treated with the old and the new anticoagulants. Curr Pharm Des. 2010;16:3478–3482.
JOURNAL REVIEW Newer Antithrombotics in AF 1 Dr Ranjith MP Senior Resident Department of Cardiology Government Medical college Kozhikode.
Date of download: 7/1/2016 Copyright © The American College of Cardiology. All rights reserved. From: ACC/AHA/ESC 2006 Guidelines for the Management of.
A Randomized Trial of Dabigatran versus Warfarin in the Treatment of Acute Venous Thromboembolism Schulman S et al. Proc ASH 2011;Abstract 205.
Study by: Granger et al. NEJM, September 2011,Vol No. 11 Presented by: Amelia Crawford PA-S2 Apixaban versus Warfarin in Patients with Atrial Fibrillation.
Managing New Oral Anticoagulants in the Perioperative and Intensive Care Unit Setting.
Patients Are Undertreated NABOR Warfarin/Warfarin + Aspirin No Treatment Patients, % Waldo AL, et al. J Am Coll Cardiol. 2005;46:  Retrospective.
Oral Rivaroxaban for Symptomatic Venous Thrombroenbolism Group /06/11.
Net clinical benefit of OAC Net clinical benefit - stroke, systemic embolism, ICH – events prevented per 100 person years Singer 2009.
Pharmacologic Profiles of Approved and Investigational Oral Anticoagulants WarfarinDabigatranRivaroxabanApixabanEdoxaban Target Vitamin K epaxide ThrombinXa.
Apixaban versus Aspirin in Atrial Fibrillation Patients ≥ 75 years old: An Analysis from the AVERROES Trial Kuan H Ng, Olga O Shestakovska, John W. Eikelboom,
The GARFIELD Registry is funded by an unrestricted research grant from Bayer Pharma AG The Role of Anticoagulants Keith A A Fox Edinburgh.
Date of download: 6/26/2016 Copyright © The American College of Cardiology. All rights reserved. From: 2014 AHA/ACC/HRS Guideline for the Management of.
The NEW ENGLAND JOURNAL of MEDICINE Idarucizumab for Dabigatran Reversal R3 김동연 / F. 김선혜.
Review on NOACs Studies DR. KOUROSH SADEGHI TEHRAN UNIVERSITY OF MEDICAL SCIENCES.
Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation Manesh R. Patel, M.D., Kenneth W. Mahaffey, M.D., Jyotsna Garg, M.S., Guohua Pan, Ph.D.,
Date of download: 7/10/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Choice of Antithrombotic Therapy for Stroke Prevention.
ARISTOTLE TRIAL Dr R Nyabadza GPST1 Ward 32. Structure AF, stroke and CHA 2 -DS 2 VASC Anticoagulant choices ARISTOTLE trial Cost NICE guidance and the.
Gli anticoagulanti diretti nel mondo reale Il neurologo: Efficacia e sicurezza Antonio Carolei* e Cindy Tiseo Clinica Neurologica e Stroke Unit Avezzano.
Spotlight Case Watch the Warfarin!. 2 Source and Credits This presentation is based on the July 2011 AHRQ WebM&M Spotlight Case –See the full article.
The Efficacy of Dabigatran versus Warfarin for Stroke Prevention in Patients With Atrial Fibrillation: Systematic Review Karim Bouferrache Pacific University.
Manesh R. Patel, M.D., Kenneth W. Mahaffey, M.D., Jyotsna Garg, M.S., Guohua Pan, Ph.D., Daniel E. Singer, M.D., Werner Hacke, M.D., Ph.D., Gunter Breithardt,
N Engl J Med 2009;361: Stuart J. Connolly, M.D., Michael D. Ezekowitz, M.B., Ch.B., D.Phil., Salim Yusuf, F.R.C.P.C., D.Phil., John Eikelboom,
I nuovi anticoagulanti orali: elementi di differenziazione farmacologica Prof. Alberto Corsini Università degli Studi di Milano.
Presented by Renato D. Lopes, MD, PhD, Duke Clinical Research Institute, Duke University, USA for the ARISTOTLE investigators. Efficacy and Safety of Apixaban.
