Warfarin Efficacy in Cancer Patients on Long-term Anticoagulation Neha Doshi, PharmD Candidate LeAnn B. Norris, PharmD, BCPS P. Brandon Bookstaver, PharmD, BCPS Julie Sease, PharmD, BCPS

Background  “Patients with cancer are at high risk to develop venous thromboembolisms, and they are also more likely to develop complications from anticoagulant treatment”  Presence of malignancy increases risk of VTE by a factor of 4 to 6 ▫ Up to 25% of patients with a malignancy will develop thrombosis ▫ Cancer patients constitute 15-20% of patients diagnosed with a VTE Brose KMJ, et al. Curr Oncol 2008;15(1):S58-67.

Background  Annual risk of recurrent VTE is 21-27%  Annual risk of major bleeding is 12-13%  Thromboembolic events = second leading cause of death in cancer patients Brose KMJ, et al. Curr Oncol 2008;15(1):S NCCN - Clinical Practice Guidelines in oncology-versus thromboembolic disease. Rose AJ, et al. Soc Gen Int Med 2007;22:

Primary Factors  Various factors contribute to the increased risk of thromboembolic and hemorrhagic events 3 ▫ Active cancer ▫ Catheters ▫ Prolonged bed rest ▫ Chemotherapy ▫ Hormone therapy Lee AY, et al. Circulation 2003;107:

Objective  Purpose ▫ Assess the effectiveness of warfarin in a population of cancer patients  Outcome ▫ Determine the proportion of time spent within INR goal ▫ Assess the rate of thromboembolic and major hemorrhagic events

Patient Selection  Documented cancer diagnosis  Active anticoagulation ▫ Any indication ▫ At least 6 months prior to diagnosis ▫ 1 year after diagnosis

Methods  Patient demographics  Primary indication for anticoagulation  Underlying comorbidities  Type of malignancy  Cancer treatment  INR values  Bleeding events

Time in Therapeutic Range (TTR)  Calculated for each patient, pre- and post- diagnosis 1. If the patient was a new start, or restarted on warfarin, we excluded values within the first 30 days of initiation due to bridging. 2. Given two INR values, we first calculated the time interval (days) between the values. 3. Then, we took the difference of the two INR values and divided it by the time interval to give us x Then we took the point at which it became not therapeutic and subtracted from last INR to give us x Divide x 1 by x 2 and this gives the amount of days in therapeutic range between the two INR values. Rosendaal FR, et al. Thromb Haemostas 1993;69(3):236-9.

TTR - Calculation Example INR 2.5 on 1/01/07 Time interval: 9 days INR 3.1 on 1/10/07 Difference of two INR’s: 3.1 – 2.5 = 1.24 Difference / Time interval: 1.24 / 9 = 0.06 Point at which INR is no longer therapeutic minus last INR: 3 – 2.5 = / 0.06 = 8.3 days is TTR

Results - Demographics - Mean age, years72.1 Gender Males17 Females0 Race Caucasian14 Non-Caucasian3 Mean height, cm179.8 Mean weight, kg93.2 Mean body mass index, kg/m INR goal Total of 60 patients screened 17 met study inclusion N=17

Results - Comorbidities -

Results - Type of Malignancies -

Results - Cancer Treatment -

Results - TTR & Bleeding Events -

Limitations  Short observation period  Small population  Isolated VA population (100% males)

Conclusions  Chemotherapy was only group with better pre-cancer TTR  Post-cancer TTR was better than pre-cancer TTR  Increased hospital visitations allowing for closer observation and adjustment  LMWH vs. warfarin  LMWH superior in efficacy and convenience, fewer drug interactions, and less hemorrhagic and thromboembolic events  Guidelines indicate LMWH is first line for cancer patients with primary or recurrent VTE

Warfarin Efficacy in Cancer Patients on Long-term Anticoagulation Neha Doshi, PharmD Candidate LeAnn B. Norris, PharmD, BCPS P. Brandon Bookstaver, PharmD, BCPS Julie Sease, PharmD, BCPS