Nonsteroidal anti-inflammatory drug use in relation to major upper gastrointestinal bleeding

Abstract

In a study in the United States, Sweden, and Hungary, 335 cases of gastric bleeding without predisposing factors were compared with 670 control subjects, and 239 cases of duodenal bleeding were compared with 489 control subjects. For aspirin taken at least every other day during the week before the onset of bleeding (regular use), the relative risk of gastric bleeding was 4.4 (95% confidence interval [CI], 2.9 to 6.7); for occasional use, it was 3.3 (95% CI, 2.1 to 5.0). For ibuprofen, the corresponding estimates were 1.0 (95% CI, 0.4 to 2.6) and 1.1 (95% CI, 0.5 to 2.4). For naproxen, the estimate for regular use was 4.0 (95% CI, 1.5 to 11). The estimates for any use of piroxicam (crude estimate), indomethacin, and diclofenac during the week before onset were 18 (95% CI, 4.1 to 83), 1.6 (95% CI, 0.4 to 5.9), and 0.9 (95% CI, 0.2 to 4.2), respectively. The corresponding relative risks of duodenal bleeding were 7.1 (95% CI, 4.2 to 12) and 2.2 (95% CI, 1.3 to 3.7) for the regular and occasional use of aspirin, 2.4 (95% CI, 0.5 to 11) and 0.8 (95% CI, 0.3 to 2.0) for ibuprofen, 12 (95% CI, 2.8 to 54) and 9.9 (95% CI, 2.3 to 44) for naproxen, 17 (95% CI, 3.6 to 79) for any use of piroxicam (crude estimate), and 1.7 (95% CI, 0.2 to 14) for any use of indomethacin. There was a significant trend in the risk of gastric bleeding with increasing dose of regular aspirin use (p = 0.002). The relative risk estimates for the regular use of 325 mg or less were significantly elevated for both gastric and duodenal bleeding at 3.1 and 6.4, respectively.

Individual NSAIDs and Upper Gastrointestinal Complications

“…[12–16,21,22,27–32,34,68] Twelve studies, all case-control studies, were field studies collecting individual information by standardized questionnaires. The 16 remaining studies used information recorded in healthcare databases.…”

“…Cases were defined as hospitalization or referral to a specialist for upper GI bleeding in 13 studies,[12,15,16,19–22,27–30,33,34] and for bleeding and/or perforation in 15 other studies; four studies also included cases of uncomplicated peptic ulcer. [14,17,33,68] The site of complication was defined as gastric and/or duodenal in all studies, and two included oesophageal complications.…”

“…Six studies conducted in healthcare databases did not conduct any validation of the cases identified. [14,17–20,68] Sixteen studies reported aggregate results for patients with and without a history of UGIC,[7,12–14,16,20–23,28,31–34,67,68] and 12 provided results for patients without a history of UGIC;[11,15,17–19,24–27,29,30,35] the remaining study was a case-crossover study. [14] Most studies excluded subjects with a history of a known cause of UGIC, including the use of gastrotoxic medications and life-threatening diseases (table II).…”

“…Four studies did not have any exclusion criteria. [20,22,28,34] Among the 14 case-control studies, seven included hospital controls;[12,13,16,21,29–31] five included both hospital and community controls;[22,27,28,32,34] one included community controls;[15] and two were case-crossover studies. [14,68] All case-control studies were matched on age, sex (except one study[16]), hospital or geographic area, and index date.…”

“…[17] In addition to age and sex, the most frequent confounders considered were a history of peptic ulcer (21 studies),[7,11,15–31,35,67] smoking (13 studies),[7,11,15,18,20,21,23,27–32] alcohol use (9 studies),[7,15,19,21,27,28,30–32] use of proton-pump inhibitors and anti-ulcer medications (11 studies),[16–23,30,67,68] and concurrent use of medications increasing the risk of UGIC (16 studies). [7,11,15,16,19–21,23,27,29–31,33,35,67,68] The quality of the studies measured with the NOS was, in general, very good: for the selection component, 12 studies had the maximum score of 4[7,11,15,22–25,32,33,35,67,68] and 13 studies had the next highest score of 3;[13,14,16–19,21,26,28,29,30,32,34] for comparability, 24 studies had the maximum score of 2;[7,11,14–19,21–33,35,67,68] and for the exposure/outcome component, 14 studies had the maximum score of 3[7,11,13,17–19,23–26,33,35,67,68] and 10 studies...…”