Download PDF
Thromb Haemost 2001; 86(02): 563-568
DOI: 10.1055/s-0037-1616087
Review Article
Schattauer GmbH

Hospitalisation for Upper Gastrointestinal Bleeding Associated with Use of Oral Anticoagulants

Søren P. Johnsen
1   Department of Epidemiology and Social Medicine, University of Aarhus, Denmark
,
Henrik Toft Sørensen
2   Department of Clinical Epidemiology at Aarhus University Hospital and Aalborg Hospital, Denmark
,
Lene Mellemkjœr
3   Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark
,
William J. Blot
4   International Epidemiology Institute, Rockville, MD, USA
5   Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
,
Gunnar Lauge Nielsen
2   Department of Clinical Epidemiology at Aarhus University Hospital and Aalborg Hospital, Denmark
6   Department of Medicine M, Aalborg Hospital, Aalborg, Denmark
,
Joseph K. McLaughlin
4   International Epidemiology Institute, Rockville, MD, USA
5   Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
,
Jørgen H. Olsen
3   Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark
› Author Affiliations
Further Information

Publication History

Received 19 October 2000

Accepted after resubmission 27 February 2001

Publication Date:
12 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

The incidence of hospitalisation for upper GI bleeding with use of oral anticoagulants (OA) alone or in combination with other drugs was examined in a cohort of 4,204 users of OA, identified through record linkage between a population-based prescription database and a hospital discharge registry in Denmark, and compared with the incidence in the general population not exposed to OA. The standardised incidence ratio (SIR) was 2.8 (95% CI = 1.6-4.5) for use of OA alone. SIRs tended to be higher for use of OA combined with acetaminophen alone (4.4, 95% CI = 1.2-11.4), non-aspirin NSAIDs alone (8.0, 95% CI = 2.1 to 20.4) or aspirin/corticosteroids alone (3.8, 95% CI = 0.8-11.0), respectively.

These results indicate that use of OA is associated with a significantly increased risk of upper GI bleeding, with still higher risks associated with the concomitant use of other medications including acetaminophen. Further research is needed to clarify the extent to which drugs interacting with oral anticoagulants may cause GI bleeding and the mechanisms through which these associations operate.

