Objectives: Nonsteroidal anti-inflammatory drug (NSAID) use is a strong risk factor for peptic ulcer perforation, yet little is known about the outcome of this condition among NSAID users. We examined 30-day mortality after peptic ulcer perforation associated with the use of traditional NSAIDs and newer selective cyclo-oxygenase-2 (COX-2) inhibitors.

Methods: We conducted a cohort study of patients with the first hospitalization for peptic ulcer perforation, identified in discharge registries of three Danish counties between 1991 and 2003. Data on preadmission NSAID use, other ulcer-related drugs, and comorbidity were likewise from population-based registries. Mortality was ascertained from the Civil Registration System. We compared 30-day mortality in NSAID users and nonusers while adjusting for age, gender, comorbidity, previous uncomplicated peptic ulcer, and ulcer medication use.

Results: Of the 2,061 patients hospitalized with peptic ulcer perforation, 38% were current NSAID users. The 30-day mortality was 25% overall, and 35% among current NSAID users. Compared with never-use, the adjusted 30-day mortality rate ratios (MRRs) were 1.8 (95% CI 1.4-2.3) for current use of NSAIDs alone and 1.6 (95% CI 1.2-2.2) for current use combined with other ulcer-associated drugs. The mortality increase associated with the use of COX-2 inhibitors was similar to that of traditional NSAIDs: adjusted MRR for users of COX-2 inhibitors alone and in combination, 2.0 (1.3-3.1) and 1.4 (0.8-2.5), and for users of traditional NSAIDs alone or in combination, 1.7 (1.3-2.3) and 1.6 (1.2-2.3).

Conclusion: Current use of NSAIDs, including COX-2 inhibitors, is associated with a poor prognosis for patients hospitalized with peptic ulcer perforation.

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