Impact of Adherence to Concomitant Gastroprotective Therapy on Nonsteroidal-Related Gastroduodenal Ulcer Complications

Background & Aims The clinical impact of nonadherence to gastroprotective agents (GPAs) coprescribed with anti-inflammatory therapies has not been evaluated. In a large, commercial, managed-care database, we retrospectively characterized the use of GPAs among patients receiving nonselective nonsteroidal anti-inflammatory drugs (ns-NSAIDs) or cyclooxygenase-2–selective inhibitors (coxibs) and determined the impact of nonadherence on the likelihood of gastroduodenal ulcer complications. Methods Analyses identified the populations of patients with concomitant histamine-2 receptor antagonist or proton pump inhibitor (PPI) therapy and determined adherence with the prescribed therapy with respect to the duration of anti-inflammatory treatment. Multivariate regression analyses modeled the association between adherence with concomitant protective therapy and the likelihood of upper gastrointestinal (GI) complications including peptic ulcer disease, ulcer, and/or upper-GI bleed. Results Among 144,203 patients newly prescribed anti-inflammatory therapies, 1.8% received concomitant GPA treatment (ns-NSAIDs, 1.4% vs coxibs, 2.6%; P < .0001). The likelihood of GPA use increased with the presence of risk factors: age older than 65 years (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.3–1.5) and prior history of peptic ulcer disease (OR, 2.5; 95% CI, 1.8–3.3), esophagitis/gastroesophageal reflux (OR, 3.8; 95% CI, 3.5–4.1), ulcer/upper-GI bleed (OR, 1.4; 95% CI, 1.2–1.5), or gastritis (OR, 2.5; 95% CI, 2.2–2.8). Of patients receiving concomitant PPI therapy, 68% had adherence rates of 80% or more. A significantly higher risk of upper-GI ulcers/complications was observed in ns-NSAID patients with adherence rates of less than 80% compared with adherence rates of 80% or more (OR, 2.4; 95% CI, 1.0–5.6), but no such relationship was observed among patients who took coxibs. Conclusions Few patients receive concomitant GPA therapy when prescribed anti-inflammatory treatment, although use increased with the presence of risk factors. Adherence to concomitant therapy is paramount to reducing GI events among ns-NSAID users and educational efforts should be undertaken to promote use of and adherence to GPA therapy among these patients.

Abbreviations used in this paper: CI, confidence interval, GERD, gastroesophageal reflux disorder, GI, gastrointestinal, GPA, gastroprotective agents, H2RA, histamine-2 receptor antagonist, ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification, ns-NSAID, nonselective nonsteroidal anti-inflammatory drug, OR, odds ratio, PPI, proton pump inhibitor, PUD, peptic ulcer disease