1. Putting Patients in the Driver Seat: Warfarin Self Management at KPCO Brandon Simmons, PharmD, BCPS Clinical Pharmacy Specialist in Anticoagulation Kaiser Permanente Colorado

2. The Plan Background Patient Self Management (PSM) Kaiser Permanente Colorado PSM –Rationale –Design Results Future direction

3. Self-monitoring of oral anticoagulation: systematic review and meta-analysis of individual patient data. Pooled results of individual patient data of anticoagulation therapy PSM 11 randomized, controlled trials –2000 to 2010 –6417 participants –12,800 person-years of follow-up

4. Modest improvements in INR control –5.13% mean improvement in time in therapeutic INR range (TTR) Reductions in thromboembolic events –HR 0.42; 95% CI 0.28–0.65 Nonsignificant differences in –Major bleeding (HR 0.86, 95% CI 0.56–1.31) –All-cause mortality (HR 0.75, 95% CI 0.42– 1.33) Self-monitoring of oral anticoagulation: systematic review and meta-analysis of individual patient data.

5. Patient Self Management (PSM) for warfarin management All warfarin PSM studies to date utilized self testing (PST) with point of care (POC) devices –Similar accuracy to venipuncture INR

6. Current Practice

7. Previous Self Management

8. CPAAS Self Management

9. KP.ORG KPCO patients can choose to have an active kp.org account –Secure, on-line system –Facilitates communication with providers –Displays information, including lab values

10. Why use not use POC? Requires additional patient training –Technique dictates accuracy POC is much more expensive –Cost of the POC machine –Cost of testing supplies PSM w/ POC devices also require weekly testing –CPAAS protocol allows up to 8 weeks

11. Process

12. 2 Hour Class 1 st hour was basics on self management –How warfarin works –How to adjust dose –How to pick a recheck date Break out practice session

13. 2 nd half focused on common anticoagulation issues –Drug interactions –Diet changes –Health changes –Complications Bleeding Clotting 2 Hour Class

14. 5 Step Process of Managing Warfarin 1.Add up your total weekly warfarin dose in milligrams (mg) 2.Determine how much to adjust dose and when to recheck using Table 1. Dosage Management Card 3.Determine new weekly dose based on Table 2. Dosage Adjustment Card 4.Determine new dosing schedule by finding your new weekly dose on Table 3. Weekly Schedule Card 5.Send message to Clinical Pharmacy Anticoagulation Service

15. PT INR ValueDosage AdjustmentRecheck INR If Next INR Unchanged (Stays in Same Row) Less than 1.5 Increase WEEKLY dose by 15 to 20% 7 daysIf next INR still less than 1.5 removed from the study 1.5 – 1.7 Increase WEEKLY dose by 5 to 10% 14 days If next INR still 1.5 to 1.7 increase WEEKLY dose by 10 to 15% and recheck in 7 days 1.8 – 1.9No Change7 days If next INR still 1.8 to 1.9 increase WEEKLY dose by 5 to 10% and recheck in 14 days 2.0 – 3.0No Change14 daysIf next INR still 2.0 to 3.0 recheck in 28 days 3.1 – 3.2No Change7 days If next INR still 3.1 to 3.2 reduce WEEKLY dose by 5 to 10% and recheck in 14 days 3.3 – 4.0 Reduce WEEKLY dose by 5 to 10% 14 days If next INR still 3.3 to 4.0 decrease WEEKLY dose by 10 to 15% and recheck in 7 days 4.1 – 4.5 Hold 1 dose then reduce WEEKLY dose by 10 to 15% 7 days If next INR still 4.1 to 4.5 hold 1 dose then decrease WEEKLY dose by 15 to 20% and recheck in 7 days Greater than 4.5 Hold 2 doses2 daysIf next INR still greater than 4.5 removed from the study Table 1: Dosage Management Card

16. Table 2: Dosage Adjustment Card Minus 20%Minus 15%Minus 10%Minus 5% Current Weekly Dose Plus 5%Plus 10%Plus 15%Plus 20% Unable to continue using 5mg tablets 17.520 22.5 1517.5 2022.5 25 17.5 20 22.525 30 20 22.5 2527.5 30 22.5 25 27.530 32.5 25 27.5 3032.5 3537.5 2527.530 32.535 37.540 27.53032.5 3537.540 42.5 30 32.53537.540 42.545 32.535 37.54042.545 47.5 32.53537.54042.54547.55052.5 3537.54042.54547.55052.555 37.54042.54547.55052.55557.5 4042.54547.55052.55557.560 42.54547.55052.55557.56062.5 4547.55052.55557.56062.565 47.55052.55557.56062.56570 47.552.55557.56062.5657072.5 505557.56062.56567.57075 52.5556062.5657072.57580 5557.5606567.5707577.582.5 55606567.570 Unable to continue using 5mg tablets

