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

Date Published: October 02, 2011

Publisher: Blackwell Publishing Ltd

Author(s): J L Goldstein, F K L Chan, A Lanas, C M Wilcox, D Peura, G H Sands, M F Berger, H Nguyen, J M Scheiman.


Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with clinically significant decreases in haemoglobin dependent and independent of acute bleeding events.

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).

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.

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].

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.

Partial Text

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely prescribed class of drugs worldwide1 because of their anti-inflammatory, anti-pyretic and analgesic properties. However, despite their well-accepted efficacy, chronic use of NSAIDs is associated with an increased risk of gastrointestinal (GI) mucosal injury and overt bleeding events.2, 3

Our study demonstrates that continuous 6-month exposure to NSAIDs is associated with a clinically meaningful decrease in haemoglobin; a meaningful decline in haemoglobin was observed in all of the treatment arms in both trials in the absence of aspirin use. However, despite differences in the study design and population of the two trials, these results were reproducible for both. Furthermore, the studies demonstrated that patients treated with diclofenac were two- to threefold more likely to reach the meaningful end point than patients treated with the COX-2 selective NSAID celecoxib. We believe that this information focused on the development of progressive haemoglobin decreases with the chronic use of NSAIDs, independent of acute bleeding events, and highlights the relatively understudied clinical issue of long-term chronic occult blood loss.