Keywords

Epidemiology - oral anticoagulant - acetaminophen - gastrointestinal bleeding
 

  • References

  • 1 Fihn SD, McDonell M, Martin D, Henikoff J, Vermes D, Kent D, White RH. Risk factors for complications of chronic anticoagulation. A multicenter study. Ann Intern Med 1993; 118: 511-20.
    CrossrefPubMedSearch in Google Scholar
  • 2 Landefeld CS, Beyth RJ. Anticoagulant-related bleeding: clinical epidemiology, prediction, and prevention. Am J Med 1993; 95: 315-28.
    CrossrefPubMedSearch in Google Scholar
  • 3 White RH, McKittrick T, Takakuwa J, Callahan C, McDonell M, Fihn S. Management and prognosis of life-threatening bleeding during warfarin therapy. Arch Intern Med 1996; 156: 1197-201.
    CrossrefPubMedSearch in Google Scholar
  • 4 Chan TYK. Adverse interactions between warfarin and nonsteroidal anti-inflammatory drugs: mechanisms, clinical significance, and avoidance. Ann Pharmacother 1995; 29: 1274-83.
    CrossrefPubMedSearch in Google Scholar
  • 5 Freedman MD, Olatidoye AG. Clinically significant drug interactions with the oral anticoagulants. Drug Saf 1994; 10: 381-94.
    CrossrefPubMedSearch in Google Scholar
  • 6 Shorr RI, Ray WA, Daugherty JR, Friffin MR. Concurrent use of nonsteroidal anti-inflammatory drugs and oral anticoagulants places elderly persons at high risk for hemorrhagic peptic ulcer disease. Arch Intern Med 1993; 153: 1665-70.
    CrossrefPubMedSearch in Google Scholar
  • 7 Hylek EM, Heiman H, Skates SJ, Sheehan MA, Singer DE. Acetaminophen and other risk factors for excessive warfarin anticoagulation. JAMA 1998; 279: 657-62.
    CrossrefPubMedSearch in Google Scholar
  • 8 Shek KLA, Chan LN, Nutescu E. Warfarin-acetaminophen drug interaction revisited. Pharmacotherapy 1999; 19: 1153-8.
    CrossrefPubMedSearch in Google Scholar
  • 9 Rockall TA, Logan RFA, Devlin HB, Northfield TC. Incidence of and mortality from acute upper gastrointestinal haemorrhage in the United Kingdom. BMJ 1995; 311: 222-6.
    CrossrefPubMedSearch in Google Scholar
  • 10 Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med 1999; 340: 1888-99.
    CrossrefPubMedSearch in Google Scholar
  • 11 Cortelazzo S, Finazzi G, Viero P, Galli M, Remuzzi A, Parenzan N, Barbui T. Thrombotic and hemorrhagic complications in patients with mechanical heart valve attending prosthesis attending an anticoagulation clinic. Thromb Haemost 1993; 69: 316-20.
    Thieme ConnectPubMedSearch in Google Scholar
  • 12 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.
    CrossrefPubMedSearch in Google Scholar
  • 13 Petitti DB, Strom BL, Melmon KL. Prothrombin time ratio and other factors associated with bleeding in patients treated with warfarin. J Clin Epidemiol 1989; 87: 759-64.
    PubMedSearch in Google Scholar
  • 14 Nielsen GL, Sørensen HT, Zhou W, Steffensen FH, Olsen J. The pharmacoepidemiologic prescription database of North Jutland – a valid tool in pharmacoepidemiological research. Int J Risk Safety Med 1997; 10: 203-5.
    PubMedSearch in Google Scholar
  • 15 Steffensen FH, Kristensen K, Ejlersen E, Dahlerup JF, Sørensen HT. Major haemorrhagic complications during oral anticoagulant therapy in a Danish population-based cohort. J Intern Med 1997; 242: 497-503.
    CrossrefPubMedSearch in Google Scholar
  • 16 Capellá D. Descriptive tools and analysis. In: Dukes MNG. ed. Drug utilization studies: methods and uses. Copenhagen: WHO Regional Publications; 1993: 55-78. (European Series no. 45).
    Search in Google Scholar
  • 17 Sørensen HT. Regional administrative health registries as a resource in clinical epidemiology. Int J Risk Safety Med 1997; 10: 1-22.
    PubMedSearch in Google Scholar
  • 18 Storm HH, Michelsen EV, Clemmensen IH, Pihl J. The Danish Cancer Registry – history, content, quality and use. Dan Med Bull 1997; 44: 535-9.
    PubMedSearch in Google Scholar
  • 19 Cattaruzzi C, Grazia Troncon M, Agostinis L, Garcia Rodriguez LA. Positive predictive value of ICD-9th codes for upper gastrointestinal bleeding and perforation in the Sistema Informativo Sanitario Regionale Database. J Clin Epidemiol 1999; 6: 499-502.
