Drugs & Aging

, Volume 14, Issue 4, pp 303–312 | Cite as

Safety of Treatment with Oral Anticoagulants in the Elderly

A Systematic Review
  • Barbara A. HuttenEmail author
  • Anthonie W. A. Lensing
  • Roderik A. Kraaijenhagen
  • Martin H. Prins
Review Article


Oral anticoagulants have documented efficacy for many indications and are widely used in elderly patients. However, there is concern about whether this treatment induces an excess of major bleeding in elderly patients. In this system atic review, the incidence of oral anticoagulant-related major bleeding among elderly patients was determined.

A total of 58 reports were identified that evaluated an oral anticoagulant, included patients with a mean age of at least 60 years, and provided data on the occurrence of major bleeding or provided separate data on the occurrence of major bleeding in elderly versus younger patients.

In 50 studies no age differentiation was given. Although the incidence of bleeding complications varied, a trend towards increased bleeding with increas ing age was shown in patients with major orthopaedic surgery and cardiac dis eases. In the 8 articles that provided separate data on the occurrence of bleeding in different age categories, there was a clear tendency towards a 2-fold increase in bleeding in elderly patients.

These findings emphasise the need for caution in the use of oral anticoagulants in elderly patients. However, the decision to start oral anticoagulant treatment should be based on an evaluation of the risk/benefit balance on a careful patient-by-patient basis. In general, if oral anticoagulant treatment is started, the lowest possible effective International Normalised Ratios (INR) should be selected and regular monitoring should be done to avoid over-anticoagulation.


