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The Effect of Cognitive Impairment in the Elderly on the Initial and Long-Term Stability of Warfarin Therapy

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Abstract

Background: Despite guidelines that clearly outline the benefits of warfarin, it remains underutilized. Various reasons are associated with the underuse of warfarin; however, cognitive impairment (CI) has been identified as one of the most common causes for not electing to anticoagulate elderly patients with atrial fibrillation. Nevertheless, there are limited data on warfarin use in such patients; therefore, we investigated anticoagulation stability in patients with and without CI.

Objectives: Our objectives were to (i) examine if mild to moderate CI delayed the time required to achieve initial therapeutic anticoagulation; (ii) determine if mild to moderate CI was associated with long-term anticoagulation instability; and (iii) assess if initial anticoagulation problems predicted long-term anticoagulation instability.

Methods: A retrospective study in a pharmacist-managed anticoagulation clinic was conducted in community-dwelling patients ≥60 years of age on warfarin therapy with a target international normalized ratio (INR) of 2.0–3.0. Our study included 57 patients; 20 were initiated on warfarin and 54 were analysed for long-term anticoagulation stability. Age, ethnicity, gender, warfarin indication, co-morbidities and caregiver involvement were recorded. We defined CI as having a Mini-Mental State Examination (MMSE) score of ≤26. To evaluate initial anticoagulation stability between groups, we analysed (i) number of clinic visits and days to achieve therapeutic INR; and (ii) minor and major adverse events upon initiation of warfarin. To evaluate long-term anticoagulation stability, we analysed (i) time in therapeutic range (TTR); (ii) the percentage of clinic visits with a reported dose mishap and the frequency of out-of-range INRs resulting from dose mishaps; and (iii) parameters associated with the intensity of clinic management: weekly warfarin dose changes, transient dose adjustments, any dose manipulation and the length of time between clinic visits.

Results: We found no difference in the number (mean±SD) of visits (control = 5.8±4.3, CI = 4.6±2.4; p = 0.44) or days (control = 51.6±45.7, CI = 35.8±30.5; p = 0.36) required to achieve initial therapeutic anticoagulation. No adverse effects were reported in either group. In terms of long-term stability, TTR (mean±SD) was similar for both groups (control = 65±20% vs CI = 61±16%; p = 0.36). Although the proportion of dose mishaps did not differ (control = 74 in 705 visits, CI = 86 in 691 visits; p = 0.18), dose mishaps resulted in a greater frequency of out-of-range INRs for patients with CI (p = 0.01). There were no differences in clinic management measures between groups (p = not statistically significant [NS] for all). Finally, we found no correlation between the time to reach initial anticoagulation stability and long-term stability for either group (p = NS for all).

Conclusion: We found mild to moderate CI neither delayed the time required to achieve therapeutic anticoagulation, nor decreased anticoagulation stability versus patients with normal cognitive function. Additionally, CI did not require more intensive clinic management. CI should not necessarily be a barrier to the use of warfarin anticoagulation in elderly patients attending an anticoagulation clinic.

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References

  1. Mant J, Hobbs FD, Fletcher K, et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007 Aug 11; 370(9586): 493–503

    Article  PubMed  CAS  Google Scholar 

  2. Go AS, Hylek EM, Borowsky LH, et al. Warfarin use among ambulatory patients with nonvalvular atrial fibrillation: the anticoagulation and risk factors in atrial fibrillation (ATRIA) study. Ann Intern Med 1999 Dec 21; 131(12): 927–34

    Article  PubMed  CAS  Google Scholar 

  3. Ingelgard A, Hollowell J, Reddy P, et al. What are the barriers to warfarin use in atrial fibrillation? Development of a questionnaire. J Thromb Thrombolysis 2006 Jun; 21(3): 257–65

