Inpatient Management of Warfarin Therapy by Pharmacists Compared to Physicians

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Juan Lansangan, Pharm.D. Candidate, 1Sangeeta Salvi, Pharm.D. Candidate, 2Jin-Hee Nomura, Pharm.D., 2 Teresa Hong, Pharm.D., 2Lynn Ishida-Kitazawa, Pharm.D., and 1,2,3Sheryl L. Chow, Pharm.D., BCPS 1Western University of Health Sciences, Pomona, CA., 2Centinela Hospital Medical Center, 3LABioMed at Harbor-UCLA Medical Center

Abstract
PURPOSE: Several studies have reported outcomes associated with pharmacist management of newly-initiated warfarin therapy in hospitalized patients. However, fluctuations in therapeutic ranges often occur in hospitalized patients on stable doses of warfarin therapy because of acute disease, drug-drug interactions, and changes in diet, requiring proactive anticoagulation management. The purpose of our study is to compare physician vs. pharmacist-directed management in hospitalized patients who are receiving chronic warfarin therapy in addition to those receiving first-time dosing. METHODS: A total of 248 consecutive hospitalized patients admitted to Centinela Hospital Medical Center from January 1, 2010 to November 17, 2011 were included in this study. These patients required initiation and/or maintenance of warfarin therapy and were managed by either a physician or a pharmacist (120 patients in the physician group, 128 patients in the pharmacist group). Patients were excluded from the study if warfarin therapy monitoring was less than 3 days with no prior warfarin use. Baseline parameters including drug interactions, indication, and warfarin use before admission were documented. The mean international normalized ratio (INR) at discharge and the rate of patients who were subtherapeutic (INR<1.5), supratherapeutic (INR>3.5), or excessively supratherapeutic (INR>6.0) were compared between groups. The impact of anticoagulation management on patient outcomes was measured by bleeding rates, length of stay (LOS), and days to reach therapeutic INR (DTTI). RESULTS: 248 patients (120 physician-directed, 128 pharmacist-directed) were included in the final analysis. The mean INR at discharge was similar between physician and pharmacist-directed management (1.9 vs. 1.9, p=0.753). Both groups demonstrated no significant differences in rates of subtherapeutic, supratherapeutic, and excessively supratherapeutic INRs. The average first 3day warfarin dose between physician- and pharmacist-directed management were 5.5 and 5.4, respectively. There was no significant differences in bleeding rates (6.7 vs. 3.1, p=0.194). Although a trend towards a reduced LOS was observed in patients treated by physicians (6.5 vs. 7.1, p=0.253), the DTTI was similar between groups (1.3 vs. 1.6, p=0.196). CONCLUSIONS: Based on the studied parameters, safety and efficacy of pharmacist-directed management is comparable to physician warfarin dosing. This indicates that pharmacists can solely manage inpatient warfarin therapy, giving physicians more time for other responsibilities.

Research Design & Methods

This study is an observational study of 248 patients who were admitted to Centinela Hospital Medical Center between January 1, 2010 to November 17, 2011. Patients were included in the study if they required initiation and/or maintenance of warfarin and were managed by either a physician or a pharmacist (120 patients in the physician group, 128 patients in the pharmacist group). Patients were excluded from the study if warfarin therapy monitoring was less than 3 days with no prior warfarin use.

Results
Table 3. Warfarin Therapy Comparison
PhysicianPharmacist-Directed Directed Table 1. Patient Mean Management Baseline Characteristics Management (N=108) (N=100)
Age, y Weight, kg Height, cm Sex, M/F, n (%) Baseline Hgb, g/dL Baseline Hct, %

PhysicianDirected Management (N=100)

DTTI, days LOS, days Mean INR at Discharge INR<1.5, Y/N, n (%) INR>3.5, Y/N, n (%) INR>6.0, Y/N, n (%) Bleeding Rates, Y/N, n (%) Days 1-3 Average Warfarin Dose

PharmacistDirected Management (N=108) 1.52.1 7.14.3 1.90.7

p-value

65.814.8 86.226.3 16912.1 35 (35)/65 (65) 11.71.9 35.15.7

103/mm3

67.415.8 85.325.9 168.213.4 50 (46.3)/58 (53.7) 122.3 367 233.192 3.10.5 64 (59.3) 39 (36.1) 28 (25.9) 7 (6.5) 16 (14.8) 5 (4.6) 25 (23.1) 7 (7)/93 (93) 5.5 4 (3.7)/104 (96.3) 5.4 1.32.1 6.64.5 1.90.6 71 (71)/29 (29) 8 (8)/92 (92) 4 (4)/96 (96) 0.47 0.42 0.61

