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Journal of Thrombosis and Thrombolysis

, Volume 40, Issue 1, pp 17–25 | Cite as

The impact of frequency of patient self-testing of prothrombin time on time in target range within VA Cooperative Study #481: The Home INR Study (THINRS), a randomized, controlled trial

  • David B. MatcharEmail author
  • Sean R. Love
  • Alan K. Jacobson
  • Robert Edson
  • Lauren Uyeda
  • Ciaran S. Phibbs
  • Rowena J. Dolor
Article

Abstract

Anticoagulation (AC) is effective in reducing thromboembolic events for individuals with atrial fibrillation (AF) or mechanical heart valve (MHV), but maintaining patients in target range for international normalized ratio (INR) can be difficult. Evidence suggests increasing INR testing frequency can improve time in target range (TTR), but this can be impractical with in-clinic testing. The objective of this study was to test the hypothesis that more frequent patient-self testing (PST) via home monitoring increases TTR. This planned substudy was conducted as part of The Home INR Study, a randomized controlled trial of in-clinic INR testing every 4 weeks versus PST at three different intervals. The setting for this study was 6 VA centers across the United States. 1,029 candidates with AF or MHV were trained and tested for competency using ProTime INR meters; 787 patients were deemed competent and, after second consent, randomized across four arms: high quality AC management (HQACM) in a dedicated clinic, with venous INR testing once every 4 weeks; and telephone monitored PST once every 4 weeks; weekly; and twice weekly. The primary endpoint was TTR at 1-year follow-up. The secondary endpoints were: major bleed, stroke and death, and quality of life. Results showed that TTR increased as testing frequency increased (59.9 ± 16.7 %, 63.3 ± 14.3 %, and 66.8 ± 13.2 % [mean ± SD] for the groups that underwent PST every 4 weeks, weekly and twice weekly, respectively). The proportion of poorly managed patients (i.e., TTR <50 %) was significantly lower for groups that underwent PST versus HQACM, and the proportion decreased as testing frequency increased. Patients and their care providers were unblinded given the nature of PST and HQACM. In conclusion, more frequent PST improved TTR and reduced the proportion of poorly managed patients.

Keywords

Anticoagulation Warfarin Patient self-testing Time in target range Prothrombin time Randomized controlled trial 

Notes

Acknowledgments

The authors want to recognize the Site Investigators at the enrolling sites that conducted the test frequency substudy: Baltimore—Carol Rudo, PharmD. Dallas—Peter Yunyongying, MD, Wen Lai, MD (past). Durham—Rowena Dolor, MD. Hines—Abdul Choudhury, MD. Loma Linda—Ronald Fernando, MD. West Haven (closed early)—Farid Jadbabaie, MD (past), Brian Abbott, MD (past). The authors also wish to acknowledge the following for the support and guidance they provided without which the THINRS study would not have been possible: Timothy J. O’Leary, MD, PhD; Acting Chief Research and Development Officer, Office of Research and Development; Grant D. Huang, MPH, PhD, MPH; Acting Director, Cooperative Studies Program; Ying Lu, PhD; Director, Palo Alto Cooperative Studies Program Coordinating Center; Mei-Chiung Shih, PhD; Acting Associate Center Director for Science and Technology and Senior Biostatistician, Palo Alto Cooperative Studies Program Coordinating Center. A complete list of the THINRS Executive Committee and Site Investigators is available in the supplementary materials for the main THINRS results paper, published in the New England Journal of Medicine, 10/21/2010. This material is based on research supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences Research and Development Service, Cooperative Studies Program, 810 Vermont Avenue, NW, Washington, DC 20420. Support for Dr. Matchar and Mr. Love was provided by a Singapore Translational Research Investigator Award from the Singapore National Medical Research Council [NMRC/STaR/0005/2009 to DB Matchar]. The views expressed are solely those of the authors and do not represent those of the Department of Veterans Affairs. Funded by the Department of Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT00032591. The preliminary results of this paper were presented at the final THINRS investigators’ meeting and as an oral presentation at the American Heart Association 2012 Scientific Sessions meeting (abstract #10606: “More Frequent Self-Testing of Prothrombin Time Results in Improved Time in Target Range”).

Conflict of interest

For potential conflicts of interest: Dr. Matchar reports receiving consulting fees from Boerhringer-Ingelheim. Dr. Jacobson reports being an advisory board member for the Anticoagulation Forum and the Loma Linda Veterans Association for Research, receiving consulting fees from Biosite, Boehringer Ingelheim, Daiichi Sankyo, Farallon Medical, Hemo-Sense, Inverness Medical, Pfizer Medical, Quality Assured Services, Roche Diagnostics, Sanofi-Aventis, Tapestry Medical and the BMS/Pfizer Alliance, receiving grants or grants pending from Biosite, Boehringer Ingelheim, Farallon Medical, HemoSense, Inverness Medical, and Sanofi-Aventis, receiving honoraria from GlaxoSmith-Kline and Tapestry Medical, and receiving fees for the development of educational presentations and for serving on speakers’ bureaus from Boehringer Ingelheim and GlaxoSmithKline and the BMS/Pfizer Alliance, and receiving travel support from Biosite, Boehringer Ingelheim, Daiichi Sankyo, GlaxoSmithKline, and Sanofi-Aventis. None of the other authors have any potential conflict of interest relevant to this manuscript to report.