17. Table 3: Weekly Schedule Card Weekly Dose (mg) Sunday mg (tablets) Monday mg (tablets) Tuesday mg (tablets) Wednesday mg (tablets) Thursday mg (tablets) Friday mg (tablets) Saturday mg (tablets) 17.52.5 (1/2 tab) 202.5 (1/2 tab) 5 (1 tab)2.5 (1/2 tab) 22.52.5 (1/2 tab)5 (1 tab)2.5 (1/2 tab) 5 (1 tab)2.5 (1/2 tab) 252.5 (1/2 tab)5 (1 tab)2.5 (1/2 tab)5 (1 tab)2.5 (1/2 tab)5 (1 tab)2.5 (1/2 tab) 27.55 (1 tab)2.5 (1/2 tab)5 (1 tab)2.5 (1/2 tab)5 (1 tab)2.5 (1/2 tab)5 (1 tab) 305 (1 tab)2.5 (1/2 tab)5 (1 tab) 2.5 (1/2 tab)5 (1 tab) 32.55 (1 tab) 2.5 (1/2 tab)5 (1 tab) 355 (1 tab) 37.55 (1 tab) 7.5 (1 & 1/2 tab)5 (1 tab) 405 (1 tab)7.5 (1 & 1/2 tab)5 (1 tab) 7.5 (1 & 1/2 tab)5 (1 tab) 42.55 (1 tab)7.5 (1 & 1/2 tab)5 (1 tab)7.5 (1 & 1/2 tab)5 (1 tab)7.5 (1 & 1/2 tab)5 (1 tab) 457.5 (1 & 1/2 tab)5 (1 tab)7.5 (1 & 1/2 tab)5 (1 tab)7.5 (1 & 1/2 tab)5 (1 tab)7.5 (1 & 1/2 tab) 47.57.5 (1 & 1/2 tab)5 (1 tab)7.5 (1 & 1/2 tab) 5 (1 tab)7.5 (1 & 1/2 tab) 507.5 (1 & 1/2 tab) 5 (1 tab)7.5 (1 & 1/2 tab) 52.57.5 (1 & 1/2 tab) 557.5 (1 & 1/2 tab) 10 (2 tabs)7.5 (1 & 1/2 tab) 57.57.5 (1 & 1/2 tab)10 (2 tabs)7.5 (1 & 1/2 tab) 10 (2 tabs)7.5 (1 & 1/2 tab) 607.5 (1 & 1/2 tab)10 (2 tabs)7.5 (1 & 1/2 tab)10 (2 tabs)7.5 (1 & 1/2 tab)10 (2 tabs)7.5 (1 & 1/2 tab) 62.510 (2 tabs)7.5 (1 & 1/2 tab)10 (2 tabs)7.5 (1 & 1/2 tab)10 (2 tabs)7.5 (1 & 1/2 tab)10 (2 tabs) 6510 (2 tabs)7.5 (1 & 1/2 tab)10 (2 tabs) 7.5 (1 & 1/2 tab)10 (2 tabs) 67.510 (2 tabs) 7.5 (1 & 1/2 tab)10 (2 tabs) 7010 (2 tabs)

18. Competency Test Composition 70% required to achieve passing score 4 multiple choice questions that assessed: –Knowledge of Vitamin Ks effect on INR –Managing drug interactions –Distinguishing serious from common bleeding –Managing missed doses 6 short-answer questions that assessed: –Ability to adjust dose based on low, slightly elevated and significantly elevated INRs –Knowledge of when to have follow-up INR based on previous INR results

19. Short-answer questions Use the following information to answer questions 5 and 6: Mr. Alfredo takes 30 mg of warfarin weekly as follows: His INR on Tuesday is 1.7. 5. What changes, if any, should he make to his warfarin dose? 6. When should he check his next INR? SundayMondayTuesdayWednesdayThursdayFridaySaturday 5 mg2.5 mg5 mg 2.5 mg5 mg SundayMondayTuesdayWednesdayThursdayFridaySaturday

20. Competency Test - Validation Based on pre- validated tests –The Oral Anticoagulation Knowledge Test –Anticoagulation Knowledge Assessment Questionnaire

21. Target Population Age > 18 years Atrial fibrillation w/ target INR is 2.5 (range 2.0 to 3.0) 5 mg warfarin tablets

22. 506 Screened 116 Failed inclusion criteria: Not active on kp.org: 49 < 6 months on warfarin: 40 Not on 5 mg tablets: 24 Other: 3 223 Met exclusion criteria: >1 missed INRs last 6 mo: 143 Staff recommendations: 26 Planned time away: 20 Planned procedure: 17 Residing at care facility: 10 Other: 7 123 Declined participation: No reason given: 77 Time Conflicts: 21 Prefers status quo: 19 Other: 6 44 Enrolled 39 Completed 3 Withdrew consent 1 Failed competency exam 1 Withdrawn 167 Eligible 28 Continued PSM Patient Disposition

23. Test Results Competency Test (n=43) Pre-Education Score, mean (SD)55.8% (19.5) Post-Education Score, mean (SD)88.8% (13.5) Change in Score, mean (SD)33.0% (19.2)p < 0.001 Patients with passing score Pre-Education (n=15)34.9% p <0.001 Post-Education (n=41)95.3%

24. PSM Results 90 day pre-PSM phase 90 day PSM phase p value TTR82.9%81.2%p=0.65 Average # INRs 2.974.38p<0.01 # Bleed / Clot Events 3/10p=0.24 210 warfarin PSM dosing decisions 208 (99.0%) implemented unchanged by CPAS pharmacists

25. Individual TTR Changes

26. Study Problems

28. Study Limitations Stringent enrollment criteria –Strong internal validity –Not very generalizable Not powered to show effect on INR –Main objective was to demonstrate feasibility –Pilot study Short follow up interval Dosing algorithm not validated

29. Future Research Larger study randomized – multiple disease states and warfarin strengths Reduced restrictions w/exclusion criteria Possible 3 arm trial –Regular Care –PSM –Attend Class only

30. Future direction Creation of dosing algorithm program Direct feeds into DAWN AC Sub-feature of DAWN with direct patient access

31. What Questions Do You Have? Thank You for Coming!

32. Putting Patients in the Driver Seat: Warfarin Self Management at KPCO Brandon Simmons, PharmD, BCPS Clinical Pharmacy Specialist in Anticoagulation Kaiser Permanente Colorado