Risk of gastrointestinal bleedings in patients with total hip/knee replacements and matched controls: A population-based cohort study in Denmark

Introduction: Gastrointestinal (GI) bleedings may impose a serious threat in patients undergoing total hip and knee replacements (THR/TKR). However, timing and risk factors of GI bleedings in THR/TKR patients versus matched controls have not been studied. Objectives were to derive time-dependent hazard ratios (HR) and determinants for GI bleedings following THR/TKR, against matched controls. Methods: In a nationwide Danish cohort study, we selected all patients with a primary THR/TKR between 1998 and 2007 (n=95,213). Three control subjects without THR/TKR were matched by age, sex, and region. We used timedependent cox models to calculate disease and medication adjusted (adj.) HRs for GI bleedings with THR/TKR versus controls. Results: We identified a 4.4-fold increased risk of GI bleedings during the first six weeks following THR (adj. HR 4.39; 95 % CI 3.79-5.09), versus matched controls. The risk remained elevated in the 6-12 weeks post-THR (adj. HR 1.61; 95 % CI 1.31-1.98), and dropped to baseline afterwards. The six-week risk was highest among NSAID users (10-fold increase). Among non-selective NSAID users, we found a lower risk in those concomitantly using proton pump inhibitors (PPI, 2.3-fold increase), as compared to those without a PPI (11-fold increase). In TKR patients, risk of GI bleedings was only increased in the first six weeks (2.3-fold increase). Conclusion: This study demonstrates an increased risk of GI bleedings during the first six weeks following THR (4.4- fold), and TKR (2.3-fold). Risk assessment of GI bleedings may be considered during the first six weeks after THR/ TKR. The use of PPIs substantially reduces risk of GI bleedings when non-selective NSAIDs are prescribed to patients with a total joint replacement.