Advertisement

Journal of General Internal Medicine

, Volume 22, Issue 7, pp 997–1002 | Cite as

Effectiveness of Warfarin among Patients with Cancer

  • Adam J. RoseEmail author
  • Jeff P. Sharman
  • Al Ozonoff
  • Lori E. Henault
  • Elaine M. Hylek
Original Article

Abstract

BACKGROUND

Among patients treated with warfarin for venous thromboembolism (VTE), cancer patients have more thrombotic and hemorrhagic events than patients without cancer. Is this also the case when cancer patients are anticoagulated for other indications?

OBJECTIVE

The objective of the study is to evaluate the effectiveness of warfarin, given for any indication, among patients with cancer in a community setting.

METHODS

We identified patients with cancer from a larger prospective cohort of 6,761 patients from 101 clinical sites in the United States, matched to controls without cancer. The proportion of time spent in the therapeutic range, international normalized ration (INR) variability, and the rate of thromboembolic and major hemorrhagic events were compared between the two groups.

RESULTS

Ninety-five patients undergoing treatment for cancer were matched to 283 patients without cancer. The cancer group spent less time in the target INR range (54 vs 66%, P < .001) and had more variable INR values (standard deviation around the mean INR value 1.30 vs 0.71, P < .001). There were more thrombotic events in the cancer group than in the control group (5 vs 0 events, P < .001). These analyses were repeated after excluding all of the patients anticoagulated for VTE; the results were unchanged.

CONCLUSIONS

Compared to matched controls, cancer patients receiving warfarin spend less time in the target INR range, have more variable INR values, and have more thrombotic events. These effects are not dependent on whether the patient is anticoagulated for VTE or another indication.

KEY WORDS

warfarin anticoagulation oncology cancer thrombosis 

Notes

Acknowledgements

This study was funded by Bristol-Myers Squibb, the makers of Coumadin® brand warfarin. Bristol-Myers Squibb had no role in the design and conduct of the study, or in the collection, analysis, and interpretation of the data, or in the preparation, review, and approval of the manuscript. Dr. Rose is supported by a grant from the Department of Veterans Affairs Office of Academic Affairs. The opinions expressed in this manuscript do not necessarily represent the views or policies of the Department of Veterans Affairs. Dr. Rose is also supported by a Physician Training Award (PTAPM-97-185-04) from the American Cancer Society.

Conflicts of Interest

Dr. Hylek has served as a consultant to and received research support from Bristol-Myers Squibb and AstraZeneca. None of the other authors report any potential conflicts of interest.

