Acutely ill patients are at risk of stress-related gastrointestinal bleeding and prophylactic acid suppressants are frequently used. In this systematic review, we assessed the effects of stress ulcer prophylaxis (SUP) with proton pump inhibitors or histamine-2 receptor antagonists versus placebo or no prophylaxis in acutely ill hospitalised patients.
We conducted the review according to the PRISMA statement, the Cochrane Handbook, and GRADE, using conventional meta-analysis and trial sequential analysis (TSA). The primary outcomes were all-cause mortality, clinically important gastrointestinal bleeding and serious adverse events (SAEs). The primary analyses included overall low risk of bias trials.
We included 65 comparisons from 62 trials (n=9713); 43 comparisons were from intensive care units. Only 3 trials (n=3596) had overall low risk of bias. We did not find an effect on all-cause mortality (RR 1.03, 95% CI 0.94-1.14; TSA-adjusted CI 0.90-1.18; high certainty). The rate of clinically important gastrointestinal bleeding was lower with SUP (RR 0.62, 95% CI 0.43-0.89; TSA-adjusted CI 0.14-2.81; moderate certainty). We did not find a difference in pneumonia rates (moderate certainty). Effects on SAEs, Clostridium difficile enteritis, myocardial ischemia and health-related quality of life (HRQoL) were inconclusive due to sparse data. Analyses of all trials regardless of risk of bias were consistent with the primary analyses.
We did not observe a difference in all-cause mortality or pneumonia with SUP. The incidence of clinically important gastrointestinal bleeding was reduced with SUP, whereas any effects on SAEs, myocardial ischemia, Clostridium difficile enteritis and HRQoL were inconclusive.

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