Celecoxib Plus Esomeprazole Reduced Risk of Recurrent GI Bleeds

HONG KONG, May 14 -- For arthritis patients with a history of upper-GI bleeds, adding the proton pump inhibitor esomeprazole (Nexium) to celecoxib (Celebrex) significantly reduced the rate of such events, researchers reported here.

Patients randomized to the celecoxib plus esomeprazole had no bleeding events over the course of 13 months compared with an 8.9% bleeding rate in patients treated with celecoxib plus placebo (P=0.0004), according to a study published in the May 12 gastroenterology theme issue of The Lancet.

Francis Ka Leung Chan, M.D., of Chinese University of Hong Kong's pharmacy school, and colleagues, recruited 273 patients from a cohort of 441 consecutive patients who came to the hospital with gastrointestinal bleeding and were taking non-selective non-steroidal anti-inflammatory drugs (NSAIDs) for arthritis. All patients tested negative for Helicobactor pylori.

Of those patients, 137 were randomized to celecoxib (200 mg bid) plus esomeprezole (20 mg bid) and 136 to celecoxib plus placebo for 12 months. The primary endpoint was bleeding during treatment or bleeding up to one month following the end of treatment.

Patients were followed by phone at one month, and with in-person visits at two, four, six, eight, 10, 12, and 13 months. Hemoglobin assay, biochemical values, and compliance with drug regimen were assessed at each follow-up visit.

There were no significant differences in patients' reports of disease activity or pain control between the two groups.

The researchers noted that they used a celecoxib dose regularly used in practice at the time of the trial, but pointed out that physicians are now advised to prescribe the lowest effective dose of COX-2 inhibitors in view of their potential cardiovascular hazards.

But because there are no data that confirm a lower risk of gastrointestinal bleeding with lower dose celecoxib, the said, proton pump prophylaxis "is still recommended in patients at risk for ulcer bleeding even if they are receiving low-dose celecoxib."

The authors acknowledged that their study was limited by the lack of a comparator arm that randomized patients to a non-selective NSAID plus esomeprezole. Moreover, they said, the study did not address a best management strategy for patients who also have a history of cardiovascular disease.

In an accompanying editorial, James M. Scheiman, M.D., and A. Mark Fendrick, M.D., of the University of Michigan School of Medicine in Ann Arbor, said that cardiovascular risk should be evaluated for all patients. The appropriate regimen should take into account the fact that recent position statements suggest that naproxen is characterized by reduced cardiovascular risk compared to other selective and non-selective agents.

"For those at highest gastrointestinal risk," they wrote, "the use of a proton-pump inhibitor and a low-dose COX-2 inhibitor seems cost effective for those without high cardiovascular risk."

But for patients in whom cardiovascular risk is at least as great a concern as gastrointestinal bleeding, "naproxen with a proton-pump inhibitor is recommended when non-NSAID approaches fail," Drs. Scheiman and Fendrick concluded.