References

  1. 1.
    Lee AY, Levine MN. Venous thromboembolism and cancer: risks and outcomes. Circulation. 2003;107:I17–21.PubMedGoogle Scholar
  2. 2.
    Bona RD, Sivjee KY, Hickey AD, Wallace DM, Wajcs SB. The efficacy and safety of oral anticoagulation in patients with cancer. Thromb Haemost. 1995;74:1055–8.PubMedGoogle Scholar
  3. 3.
    Gitter MJ, Jaeger TM, Petterson TM, Gersh BJ, Silverstein MD. Bleeding and thromboembolism during anticoagulant therapy: a population-based study in Rochester, Minnesota. Mayo Clin Proc. 1995;70:725–33.PubMedGoogle Scholar
  4. 4.
    Landefeld CS, Goldman L. Major bleeding in outpatients treated with warfarin: incidence and prediction by factors known at the start of outpatient therapy. Am J Med. 1989;87:144–52.PubMedCrossRefGoogle Scholar
  5. 5.
    Palareti G, Legnani C, Lee A, et al. A comparison of the safety and efficacy of oral anticoagulation for the treatment of venous thromboembolic disease in patients with or without malignancy. Thromb Haemost. 2000;84:805–10.PubMedGoogle Scholar
  6. 6.
    Prandoni P, Lensing AW, Piccioli A, et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood. 2002;100:3484–8.PubMedGoogle Scholar
  7. 7.
    Wester JP, de Valk HW, Nieuwenhuis HK, et al. Risk factors for bleeding during treatment of acute venous thromboembolism. Thromb Haemost. 1996;76:682–8.PubMedGoogle Scholar
  8. 8.
    White RH, Beyth RJ, Zhou H, Romano PS. Major bleeding after hospitalization for deep-venous thrombosis. Am J Med. 1999;107:414–24.PubMedGoogle Scholar
  9. 9.
    Hylek EM, Heiman H, Skates SJ, Sheehan MA, Singer DE. Acetaminophen and other risk factors for excessive warfarin anticoagulation. JAMA. 1998;279:657–62.PubMedGoogle Scholar
  10. 10.
    Hylek EM, Regan S, Go AS, Hughes RA, Singer DE, Skates SJ. Clinical predictors of prolonged delay in return of the international normalized ratio to within the therapeutic range after excessive anticoagulation with warfarin. Ann Intern Med. 2001;135:393–400.PubMedGoogle Scholar
  11. 11.
    Lee AY, Levine MN, Baker RI, et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003;349:146–53.PubMedGoogle Scholar
  12. 12.
    Lee AY, Rickles FR, Julian JA, et al. Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism. J Clin Oncol. 2005;23:2123–9.PubMedGoogle Scholar
  13. 13.
    Meyer G, Marjanovic Z, Valcke J, et al. Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study. Arch Intern Med. 2002;162:1729–35.PubMedGoogle Scholar
  14. 14.
    Buller HR, Agnelli G, Hull RD, Hyers TM, Prins MH, Raskob GE. Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126:401S–4028S.PubMedGoogle Scholar
  15. 15.
    Practice Guidelines in Oncology-Venous Thromboembolic Disease: National Comprehensive Cancer Network; 2006.Google Scholar
  16. 16.
    Hylek EM. Trends in anticoagulation management across community-based practices in the United States: the Anticoagulation Consortium to Improve Outcomes Nationally (ACTION) study. J Thromb Thrombolysis. 2003;16:83–6.PubMedGoogle Scholar
  17. 17.
    Rosendaal FR, Cannegieter SC, van der Meer FJ, Briet E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost. 1993;69:236–9.PubMedGoogle Scholar
  18. 18.
    Fihn SD, Callahan CM, Martin DC, McDonell MB, Henikoff JG, White RH. The risk for and severity of bleeding complications in elderly patients treated with warfarin. The National Consortium of Anticoagulation Clinics. Ann Intern Med. 1996;124:970–9.PubMedGoogle Scholar
  19. 19.
    Kent DL, Vermes D, McDonell M, Henikoff J, Fihn SD. A model for planning optimal follow-up for outpatients on warfarin anticoagulation. Warfarin Optimal Outpatient Follow-up Study Group. Med Decis Making. 1992;12:132–41.PubMedGoogle Scholar
  20. 20.
    Elting LS, Escalante CP, Cooksley C, et al. Outcomes and cost of deep venous thrombosis among patients with cancer. Arch Intern Med. 2004;164:1653–61.PubMedGoogle Scholar
  21. 21.
    Hutten BA, Prins MH, Gent M, Ginsberg J, Tijssen JG, Buller HR. Incidence of recurrent thromboembolic and bleeding complications among patients with venous thromboembolism in relation to both malignancy and achieved international normalized ratio: a retrospective analysis. J Clin Oncol. 2000;18:3078–83.PubMedGoogle Scholar
  22. 22.
    Levine MN, Gent M, Hirsh J, et al. The thrombogenic effect of anticancer drug therapy in women with stage II breast cancer. N Engl J Med. 1988;318:404–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Shah HR, Ledbetter L, Diasio R, Saif MW. A retrospective study of coagulation abnormalities in patients receiving concomitant capecitabine and warfarin. Clin Colorectal Cancer. 2006;5:354–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Zangari M, Anaissie E, Barlogie B, et al. Increased risk of deep-vein thrombosis in patients with multiple myeloma receiving thalidomide and chemotherapy. Blood. 2001;98:1614–5.PubMedGoogle Scholar
  25. 25.
    van Walraven C, Jennings A, Oake N, Fergusson D, Forster AJ. Effect of study setting on anticoagulation control: a systematic review and metaregression. Chest. 2006;129:1155–66.PubMedGoogle Scholar
  26. 26.
    Sconce E, Avery P, Wynne H, Kamali F. Vitamin K supplementation can improve stability of anticoagulation for patients with unexplained variability in response to warfarin. Blood. 2007;109:2419–23.PubMedGoogle Scholar
  27. 27.
    Sorano GG, Biondi G, Conti M, Mameli G, Licheri D, Marongiu F. Controlled vitamin K content diet for improving the management of poorly controlled anticoagulated patients: a clinical practice proposal. Haemostasis. 1993;23:77–82.PubMedGoogle Scholar

Copyright information

© Society of General Internal Medicine 2007

Authors and Affiliations

  • Adam J. Rose
    • 1
    • 2
    • 5
    Email author
  • Jeff P. Sharman
    • 3
  • Al Ozonoff
    • 4
  • Lori E. Henault
    • 1
  • Elaine M. Hylek
    • 1
  1. 1.Department of Medicine, Research Unit-Section of General Internal MedicineBoston University School of Medicine, Boston Medical CenterBostonUSA
  2. 2.Center for Health Quality, Outcomes and Economic ResearchBedford VA Medical CenterBedfordUSA
  3. 3.Department of Medicine, Division of OncologyStanford UniversityStanfordUSA
  4. 4.Department of BiostatisticsBoston University School of Public HealthBostonUSA
  5. 5.Section of General Internal MedicineBostonUSA

Personalised recommendations