Case-Control Study of Major Upper Gastrointestinal Bleeding (UGIB) and Gastric Ulceration

Objectives

To evaluate the risk of major upper gastrointestinal bleeding (UGIB) in relation to the use of drugs, in particular nonnarcotic analgesics and NSAIDs.

To quantify associations between individual analgesics and NSAIDs and UGIB.

To quantify associations between other factors and UGIB, where numbers permit.

Methods

For this case-control study, newly diagnosed cases of UGIB were identified from 25 hospitals in Eastern Massachusetts, 18 hospitals in the region of Stockholm , Sweden , and 12 hospitals in Budapest , Hungary . For each case, 2-3 neighbor ( U.S. and Sweden ) or hospital ( Hungary ) controls of the same age and sex as the cases were enrolled; the community controls were identified from census lists. Cases and controls were interviewed at home by telephone (U.S. and Sweden) or in person in the hospital (Hungary) to obtain information on recent analgesic and other drug use (including the duration, frequency, and for analgesics, dose of each episode), personal data and habits (e.g., marital status, cigarette smoking, alcohol consumption), and relevant medical history. For the cases, information on the symptoms and clinical course of their illness were also obtained, along with a copy of their hospital discharge summary. There were 1450 cases of UGIB and 3400 controls included in the study.

Results

Key published findings include associations with various NSAIDs; a dose-response relation of UGIB with alcohol consumption; a similar risk due to enteric coated and buffered aspirin compared with regular aspirin; and a lack of association with calcium channel blockers. The combined effects of NSAIDS and alcohol have also been documented, and the clinical characteristics of UGIB have been described.

Investigators and Study Staff

David Kaufman, Sc.D., Principal Investigator
Judith Kelly, M.S., Co-Investigator
Bengt-Erik Wiholm, M.D., Co-Investigator
Laszlo Andras, M.D., Co-Investigator

Study Details

Sources of Funding:

  • National Institute of Diabetes and Digestive and Kidney Diseases
  • National Corporation of Swedish Pharmacies
  • Multiple pharmaceutical companies

Study Period:

January 1987 to June 1996

Publications

  • Kelly JP, Laszlo A, Kaufman DW, Sundstrom A, Shapiro S. Major upper gastrointestinal bleeding and the use of calcium channel blockers [research letter]. Lancet 1999;353:559.
  • Kaufman DW, Kelly JP, Wiholm BE, Laszlo A, Sheehan JE, Koff RS, Shapiro S. The risk of acute major upper gastrointestinal bleeding among users of aspirin and ibuprofen at various levels of alcohol consumption. Am J Gastroenterol 1999;94:3189-96.
  • László A, Kelly JP, Kaufman DW, Sheehan JE, Rétsági G, Wilholm BE, Koff RS, Sundström A, Shapiro S. Clinical aspects of upper gastrointestinal bleeding associated with the use of nonsteroidal anti-inflammatory drugs. Am J Gastroenterol 1998;93:721-5.
  • 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.
  • Kelly JP, Kaufman DW, Koff RS, Laszlo A, Wiholm BE, Shapiro S. Alcohol consumption and the risk of major upper gastrointestinal bleeding. Am J Gastroenterol 1995;90:1058-64.
  • Kaufman DW, Kelly JP, Sheehan JE, Laszlo A, Wilhom BE, Alfredsson L, Koff R, Shapiro S. Nonsteroidal anti-inflammatory drug use in relation to major upper gastrointestinal bleeding. Clin Pharmacol Ther 1993;53:485-94.