Objectives. Oral Anticoagulants. Assessment Question No. 1. FDA Approved Indications. Warfarin

Assessment of Target Specific Oral Anticoagulant Prescribing Rationale and Adverse Event Pilot Comparison in Veterans Receiving Oral Anticoagulation Therapy Angela Mechelay, Pharm.D. PGY1 Pharmacy Resident Oklahoma City VA Medical Center Oklahoma City, OK Objectives Identify preferable characteristics of target specific oral anticoagulants (TSOACs) over Discover the factors influencing provider selection of TSOACs OSHP 2015 Annual Meeting March 27, 2015 1 2 Assessment Question No. 1 Which of the following is an advantage for the use of TSOACs compared to? A. Therapeutic monitoring is required B. Quick onset of action C. Reversal agents available D. Cost Oral Anticoagulants Warfarin TSOACs Dabigatran (Pradaxa ) Rivaroxaban (Xarelto ) Apixaban (Eliquis ) Edoxaban (Savaysa ) 3 4 Weitz JI. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12e. 2011. FDA Approved Indications Warfarin VTE treatment Postop Thromboprophylaxis Nonvalvular AF Heart valve replacement Post MI Warfarin X X X X X Dabigatran X X Rivaroxaban X X X Apixaban X X X Edoxaban X X Advantages Known efficacy Clinical experience Reversal agent available Low cost Disadvantages Narrow therapeutic index Frequent monitoring Unpredictable pharmacokinetics & pharmacodynamics Drug and food interactions Slow onset and offset Increased bleeding risk http://www.pbm.va.gov/pbm/clinicalguidance/drugclassreviews http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm429523.htm 5 January CT, et al. Circulation. 2014. 6

TSOACs TSOACs Utilization in AF Advantages Quick onset of action Predictable pharmacokinetic profile Therapeutic monitoring not required Fewer drug and food interactions Disadvantages Short half-life Patient compliance Lack reversal agents Costly Less clinical experience Dabigatran (Pradaxa) Prescribing Information. April 2014. Rivaroxaban (Xarelto) Prescribing Information. March 2014. Apixaban (Eliquis) Prescribing Information. August 2014. 7 Desai NR, et al, Am J Med. 2014. 8 Dabigatran Prescribing Rationale Limitations For Prescribing Reduced clinic visits Unstable INR without non-compliance Less drug/food interactions Patient request For Not Prescribing Cost Well controlled on Limited experience Lack of reversal agent Limited clinical studies Small sample size Low response rate Rely on physician responses No data on prescribing patterns in practice No data on patient population Newest TSOACs not included 9 10 Huang C, et al. J Eval Clin Pract. 2013. Research Goals Contribute to the understanding of TSOACs utilization within the veteran population TSOACs non-formulary agents Require prior approval Identify educational needs Assist with local formulary management decisions Describe TSOAC adverse event rates outside of the landmark trials Objectives To evaluate the prescribing rationale for initiation or therapeutic substitution of TSOACs in veterans prescribed anticoagulation therapy. To compare the incidence of hemorrhagic and thrombotic adverse events in veterans prescribed TSOACs versus. 11 12

Endpoints Primary: Description of provider prescribing rationale for initiation or therapeutic substitution of TSOACs Secondary: Hemorrhagic and thrombotic events rates of TSOACs compared to Methods Design: Retrospective, observational chart review and pilot comparison Setting: Oklahoma City VA Medical Center 192-bed teaching hospital and tertiary care facility Serves a veteran population of 225,000 Anticoagulation Management 13 14 Methods (cont.) Study Period: January 1, 2011 to August 31, 2014 Adverse event data up to 6 months postinitiation of oral anticoagulation therapy Study Population: Veteran patients 18 years of age who filled a new outpatient prescription for TSOACs Veterans included in the Anticoagulation Management Program quality assurance reports Data Collection New outpatient TSOAC prescriptions identified through the veterans health information system database Electronic medical record Patient demographics and medical history Laboratory values Progress notes, non-formulary and criteriarestricted drug requests Anticoagulation Management Program quality assurance reports 15 16 Statistical Analysis Formal power analysis not applicable Descriptive statistics Patient demographics Prescribing rationale Categorical variables: Chi-square test Continuous variables: Wilcoxon test Current Status IRB: November 2014 Research & Development: December 2014 Primary endpoint data collection complete Adverse event data collection underway Data analysis underway 17 18