Atrial Fibrillation Warfarin Adis International Limited Deep Vein Thrombosis International Normalise Ratio 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Hirsh J. Oral anticoagulant drugs. N Engl J Med 1991; 324(26): 1865–75PubMedCrossRefGoogle Scholar
  2. 2.
    Dalen JE, Hirsh J, editors. Fourth ACCP Consensus Conference on Antithrombotic Therapy. Chest 1995; 108 (4 Suppl.): 225S–522Google Scholar
  3. 3.
    Levine MN, Raskob G, Landefeld S, et al. Hemorrhagic com plications of anticoagulant treatment. Chest 1995; 108 (4 Suppl.): 276S–90PubMedCrossRefGoogle Scholar
  4. 4.
    Van der Meer FJ, Rosendaal FR, Vandenbroucke JP, et al. As sessment of a bleeding risk index in two cohorts of patients treated with oral anticoagulants. Thromb Haemost 1996; 76(1): 12–6PubMedGoogle Scholar
  5. 5.
    Coon WW, Willis PW. Hemorrhagic complications of anticoag ulant therapy. Arch Intern Med 1974; 133(3): 386–92PubMedCrossRefGoogle Scholar
  6. 6.
    Petitti DB, Strom BL, Melmon KL. Prothrombin time ratio and other factors associated with bleeding in patients treated with warfarin. J Clin Epidemiol 1989; 42(8): 759–64PubMedCrossRefGoogle Scholar
  7. 7.
    Van der Meer FJ, Rosendaal FR, Vandenbroucke JP, et al. Bleed ing complications in oral anticoagulant therapy. Arch Intern Med 1993; 153: 1557–62PubMedCrossRefGoogle Scholar
  8. 8.
    Gurwitz JH, Goldberg RJ, Holden A, et al. Age-related risks of long-term oral anticoagulant therapy. Arch Intern Med 1988; 148(8): 1733–6PubMedCrossRefGoogle Scholar
  9. 9.
    Davis KB, Estruch MT, Samson-Corvera EB, et al. Manage ment of anticoagulation in outpatients: experience with an anticoagulation service in a municipal hospital setting. Arch Intern Med 1977; 137(2): 197–202PubMedCrossRefGoogle Scholar
  10. 10.
    Petty GW, Lennihan L, Mohr JP, et al. Complications of long-term anticoagulation. Ann Neurol1988; 23(6): 570–4PubMedCrossRefGoogle Scholar
  11. 11.
    Beyth RJ, Landefeld CS. Anticoagulants in older patients: a safety perspective. Drug Aging 1995; 6(1): 45–54CrossRefGoogle Scholar
  12. 12.
    Graafsma YP, Prins MH, Lensing AW, et al. Bleeding classifi cation in clinical trials: observer variability and clinical rele vance. Thromb Haemost 1997; 78(4): 1189–92PubMedGoogle Scholar
  13. 13.
    Hirsh J, Poller L. The international normalized ratio: a guide to understanding and correcting its problems. Arch Intern Med 1994; 154(3): 282–8PubMedCrossRefGoogle Scholar
  14. 14.
    Bussey HI, Force RW, Bianco TM, et al. Reliance on prothrombin time ratios causes significant errors in anticoagulation therapy. Arch Intern Med 1992; 152(2): 278–82PubMedCrossRefGoogle Scholar
  15. 15.
    Hirsh J, Deykin D, Poller L. ‘Therapeutic range’ for oral anti coagulant therapy. Chest 1986; 89 (2 Suppl.): 11S–15PubMedGoogle Scholar
  16. 16.
    Stroke Prevention in Atrial Fibrillation Investigators. Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: Stroke Prevention in Atrial Fibrillation II study. Lancet 1994; 343(8899): 687–91Google Scholar
  17. 17.
    O’Neill PA, Crossley D, Taberner DA, et al. Safety of anticoagulation in the elderly: reasons for discontinuing therapy. Postgrad Med J 1992; 68: 824–8PubMedCrossRefGoogle Scholar
  18. 18.
    Palareti G, Leali N, Coccheri S, et al. Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospec tive collaborative study. Italian Study on Complications of Oral Anticoagulant Therapy (ISCOAT). Lancet 1996; 348(9025): 423–8PubMedCrossRefGoogle Scholar
  19. 19.
    Cortelazzo S, Finazzi G, Viero P, et al. Thrombotic and hemorrhagic complications in patients with mechanical heart valve prosthesis attending an anticoagulation clinic. Thromb Haemost 1993; 69(4): 316–20PubMedGoogle Scholar
  20. 20.
    Fihn SD, Callahan CM, Martin DC, The National Consortium of Anticoagulation Clinics, et al. The risk for and severity of bleeding complications in elderly patients treated with war farin. Ann Intern Med 1996; 124(11): 970–9PubMedGoogle Scholar
  21. 21.
