Celecoxib superior to naproxen for reducing risk of recurrent GI bleeding

Last Updated: 2017-04-28

By Megan Brooks

NEW YORK (Reuters Health) - For patients with a history of upper GI bleeding while taking a non-steroidal anti-inflammatory drug (NSAID) and aspirin who need to continue both drugs, celecoxib with a proton-pump inhibitor (PPI) is “the preferred treatment” to reduce the risk of recurrent GI bleeding, researchers advise based on results of the CONCERN study.

“Naproxen should be avoided despite its perceived cardiovascular safety,” the investigators conclude in their report online April 11 in The Lancet.

In a joint email to Reuters Health, lead investigators Dr. Francis Chan and Dr Moe Kyaw of The Chinese University of Hong Kong noted that there are at least seven national and international guidelines on the use of NSAIDs.

“For patients with high GI risk and high cardiovascular risks requiring concomitant aspirin and NSAIDs, the guidelines are very conflicting. They either offer no advice or suggest avoidance of all NSAIDs, or advocate naproxen as the preferred NSAID. None of these recommendations are evidence-based,” they said.

The CONCERN study tested whether the COX-2 selective NSAID celecoxib plus a PPI is superior to the non-selective NSAID naproxen plus a PPI for prevention of recurrent ulcer bleeding in concomitant users of aspirin with previous GI bleeding.

The study enrolled 514 H. pylori-negative patients who presented with upper GI bleeding, were on NSAIDs and required concomitant aspirin. After ulcer healing, patients were randomly allocated (1:1) to esomeprazole 20 mg once daily plus either celecoxib 100 mg twice daily or naproxen 500 mg twice daily. All patients resumed aspirin 80 mg once daily.

Recurrent upper GI bleeding within 18 months (the primary outcome) occurred in fewer patients on celecoxib (14 patients, nine gastric ulcers and five duodenal ulcers) than on naproxen (31 patients, 25 gastric ulcers, three duodenal ulcers, one gastric ulcer and duodenal ulcer, and two bleeding erosions).

The cumulative incidence of recurrent bleeding in 18 months was 5.6% in the celecoxib group versus 12.3% in the naproxen group (p=0.008; crude hazard ratio, 0.44, p=0.010).

Twenty-one (8%) patients in the celecoxib group and 17 (7%) in the naproxen group had adverse events leading to discontinuation of treatment. There were no treatment-related deaths.

“Our findings have shown that among these high risk patients, naproxen plus aspirin should be avoided despite co-therapy with a PPI. Instead, a combination of celecoxib, aspirin and PPI is the preferred treatment if pain cannot be relieved by simple analgesics,” said Dr. Chan and Dr. Kyaw. “Therefore, we believe our findings provide important novel data for various guideline committees towards revising their recommendations to improve our care for these high-risk patients.”

The authors of a linked comment note that while celecoxib was shown to be superior to naproxen, “the superiority is relative,” as neither option was safe given the cumulative incidence of recurrent GI bleeding of 5.6% with celecoxib and 12.3% with naproxen.

“From a public health perspective, the trial adds modestly to the body of knowledge on the benefit-risk balance of NSAID use, albeit for a very select population of patients,” write Dr. Patricia McGettigan from Queen Mary University of London, U.K., and Dr. Anne-Marie Schjerning Olsen of Copenhagen University Hospital, Denmark.

“Because the trial provides no way of knowing if the proportion of patients with upper gastrointestinal bleeding exceeded what would happen with non-use of NSAIDs, patients, clinicians, and guideline writers are left to make a lesser of two evils recommendation as opposed to knowing the excess risk of either NSAID over simple analgesia. Until this is known and in the absence of explicit criteria defining NSAID need, the substantial proportion of patients with rebleeding reported in the Article should reinforce NSAID avoidance in people with previous upper gastrointestinal bleeding,” they conclude.

The CONCERN study was funded by The Research Grant Council of Hong Kong. Dr. Chan reported financial ties to Pfizer, which sells celecoxib as Celebrex.

SOURCE: http://bit.ly/2pmBTxK and http://bit.ly/2qbeMGB

Lancet 2017.