Preliminary Results Charts reviewed: 197 Baseline Information: Preliminary Results (cont.) Prescribing rationale for initiation of TSOACs over : Indication Patients (%) Atrial fibrilation 78 DVT 12 PE 6 Other 4 TSOAC Dabigatran 63 Rivaroxaban 32 Apixaban 3 19 Rationale Patients (%) Labile INR 39 Monitoring issues 20 Drug-drug interactions 3 Drug-food interactions 2 Adverse reaction to 18 Patient request 11 Other 7 20 Conclusion Assessment Question No. 2 TSOACs offer advantages and disadvantages over. Expect the use of TSOACs to continue to increase over time. Factors influencing provider selection of TSOACs include labile INR, monitoring issues, adverse effects, and others. Which of the following factors influence provider selection of TSOACs over? A. Patient request B. Poor patient compliance C. History of a stable INR D. Reversal agent available 21 22 Questions? 23

Assessment of Target Specific Oral Anticoagulant Prescribing Rationale and Adverse Event Pilot Comparison in Veterans Receiving Oral Anticoagulation Therapy Primary Author: Additional Authors: Angela Mechelay, Pharm.D. Rona Furrh, Pharm.D., BCPS Jennifer Bird, Pharm.D., BCPS, CACP Marcenia Knight, Pharm.D., BCPS Chris Gentry, Pharm.D., BCPS Objectives 1. Identify preferable characteristics of target specific oral anticoagulants (TSOACs) over 2. Discover the factors influencing provider selection of TSOACs Recommended Reading 1. Prosser H, Almond S, Walley T. Influences on GPs' decision to prescribe new drugs-the importance of who says what. Fam Pract. 2003;20(1):61-68. 2. Schumock GT, Walton SM, Park HY, et al. Factors that influence prescribing decisions. Ann Pharmacother. 2004;38(4):557-562. 3. Huang C, Siu M, Vu L, Wong S, Shin J. Factors influencing doctors' selection of dabigatran in non-valvular atrial fibrillation. J Eval Clin Pract. 2013;19(5):938-943. Self-Assessment Questions: 1. Which of the following is an advantage for the use of TSOACs compared to? a. Therapeutic monitoring is required b. Quick onset of action c. Reversal agents available d. Cost 2. Which of the following factors influence provider selection of TSOACs over? a. Patient request b. Poor patient compliance c. History of stable INR d. Reversal agent available

References: 1. Heron M. Deaths: leading causes for 2010. Natnl Vital Stat Rep. 2013;62(6):1-97. 2. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS Guideline 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 Heart Rhythm Society. Circulation. 2014;CIR.0000000000000041. doi:10.1161/cir.0000000000000041. 3. Falck-ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e278S-325S. 4. 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(2 Suppl):e419S- 494S. 5. You JJ, Singer DE, Howard PA, et al. Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e531S- 575S. 6. Beckman MG, Hooper WC, Critchley SE, Ortel TL. Venous thromboembolism: a public health concern. Am J Prev Med. 2010;38(4 Suppl):S495-501. 7. Gage BF, Waterman AD, Shannon W, et al. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA. 2001;285(22):2864-2870. 8. Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest. 2010;137(2):263 272. 9. Mueller RL, Scheidt S. History of drugs for thrombotic disease. Discovery, development, and directions for the future. Circulation. 1994;89(1):432-449. 10. Weitz JI. Blood Coagulation and Anticoagulant, Fibrinolytic, and Antiplatelet Drugs. In: Brunton LL, Chabner BA, Knollmann BC. eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12e. New York, NY: McGraw-Hill; 2011. http://accesspharmacy.mhmedical.com/content.aspx? bookid=374&sectionid=41266237. Accessed August 27, 2014. 11. Kirley K, Qato DM, Kornfield R, Stafford RS, Alexander GC. National trends in oral anticoagulant use in the United States, 2007 to 2011. Circ Cardiovasc Qual Outcomes. 2012;5(5):615-621. 12. Ageno W, Gallus AS, Wittkowsky A, et al. Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e44S-88S. 13. Dabigatran (Pradaxa) Prescribing Information. Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT. April 2014. 14. Rivaroxaban (Xarelto) Prescribing Information. Janssen Pharmaceuticals, Inc. Titusville, NJ. March 2014. 15. Apixaban (Eliquis) Prescribing Information. Bristol-Myers Squibb, Princeton NJ and Pfizer Inc. New York, NY. August 2014. 16. Prosser H, Almond S, Walley T. Influences on GPs' decision to prescribe new drugs-the importance of who says what. Fam Pract. 2003;20(1):61-68.

17. Schumock GT, Walton SM, Park HY, et al. Factors that influence prescribing decisions. Ann Pharmacother. 2004;38(4):557-562. 18. Huang C, Siu M, Vu L, Wong S, Shin J. Factors influencing doctors' selection of dabigatran in non-valvular atrial fibrillation. J Eval Clin Pract. 2013;19(5):938-943.