Variation in the risk of peptic ulcer complications with nonsteroidal antiinflammatory drug therapy

Abstract

Objective. To assess the risk of perforation or hemorrhage of peptic ulcer on treatment with nonsteroidal antiinflammatory drugs (NSAIDs), both as a class and as individual agents.Methods. A case-control study of medication histories in 494 patients and 972 matched control subjects.Results. The increase in risk (odds ratio) with NSAID therapy was 5.1 times the risk in controls. The odds ratio for piroxicam was 6.3 (95% confidence interval [CI] 3.3-12.0), as compared with 2.9 for diclofenac, ketoprofen, and sulindac combined (95% CI 2.0-4.2). The effect of other risk factors was also considered, and the adjusted odds ratios were 4.1 for all NSAIDs, 6.4 (95% CI 2.8-15.0) for piroxicam, and 3.3 (95% CI 2.G5.5) for diclofenac, ketoprofen, and sulindac combined.Conclusion. in other studies. There appear to be differences in risk between agents.It is well known that treatment with nonsteroidal antiinflammatory drugs (NSAIDs) is associated with unwanted gastrointestinal (GI) side effects. Retrospective studies have suggested that NSAIDs are associated with an increased risk of perforated peptic ulcer (1,2), and case-control studies have shown a risk factor of 2-4 for hemorrhage of peptic ulcers (3,4) in patients aged 60 years and over. Data from the UK Committee on Safety of Medicines ( 5 ) showed that for the NSAIDs currently available in New Zealand, reports of GI reactions ranged from 21 to 75 per million prescriptions.To ascertain the relative risks with the various NSAIDs, a case-control study of hemorrhage and perforation of peptic ulcer was begun early in 1986. The aim of this study was to confirm an increased risk of complications of peptic ulcer with NSAIDs and to determine whether there are significant differences between the available agents. PATIENTS AND METHODSSelection of patient population. It was estimated that to detect a 3-fold underrepresentation or a 2-fold overrepresentation in the case group of individual NSAIDs having 15% or more of the market share, and assuming an overall increase in risk of 3-fold, the study would require 450 index patients and 900 control subjects (a = 0.05, p = 1 -0.8). To this end, patients in Christchurch and surrounding areas (population 350,000) who were admitted to the hospital because of GI hemorrhage or possible perforation were identified within 24 hours by either the admitting diagnosis or the findings after admission. All such cases are admitted to

Individual NSAIDs and Upper Gastrointestinal 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...…”

Association between aspirin and upper gastrointestinal complications: Systematic review of epidemiologic studies

“…Studies often had the following exclusion criteria: cancer (n=10), oesophageal varices (n=10), Mallory-Weiss disease (n=10), alcoholism (n=7), chronic liver disease (n=7) or/and coagulopathies (n=6). Aspirin exposure was de®ned as use during the last week in nine studies, use in the last month in three studies, and use reaching the index date or prescriptions that would cover the index date in the other 1 2 De Abajo [58] 3 4 5 6 7 8 9 10 11 12 Sorensen [57] García Rodríguez [55] Pérez Gutthan [54] McMahon [52] Hallas [49] Cohorts Lanas [56] Wilcox [53] Matikainen [52] Kelly [51] Weil [48] Savage [47] Henry [46] Keating [45] Nobili [38] Holvoet [44] Laporte [43] Case/control 0 1 3 14 15 2.2 3.1 Figure 1 Relative risks and 95% con®dence interval reported in original publications on aspirin use and UGIC during 1990 ±2001, strati®ed by study design. ®ve studies.…”

“…However, the risk was still elevated for doses up to 300 mg day x1 . Studies reported a signi®cantly increased risk of UGIC with daily doses below 300 mg, [47,56] 150 mg [46,57], and even as low as 75 mg [48,58] (Table 3).…”