Supplementary material

11239_2014_1128_MOESM1_ESM.pdf (790 kb)
Supplementary material 1 (PDF 790 kb)

References

  1. 1.
    Fitzmaurice DA, Gardiner C, Kitchen S et al (2005) An evidence-based review and guidelines for patient self-testing and management of oral anticoagulation. Br J Haematol 131:156–165CrossRefPubMedGoogle Scholar
  2. 2.
    Szucs TD, Bramkamp M (2006) Pharmacoeconomics of anticoagulation therapy for stroke prevention in atrial fibrillation: a review. Thromb and Haemost. 4:1180–1185CrossRefGoogle Scholar
  3. 3.
    Christensen TD, Johnsen SP, Hjortdal VE et al (2007) Self-management of oral anticoagulant therapy: a systematic review and meta-analysis. Int J Cardiol 118:54–61CrossRefPubMedGoogle Scholar
  4. 4.
    Garcia-Alamino JM, Ward AM, Alonso-Coello P et al (2010) Self-monitoring and self-management of oral anticoagulation. Cochrane Database Syst Rev 4:CD003839PubMedGoogle Scholar
  5. 5.
    Garcia D, Ageno W, Bussey H et al (2009) Prevention and treatment of bleeding complications in patients receiving vitamin K antagonists, part 1: prevention. Am J Hematol 84(9):579–583CrossRefPubMedGoogle Scholar
  6. 6.
    Eikelboom JW, Connolly SJ, Brueckmann M et al (2013) Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med 369:1206–1214CrossRefPubMedGoogle Scholar
  7. 7.
    Bauer KA (2012) Pros and cons of new oral anticoagulants. Hematol Am Soc Hematol Educ Program 2013:464–470CrossRefGoogle Scholar
  8. 8.
    Samsa GP, Matchar DB (2000) Relationship between test frequency and outcomes of anticoagulation: a literature review and commentary with implications for the design of randomized trials of patient self-management. J Thromb Thrombolysis 9(3):283–292CrossRefPubMedGoogle Scholar
  9. 9.
    Oden A, Fahlen M (2002) Oral anticoagulation and risk of death: a medical record linkage study. BMJ 325:1073–1075CrossRefPubMedCentralPubMedGoogle Scholar
  10. 10.
    White HD, Gruber M, Feyzi J et al (2007) Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control. Arch Intern Med 167:239–245CrossRefPubMedGoogle Scholar
  11. 11.
    Connolly SJ, Pogue J, Eikelboom J et al (2008) Benefit of oral anticoagulant over antiplatelet therapy in atrial fibrillation depends on the quality of international normalized ratio control achieved by centers and countries as measured by time in therapeutic range. Circulation 118(20):2029–2037CrossRefPubMedGoogle Scholar
  12. 12.
    Heneghan C, Ward A, Perera R et al (2012) Self-monitoring of oral anticoagulation: systematic review and meta-analysis of individual patient data. Lancet 379:322–334CrossRefPubMedGoogle Scholar
  13. 13.
    Matchar DB, Jacobson A, Dolor R et al (2010) Effect of home testing of international normalized ratio on clinical events. New Engl J Med 363:1608–1620CrossRefPubMedGoogle Scholar
  14. 14.
    Heneghan C, Alonso-Coello P, Garcia-Alamino JM et al (2006) Self-monitoring of oral anticoagulation: a systematic review and meta-analysis. Lancet 367:404–411CrossRefPubMedGoogle Scholar
  15. 15.
    Holbrook A, Schulman S, Witt DM et al (2012) 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 141:e152S–e184SCrossRefPubMedCentralPubMedGoogle Scholar
  16. 16.
    Matchar DB, Jacobson AK, Edson RG et al (2005) The impact of patient self-testing of prothrombin time for managing anticoagulation: rationale and design of VA Cooperative Study #481-The Home INR Study (THINRS). J Thromb Thrombolysis 19:163–172CrossRefPubMedGoogle Scholar
  17. 17.
    Matchar DB, Samsa GP, Cohen SJ et al (2000) Community impact of anticoagulation services: rationale and design of Managing Anticoagulation Services Trial (MAST). J Thromb Thrombolysis 9(Suppl. 1):S7–S11CrossRefPubMedGoogle Scholar
  18. 18.
    Matchar DB, Samsa GP, Cohen SJ et al (2002) Improving the quality of anticoagulation of patients with atrial fibrillation in managed care organizations: results of the Managing Anticoagulation Services Trial. Am J Med 113(1):42–51CrossRefPubMedGoogle Scholar
  19. 19.
    Rosendaal FR, Cannegieter SC, van der Meer F et al (1993) A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost 69:236–239PubMedGoogle Scholar
  20. 20.
    Horsman J, Furlong W, Feeny D et al (2003) The Health Utilities Index (HUI): concepts, measurement properties and applications. Health Qual Life Outcomes. 1:54CrossRefPubMedCentralPubMedGoogle Scholar
