Warfarin Efficacy in Cancer

Patients on Long-term

AnticoagulationNeha Doshi, PharmD CandidateLeAnn B. Norris, PharmD, BCPS

P. Brandon Bookstaver, PharmD, BCPSJulie 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):S58-67. 2006 NCCN - Clinical Practice Guidelines in oncology-versus thromboembolic disease. Rose AJ, et al. Soc Gen Int Med 2007;22:997-1002.

Primary Factors

Various factors contribute to the increased risk of thromboembolic and hemorrhagic events3

▫ Active cancer▫ Catheters▫ Prolonged bed rest▫ Chemotherapy▫ Hormone therapy

Lee AY, et al. Circulation 2003;107:117-21.

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 x1.

4. Then we took the point at which it became not therapeutic and subtracted from last INR to give us x2.

5. Divide x1 by x2 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 daysINR 3.1 on 1/10/07 Difference of two INR’s: 3.1 – 2.5 = 1.24Difference / Time interval: 1.24 / 9 = 0.06Point at which INR is no longer therapeutic minus last INR: 3 – 2.5 = 0.50.5 / 0.06 = 8.3 days is TTR

Results- Demographics -

Mean age, years 72.1

Gender 

Males 17

Females 0

Race

Caucasian 14

Non-Caucasian 3

Mean height, cm179.8

Mean weight, kg 93.2

Mean body mass index, kg/m2 28.9

INR goal 2-3 17

Total of 60 patients screened

17 met study inclusion

N=17

Results- Comorbidities -

0%10%20%30%40%50%60%70%80%90%

100%

Prev

alen

ce

Results- Type of Malignancies -

0% 5% 10% 15% 20% 25% 30% 35%

Breast

Bone

Skin

Lung

Prostate

Leukemia

Colon

Liver

Head/neck

Bladder

Mal

ign

ancy

Typ

e

Percent of Population

Results- Cancer Treatment -

Radiation18%

Surgery40%Hormonal

18%

Chemotherapy24%

Results- TTR & Bleeding Events -

Comparison of Time in Therapeutic Range (TTR) and Bleeding Events

66% 67%

29%12%

0%

20%

40%

60%

80%

100%

120%

Pre-cancer Post-cancer

BleedingeventsTTR

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

AnticoagulationNeha Doshi, PharmD CandidateLeAnn B. Norris, PharmD, BCPS

P. Brandon Bookstaver, PharmD, BCPSJulie Sease, PharmD, BCPS