November/December 2014

Home INR Monitoring Improves Warfarin Therapy
By Jack Ansell, MD, MACP
Today's Geriatric Medicine
Vol. 7 No. 6 P. 28

Download table here; download figure here.

Warfarin has been the principal oral anticoagulant in use since the 1950s in the United States for a variety of blood clotting disorders. Warfarin therapy, however, has many drawbacks, principally among them the complexity and labor-intensiveness of managing therapy and the high risk of adverse events, often due to poor dose management.1 Anticoagulation clinics, focusing predominantly on managing warfarin dosing, are commonplace, and generally result in better outcomes than individual physicians managing small groups of patients (denoted as usual care to differentiate it from anticoagulation clinic care).2

In the late 1980s, a new technology for monitoring the prothrombin time or international normalized ratio (INR) was introduced, employing small portable instruments that made it possible for patients to perform an INR from a finger stick sample of blood, much as blood sugar is measured in patients with diabetes.3 These point-of-care instruments are now widely used in physician offices. Given their size, portability, and ease of use, these devices also allow patients to measure their own INR at home, known as patient self-testing, and with proper education, manage their own anticoagulation dosing (patient self-management). Exhaustive correlation studies have been done to assess the accuracy and precision of point-of-care instruments with INRs drawn from an arm vein.4 When tested under controlled conditions, point-of-care devices have consistently confirmed the adequacy of this methodology for the monitoring of oral anticoagulation.

Home INR Monitoring
There was great hope that developing home monitoring models of warfarin management would vastly improve the outcomes of therapy, and this hope has been realized. A number of clinical trials demonstrated improved quality of care as reflected by patients being in therapeutic INR range a greater percentage of time, as well as a reduction in major complications such as major bleeding or thrombosis when compared with other models of care.5,6 Heneghan et al performed an individual meta-analysis of more than 6,000 patients from 11 clinical trials and showed a reduction in thromboembolic events in the self-monitoring group (HR 0.51; 95%CI 0.31-0.85) with no significant difference in major bleeding events or death compared with the control arms.5

Analysis of major outcomes in the very elderly (>85 years) showed no significant adverse effects of the intervention for all outcomes. Bloomfield et al also performed a meta-analysis of 22 trials of home monitoring.6 Like Heneghan, they also found a significant reduction in thromboembolism (HR 0.58; 95%CI 0.45-0.75) and no increased risk for major bleeding. Furthermore, they also found a significant reduction in mortality (HR 0.74; 95%CI 0.63-0.87).

In light of these many studies, the hoped-for widespread application of such testing in the United States did not develop until recently. Currently, more than 100,000 individuals are monitoring their own therapy at home, but this represents only a small fraction of the potentially eligible patients. Matchar et al, in the largest randomized trial to date of patient self-testing, showed that at least 80% of patients can successfully perform home monitoring.7 In the United States, an estimated 3 million individuals are on warfarin; thus, only about 3% of patients are currently performing home monitoring. 

Since the benefits of home INR monitoring have been demonstrated in clinical trials that may not reflect the outcomes seen in everyday care, a recent study assessed how well patients perform in the real world. DeSantis et al recently published a retrospective analysis of the quality of INR home monitoring in a large cohort of patients extracted from the database of a home health care company that supports home INR monitoring, as measured by the time in therapeutic INR range.8 This retrospective analysis queried the database of an independent diagnostic testing facility over a 2 1/2- year period (January 2008 through June 2011) and patient time in therapeutic range (TTR) was analyzed based on frequency of testing, age, gender, indication for therapy, duration of therapy, and critical value occurrence.

Based on a population of 29,457 patients with multiple indications for warfarin therapy and with 80% >65 years of age, investigators found that the mean TTR for the entire group was 69.7%, with weekly testers achieving a TTR of 74% vs 68.9% for variable testers (testing every two to four weeks) (p <0.0001). In all categories analyzed (age, indication for anticoagulation, and referral site volume), weekly testers performed significantly better than variable testers. Older individuals (>65 years) had a higher TTR than younger patients (see Table 1). Of note, 2,267 patients were between the ages of 85 and 105. Weekly testers experienced significantly fewer critical values (INR <1.5 or >5.0) than did variable testers.

This retrospective observational analysis is the largest nonclinical trial study published to date, and it is the first to show that patients perform well with self-testing as an adjunct to warfarin therapy outside of clinical trial settings with an overall high mean TTR (69.7%), exceeding the TTR of published randomized controlled trials9 and meta-analyses5,6 as well as warfarin control comparators in studies of new target-specific oral anticoagulants (see figure).10-12 Self-testing on a weekly basis provided the best TTR of 74%, and weekly testers were less likely to have significantly out-of-range values. Because the elderly are often considered to be at higher risk of bleeding, it is important to note that patients aged 75 and older performed well, with a mean TTR above 73% for weekly testers.

Viable Solution
Home monitoring provides four major benefits, including convenience for the patient, the ability to monitor an INR frequently, consistency of testing reagents and instrument, and patient empowerment by involvement in their own care. It is particularly beneficial for those individuals who travel and monitor their INR while away from home.

