The role of factor Xa inhibitors in venous thromboembolism treatment

Katherine P Cabral, Jack E Ansell, Katherine P Cabral, Jack E Ansell

Abstract

Three factor Xa inhibitors have been studied in the treatment of venous thromboembolism, both for acute therapy and as extended therapy to prevent recurrent events. Rivaroxaban, apixaban, and edoxaban have all proven to be effective in Phase III clinical trials for this indication when compared to current standard of therapy with similar or less bleeding. Nevertheless, the agents all offer different pharmacological profiles, which have an impact on patient selection and potential advantages in clinical practice.

Keywords: anti-Xa inhibitors; apixaban; edoxaban; rivaroxaban; venous thromboembolism.

References

    1. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(Suppl 2):e419S–e494S.
    1. Eriksson BI, Quinlan DJ, Weitz JI. Comparative pharmacodynamics and pharmacokinetics of oral direct thrombin and factor xa inhibitors in development. Clin Pharmacokinet. 2009;48:1–22.
    1. Alexander JH, Singh KP. Inhibition of Factor Xa: A potential target for the development of new anticoagulants. Am J Cardiovasc Drugs. 2005;5(5):279–290.
    1. Rai R, Sprengeler PA, Elrod KC, Young WB. Perspectives on factor Xa inhibition. Curr Med Chem. 2001;8:101–119.
    1. Kubitza D, Becka M, Wensing G, Voith B, Zuehlsdorf M. Safety, pharmacodynamics, and pharmacokinetics of BAY 59-7939 – an oral, direct Factor Xa inhibitor – after multiple dosing in healthy male subjects. Eur J Clin Pharmacol. 2005;61:873–880.
    1. Janssen Pharmaceuticals, Inc . Xarelto®: Highlights of Prescribing Information. Janssen Pharmaceuticals, Inc; 2011. [Accessed March 28, 2014]. Available from: .
    1. Bristol-Myers Squibb . Eliquis: Highlights of Prescribing Information. Bristol-Myers Squibb; 2014. [Accessed October 19, 2014]. Available from: .
    1. Ogata K, Mendell-Harary J, Tachibana M, et al. Clinical safety, tolerability, pharmacokinetics, and pharmacodynamics of the novel factor Xa inhibitor edoxaban in healthy volunteers. J Clin Pharmacol. 2010;50(7):743–753.
    1. Matsushima N, Lee F, Sato T, Weiss D, Mendell J. Bioavailability and safety of the factor Xa inhibitor edoxaban and the effects of quinidine in healthy subjects. Clinical Pharmacology in Drug Development. 2013;2:358–366.
    1. Frost C, Wang J, Nepal S, et al. Apixaban, an oral, direct factor Xa inhibitor: single-dose safety, pharmacokinetics, pharmacodynamics and food effect in healthy subjects. Br J Clin Pharmacol. 2013;75(2):476–487.
    1. Frost C, Yu Z, Shenker A, et al. Food does not affect the pharmacokinetics of apixaban, an oral, factor Xa inhibitor. Can J Clin Pharmacol. 2008;15:e469. Abstract.
    1. Mendell J, Tachibana M, Shi M, Kunitada S. Effects of food on the pharmacokinetics of edoxaban, an oral direct factor Xa inhibitor, in healthy volunteers. J Clin Pharmacol. 2011;51:687–694.
    1. Furugohri T, Isobe K, Honda Y, et al. DU-176b, a potent and orally active factor Xa inhibitor: in vitro and in vivo pharmacological profiles. J Thromb Haemost. 2008;6(9):1542–1549.
    1. Camm AJ, Bounameaux H. Edoxaban: a new oral direct factor xa inhibitor. Drugs. 2011;71(12):1503–1526.
    1. Gulseth MP, Michaud J, Nutescu EA. Rivaroxaban: an oral direct inhibitor of factor Xa. Am J Health Syst Pharm. 2008;65:1520–1529.
    1. Bathala MS, Masumoto H, Oguma T, He L, Lowrie C, Mendell J. Pharmacokinetics, biotransformation, and mass balance of edoxaban, a selective, direct factor xa inhibitor, in humans. Drug Metab Dispos. 2012;40:2250–2255.
    1. EINSTEIN Investigators. Bauersachs R, Berkowitz SD, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363(26):2499–2510.
    1. EINSTEIN–PE Investigators. Büller HR, Prins MH, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366(14):1287–1297.
    1. Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013;369(9):799–808.
    1. Hokusai-VTE Investigators. Büller HR, Décousus H. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013;369(15):1406–1415.
    1. Agnelli G, Buller HR, Cohen A, et al. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013;368:699–708.
    1. Nutescu E, Chuatrisorn I, Hellenbart E. Drug and dietary interactions of warfarin and novel oral anticoagulants: an update. J Thromb Thrombolysis. 2011;31:326–343.
    1. Frost C, Wang J, Nepal S, et al. Effect of ketoconazole and diltiazem on the pharmacokinetics of apixaban, an oral direct factor Xa inhibitor. J Clin Pharmacol. 2009;49:1091–1130. Abstract.
    1. Mendell J, Zahir H, Matsushima N, et al. Drug-drug interaction studies of cardiovascular drugs involving P-glycoprotein, an efflux transporter, on the pharmacokinetics of edoxaban, an oral factor Xa inhibitor. Am J Cardiovasc Drugs. 2013;13:331–342.
    1. Ruff CT, Giugliano RP, Antman EM, et al. Evaluation of the novel factor Xa inhibitor edoxaban compared with warfarin in patients with atrial fibrillation: design and rationale for the Effective aNticoaGulation with factor xA next GEneration in Atrial Fibrillation-Thrombolysis in Myocardial Infarction study 48 (ENGAGE AF-TIMI 48) Am Heart J. 2010;160:635–641.
    1. Gruber A, Marzec UM, Buetehorn U, Hanson S, Perzborn E. Potential of activated prothrombin complex concentrate and activated factor VII to reverse the anticoagulant effects of rivaroxaban in primates. Blood. 2008;112:1307. abstract 3825.
    1. Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in health subjects. Circulation. 2011;124:1573–1579.
    1. Daiichi Sankyo Inc A Two-part Study in Edoxaban-treated Healthy Subjects to a Punch Biopsy Bleeding Model Establish and to Evaluate the Effect of a 4-factor Prothrombin Complex Concentrate on Anticoagulation. [Accessed July 12, 2014]. Available from: .
    1. Andexanet alfa: FXa Inhibitor Antidote [webpage on the Internet] South San Francisco: Portola Pharmaceuticals Inc; [Accessed June 2, 2014].
    1. Lu G, DeGuzman FR, Lakhotia S, Hollenback SJ, Phillips DR, Sinha U. Recombinant antidote for reversal of anticoagulation by factor Xa inhibitors. Blood. 2008;112 abstract 983.
    1. Mantha S, Ansell J. Indirect comparison of dabigatran, rivaroxaban, apixaban and edoxaban for the treatment of acute venous thromboembolism. J Thromb Thrombolys. 2014 Jul 3; Epub.

Source: PubMed

3
Abonneren