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Semin Thromb Hemost 2015; 41(04): 389-394
DOI: 10.1055/s-0035-1550158
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Direct Oral Anticoagulants in Frail Older Adults: A Geriatric Perspective

Prahlad Ho
1   The Northern Hospital, Epping, Victoria, Australia
,
Beth La Brooy
1   The Northern Hospital, Epping, Victoria, Australia
,
Lachlan Hayes
1   The Northern Hospital, Epping, Victoria, Australia
,
Wen Kwang Lim
1   The Northern Hospital, Epping, Victoria, Australia
› Author Affiliations
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Publication History

Publication Date:
14 May 2015 (online)

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Abstract

Direct oral anticoagulants (DOACs) have changed the paradigm of anticoagulation management, improving patient convenience as well as possibly reducing the incidence of spontaneous intracranial hemorrhage. However, concerns remain with these agents because of the lack of monitoring capacity and availability of readily accessible specific antidotes. This is particularly pertinent in the older population, specifically the frail older adults who have multiple comorbidities, higher risk of falls, and increased bleeding risk. This group has not been specifically studied in the DOAC randomized controlled trials and, hence, extrapolation of these data into this population should be done cautiously. We provide a review of the use of DOACs in the older frail population from both hematological and geriatric perspectives, as well as propose an algorithm for how these agents may be used in this frail population.

