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

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1 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 (TSOACs) used for prevention of stroke in. Objectives For Pharmacists: Compare the pharmacology between target specific oral anticoagulants Recall two differences in dosing strategies for the target specific oral anticoagulants Select optimal medication therapy for stroke prevention in patients with using the 2012 CHEST guidelines Identify appropriate patients to receive target specific oral anticoagulant therapy using efficacy and safety data from the,, and trials Describe three roles for a pharmacist in the management of target specific oral anticoagulant therapy For Technicians: Recognize available dosage forms and appropriate dosing strategies for the target specific oral anticoagulants Define the technician s role in the appropriate dispensing of target specific oral anticoagulant therapy FDA Approved Indications Dabigatran (Pradaxa) Rivaroxaban (Xarelto) Prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE) in patients undergoing knee or hip replacement surgery Treatment of DVT, PE, and reduction in the risk of recurrence of DVT and PE Apixaban (Eliquis)

2 Mechanism of Action Study Characteristics Comparison Study Design Randomized, open label Randomized, double blind, double dummy Randomized, double blind, double dummy Analysis Non inferiority Non inferiority Non inferiority # 18,113 14,264 18,201 Follow up 2 years 1.9 years 1.8 years Treatment Intervention Blinded dabigatran BID or BID Rivaroxaban 20 mg daily Apixaban 5 mg BID Comparator Intervention Open label dose adjusted warfarin Dose adjusted warfarin Dose adjusted warfarin

3 Population Comparison Age (years) 71.5 ± (65 78) 70 (63 76) Weight (kg) 82.9 ± (70 96) BMI (kg/m 2 ) 28.3 ( ) Male sex (%) CHADS 2 (mean) Efficacy Comparison Rate of stroke or systemic embolism, treatment ( ) ( ) ( ) ( ) p(s)<0.001 p(s)=0.12 p(s)=0.01 Rate of stroke or systemic embolism, warfarin *NI=non inferiority; S=superiority Safety Comparison: Major Bleeding Major bleeding, treatment ( ) ( ) ( ) ( ) p=0.003 p=0.31 p=0.58 Major bleeding, warfarin

4 Safety Comparison: Intracranial Bleeding Intracranial bleeding, treatment ( ) ( ) ( ) ( ) p=0.02 Intracranial bleeding, warfarin Safety Comparison: Gastrointestinal (GI) Bleeding GI bleeding, treatment ( ) ( ) ( ) P=0.43 p=0.37 GI bleeding, warfarin

5 References Chan LL, Crumpter WL, Jacobson AK. Implementation of pharmacist managed anticoagulation in patients receiving newer anticoagulants. Am J Health System Pharm. 2013;70: Connolly SJ, Ezekowitz MD, Yusef S, et al. Dabigatran versus warfarin in patients with. N Engl J Med. 2009;361: Connolly SJ, Wallentin L, Ezekowitz MD, et al. The long term multicenter observational study of dabigatran treatment in patients with (RELY ABLE) study. Circulation. 2013;128: Dipiro J, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach. 8 th ed. New York, NY: McGraw Hill Medical; Dunn SP. Newer anticoagulation strategies in. In: Pharmacotherapy Self Assessment Program: Cardiology/Endocrinology. Lenexa, KS: ACCP; 2013: Eliquis [package insert]. Princeton, NJ: Bristol Myers Squibb Company; Granger CB, Alexander JH, McMurray JV, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365: Lu G, DeGuzman FR, Hollenbach SJ, et al. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat Med. 2013;19(4): Miyares MA, Davis K. Newer oral anticoagulants: a review of laboratory monitoring options and reversal agents in the hemorrhagic patient. Am J Health Syst Pharm. 2012;69: New/Novel Oral Anticoagulant Resource Page. University of Utah Health Care Website. Accessed July 30, Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular. N Engl J Med. 2011;365: Pradaxa [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; University of New Mexico Hospitals Target Specific Oral Anticoagulants Guideline Page. Anticoagulation Forum Website. Accessed July 30, US National Institutes of Health. ClinicalTrials.gov. Accessed September 4, VanRyn J, Litzenburger T, Schurer J. Abstract 9928: Reversal of anticoagulant activity of dabigatran and dabigatran induced bleeding in rats by a specific antidote (antibody fragment). Circulation. 2012;126:A9928. Viles Gonzalez JF, Fuster V, Halperin JL. New anticoagulants for prevention of stroke in patients with. J Cardiovasc Electrophysiol. 2011;22: Weltz JI, Connolly SJ, Patel I, et al. Randomized, parallel group, multicenter, multinational phase 2 study comparing edoxaban, an oral factor Xa inhibitor, with warfarin for stroke prevention in patients with. Thromb Haemost. 2010;104: Xarelto [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; You JJ, Singer DE, Howard PA, et al. Antithrombotic therapy for. CHEST. 2012;141(2)(suppl):e531s e575s.