Risk of Recurrent Peptic Ulcer Disease in Patients Receiving Cumulative Defined Daily Dose of Nonsteroidal Anti-Inflammatory Drugs

The purpose of this population-based case–control study was to clarify the impact of cumulative dosage of nonsteroidal anti-inflammatory drugs (NSAIDs) on recurrent peptic ulcers among chronic users after Helicobacter pylori (H. pylori) eradication. We analyzed data of 203,407 adult peptic ulcer disease (PUD) patients from the National Health Insurance Research Database in Taiwan entered between 1997 and 2013. After matching for age/gender frequencies and the length of follow-up time in a ratio of 1:1, the matched case–control groups comprised 1150 patients with recurrent PUD and 1150 patients without recurrent PUD within 3 years of follow-up. More recurrent PUDs occurred in NSAID users than in the control group (75.30% versus 69.74%; p = 0.0028). Independent risk factors for recurrent PUD included patients using NSAIDs (adjusted OR (aOR): 1.34, p = 0.0040), H. pylori eradication (aOR: 2.73; p < 0.0001), concomitant H2 receptor antagonist (aOR: 1.85; p < 0.0001) and anti-coagulant (aOR: 4.21; p = 0.0242) use. Importantly, in the initial subgroup analysis, the risk ratio of recurrent PUD did not increase in NSAID users after H. pylori eradication compared with that in non-users (p = 0.8490) but a higher risk for recurrent PUD with the increased doses of NSAIDs without H. pylori eradication therapy (aOR: 1.24, p = 0.0424; aOR: 1.47, p = 0.0074; and aOR: 1.64, p = 0.0152 in the groups of ≤28, 29–83, and ≥84 cumulative defined daily doses, respectively). The current study suggested that H. pylori eradication therapy could decrease the risk of recurrent PUD among patients with high cumulative doses of NSAIDs.