Keywords

direct oral anticoagulants - older adults - frailty - bleeding
 

  • References

  • 1 Hankey GJ. Intracranial hemorrhage and novel anticoagulants for atrial fibrillation: what have we learned?. Curr Cardiol Rep 2014; 16 (5) 480
    CrossrefPubMedGoogle Scholar
  • 2 Breithardt G, Baumgartner H, Berkowitz SD , et al; ROCKET AF Steering Committee & Investigators. Clinical characteristics and outcomes with rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation but underlying native mitral and aortic valve disease participating in the ROCKET AF trial. Eur Heart J 2014; 35 (47) 3377-3385
    CrossrefPubMedGoogle Scholar
  • 3 Connolly SJ, Wallentin L, Ezekowitz MD , et al. The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study. Circulation 2013; 128 (3) 237-243
    CrossrefPubMedGoogle Scholar
  • 4 Granger CB, Lopes RD, Hanna M , et al. Clinical events after transitioning from apixaban versus warfarin to warfarin at the end of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. Am Heart J 2015; 169 (1) 25-30
    CrossrefPubMedGoogle Scholar
  • 5 Agnelli G, Buller HR, Cohen A , et al; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013; 369 (9) 799-808
    CrossrefPubMedGoogle Scholar
  • 6 Prins MH, Lensing AW, Bauersachs R , et al; EINSTEIN Investigators. Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies. Thromb J 2013; 11 (1) 21
    CrossrefPubMedGoogle Scholar
  • 7 Ma TK, Yan BP, Lam YY. Dabigatran etexilate versus warfarin as the oral anticoagulant of choice? A review of clinical data. Pharmacol Ther 2011; 129 (2) 185-194
    CrossrefPubMedGoogle Scholar
  • 8 Cuker A, Siegal DM, Crowther MA, Garcia DA. Laboratory measurement of the anticoagulant activity of the non-vitamin K oral anticoagulants. J Am Coll Cardiol 2014; 64 (11) 1128-1139
    CrossrefPubMedGoogle Scholar
  • 9 van Ryn J, Stangier J, Haertter S , et al. Dabigatran etexilate—a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost 2010; 103 (6) 1116-1127
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Frost C, Nepal S, Wang J , et al. Safety, pharmacokinetics and pharmacodynamics of multiple oral doses of apixaban, a factor Xa inhibitor, in healthy subjects. Br J Clin Pharmacol 2013; 76 (5) 776-786
    CrossrefPubMedGoogle Scholar
  • 11 Kubitza D, Becka M, Voith B, Zuehlsdorf M, Wensing G. Safety, pharmacodynamics, and pharmacokinetics of single doses of BAY 59-7939, an oral, direct factor Xa inhibitor. Clin Pharmacol Ther 2005; 78 (4) 412-421
    CrossrefPubMedGoogle Scholar
  • 12 Sardar P, Chatterjee S, Chaudhari S, Lip GY. New oral anticoagulants in elderly adults: evidence from a meta-analysis of randomized trials. J Am Geriatr Soc 2014; 62 (5) 857-864
    CrossrefPubMedGoogle Scholar
  • 13 Coppens M, Synhorst D, Eikelboom JW, Yusuf S, Shestakovska O, Connolly SJ. Efficacy and safety of apixaban compared with aspirin in patients who previously tried but failed treatment with vitamin K antagonists: results from the AVERROES trial. Eur Heart J 2014; 35 (28) 1856-1863
    CrossrefPubMedGoogle Scholar
  • 14 Gomes T, Mamdani MM, Holbrook AM, Paterson JM, Hellings C, Juurlink DN. Rates of hemorrhage during warfarin therapy for atrial fibrillation. CMAJ 2013; 185 (2) E121-E127
    CrossrefPubMedGoogle Scholar
  • 15 Tran H, Joseph J, Young L , et al; Australasian Society of Thrombosis and Haemostasis. New oral anticoagulants: a practical guide on prescription, laboratory testing and peri-procedural/bleeding management. Intern Med J 2014; 44 (6) 525-536
    CrossrefPubMedGoogle Scholar
  • 16 Cohen AT, Spiro TE, Büller HR , et al; MAGELLAN Investigators. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med 2013; 368 (6) 513-523
    CrossrefPubMedGoogle Scholar
  • 17 Lambourne MD, Eltringham-Smith LJ, Gataiance S, Arnold DM, Crowther MA, Sheffield WP. Prothrombin complex concentrates reduce blood loss in murine coagulopathy induced by warfarin, but not in that induced by dabigatran etexilate. J Thromb Haemost 2012; 10 (9) 1830-1840
    CrossrefPubMedGoogle Scholar
  • 18 Pragst I, Zeitler SH, Doerr B , et al. Reversal of dabigatran anticoagulation by prothrombin complex concentrate (Beriplex P/N) in a rabbit model. J Thromb Haemost 2012; 10 (9) 1841-1848
    CrossrefPubMedGoogle Scholar
  • 19 Marlu R, Hodaj E, Paris A, Albaladejo P, Cracowski JL, Pernod G. Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban: a randomised crossover ex vivo study in healthy volunteers. Thromb Haemost 2012; 108 (2) 217-224
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation 2011; 124 (14) 1573-1579
    CrossrefPubMedGoogle Scholar