  21. 21.
    Samsa GP, Matchar DB, Dolor RJ et al (2004) A new instrument for measuring anticoagulation-related quality of life: development and preliminary validation. Health Qual Life Outcomes 2:22CrossRefPubMedCentralPubMedGoogle Scholar
  22. 22.
    Sawicki PT (1999) A structured teaching and self-management program for patients receiving oral anticoagulation: a randomized controlled trial. JAMA 271:145–150CrossRefGoogle Scholar
  23. 23.
    White RH, MuCurdy SA, von Marensdorff H et al (1989) Home prothrombin time monitoring after the initiation of warfarin therapy: a randomized, prospective study. Ann Intern Med 111:730–737CrossRefPubMedGoogle Scholar
  24. 24.
    Horstkotte D, Piper C, Wiemer M (1998) Optimal frequency of patient monitoring and intensity of oral anticoagulation therapy in valvular heart disease. J Thromb Thrombolysis 1(3):19–24CrossRefGoogle Scholar
  25. 25.
    Koertke H, Minami K, Breymann T, et al. INR self-management following mechanical heart valve replacement: are education level and therapeutic compliance connected? Presents to the Anticoagulation Forum, Vancouver BC, May 1999, and in submission to J Thromb ThrombolysGoogle Scholar
  26. 26.
    Hasenkam JM, Kimose HH, Knudsen L et al (1997) Self-management of oral anticoagulant therapy after heart valve replacement. Eur J Cardiothrac Surg 11:935–942CrossRefGoogle Scholar
  27. 27.
    Ansell JE, Patel N, Ostrovsky D et al (1995) Long-term patient self-management of oral anticoagulation. Arch Intern Med 155:2185–2189CrossRefPubMedGoogle Scholar
  28. 28.
    Bernardo A (1996) Experience with patient self-management of oral anticoagulation. J Thromb Thrombolysis 2:321–325CrossRefGoogle Scholar
  29. 29.
    Beyth RJ, Landefeld CS (1997) Prevention of major bleeding in older patients treated with warfarin: results of a randomized trial (abstract). J Gen Intern Med 12:66Google Scholar
  30. 30.
    Ryan F, Byrne S, O’Shea S (2009) Randomized controlled trial of supervised patient self-testing of warfarin therapy using an internet-based expert system. Thromb Haemost 7(8):1284–1290CrossRefGoogle Scholar
  31. 31.
    DeSantis G, Hogan-Schlientz J, Liska G et al (2014) STABLE results: warfarin home monitoring achieves excellent INR control. Am J Manag Care 20(3):202–209PubMedGoogle Scholar
  32. 32.
    Rose AJ, Ozonoff A, Berlowitz DR et al (2011) Reexamining the recommended follow-up interval after obtaining an in-range international normalized ratio value: results from the Veterans Affairs Study to Improve Anticoagulation. Chest 140(2):359–365CrossRefPubMedGoogle Scholar
  33. 33.
    Rose AJ, Hylek EM, Berlowitz DR et al (2011) Prompt repeat testing after out-of-range INR values: a quality indicator for anticoagulation care. Circ Cardiovasc Qual Outcomes 4(3):276–282CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • David B. Matchar
    • 1
    • 2
    • 3
    Email author
  • Sean R. Love
    • 3
    • 9
  • Alan K. Jacobson
    • 4
    • 5
  • Robert Edson
    • 6
  • Lauren Uyeda
    • 6
  • Ciaran S. Phibbs
    • 7
    • 8
    • 10
  • Rowena J. Dolor
    • 2
  1. 1.Durham VA Medical CenterDurhamUSA
  2. 2.Division of General Internal Medicine, Department of Medicine and Center for Clinical Health Policy ResearchDuke University Medical CenterDurhamUSA
  3. 3.Health Services and Systems Research ProgramDuke-National University of Singapore Graduate Medical SchoolSingaporeSingapore
  4. 4.Research and Development Service (151)Jerry L. Pettis VA Medical CenterLoma LindaUSA
  5. 5.Department of Internal Medicine, Loma Linda Healthcare SystemLoma Linda UniversityLoma LindaUSA
  6. 6.Cooperative Studies Program Coordinating Center (151K)VA Palo Alto Health Care SystemMountain ViewUSA
  7. 7.Health Economics Resource CenterVA Palo Alto Health Care SystemMountain ViewUSA
  8. 8.Department of Pediatrics and Center for Primary Care and Outcomes ResearchStanford University School of MedicineStanfordUSA
  9. 9.Warren Alpert Medical School of Brown UniversityProvidenceUSA
  10. 10.Health Economic Resource Center (152)VA Palo Alto Health Care SystemMenlo ParkUSA

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