Questions for part B
Henry J. Woodford in Essential Geriatrics, 2022
A 74-year-old woman was admitted to hospital with a sudden onset of right-sided weakness. An urgent CT scan showed a left intracerebral haematoma. She is taking apixaban for atrial fibrillation. Which would be the best strategy to rapidly reverse the anticoagulant effect of apixaban?Andexanet alfaFresh frozen plasmaIdarucizumabProthrombin complex concentrateTranexamic acid
Stroke and Transient Ischemic Attacks of the Brain and Eye
Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw in Hankey's Clinical Neurology, 2020
Andexanet alfa is a modified recombinant inactive form of human factor Xa that acts as a decoy by binding and sequestering factor Xa inhibitors with a similar affinity to that of native factor Xa, thereby reducing anti–factor Xa activity, and reversing the anticoagulant effects of Xa inhibitors rapidly and nearly completely. In patients with acute major bleeding associated with the use of a factor Xa inhibitor, treatment with andexanet markedly reduced anti–factor Xa activity, and 82% of patients had excellent or good hemostatic efficacy at 12 hours.57 Two dosage regimens of andexanet alfa are recommended, based on the factor Xa inhibitor taken, its dose, and the time since the last factor Xa inhibitor dose. Patients taking <10 mg of rivaroxaban or <5 mg of apixaban per dose should receive the low-dose regimen, a 400-mg IV bolus dose of andexanet alfa over 15–30 minutes, followed by a 4 mg/min continuous infusion over 2 hours. Patients taking >10 mg of rivaroxaban or >5 mg of apixaban per dose should receive the high-dose regimen, an 800-mg IV bolus dose of andexanet alfa, followed by an 8 mg/min continuous infusion for up to 120 minutes if their last dose was <8 hours before starting andexanet alfa; if the last dose was >8 hours before starting andexanet alfa, the low-dose regimen should be used. If the dose and/or timing since the last dose of the factor Xa inhibitor is unknown, the high-dose regimen should be used. The optimal dosage of andexanet alfa for patients taking other factor Xa inhibitors has not been established.
Cerebrovascular disease in the elderly patient
Wilbert S. Aronow, Jerome L. Fleg, Michael W. Rich in Tresch and Aronow’s Cardiovascular Disease in the Elderly, 2019
A new category of anticoagulants for primary prevention of stroke in AF have been developed that may have some advantages over anticoagulation with warfarin: the direct thrombin inhibitor dabigatran and the factor Xa inhibitors rivaroxaban, apixaban, and edoxaban (100-103). Dabigatran 150 mg twice daily was associated with a lower incidence of stroke compared to warfarin and equal incidence of hemorrhagic complications (100). However, in post-marketing experience, the higher dose of dabigatran has been associated higher risk of hemorrhagic complications than the original study, particularly in the elderly. Rivaroxaban 20 mg daily was more effective than warfarin with an equal rate of hemorrhagic complications but a significantly lower rate of intracranial hemorrhage (101). Apixaban 5 mg twice daily had a lower risk of stroke compared to warfarin as well as lower rate of hemorrhagic complications. Apixaban must be dose adjusted in patients above 80 with low body weight, elevated creatinine, and certain drug interactions (85,102). The slightly higher efficacy and lower rate of hemorrhagic complications has made apixaban a popular choice among cardiologists and vascular neurologists. Edoxaban, the last to be approved, was approved at a dose of 60 mg daily for secondary prevention of stroke in AF. When compared to warfarin, the hazard of ischemic stroke was equivalent but hemorrhagic stroke significantly lower (103).
Payer formulary tier increases of apixaban: how patients respond and potential implications
Published in Current Medical Research and Opinion, 2023
Steven Deitelzweig, Emi Terasawa, Nipun Atreja, Amiee Kang, Dionne M. Hines, Amol D. Dhamane, Melissa Hagan, Ahmed Noman, Xuemei Luo
In a recent published paper, we presented a descriptive analysis of apixaban-treated patients with traditional Medicare coverage who faced formulary exclusion of apixaban by their Part D prescription drug plan (PDP) in 201712. Apixaban is an oral anticoagulant (OAC) with established efficacy/effectiveness and safety for preventing stroke and systemic embolism (SE), potentially life-threatening events, in patients with atrial fibrillation (AF)13–27. In this article, we address a related subgroup—apixaban-treated patients who faced a formulary tier increase for apixaban by their PDP in 2017. In this companion piece to the previously published article12, we examine the potential impacts of formulary tier increases for apixaban in patients with AF. In particular, we focus on apixaban-treated patients with AF who had traditional Medicare coverage and faced a formulary tier increase for apixaban in 2017, a year in which multiple PDPs enacted such changes. We describe these patients’ tier increases for apixaban and estimate the increase in their out-of-pocket costs for apixaban. We also describe these patients’ observed behaviors, including treatment patterns and pre-emptive switching to a different PDP.
Surgical intervention in patients with proximal femoral fractures confirmed positive for COVID-19—a report of 2 cases
Published in Acta Orthopaedica, 2020
Suk Kyoon Song, Won Kee Choi, Myung Rae Cho
Both patients had a considerably long waiting time before surgery. The procedures for diagnosing COVID-19 and preoperative cardiopulmonary risk assessment were the main causes of delay. In particular, the first patient had to halt apixaban for 2 days in order to reduce bleeding risk. Apixaban is recommended to be discontinued 48 hours before high-bleeding-risk procedures such as major orthopedic surgery (Mandernach et al. 2015). (We discussed this matter with the department of cardiology.) The second patient initially was admitted to a local clinic for other causes and later referred to our hospital after the fracture event. It took several days to assess comorbidities and preoperative risks. We would have postponed surgery if the risks of COVID-19 were more severe than the risks of surgical delay (e.g., severe or bilateral pneumonia, high oxygen demand).
A comprehensive evaluation of apixaban in the treatment of venous thromboembolism
Published in Expert Review of Hematology, 2020
Jennifer L Koehl, Bryan D. Hayes, Hanny Al‐Samkari, Rachel Rosovsky
Apixaban is a highly selective (>30 000‐fold selectivity over other coagulation proteases), reversible and potent (Ki = .08 nm) direct factor Xa inhibitor which prevents the conversion of prothrombin to thrombin, the final enzyme in the coagulation cascade that is responsible for fibrin clot formation. Apixaban inhibits both free and clot bound factor Xa [17–19], as well as prothrombinase activity [17,18]. It has no direct effect on platelet aggregation, but it indirectly inhibits aggregation induced by thrombin. More specifically, the direct inhibition of factor Xa differs from the direct inhibition of thrombin as the former preserves hemostatic function by attenuating the generation, but not the activity of thrombin [20]. As a result, apixaban has no direct effects on the actual activity of thrombin, rather indirectly inhibits this process by reducing thrombin generation [21,22] which in turn decreases fibrin clot development.
Related Knowledge Centers
- Anticoagulant
- Atrial Fibrillation
- Bleeding
- Warfarin
- Stroke
- Venous Thrombosis
- Hip Replacement
- Knee Replacement
- Oral Administration
- Spinal Epidural Hematoma