    Article  PubMed  Google Scholar 

  4. Dharmarajan TS, Varma S, Akkaladevi S, et al. To anti-coagulate or not to anticoagulate? A common dilemma for the provider: physicians’ opinion poll based on a case study of an older long-term care facility resident with dementia and atrial fibrillation. J Am Med Dir Assoc 2006 Jan; 7(1): 23–8

    Article  PubMed  CAS  Google Scholar 

  5. Brodsky MA, Chun JG, Podrid PJ, et al. Regional attitudes of generalists, specialists, and subspecialists about management of atrial fibrillation. Arch Intern Med 1996 Dec 9–23; 156(22): 2553–62

    Article  PubMed  CAS  Google Scholar 

  6. Chang HJ, Bell JR, Deroo DB, et al. Physician variation in anticoagulating patients with atrial fibrillation. Dartmouth Primary Care COOP Project. Arch Intern Med 1990 Jan; 150(1): 83–6

    Article  PubMed  CAS  Google Scholar 

  7. Kutner M, Nixon G, Silverstone F. Physicians’ attitudes toward oral anticoagulants and antiplatelet agents for stroke prevention in elderly patients with atrial fibrillation. Arch Intern Med 1991 Oct; 151(10): 1950–3

    Article  PubMed  CAS  Google Scholar 

  8. Lip GY, Zarifis J, Watson RD, et al. Physician variation in the management of patients with atrial fibrillation. Heart 1996 Feb; 75(2): 200–5

    Article  PubMed  CAS  Google Scholar 

  9. McCrory DC, Matchar DB, Samsa G, et al. Physician attitudes about anticoagulation for nonvalvular atrial fibrillation in the elderly. Arch Intern Med 1995 Feb 13; 155(3): 277–81

    Article  PubMed  CAS  Google Scholar 

  10. Monette J, Gurwitz JH, Rochon PA, et al. Physician attitudes concerning warfarin for stroke prevention in atrial fibrillation: results of a survey of long-term care practitioners. J Am Geriatr Soc 1997 Sep; 45(9): 1060–5

    PubMed  CAS  Google Scholar 

  11. van Deelen BA, van den Bemt PM, Egberts TC, et al. Cognitive impairment as determinant for sub-optimal control of oral anticoagulation treatment in elderly patients with atrial fibrillation. Drugs Aging 2005; 22(4): 353–60

    Article  PubMed  Google Scholar 

  12. Rose AJ, Hylek EM, Ozonoff A, et al. Patient characteristics associated with oral anticoagulation control: results of the Veterans AffaiRs Study to Improve Anticoagulation (VARIA). J Thromb Haemost 2010 Oct; 8(10): 2182–91

    Article  PubMed  CAS  Google Scholar 

  13. Lackie CL, Garbarino KA, Pruetz JA. Warfarin therapy for atrial fibrillation in the elderly. Ann Pharmacother 2002 Feb; 36(2): 200–4

    Article  PubMed  CAS  Google Scholar 

  14. 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 Aug; 87(2): 144–52

    Article  PubMed  CAS  Google Scholar 

  15. Kleinow ME, Garwood CL, Clemente JL, et al. Effect of chronic kidney disease on warfarin management in a pharmacist-managed anticoagulation clinic. J Manag Care Pharm 2011 Sep; 17(7): 523–30

    PubMed  Google Scholar 

  16. Holbrook AM, Pereira JA, Labiris R, et al. Systematic overview of warfarin and its drug and food interactions. Arch Intern Med 2005 May; 165(10): 1095–106

    Article  PubMed  CAS  Google Scholar 

  17. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975 Nov; 12(3): 189–98

    Article  PubMed  CAS  Google Scholar 

  18. Flaker GC, Pogue J, Yusuf S, et al. Cognitive function and anticoagulation control in patients with atrial fibrillation. Circ Cardiovasc Qual Outcomes 2010 May; 3(3): 277–83

    Article  PubMed  Google Scholar 

  19. Rosendaal FR, Cannegieter SC, van der Meer FJ, et al. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost 1993 Mar 1; 69(3): 236–9