To be eligible for home monitoring, in general, patients must be willing, able, and compliant with monitoring. Thus, a patient should show good compliance with previous anticoagulation management, have the manual and visual dexterity to perform self-testing or have a care provider at home who can perform the test, and have a physician who supports home monitoring.

Several factors have served as barriers to implementing home monitoring in the United States. The lack of physician education on the benefits of this technology has created a barrier. Questions about the safety and accuracy, as well as physician liability, have also become a barrier. Finally, the long delay in Medicare approval for reimbursement for the cost of the instrument, for implementation of home monitoring, and for physician management has been a significant barrier.

Recently, Medicare expanded its reimbursement policy to include patients who are anticoagulated for mechanical heart valves, atrial fibrillation, and venous thrombosis. Home monitoring is now largely implemented through companies called independent diagnostic testing facilities. These businesses provide instruments, train patients, and often keep track of the INRs for physicians who prescribe home monitoring. Reimbursement is provided on a per-test basis after the initial reimbursement for training and implementation.

The problem of reimbursement for home monitoring is not unique to this country; it is a problem throughout the world. As a result, patient advocacy groups have sprung up in numerous countries to lobby their respective health care systems to cover such services, and many of these groups have been successful (see http://ismaap.org to learn more about these international advocacy groups). In the United States, no specific groups currently exist, but the National Blood Clot Alliance, a patient advocacy group for individuals with blood-clotting problems, promotes this model of anticoagulant care. Moreover, INR home monitoring is recommended by the most recent guidelines of the American College of Chest Physicians.13

Conclusion
For now, individual physicians manage most anticoagulation therapy in the United States. While anticoagulation clinics managing large panels of patients continue to grow at a rapid rate, the rate of patient home monitoring growth is also expanding. This mode of therapy, proven both safe and effective, is as good as anticoagulation clinic care, if not better. Age is not a barrier to use, and older individuals perform as well as younger patients.

Home INR monitoring provides convenience, facilitates more frequent monitoring, and has the potential to reduce adverse events in patients on warfarin. Although we are seeing dramatic changes in the landscape of oral anticoagulant therapy with the introduction of new target-specific oral anticoagulants, warfarin therapy remains the predominant oral anticoagulant and will continue to be an important antithrombotic therapy for years to come. The outcomes of warfarin therapy, when well managed, are hard to beat, and the best outcomes are achieved in patients managed by specialized anticoagulation clinics or by home INR monitoring.

— Jack Ansell, MD, MACP, is past chair of medicine at Lenox Hill Hospital in New York City and a professor of medicine at Hofstra North Shore-LIJ School of Medicine. A clinical investigator with a principal focus on the clinical problems of thrombosis, antithrombotic therapy, and the application of new modes of delivering and monitoring anticoagulants, he has helped to identify and provide an understanding of the problems related to warfarin therapy management and was one of the first investigators to identify and show that patients can manage their own therapy through home monitoring.

References
1. Ansell JE. Optimizing the efficacy and safety of oral anticoagulant therapy: high quality dose management, anticoagulation clinics, and patient self-management. Semin Vas Med. 2003;3 (3):261-269.

2. Ansell JE. Anticoagulation management clinics for the out-patient control of oral anticoagulants. Curr Opin Pulm Med. 1998;4(4):215-219.

3. Ansell JE, Hughes R. Evolving models of warfarin management: anticoagulation clinics, patient self-monitoring, and patient self-management. Am Heart J. 1996;132(5):1095-1100.

4. Karon BS, McBane RD, Chaudhry R, Beyer LK, Santrach PK. Accuracy of capillary whole blood international normalized ratio on the CoaguChek S, CoaguChek XS, and i-STAT 1 point-of-care analyzers. Am J Clin Pathol. 2008;130(1):88-92.

5. Heneghan C, Ward A, Perera R, et al. Self-monitoring of oral anticoagulation: systematic review and meta-analysis of individual patient data. Lancet. 2012;379(9813):322-334.

6. Bloomfield HE, Krause A, Greer N, et al. Meta-analysis: effect of patient self-testing and self-management of long-term anticoagulation on major clinical outcomes. Ann Intern Med. 2011;154(7):472-482.

7. Matchar DB, Jacobson A, Dolor R, et al. Effect of home testing of international normalized ratio on clinical events. N Eng J Med. 2010;363(17):1608-1620.

8. DeSantis G, Hogan-Schlientz J, Liska G, et al. STABLE results: warfarin home monitoring achieves excellent INR control in non-study setting. Am J Manag Care. 2014;20(3):202-209.

9. Wan Y, Heneghan C, Perera R, et al. Anticoagulation control and prediction of adverse events in patients with atrial fibrillation: a systematic review. Circ Cardiovasc Qual Outcomes. 2008;1(2):84-91.

10. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-1151.

11. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883-891.

12. Granger CB, Alexander JH, McMurray JJV, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981-992.

13. Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis. 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e152S-e184S.