Systematic review with meta-analysis: the gastrointestinal benefits of COX-2 selective inhibitors with concomitant use of low-dose aspirin

BACKGROUND: It is uncertain whether concurrent use of low-dose aspirin removes the gastrointestinal benefit displayed by COX-2 selective inhibitors (coxibs) when compared to traditional nonsteroidal anti-inflammatory drugs (NSAIDs).

AIM: To evaluate the gastrointestinal risks associated with coxibs and traditional NSAIDs and the interaction with concurrent use of low-dose aspirin.

METHODS: We searched MEDLINE, EMBASE and the Cochrane Library through April 2016 to identify randomised trials comparing the gastrointestinal risk between coxibs and traditional NSAIDs in patients taking or not taking low-dose aspirin. Results were combined using random effects meta-analysis. Subgroup analyses by concurrent use of aspirin were undertaken.

RESULTS: Eleven trials (84 150 participants) were included. The overall relative risk (RR) of coxibs vs. traditional NSAIDs for complicated gastrointestinal events was 0.54 (95% CI, confidence interval 0.32-0.92), with a significant subgroup difference (P = 0.04) according to concurrent use of aspirin (used: RR = 0.96, 95% CI 0.66-1.24; not used: RR = 0.33, 95% CI 0.14-0.83). The overall RR for clinical gastrointestinal events was 0.59 (95% CI 0.47-0.75), with a significant subgroup difference according to aspirin usage (P = 0.008; used: RR = 0.77, 95% CI 0.62-0.95; not used: RR = 0.50, 95% CI 0.39-0.64). Overall coxibs were associated with significantly lower risk of symptomatic ulcers (RR = 0.60, 95% CI 0.50-0.72) and endoscopic ulcers (RR = 0.29, 95% CI 0.16-0.53) than traditional NSAIDs; a significant subgroup difference was shown for endoscopic ulcers (P = 0.05) but not for symptomatic ulcers (P = 0.27).

CONCLUSION: Concomitant use of low-dose aspirin reduces but does not completely eliminate the gastrointestinal benefit of coxibs over traditional NSAIDs.