Haemoglobin decreases in NSAID users over time: an analysis of two large outcome trials

Abstract

Aliment Pharmacol Ther 2011; 34: 808–816 Summary Background Nonsteroidal anti‐inflammatory drugs (NSAIDs) have been associated with clinically significant decreases in haemoglobin dependent and independent of acute bleeding events. Aim To evaluate the incidence and time to a clinically meaningful decrease in haemoglobin in two double‐blind, prospective randomised clinical trials comparing NSAIDs in patients with osteoarthritis (OA) or rheumatoid arthritis (RA). Methods In CLASS, patients with OA/RA who were aged ≥18 years and required continuous NSAID treatment were included; patients who were Helicobacter pylori positive and/or using aspirin were not excluded. In contrast, in the CONDOR trial, comparing celecoxib alone to diclofenac sustained release (plus omeprazole), patients were aged ≥60 years or ≥18 years with a history of gastroduodenal ulcer and were H. pylori negative; aspirin or other anti‐platelet users were excluded. To make a parallel post hoc analysis we limited our study to 6 months and the populations to only the non‐aspirin users in CLASS and those patients receiving either celecoxib or diclofenac. A decrease in haemoglobin of ≥2 g/dL defined the primary end point. Results At 6 months, in the CLASS and CONDOR trials, 1.9% and 2.0% of patients treated with celecoxib and 3.3% and 5.7% of patients treated with diclofenac developed a ≥2 g/dL decrease in haemoglobin, respectively, [CLASS: odds ratio (OR) 1.80 (95% confidence interval (CI), 1.22–2.65) and CONDOR: OR 2.93 (95% CI, 2.06–4.15), respectively]. Conclusion In these two large, independent trials, clinically‐meaningful decreases in haemoglobin ≥2 g/dL occurred in a relatively similar fashion over time despite differences in trial designs.