    PubMed  CAS  Google Scholar 

  20. Cannegieter SC, Rosendaal FR, Wintzen AR, et al. Optimal oral anticoagulant therapy in patients with mechanical heart valves. N Engl J Med 1995 Jul 6; 333(1): 11–7

    Article  PubMed  CAS  Google Scholar 

  21. White HD, Gruber M, Feyzi J, et al. Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control: results from SPORTIF III and V. Arch Intern Med 2007 Feb 12; 167(3): 239–45

    Article  PubMed  CAS  Google Scholar 

  22. 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 Nov; 1(2): 84–91

    Article  PubMed  Google Scholar 

  23. Diug B, Evans S, Lowthian J, et al. The unrecognized psy-chosocial factors related to bleeding risk in warfarin therapy. Stroke 2011 Oct; 42(10): 2866–71

    Article  PubMed  Google Scholar 

  24. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009 Sep 17; 361(12): 1139–51

    Article  PubMed  CAS  Google Scholar 

  25. Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous throm-boembolism. N Engl J Med 2009 Dec 10; 361(24): 2342–52

    Article  PubMed  CAS  Google Scholar 

  26. Connolly SJ, Eikelboom J, Joyner C, et al. Apixaban in patients with atrial fibrillation. N Engl J Med 2011 Mar 3; 364(9): 806–17

    Article  PubMed  CAS  Google Scholar 

  27. Bauersachs R, Berkowitz SD, Brenner B, et al. Oral rivarox-aban for symptomatic venous thromboembolism. N Engl J Med 2010 Dec 23; 363(26): 2499–510

    Article  PubMed  CAS  Google Scholar 

  28. Pradaxa® (dabigatran etexilate tablets) [package insert]. Ridge-water (CT): Boehringer Ingelheim Pharmaceuticals, 2010 Oct

  29. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011 Sept 8; 365(10): 883–91

    Article  PubMed  CAS  Google Scholar 

  30. Xarelto® (rivaroxaban tablets) [package insert]. Titusville (NJ): Janssen Pharmaceuticals, 2011 Dec

  31. Garwood CL, Clemente JL, Ibe GN, et al. Warfarin maintenance dose in older patients: higher average dose and wider dose frequency distribution in patients of African ancestry than those of European ancestry. Blood Cells Mol Dis 2010 Jun 15; 45(1): 93–7

    Article  PubMed  CAS  Google Scholar 

  32. Rudd KM, Dier JG. Comparison of two different models of anticoagulation management services with usual medical care. Pharmacotherapy 2010 Apr; 30(4): 330–8

    Article  PubMed  Google Scholar 

  33. Witt DM, Delate T, Clark NP, et al. Outcomes and predictors of very stable INR control during chronic anti-coagulation therapy. Blood 2009 Jul 30; 114(5): 952–6

    Article  PubMed  CAS  Google Scholar 

  34. Lowthian JA, Diug BO, Evans SM, et al. Who is responsible for the care of patients treated with warfarin therapy? Med J Aust 2009 Jun; 190(12): 674–7

    PubMed  Google Scholar 

  35. Fihn SD, Gadisseur AA, Pasterkamp E, et al. Comparison of control and stability of oral anticoagulant therapy using acenocoumarol versus phenprocoumon. Thromb Haemost 2003 Aug; 90(2): 260–6

    PubMed  CAS  Google Scholar 

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Acknowledgements

There was no source of funding for this study. None of the authors have any conflicts of interest to report.

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Correspondence to Candice L. Garwood Pharm.D., BCPS.

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Khreizat, H.S., Whittaker, P., Curtis, K.D. et al. The Effect of Cognitive Impairment in the Elderly on the Initial and Long-Term Stability of Warfarin Therapy. Drugs Aging 29, 307–317 (2012). https://doi.org/10.2165/11599060-000000000-00000

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