74 (68.5)/34 (31.5) 0.7 10 (9.3)/98 (90.7) 1 (0.9)/107 (99.1) 0.75 0.15 Fishers: 0.2 0.29 Fishers: 0.36 __

Documentation and collection:

Patient demographics, indications for warfarin use, method of warfarin management, daily warfarin dose, daily INR measurement, time to reach INR goal, concomitant medications, major drug-drug interactions, bleeding rates, length of stay, prior warfarin use, and other laboratory measures were documented. The mean INR at discharge and the rate of patients who were subtherapeutic (INR<1.5), supratherapeutic (INR>3.5), or excessively supratherapeutic (INR>6.0) were compared between physician and pharmacist groups. Therapeutic INR is defined as 2-3 or 2.5-3.5 in patients with prosthetic heart valves. Maintenance of achieved therapeutic INR goal was also documented.
* *

Baseline Platelets, x Albumin Level, g/dL

233.589.3 3.10.6 64 (64) 44 (44) 12 (12) 6 (6) 16 (16) 7 (7) 30 (30)

Prior Warfarin Use, n (%) Indications Atrial Fibrillation, n (%) DVT, n (%)* DVT with PE, n (%) PE alone, n (%) Mechanical valve, n (%) Other, n (%)a

Discussion
Limitations

*For p0.05 DVT=deep vein thrombosis, PE=pulmonary embolism a=coagulopathy, stroke, pacemaker, arthroplasty, peripheral vascular disease

No standardized algorithm which leads to variation in pharmacists warfarin therapy monitoring. Data collected reflects inpatient values and results cannot be extrapolated to long-term management.

Table 2. Major Drug-Drug Interactions

Physician-Directed Management (N=100)

Sample size and statistics: . Statistical analysis was performed using the program SAS.
Allopurinol, n (%) Amiodarone, n (%) Aspirin, n (%) Clopidogrel, n (%) Fluconazole, n (%) Levofloxacin, n (%)

PharmacistDirected Management (N=108) 0 (0) 9 (8.3) 22 (20.4) 4 (3.7) 2 (1.9) 0 (0) 6 (5.6) 1 (0.9) 2 (1.9) 0 (0) 3 (2.8) 4 (3.7)

Conclusion
Safety and efficacy of pharmacist-directed management is comparable to physician warfarin dosing. This indicates that pharmacists can solely manage inpatient warfarin therapy, allowing physicians more time for other responsibilities.

Introduction
Optimal dosing of warfarin is complex due to several factors including unpredicatable pharmacodynamics and differences in inter-individual patient sensitivity. Warfarin has an initial effect on the INR around 3 days, depending on the dose,. Most patients do not have a stable INR until 5 to 6 days after the initiation of warfarin due to the long half-lives of vitamin K-dependent clotting VII, IX, X, and II. Several studies have reported that management of inpatients anticoagulation therapy by pharmacists had several benefits, including reduction in titration time to reach therapeutic range, reduction in the incidence of supratherapeutic INR, and reduction in the length and cost of inpatient stay.

1 (1) 11 (11) 24 (24) 2 (2) 3 (3) 1 (1) 3 (3) 0 (0) 5 (5) 1 (1) 1 (1) 4 (4)

Analysis of continuous variables was conducted using a twosample t-Test

Discrete variables was assessed using a c analysis.

Fishers exact test was used in the analysis of two-way tables when sample sizes were small. Significance was set at <0.05.

Levothyroxine, n (%) Methimazole, n (%) Metronidazole, n (%) Nafcillin, n (%) Phenytoin, n (%) Sulfamethoxazole and Trimethoprim, n (%) * For p0.05

Acknowledgements: David Yuan, Jennifer Borna, Kim Tran, Lenora Radparvar, Maria De La Rosa, Sheila Solymani, Toni Codling, Yuriy Nazarchuk
1. Wong KM et al. Efficacy and Safety of a pharmacist-managed inpatient anticoagulation service for warfarin initiation and titration. J. Clin. Pharm Ther. 2010;10:1365-2710. 2. Dager et al. Optimization of Inpatient Warfarin Therapy: Impact of Daily Consultation by a Pharmacist-Managed Anticoagulation Service. The Annals of Pharmacotherapy. 2000;34:567-572. 3. Ansell J et al. Pharmacology and Management of the Vitamin K Antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133:160S-198S.