Korean Circulation Journal

The Korean Society of Cardiology (대한심장학회)
권호 표지
DOI QR코드

DOI QR Code

Long-Term Anticoagulation in the Extreme Elderly with the Newer Antithrombotics: Safe or Sorry?

  • Chiong, Jun R. (Loma Linda University School of Pharmacy) ;
  • Cheung, Rebecca J. (Loma Linda University School of Pharmacy)
  • Published : 2013.05.30
⟨ Previous Next ⟩

Abstract

Background and Objectives: The prevalence of atrial fibrillation (AF) doubles in the extreme elderly and is higher than in the rest of the population. Warfarin therapy to prevent thromboembolic events secondary to AF is often underutilized and under-prescribed in this subgroup, due to the fear of bleeding and other complications. Newer oral anticoagulants such as rivaroxaban and dabigatran offer alternative therapeutic options for the extreme elderly. We review the clinical trial data of these newer agents in the extreme elderly population. Subjects and Methods: The primary literature was identified through PubMed, using the following search terms: anticoagulation, rivaroxaban, dabigatran, warfarin, elderly, AF, bleeding, stroke, and aging. Additional references were identified through the review of references from the articles obtained. We included clinical studies evaluating anticoagulation therapies in AF. Selection emphasis was placed on those evaluating anticoagulation in the elderly population. Results: Dabigatran and rivaroxaban have predictable, dose-proportional pharmacokinetic and pharmacodynamic properties, which make them favorable options for the elderly. Fewer monitoring parameters and drug interactions allow for the greater ease of use. A landmark trial shows that the rate of intracranial hemorrhage with dabigatran is lower in this population compared to warfarin. However, the data is based on a small number of subjects enrolled in the clinical trials. As such, the real-world use of these agents may not replicate the published rates of bleeding and thrombosis in the study populations. Conclusion: More research is needed in this area, specifically in this population, before newer agents such as rivaroxaban and dabigatran are widely recommended for use in the extreme elderly patients.

