Celecoxib atop PPI bests naproxen in cutting recurrent GI bleeds
Celecoxib is preferred over naproxen when added to proton-pump inhibitor (PPI) for preventing recurrent upper gastrointestinal (GI) bleeding in patients at high risk of both GI and cardiovascular (CV) events, who require concomitant aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs), according to the CONCERN* study.
Current guidelines provide conflicting recommendations for this group of high-risk patients who continue to require NSAIDs, according to the researchers. There were also concerns that “the superior gastric safety of COX-2**-selective NSAIDs over nonselective NSAIDs might disappear with the concomitant use of aspirin.”
“Contrary to present guidelines, we found that naproxen cannot be recommended to these high-risk patients despite its perceived CV benefit,” they claimed.
Of the 45 cases of recurrent upper GI bleeding identified by an adjudication committee, 14 cases were reported in the celecoxib group compared with 31 cases in the naproxen group. None of them had recurrent Helicobacter pylori infection. [Lancet 2017;doi:10.1016/S0140-6736(17)30981-9]
At 18 months, recurrent upper GI bleeding occurred in a significantly lower proportion of patients in the celecoxib group compared with the naproxen group (cumulative incidence, 5.6 percent vs 12.3 percent; p=0.008, and crude hazard ratio [HR], 0.44; p=0.01). According to the researchers, the HR remained the same after adjusting for concomitant aspirin use.
“Importantly, these high-risk patients should avoid using naproxen because even cotherapy with [PPI] does not adequately prevent recurrent bleeding,” they added.
Although the researchers noted that the study was not powered to evaluate CV safety of NSAIDs, no statistically significant difference was found between the two groups (cumulative incidence of CV events, 4.4 percent vs 5.5 percent; p=0.543, and crude HR, 0.78; p=0.544).
Excluding those who had reached study endpoints, the proportion of patients who discontinued treatment due to adverse events was similar in both celecoxib and naproxen groups (8 percent [n=21] vs 7 percent [n=17]). There was no death related to the study drugs.
The single-centre, double-blind, double-dummy trial enrolled patients with cardiothrombotic diseases and arthritis who presented with upper GI bleeding and who required concomitant NSAIDs and aspirin. After ulcer healing, 514 patients (54 percent males) negative for H. pylori were randomized on a 1:1 ratio to receive esomeprazole 100 mg once daily plus either celecoxib 100 mg twice daily or naproxen 500 mg twice daily for 18 months. All patients continued with aspirin 80 mg once daily.
“Avoidance of all NSAIDs will be the safest approach in these high-risk patients, but in patients who continue to require concomitant NSAIDs and aspirin, celecoxib plus a [PPI] encompass the least risk of recurrent upper [GI] bleeding,” said the researchers.
“From a GI perspective, naproxen is known to be riskier than celecoxib,” said Drs Patricia McGettigan and Anne-Marie Schjerning Olsen of Queen Mary University of London, UK, and Copenhagen University Hospital Herlev and Gentofte in Denmark, respectively in a separate commentary. “However, the superiority [of celecoxib] is relative. Neither option was safe.” [Lancet 2017;doi:10.1016/S0140-6736(17)30980-7
“The trial’s lost opportunity to fully inform guidelines is its failure to include a non-NSAID treatment group [in aspirin users],” they continued. “[Therefore, clinicians] are left to make a lesser of two evils recommendation as opposed to knowing the excess risk of either NSAID over simple analgesia [without NSAID].”