How I treat with anticoagulants in 2012: new and old anticoagulants, and when and how to switch

Abstract

Two novel oral anticoagulants, dabigatran and rivaroxaban, have recently been approved. They differ in many ways from warfarin, including rapid onset of action, shorter half-life, fewer drug-drug interactions, lack of need for monitoring, and no need for titration or dose adjustments. These novel agents represent a landmark shift in anticoagulant care; however, many aspects of their use will be unfamiliar to practicing clinicians, despite the imminent widespread use of these agents in the community. The management of these anticoagulants when transitioning from or back to warfarin, around surgery or in case of major hemorrhage, requires knowledge of their pharmacokinetics and mechanism of action. Unfortunately, there is a limited evidence base to inform decisions around management of these agents. We present our practice in these settings supported, where available, with literature evidence. (Blood. 2012;119(13): 3016-3023) IntroductionDabigatran has become available for long-term use in the United States and Canada at the end of 2010 and is the first novel antithrombotic agent approved for stroke prophylaxis in atrial fibrillation since the introduction of warfarin more than 50 years ago. 1 The Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) study provided high-quality evidence that, when administered at a dose of 150 mg twice daily, dabigatran is associated with a reduced risk of stroke and a similar risk of bleeding as warfarin when targeted to an international normalized ratio (INR) of 2.0 to 3.0. 2 When administered at a dose of 110 mg twice daily, the risk of stroke with dabigatran is similar to that of warfarin while producing less bleeding. This dose is approved in Canada but not in the United States because it did not reduce the risk of stroke compared with warfarin and stroke prevention was considered more important than the benefit of decreased risk for extracranial major bleeding. The dose of 75 mg twice daily is, however, recommended in the United States for patients with severe renal failure (calculated creatinine clearance 15-30 mL/ min). Dabigatran has also been approved for the prevention of deep vein thrombosis after orthopedic surgery in Canada, Europe, 3 and several other countries, and has been studied in the setting of long-term secondary prevention for venous thromboembolism. 4 Peer organization guidelines now recommend the use of dabigatran for many patients with atrial fibrillation. 5 The oral factor Xa inhibitor, rivaroxaban, has also been approved for prevention of stroke in atrial fibrillation and of venous thrombosis after orthopedic surgery. 6 Clinicians are intimately familiar with warfarin. It has 100% name recognition internationally, monitoring for its anticoagulant effect is routinely available, and physicians are aware of the need to interrupt warfarin for many interventional procedures. 7 There are established and highly effective treatment strategies for bleeding in patients receiving warfarin and for the management of unanticipated excess anticoagulant effe...

New Oral Anticoagulants and the Cancer Patient

“…The anticoagulant effects more quickly dissipate when therapy is stopped. Plasma elimination half-lives are 12-14 hours for rivaroxaban, 12 hours for apixaban, and 9-13 hours for dabigatran [37].This is beneficial when anticoagulation must be reversed for an elective invasive procedure [38] but also makes the NOACs less forgiving drugs in patients who are inconsistently compliant with therapy.…”

Practical aspects of new oral anticoagulant use in atrial fibrillation

“…17 Hemodialysis removes dabigatran (but not rivaroxaban or apixaban) and should be considered in patients with life-threatening bleeding. 16,17,38 Platelet transfusion is recommended and used in bleeding patients on TSOACs who also have thrombocytopenia or impaired platelet function for example due to the use of antiplatelet agents. 16,17 Also, antifibrinolytics such as tranexamic acid and ε-aminocaproic acid might be useful in severe bleeding on TSOACs, particularly, in the perioperative period, although their hemostatic efficacy is unknown in this setting.…”

Oral Direct Anticoagulants in Thrombosis Management in Anti-Phospholipid Syndrome: Unanswered Questions

“…The necessity to convert patients from one anticoagulant to another needs careful assessment of coagulation profile in case of VKA and good history taking to define exact timing of switching to avoid over or under coagulation as follows [25,41]. …”