    PubMedSearch in Google Scholar
  • 20 Guess HA, West R, Strand LM, Helston D, Lydick EG, Bergman U, Wolski K. Fatal upper gastrointestinal hemorrhage or perforation among users and nonusers of anti-inflammatory drugs in Saskatchewan, Canada 1983. J Clin Epidemiol 1988; 41: 35-45.
    CrossrefPubMedSearch in Google Scholar
  • 21 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.
    CrossrefPubMedSearch in Google Scholar
  • 22 Tulloch J, Wright IS. Long-term anticoagulant therapy: further experiences. Circulation 1984; 9: 823-34.
    PubMedSearch in Google Scholar
  • 23 Wintzen AR, Tijsen JGP, De Vries WA, Loeliger EA, Roos J. Risks of long-term oral anticoagulant therapy in elderly patients after myocardial infarction. Second report of the Sixty Plus Reinfarction Study Research Group. Lancet 1982; 1: 64-8.
    PubMedSearch in Google Scholar
  • 24 Thrombosis prevention trial: randomised trial of low-density oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk.. The Medical Research Council’s General Practice Research Framework. Lancet 1998; 351: 233-41.
    CrossrefPubMedSearch in Google Scholar
  • 25 Gullov AL, Koefoed BG, Petersen P. Bleeding during warfarin and aspirin therapy in patients with atrial fibrillation: the AFASAK 2 study. Atrial fibrillation Asprin and Anticoagulation. Arch Intern Med 1999; 159: 1322-8.
    CrossrefPubMedSearch in Google Scholar
  • 26 Palareti G, Hirsh J, Legnani C, Manotti C, D’Angelo A, Pengo V, Moia M, Guazzaloca G, Musolesi S, Coccheri S. Oral anticoagulation treatment in the elderly. Arch Intern Med 2000; 160: 470-8.
    CrossrefPubMedSearch in Google Scholar
  • 27 Fihn SD, Callahan CM, Martin DC, McDonell MB, Henikoff JG, White RH. The risk and severity in elderly patients treated with warfarin. Ann Intern Med 1996; 124: 970-9.
    CrossrefPubMedSearch in Google Scholar
  • 28 Levy M, Miller DR, Kaufman DW, Siskind V, Schwingl P, Rosenberg L, Strom B, Shapiro S. Major upper gastrointestinal tract bleeding. Relation to the use of aspirin and other nonnarcotic analgesics. Arch Intern Med 1998; 148: 281-5.
    PubMedSearch in Google Scholar
  • 29 Weil J, Colin-Jones D, Langman M, Lawson D, Logan R, Murphy M, Rawlins M, Vessey M, Wainwright P. Prophylactic aspirin and risk of peptic ulcer bleeding. BMJ 1995; 310: 827-30.
    CrossrefPubMedSearch in Google Scholar
  • 30 Kelly JP, Kaufman DW, Jurgelon JM, Sheehan J, Koff RS, Shapiro S. Risk of aspirin-associated major upper gastrointestinal bleeding with enteric-coated or buffered product. Lancet 1996; 348: 1413-6.
    CrossrefPubMedSearch in Google Scholar
  • 31 Griffin MR, Piper JM, Daugherty JR, Snowden M, Ray WA. Nonsteroidal anti-inflammatory drug use and increased risk for peptic ulcer disease in elderly persons. Ann Intern Med 1991; 114: 257-63.
    CrossrefPubMedSearch in Google Scholar
  • 32 Singh G, Triadafilopoulus G. Epidemiology of NSAID-induced GI complications. J Rheumatol 1999; 26 (Suppl. 26) 18-24.
    PubMedSearch in Google Scholar
  • 33 Conn H, Poynard T. Corticosteroids and peptic ulcer: metaanalysis of adverse events during steroid therapy. J Intern Med 1994; 236: 619-32.
    CrossrefPubMedSearch in Google Scholar
  • 34 Piper JM, Ray WA, Daugherty JR, Griffin MR. Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. Ann Intern Med 1991; 114: 735-40.
    CrossrefPubMedSearch in Google Scholar
  • 35 Errichetti AM, Holden A, Ansell J. Management of oral anticoagulant therapy: experience with an anticoagulation clinic. Arch Intern Med 1984; 144: 1966-8.
    CrossrefPubMedSearch in Google Scholar
  • 36 LaPorte JR, Carne X, Vidal X, Moreno V, Juan J. Upper gastrointestinal bleeding in relation to previous use of analgesics and nonsteroidal anti-inflammatory drugs. Lancet 1991; 337: 85-9.
    CrossrefPubMedSearch in Google Scholar
  • 37 Aithal GP, Day CP, Kesteven PJ, Daly AK. Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirements and risk of bleeding complications. Lancet 1999; 353: 717-9.
    CrossrefPubMedSearch in Google Scholar