STABLE Results: Warfarin Home Monitoring Achieves Excellent INR Control
Published Online: March 18, 2014
Grace DeSantis, PhD; Jackie Hogan-Schlientz, RN, BSN; Gary Liska, BS; Shari Kipp, BS; Ramarion Sallee; Mark Wurster, MD; Kenneth Kupfer, PhD; and Jack Ansell, MD
Approximately 4 million people in the United States receive oral anticoagulation therapy with the vitamin K antagonist (VKA) warfarin,1 and require frequent international normalized ratio (INR) monitoring to maintain time in the therapeutic range.2 There are several models of warfarin management designed to maintain the patients’ INR within these desired parameters.3 These include usual care (UC), which means an individual physician manages multiple patients without formal systematic monitoring policies or procedures to focus on dose management; anticoagulation clinic care (AC), which means dose management is overseen by a healthcare provider (usually a nurse or pharmacist) under physician leadership with systematic policies and procedures in place; and patient self-testing (PST) or patient self-management (PSM), which means patients perform their own INR test at home with a portable point-of-care (POC) instrument and receive dose instructions from a healthcare provider (PST) or manage their own dose (PSM). Under UC or AC, test frequency may be irregular, and is often determined by a patient’s ability to travel to a lab or clinic to obtain the INR test result, rather than INR testing frequency depending on the pharmacology and metabolism of warfarin.4
Clinical evidence has demonstrated that more frequent testing improves warfarin safety and reduces risks for thromboembolic and major bleeding events.5 The advent of POC INR devices and home monitoring has facilitated more frequent testing, provided greater consistency in testing reagents and instrumentation, and increased patient empowerment. Since 2004, the American College of Chest Physicians (ACCP) has recommended PST as a means of warfarin dose management, and according to the 2012 ACCP guidelines,6 “for patients who are motivated and can demonstrate competency, PSM is recommended over UC (Grade 2B).” This recommendation is based on the results of numerous clinical trials of PST/PSM compared with both UC and AC care. Recently, Heneghan, et al, and Bloomfield, et al, have performed independent meta-analyses of a number of clinical trials documenting the benefit of PST or PSM.7,8 Depending on how the analyses are done, each investigative group has shown greater efficacy of PST/PSM with a reduction in thromboembolism risk and/or major bleeding risk. However, there is little evidence to date, outside of randomized clinical trials (RCTs), to assess outcomes for patients who perform PST or PSM.9 We evaluated the quality of PST anticoagulation management as reflected by time in therapeutic INR range (TTR) in a large cross-section of real world (non-study) patients from the United States enrolled in a home monitoring program and sought to determine whether INR testing frequency had an impact on TTR.
Alere Inc, an independent diagnostic testing facility (IDTF), has a database that includes anticoagulation patient data starting in 1993 and PST data starting in 1998. It includes data from over 68,000 PSTs (>3.1 million INR results) who were referred from a variety of settings ranging from office practices (cardiology, internal medicine, family practice, hematology, oncology) to large organized clinics, and enrolled in a comprehensive PST support service.
Prescribing physicians generally select PST candidates based on whether the patient is able, willing, and reliable enough to measure their INR on a POC instrument at home.10,11 Then, physicians complete prescription forms for patient submission to the IDTF. Patients are then individually trained. Standardized protocols developed by Alere, based on human factors, support training retention and positive testing behaviors.12 All patients in this analysis were trained by experienced healthcare professionals, and immediate follow-up was provided, as needed. Following physician instructions for data and adherence management, Alere helped each patient to initiate PST, become adherent to testing, and remain adherent to therapy. Clinicians were notified of all INR results, and if patients were nonadherent.
This Self-Testing Analysis Based on Long-term Evaluation (STABLE) is a retrospective cohort analysis of data from real-world PST assessing 2 groups: variable and weekly testing cohorts. A query was developed to collect data on all patients who were trained on or after January 1, 2008, and who completed at least 6 months of PST before June 30, 2011 (Figure 1). This window of observation was selected to capture a large cross-section of patients who qualified for PST before and after the Centers for Medicare & Medicaid Services (CMS) expanded Medicare coverage to more indications.
To eliminate potential bias as a result of individual differences in learning aptitude and time to mastery, we excluded the first 3 months of PST results after the training date, considering this to be the initiation period,13 thus offering at least 3 months of PST data to evaluate. In addition, we excluded patients with results greater than 56 days between tests (DBT) as per the Rosendaal methodology,14 patients with INR target range widths other than 1.0 (to comply with ACCP guideline ranges that are all 1.0 INR in width [eg, 2.0-3.0, 2.5-3.5]) and patients younger than 18 years (to maintain focus of this analysis on adults).
The PST prescription form requires the physician to direct the test frequency (TF), with selections that accommodate ACCP Guidelines for weekly, or options for 1 to 4 times per month (variable). Since not all patients adhere to their prescribed TF, the actual TF for each patient was established and reported. The definition adopted for this study was based on the THINRS trial that defined weekly testing as 5 to 9 days between tests (7 + 2 DBT).13 The definition of monthly testing varies in the literature. THINRS defined monthly clinic testing as 21 to 49 DBT (35 + 14 DBT), but patients showed a very low adherence rate of only 52% in that study. STABLE adopted a tighter range of 24 to 38 DBT (31 + 7 DBT).
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