Keywords

References

  1. Lakshminarayan K, Solid CA, Collins AJ, Anderson DC, Herzog CA. Atrial fibrillation and stroke in the general medicare population: a 10-year perspective (1992 to 2002). Stroke 2006;37:1969-74. https://doi.org/10.1161/01.STR.0000230607.07928.17
  2. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001;285:2370-5. https://doi.org/10.1001/jama.285.18.2370
  3. Goto S, Hankey G, Hills MT, et al. How can we avoid a stroke crisis in the Asia-Pacific region? Working group report: stroke prevention in patients with atrial fibrillation [Internet]. Chameleon Communications International; 2011 [cited 2012 Aug 14]. 23 p. Available from: http://www.signagainststroke. com/media/whatisaf/110323strokereport.pdf.
  4. Jeong JH. Prevalence of and risk factors for atrial fibrillation in Korean adults older than 40 years. J Korean Med Sci 2005;20:26-30.
  5. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991;22:983-8. https://doi.org/10.1161/01.STR.22.8.983
  6. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation: a major contributor to stroke in the elderly. The Framingham Study. Arch Intern Med 1987;147:1561-4. https://doi.org/10.1001/archinte.1987.00370090041008
  7. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139-51. https://doi.org/10.1056/NEJMoa0905561
  8. Olsson SB; Executive Steering Committee of the SPORTIF III Investigators. Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III): randomised controlled trial. Lancet 2003;362:1691-8. https://doi.org/10.1016/S0140-6736(03)14841-6
  9. Albers GW, Diener HC, Frison L, et al. Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a randomized trial. JAMA 2005;293:690-8. https://doi.org/10.1001/jama.293.6.690
  10. Hylek EM, Evans-Molina C, Shea C, Henault LE, Regan S. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007;115:2689-96. https://doi.org/10.1161/CIRCULATIONAHA.106.653048
  11. Torn M, Bollen WL, van der Meer FJ, van der Wall EE, Rosendaal FR. Risks of oral anticoagulant therapy with increasing age. Arch Intern Med 2005;165:1527-32. https://doi.org/10.1001/archinte.165.13.1527
  12. Fang MC, Go AS, Chang Y, et al. Death and disability from warfarinassociated intracranial and extracranial hemorrhages. Am J Med 2007;120:700-5. https://doi.org/10.1016/j.amjmed.2006.07.034
  13. Fang MC, Chang Y, Hylek EM, et al. Advanced age, anticoagulation intensity, and risk for intracranial hemorrhage among patients taking warfarin for atrial fibrillation. Ann Intern Med 2004;141:745-52. https://doi.org/10.7326/0003-4819-141-10-200411160-00005
  14. Poli D, Antonucci E, Testa S, Tosetto A, Ageno W, Palareti G; Italian Federation of Anticoagulation Clinics. Bleeding risk in very old patients on vitamin K antagonist treatment: results of a prospective collaborative study on elderly patients followed by Italian Centres for Anticoagulation. Circulation 2011;124:824-9. https://doi.org/10.1161/CIRCULATIONAHA.110.007864
  15. Tincani E, Baldini P, Crowther MA, et al. Bleeding rates in patients older than 90 years of age on vitamin K antagonist therapy for nonvalvular atrial fibrillation. Blood Coagul Fibrinolysis 2009;20:47-51. https://doi.org/10.1097/MBC.0b013e32831be9da
  16. 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;370:493-503. https://doi.org/10.1016/S0140-6736(07)61233-1
  17. Lip GY, Frison L, Halperin JL, Lane DA. Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED (Hypertension, Abnormal Renal/ Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score. J Am Coll Cardiol 2011;57:173-80. https://doi.org/10.1016/j.jacc.2010.09.024
  18. Chen WT, White CM, Phung OJ, et al. Association between CHADS2 risk factors and anticoagulation-related bleeding: a systematic literature review. Mayo Clin Proc 2011;86:509-21. https://doi.org/10.4065/mcp.2010.0755
  19. Zimetbaum PJ, Thosani A, Yu HT, et al. Are atrial fibrillation patients receiving warfarin in accordance with stroke risk? Am J Med 2010;123:446-53. https://doi.org/10.1016/j.amjmed.2009.11.015
  20. Jacobs JM, Stessman J. New anticoagulant drugs among elderly patients is caution necessary?: Comment on "The use of dabigatran in elderly patients". Arch Intern Med 2011;171:1287-8. https://doi.org/10.1001/archinternmed.2011.308
  21. Hylek EM, D'Antonio J, Evans-Molina C, Shea C, Henault LE, Regan S. Translating the results of randomized trials into clinical practice: the challenge of warfarin candidacy among hospitalized elderly patients with atrial fibrillation. Stroke 2006;37:1075-80. https://doi.org/10.1161/01.STR.0000209239.71702.ce
  22. Singer DE, Chang Y, Fang MC, et al. The net clinical benefit of warfarin anticoagulation in atrial fibrillation. Ann Intern Med 2009;151:297-305. https://doi.org/10.7326/0003-4819-151-5-200909010-00003
  23. Coumadin [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2011.
  24. Pradaxa [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc;2012.
  25. Xarelto [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc;2011.
  26. Lam MP, Cheung BM. The pharmacogenetics of the response to warfarin in Chinese. Br J Clin Pharmacol 2012;73:340-7. https://doi.org/10.1111/j.1365-2125.2011.04097.x
  27. Eikelboom JW, Wallentin L, Connolly SJ, et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation 2011;123:2363-72. https://doi.org/10.1161/CIRCULATIONAHA.110.004747
  28. Hart RG, Diener HC, Yang S, et al. Intracranial hemorrhage in atrial fibrillation patients during anticoagulation with warfarin or dabigatran: the RE-LY trial. Stroke 2012;43:1511-7. https://doi.org/10.1161/STROKEAHA.112.650614
  29. Kowey PR, Naccarelli GV. The Food and Drug Administration decision not to approve the 110 mg dose of dabigatran: give us a way out. Am J Med 2012;125:732. https://doi.org/10.1016/j.amjmed.2011.10.035
  30. Sinnaeve PR, Brueckmann M, Clemens A, Oldgren J, Eikelboom J, Healey JS. Stroke prevention in elderly patients with atrial fibrillation: challenges for anticoagulation. J Intern Med 2012;271:15-24. https://doi.org/10.1111/j.1365-2796.2011.02464.x

Cited by

  1. Novel Anticoagulants in Atrial Fibrillation: Monitoring, Reversal and Perioperative Management vol.2015, pp.None, 2013, https://doi.org/10.1155/2015/424031
  2. Optimizing Anticoagulation in Older Patients with Nonvalvular Atrial Fibrillation vol.13, pp.2, 2013, https://doi.org/10.1007/s12170-019-0599-8