  • 21 van Ryn JRD, Priepke H, Hauel N, Wienen W. Reversibility of the anticoagulant effect of high doses of direct thrombin inhibitor, dabiagtran, but recombnant activated factor VIIa or activated prothrombin complex. Presented at: 13th Congress of the European Haematology Association; Copenhagen, Denmark: Haematologica; 2008:148
    PubMedGoogle Scholar
  • 22 Ho WK, Hankey GJ, Eikelboom JW. The incidence of venous thromboembolism: a prospective, community-based study in Perth, Western Australia. Med J Aust 2008; 189 (3) 144-147
    PubMedGoogle Scholar
  • 23 Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest 2010; 137 (2) 263-272
    CrossrefPubMedGoogle Scholar
  • 24 Rockwood PR, Horne JG, Cryer C. Hip fractures: a future epidemic?. J Orthop Trauma 1990; 4 (4) 388-393
    CrossrefPubMedGoogle Scholar
  • 25 Morley JE, Vellas B, van Kan GA , et al. Frailty consensus: a call to action. J Am Med Dir Assoc 2013; 14 (6) 392-397
    CrossrefPubMedGoogle Scholar
  • 26 Rockwood K, Song X, MacKnight C , et al. A global clinical measure of fitness and frailty in elderly people. CMAJ 2005; 173 (5) 489-495
    CrossrefPubMedGoogle Scholar
  • 27 Hubbard RE, O'Mahony MS, Woodhouse KW. Medication prescribing in frail older people. Eur J Clin Pharmacol 2013; 69 (3) 319-326
    CrossrefPubMedGoogle Scholar
  • 28 Collard RM, Boter H, Schoevers RA, Oude Voshaar RC. Prevalence of frailty in community-dwelling older persons: a systematic review. J Am Geriatr Soc 2012; 60 (8) 1487-1492
    CrossrefPubMedGoogle Scholar
  • 29 Fried LP, Tangen CM, Walston J , et al; Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001; 56 (3) M146-M156
    CrossrefPubMedGoogle Scholar
  • 30 Frey PM, Méan M, Limacher A , et al. Physical activity and risk of bleeding in elderly patients taking anticoagulants. J Thromb Haemost 2015; 13 (2) 197-205
    CrossrefPubMedGoogle Scholar
  • 31 Watts G. Why the exclusion of older people from clinical research must stop. BMJ 2012; 344: e3445 . doi: 10.1136/bmj.e3445
    CrossrefPubMedGoogle Scholar
  • 32 Van Spall HG, Toren A, Kiss A, Fowler RA. Eligibility criteria of randomized controlled trials published in high-impact general medical journals: a systematic sampling review. JAMA 2007; 297 (11) 1233-1240
    CrossrefPubMedGoogle Scholar
  • 33 Mitnitski AB, Mogilner AJ, Rockwood K. Accumulation of deficits as a proxy measure of aging. ScientificWorldJournal 2001; 1: 323-336
    CrossrefPubMedGoogle Scholar
  • 34 Morley JE, Malmstrom TK, Miller DK. A simple frailty questionnaire (FRAIL) predicts outcomes in middle aged African Americans. J Nutr Health Aging 2012; 16 (7) 601-608
    CrossrefPubMedGoogle Scholar
  • 35 Lopez D, Flicker L, Dobson A. Validation of the frail scale in a cohort of older Australian women. J Am Geriatr Soc 2012; 60 (1) 171-173
    CrossrefPubMedGoogle Scholar
  • 36 Subra J, Gillette-Guyonnet S, Cesari M, Oustric S, Vellas B ; Platform Team. The integration of frailty into clinical practice: preliminary results from the Gérontopôle. J Nutr Health Aging 2012; 16 (8) 714-720
    CrossrefPubMedGoogle Scholar
  • 37 Sujino Y, Tanno J, Nakano S , et al. Impact of hypoalbuminemia, frailty, and body mass index on early prognosis in older patients (≥85 years) with ST-elevation myocardial infarctions (epub ahead of print). J Cardiol 2014;
    PubMedGoogle Scholar
  • 38 Jung P, Pereira MA, Hiebert B , et al. The impact of frailty on postoperative delirium in cardiac surgery patients. J Thorac Cardiovasc Surg 2015; 149 (3) 869-875
    CrossrefPubMedGoogle Scholar
  • 39 Goldstein J, Hubbard RE, Moorhouse P, Andrew MK, Mitnitski A, Rockwood K. The validation of a care partner-derived frailty index based upon comprehensive geriatric assessment (CP-FI-CGA) in emergency medical services and geriatric ambulatory care. Age Ageing 2015; 44 (2) 327-330
    CrossrefPubMedGoogle Scholar
  • 40 Coresh J, Selvin E, Stevens LA , et al. Prevalence of chronic kidney disease in the United States. JAMA 2007; 298 (17) 2038-2047
    CrossrefPubMedGoogle Scholar
  • 41 Anderson S, Halter JB, Hazzard WR , et al; workshop participants. Prediction, progression, and outcomes of chronic kidney disease in older adults. J Am Soc Nephrol 2009; 20 (6) 1199-1209
    CrossrefPubMedGoogle Scholar
  • 42 Pather M. The prevalence of renal impairment in the elderly hospitalized population. Int J Gen Med 2009; 2: 117-119
    PubMedGoogle Scholar
  • 43 Lane DA, Lip GY. Use of the CHA(2)DS(2)-VASc and HAS-BLED scores to aid decision making for thromboprophylaxis in nonvalvular atrial fibrillation. Circulation 2012; 126 (7) 860-865
    CrossrefPubMedGoogle Scholar
  • 44 Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 2010; 138 (5) 1093-1100
    CrossrefPubMedGoogle Scholar