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GI Safety of COX-2 Inhibitors: Cochrane Collaboration Systematic Review
Adverse GI events are less common with COX-2 inhibitors than with NSAIDs, but we still have to weigh overall harms and benefits before prescribing these agents.
Many trials have indicated that individual selective cyclooxygenase (COX)-2 inhibitors lower risk for gastrointestinal complications and ulcers compared with nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). Although some of these head-to-head trials have been very large, researchers have never performed a large trial to evaluate the effects of COX-2 inhibitors as a drug class.
To address this gap, investigators with the Cochrane Collaboration performed a systematic review of data from head-to-head trials of individual COX-2 inhibitors (celecoxib, rofecoxib, etoricoxib, valdecoxib, or lumiracoxib) versus nonselective NSAIDs or placebo. An extensive literature search identified 69 randomized controlled trials (some unpublished) in which ulcer complications, endoscopic ulcers, or adverse GI symptoms were reported.
The meta-analysis showed that, compared with nonselective NSAIDs, COX-2 inhibitors were associated with significantly fewer gastroduodenal ulcers (relative risk, 0.26; 95% CI, 0.23–0.30), important ulcer complications (RR, 0.39; 95% CI, 0.31–0.50), and study withdrawals for GI symptoms (RR, 0.65; 95% CI, 0.57–0.73). Concomitant use of aspirin, however, lowered the protective effect of COX-2 in subgroup analyses. The authors concluded that selective COX-2 inhibitors offered a clear GI safety and tolerability advantage over nonselective NSAIDs, but that this benefit must be weighed against the increased cardiovascular risk seen with some coxibs. They also note that coadministering aspirin has not been effective for lowering cardiovascular risk and can mitigate the GI advantages of COX-2 inhibitors.
Comment: Cochrane reviews, such as this, are particularly valuable because of the rigorous methodology used to identify relevant studies and combine data. In this case, some of the studies were available only on the FDA website. The review also contains additional analyses on individual NSAIDs and the effect of drug dose on risk. Although the results of this meta-analysis are consistent with large trials of individual drugs, the combined analysis of COX-2 inhibitors as a drug class provides important information for clinicians. That COX-2 inhibitors offer a significant GI safety advantage over nonselective NSAIDs is clear; however, as with any other therapy, potential risks associated with treatment (in this case, more adverse cardiovascular events) must be weighed against potential benefits (in this case, fewer GI complications). As new COX-2 inhibitors are introduced and older agents are reintroduced, this balance between safety and harm will become the critical decision point for determining which NSAID to prescribe to patients who have risk factors for GI complications.
— David J. Bjorkman, MD, MSPH (HSA), SM (Epid.)
Published in Journal Watch Gastroenterology September 21, 2007
Citation(s):
Rostom A et al. Gastrointestinal safety of cyclooxygenase-2 inhibitors: A Cochrane Collaboration systematic review. Clin Gastroenterol Hepatol 2007 Jul; 5:818.
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