    Steffensen FH, Kristensen K, Ejlersen E, et al. Major haemorrhagic complications during oral anticoagulant therapy in a Danish population-based cohort. J Intern Med 1997; 242: 497–503PubMedCrossRefGoogle Scholar
  22. 22.
    Columbus Investigators. Low-molecular-weight heparin in the treatment of patients with venous thromboembolism. N Engl J Med 1997; 337(10): 657–62CrossRefGoogle Scholar
  23. 23.
    Koopman MM, Prandoni P, Piovella F et al. Treatment of ve nous thrombosis with intravenous unfractionated heparin ad ministered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. N Engl J Med 1996; 334(11): 682–7PubMedCrossRefGoogle Scholar
  24. 24.
    Salzman EW, Harris WH, DeSanctis RW. Anticoagulation for prevention of thromboembolism following fractures of the hip. N Engl J Med 1966; 275(3): 122–30PubMedCrossRefGoogle Scholar
  25. 25.
    Morris GK, Mitchell JR. Warfarin sodium in prevention of deep venous thrombosis and pulmonary embolism in patients with fractured neck of femur. Lancet 1976; II(7991): 869–72CrossRefGoogle Scholar
  26. 26.
    Eskeland G, Solheim K, Skjorten F. Anticoagulant prophylaxis, thromboembolism and mortality in elderly patients with hip fractures: a controlled clinical trial. Acta Chir Scand 1966; 131(1): 16–29PubMedGoogle Scholar
  27. 27.
    Powers PJ, Gent M, Jay RM, et al. A randomized trial of less intense postoperative warfarin or aspirin therapy in the pre vention of venous thromboembolism after surgery for frac tured hip. Arch Intern Med 1989; 149(4): 771–4PubMedCrossRefGoogle Scholar
  28. 28.
    RD Heparin Arthroplasty Group. RD heparin compared with warfarin for prevention of venous thromboembolic disease following total hip or knee arthroplasty. J Bone Joint Surg Am 1994; 76(8): 1174–85Google Scholar
  29. 29.
    Hamulyak K, Lensing AW, van der Meer J, Fraxiparine Oral Anticoagulant Study Group, et al. Subcutaneous low-molecular weight heparin or oral anticoagulants for the pre vention of deep-vein thrombosis in elective hip and knee replacement? Thromb Haemost 1995; 74(6): 1428–31PubMedGoogle Scholar
  30. 30.
    Francis CW, Marder VJ, Evarts CM, et al. Two-step warfarin therapy: prevention of postoperative venous thrombosis with out excessive bleeding. JAMA 1983; 249(3): 374–8PubMedCrossRefGoogle Scholar
  31. 31.
    Hull R, Raskob G, Pineo G, et al. Acomparison of subcutaneous low-molecular-weight heparin with warfarin sodium for pro phylaxis against deep-vein thrombosis after hip or knee im plantation. N Engl J Med 1993; 329(19): 1370–6PubMedCrossRefGoogle Scholar
  32. 32.
    Simonneau G, Sors H, Charbonnier B, The THÉSÉE Study Group, et al. A comparison of low-molecular-weight heparin with unfractionated heparin for acute pulmonary embolism. N Eng J of Med 1997; 337(10): 663–9CrossRefGoogle Scholar
  33. 33.
    Prandoni P, Lensing AW, Buller HR, et al. Comparison of sub cutaneous low-molecular-weight heparin with intravenous standard heparin in proximal deep-vein thrombosis. Lancet 1992; 339(8791): 441–5PubMedCrossRefGoogle Scholar
  34. 34.
    Schulman S, Granqvist S, Holmstrom M, et al. The duration of oral anticoagulant therapy after a second episode of venous thromboembolism. N Engl J Med 1997; 336(6): 393–8PubMedCrossRefGoogle Scholar
  35. 35.
    Levine MN, Hirsh J, Gent M, et al. Optimal duration of oral anticoagulant therapy: a randomized trial comparing four weeks with three months of warfarin in patients with proximal deep vein thrombosis. Thromb Haemost 1995; 74(2): 606–11PubMedGoogle Scholar
  36. 36.
    Simonneau G, Charbonnier B, Decousus H, et al. Subcutaneous low-molecular-weight heparin compared with continuous intravenous unfractionated heparin in the treatment of proxi mal deep vein thrombosis. Arch Intern Med 1993; 153(13): 1541–6PubMedCrossRefGoogle Scholar
  37. 37.
    Holmgren K, Andersson G, Fagrell B, et al. One-month versus six-month therapy with oral anticoagulants after symptomatic deep vein thrombosis. Acta Med Scand 1985; 218(3): 279–84PubMedCrossRefGoogle Scholar
  38. 38.
    Schulman S, Lockner D, Juhlin-Dannfelt A. The duration of oral anticoagulation after deep vein thrombosis: a randomized study. Acta Med Scand 1985; 217(5): 547–52PubMedCrossRefGoogle Scholar
