New research recommends celecoxib coadministration with a proton pump inhibitor over naproxen to prevent upper gastrointestinal bleeding in patients with arthritis who are at high risk for cardiovascular and gastrointestinal events but need to continue using nonsteroidal anti-inflammatory drugs (NSAIDs), according to recent research published in the Lancet.
“[C]elecoxib plus proton-pump inhibitor is the preferred treatment to reduce the risk of recurrent upper gastrointestinal bleeding in patients at high risk of both cardiovascular and gastrointestinal events who require aspirin and NSAID for cardiovascular and anti-inflammatory therapies,” Francis K.L. Chan, MD, from the Department of Medicine & Therapeutics and Institute of Digestive Disease at the Chinese University of Hong Kong in China, and colleagues wrote in their study.
“Contrary to present guidelines, naproxen should be avoided despite its perceived cardiovascular benefit. Our findings provide novel data toward future practice guidelines in NSAID choice for very high-risk patients.”
Dr Chan and colleagues enrolled 514 patients with arthritis and cardiothrombotic disease at high risk for gastrointestinal and cardiovascular events between May 2005 and November 2012 in a double-blinded, double-dummy, industry-independent trial to receive either celecoxib with a proton pump inhibitor or naproxen, according to the abstract.
Patients were taking NSAIDs with concomitant aspirin, had upper gastrointestinal bleeding, had a history of ulcer bleeding, and tested negative for Helicobacter pylori after ulcer healing.
High Yield Data Summary
- Study results suggest avoiding adding proton pump inhibitors to naproxen since no evidence was found to support that the treatment reduces the risk for recurrent bleeding in certain patients
The researchers randomly assigned patients to receive either twice-daily naproxen (500 mg) with once-daily esomeprazole (20 mg) or twice-daily celecoxib (100 mg) with once-daily esomeprazole (20 mg) for 18 months, in addition to once-daily aspirin (80 mg).
There were 14 patients in the celecoxib group and 31 patients in the naproxen group who developed recurrent upper gastrointestinal bleeding, which included 9 cases of gastric ulcers and 5 cases of duodenal ulcers in the celecoxib group and 25 cases of gastric ulcers, 3 cases of duodenal ulcers, 1 case of combination gastric and duodenal ulcers and 2 cases of bleeding erosions in the naproxen group.
Dr Chan and colleagues found 5.6% recurrent risk of developing recurrent bleeding in the celecoxib group (95% CI, 3.3%-9.2%) and a 12.3% risk for recurrent bleeding in the naproxen group (95% CI, 8.8%-17.1%).
Regarding adverse events, 8% of patients (n=21) in the celecoxib group and 7% of patients (n=17) in the naproxen group discontinued treatment; however, there were no deaths in the study.
Summary & Clinical Applicability
The researchers recommended avoiding naproxen with a proton pump inhibitor because the treatment does not reduce the risk for recurrent bleeding in these patients.
“Our findings address the major unmet need in the present guidelines on the management of patients at high risk of both cardiovascular and gastrointestinal events who continue to require anti-inflammatory analgesics,” Dr Chan and colleagues wrote.
“These patients have been largely neglected because none of the published studies sought to identify treatments to reduce the risk of life-threatening complications in these patients.”
Limitations & Disclosures
The researchers did not test the cardiovascular safety of celecoxib or the safety profile of naproxen at lower doses, and acknowledge the single-center nature of the study, in addition to the long requirement time potentially creating confounders.
Dr Chan is a consultant for Eisai, Pfizer, Takeda, and Otsuka, and is on the speaker’s bureau for Eisai, Pfizer, AstraZeneca, and Takeda. Dr Ng is on the speaker’s bureau for Ferring and Takeda. Dr Wu received grants from the National Institutes of Health and is on the speaker’s bureau for AstraZeneca and Takeda. The other researchers have no relevant financial disclosures.
Chan FKL, Ching JYL, Tse, YK, et al. Gastrointestinal safety of celecoxib versus naproxen in patients with cardiothrombotic diseases and arthritis after upper gastrointestinal bleeding (CONCERN): an industry-independent, double-blind, double-dummy, randomised trial [published online April 11, 2017]. Lancet. doi: 10.1016/S0140-6736(17)30981-9.