Comparison of Dabigatran and Warfarin in Patients With Atrial Fibrillation and Valvular Heart DiseaseClinical Perspective by Michael D. Ezekowitz, Rangadham.
The EINSTEIN PE Study 'Xarelto' for the Acute and Continued Treatment of Symptomatic Pulmonary Embolism.
How to Navigate the New Oral Anticoagulants and Deal With Triple Therapy Dr. Morteza Safi Professor of interventional cardiology Cardiovascular Research.
The EINSTEIN DVT Study 'Xarelto' for the Acute and Continued Treatment of Symptomatic Deep Vein Thrombosis.
Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.
The Changing Landscape of Anticoagulation William D. Cahoon, Jr., PharmD, BCPS Cardiology Clinical Pharmacist VCU Health System April 12, 2012.
Atrial Fibrillation Warfarin and its newer alternatives Dr Mark Abelson Cardiologist Somerset West.
UK/CVS (1) | February 2013 Emerging technologies for stroke prevention in atrial fibrillation UK/CVS (1) | Date of preparation: February 2013.
CLINICAL CASES. Atrial Fibrillation Case Study #2 ► An 81-year-old white female with a history of chronic, non-valvular AF, a history of a previous ischemic.
New Oral Anticoagulant R2 Patcharee Seesongsom R2 Sirada Phojai Advisor AJ Tachawan Jiratiwanon.
A Screening Test for Xa based DOACs Uzma Ahmad BMS Haematology at The Mid Yorkshire Hospitals NHS Trust Introduction A study was undertaken to investigatie.
R4 문정락 / IC prof. 김진배 Lancet Haematol 2015;2: e150–59.
Venous thromboembolism: how long to treat? Eliot Williams, MD PhD Department of Medicine Division of Hematology & Medical Oncology.
Anti-thrombotic agents. New and Emerging Anticoagulants Anti – Xa : direct Rivaroxaban (oral) Apixaban (oral) Betrixiban (oral) Edoxaban (oral)
Pulmonary Embolism Treatment in Cancer - Is It Different 34th Brazilian Thoracic Conference 6th ALAT Congress 5th Brazil-Portugal Congress Brazilia/DF.
Supervisor: Vs 余垣斌 Presenter: CR 周益聖. INTRODUCTION.
Rohan Subasinghe. Non valvular aF increases with age from 0.5 % at age to 9 % at age AF is an independent Risk factor for CVA Patients.
New Oral Anticoagulants (NOACs) Dabigatran and Rivaroxaban for the prevention of stroke and systemic embolism in nonvalvular atrial fibrillation Dr Dipti.
The EINSTEIN EXT Study 'Xarelto' for the Long-Term Prevention of Recurrent Venous Thromboembolism.
Praxbind ® - Idarucizumab Manufacturer: Boehringer Ingelheim Pharmaceuticals, Inc. FDA Approval Date: 10/16/2015.
Dr. MUHAMMAD SYUKRI, Sp JP PUSAT JANTUNG Regional BAGIAN KARDIOLOGI DAN KEDOKTERAN VASKULAR FKUA/PUSAT JANTUNG RS. DR. M DJAMIL, PADANG.
WARFARIN AN OVERVIEW. HEMOSTASIS VASCULAR SPASM PLATELET PLUG BLOOD COAGULATION GROWTH OF FIBROUS TISSUE IN CLOT.
Bleeding complications and management in patients treated with NOACs Nico De Crem ASO Interne Geneeskunde.
+ Impact of New Anticoagulants on the Blood Bank January 24 th, 2012 Transfusion Medicine Resident Teaching Session Dr. Sudeep Shivakumar, Hematology.
Describe the activities of clinical pharmacists Define Therapeutic Drug Monitoring Discuss the pharmacist role in Therapeutic Drug Monitoring.
The New Oral Anticoagulants: Handle with Care Philip C. Comp, M.D., Ph.D. October 18, 2013.
© 2017 SlidePlayer.com Inc. All rights reserved.