  39. 39.
    Schulman S, Rhedin AS, Lindmarker P, Duration of Anticoag ulation Trial Study Group, et al. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. N Engl J Med 1995; 332(25): 1661–5PubMedCrossRefGoogle Scholar
  40. 40.
    Pini M, Aiello S, Manotti C, et al. Low molecular weight hep arin versus warfarin in the prevention of recurrences after deep vein thrombosis. Thromb Haemost 1994; 72(2): 191–7PubMedGoogle Scholar
  41. 41.
    Lindmarker P, Holmstrom M, Granqvist S et al. Comparison of once-daily subcutaneous Fragmin with continuous intraven ous unfractionated heparin in the treatment of deep vein thrombosis. Thromb Haemost 1994; 72(2): 186–90PubMedGoogle Scholar
  42. 42.
    Hull RD, Raskob GE, Pineo GF, et al. Subcutaneous low-molecular-weight heparin compared with continuous intrave nous heparin in the treatment of proximal-vein thrombosis. N Engl J Med 1992; 326(15): 975–82PubMedCrossRefGoogle Scholar
  43. 43.
    Hull RD, Raskob GE, Rosenbloom D, et al. Heparin for 5 days as compared with 10 days in the initial treatment of proximal venous thrombosis. N Engl J Med 1990; 322(18): 1260–4PubMedCrossRefGoogle Scholar
  44. 44.
    Hull RD, Raskob GE, Hirsh J, et al. Continuous intravenous heparin compared with intermittent subcutaneous heparin in the initial treatment of proximal-vein thrombosis. N Engl J Med 1986; 315(18): 1109–14PubMedCrossRefGoogle Scholar
  45. 45.
    Hull R, Hirsh J, Jay R, et al. Different intensities of oral antico agulant therapy in the treatment of proximal-vein thrombosis. N Engl J Med 1982; 307(27): 1676–81PubMedCrossRefGoogle Scholar
  46. 46.
    Hull R, Delmore T, Carter C, et al. Adjusted subcutaneous hep arin versus warfarin sodium in the long-term treatment of venous thrombosis. N Engl J Med 1982; 306(4): 189–94PubMedCrossRefGoogle Scholar
  47. 47.
    Hull R, Delmore T, Genton E, et al. Warfarin sodium versus low-dose heparin in the long-term treatment of venous throm bosis. N Engl J Med 1979; 301(16): 855–8PubMedCrossRefGoogle Scholar
  48. 48.
    Petersen P, Boysen G, Godtfredsen J, et al. Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation: the Copenhagen AFASAK study. Lancet 1989; I(8631): 175–9CrossRefGoogle Scholar
  49. 49.
    The Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators. The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. N Engl J Med 1990; 323(22): 1505–11CrossRefGoogle Scholar
  50. 50.
    Lundstrom T, Ryden L. Haemorrhagic and thromboembolic complications in patients with atrial fibrillation on anticoag ulant prophylaxis. J Intern Med 1989; 225(2): 137–42PubMedCrossRefGoogle Scholar
  51. 51.
    The Sixty Plus Reinfarction Study Research Group. Risks of long-term oral anticoagulant therapy in elderly patients after myocardial infarction. Lancet 1982; I(8263): 64–8Google Scholar
  52. 52.
    Connolly SJ, Laupacis A, Gent M, et al. Canadian Atrial Fibril lation Anticoagulation (CAFA) study. J Am Coll Cardiol 1991; 18(2): 349–55PubMedCrossRefGoogle Scholar
  53. 53.
    Ezekowitz MD, Bridgers SL, James KE, Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators, et al. Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. N Engl J Med 1992; 327(20): 1406–12PubMedCrossRefGoogle Scholar
  54. 54.
    Stroke Prevention in Atrial Fibrillation Investigators. Stroke Prevention in Atrial Fibrillation Study: final results. Circulation 1991; 84(2): 527–39CrossRefGoogle Scholar
  55. 55.
    Anticoagulants in the Secondary Prevention of Events in Coronary Thrombosis (ASPECT) Research Group. Effect of long-term oral anticoagulant treatment on mortality and cardiovascular morbidity after myocardial infarction. Lancet 1994; 343(8896): 499–503Google Scholar
  56. 56.
    Fitzpatrick MA, McCone F. An audit of anticoagulation and endocarditis prophylaxis after heart valve surgery. NZ Med J 1991; 104(907): 85–8Google Scholar
  57. 57.
    Chesebro JH, Fuster V, Elveback LR, et al. Trial of combined warfarin plus dipyridamole or aspirin therapy in prosthetic heart valve replacement: danger. Am J Cardiol 1983; 51(9): 1537–41PubMedCrossRefGoogle Scholar
  58. 58.
    Smith P, Arnesen H, Holme I. The effect of warfarin on mortal ity and reinfarction after myocardial infarction. N Engl J Med 1990; 323(3): 147–52PubMedCrossRefGoogle Scholar
  59. 59.
    Turpie AG, Gunstensen J, Hirsh J, et al. Randomised compari son of two intensities of oral anticoagulant therapy after tissue heart valve replacement. Lancet 1988; I(8597): 1242–5CrossRefGoogle Scholar
  60. 60.
    Morocutti C, Amabile G, Fattapposta F, Studio Italiano Fibrillazione Atriale (SIFA) Investigators, et al. Indobufen versus warfarin in the secondary prevention of major vascular events in nonrheumatic atrial fibrillation. Stroke 1997; 28(5): 1015–21PubMedCrossRefGoogle Scholar
  61. 61.
    Yamanouchi H, Nagura H, Ohkawa Y, et al. Anticoagulant ther apy in recurrent cerebral embolism: a retrospective study in non-valvular atrial fibrillation. JNeurol 1988; 235(7): 407–10Google Scholar
  62. 62.
    European Atrial Fibrillation Trial (EAFT) Study Group. Sec ondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke. Lancet 1993; 342(8882): 1255–62Google Scholar
  63. 63.
    Olsson JE, Brechter C, Backlund H, et al. Anticoagulant vs anti-platelet therapy as prophylactic against cerebral infarc tion in transient ischemic attacks. Stroke 1980; 11(1): 4–9PubMedCrossRefGoogle Scholar
  64. 64.
    The Stroke Prevention In Reversible Ischemia Trial (SPIRIT) Study Group. A randomized trial of anticoagulants versus as pirin after cerebral ischemia of presumed arterial origin. Ann Neurol 1997; 42(6): 857–65CrossRefGoogle Scholar
  65. 65.
    Eriksson SE, Link H. Evaluation of anticoagulants in patients with cerebral infarction with slight to moderate neurological deficit. Acta Neurol Scand 1983; 68(2): 96–106PubMedCrossRefGoogle Scholar
  66. 66.
    Baker RN, Schwartz WS, Rose AS. Transient ischemic strokes: a report of a study of anticoagulant therapy. Neurology 1966; 16(9): 841–7CrossRefGoogle Scholar
  67. 67.
    Gårde A, Samuelsson K, Fahlgren H, et al. Treatment after tran sient ischemic attacks: a comparison between anticoagulant drug and inhibition of platelet aggregation. Stroke 1983; 14(5): 677–81PubMedCrossRefGoogle Scholar
  68. 68.
    Joglekar M, Mohanaruban K, Bayer AT, et al. Can old people on oral anticoagulants be safely managed as out-patients? Postgrad Med J 1988; 64(756): 775–7PubMedCrossRefGoogle Scholar
  69. 69.
    Do DD, Mahler F. Low-dose aspirin combined with dipyridam ole versus anticoagulants after femoropopliteal percutaneous transluminal angioplasty. Radiology 1994; 193(2): 567–71PubMedGoogle Scholar
  70. 70.
    Launbjerg J, Egeblad H, Heaf J, et al. Bleeding complications to oral anticoagulant therapy: multivariate analysis of 1010 treatment years in 551 outpatients. J Intern Med 1991; 229(4): 351–5PubMedCrossRefGoogle Scholar
  71. 71.
    Hurlen M, Erikssen J, Smith P, et al. Comparison of bleeding complications of warfarin and warfarin plus acetylsalicylic acid: a study in 3166 outpatients. J Intern Med 1994; 236(3): 299–304PubMedCrossRefGoogle Scholar
  72. 72.
    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(2): 144–52PubMedCrossRefGoogle Scholar
  73. 73.
    Bona RD, Sivjee KY, Hickey AD, et al. The efficacy and safety of oral anticoagulation in patients with cancer. Thromb Haemost 1995; 74(4): 1055–8PubMedGoogle Scholar
  74. 74.
    Saour JN, Sieck JO, Mamo LA, et al. Trial of different intensi ties of anticoagulation in patients with prosthetic heart valves. N Engl J Med 1990; 322(7): 428–32PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1999

Authors and Affiliations

  • Barbara A. Hutten
    • 1
    Email author
  • Anthonie W. A. Lensing
    • 2
  • Roderik A. Kraaijenhagen
    • 2
  • Martin H. Prins
    • 1
  1. 1.Department of Clinical Epidemiology and BiostatisticsUniversity of AmsterdamThe Netherlands
  2. 2.Department of Vascular Medicine, Academic Medical CenterUniversity of AmsterdamThe Netherlands

Personalised recommendations