Prophylactic use of acid suppressants in adult acutely ill hospitalised patients: A systematic review with meta‐analysis and trial sequential analysis

Background Acutely ill patients are at risk of stress‐related gastrointestinal (GI) 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 (PPIs) or histamine‐2 receptor antagonists (H2RAs) versus placebo or no prophylaxis in acutely ill hospitalised patients. Methods 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 GI bleeding and serious adverse events (SAEs). The primary analyses included overall low risk of bias trials. Results We included 65 comparisons from 62 trials (n = 9713); 43 comparisons were from intensive care units. Only three 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 to 1.14; TSA‐adjusted CI 0.90 to 1.18; high certainty). The rate of clinically important GI bleeding was lower with SUP (RR 0.62, 95% CI 0.43 to 0.89; TSA‐adjusted CI 0.14 to 2.81; moderate certainty). We did not find a difference in pneumonia rates (moderate certainty). Effects on SAEs, Clostridium difficile enteritis, myocardial ischaemia 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. Conclusions We did not observe a difference in all‐cause mortality or pneumonia with SUP. The incidence of clinically important GI bleeding was reduced with SUP, whereas any effects on SAEs, myocardial ischaemia, Clostridium difficile enteritis and HRQoL were inconclusive. Study registration PROSPERO registration number CRD42017055676; published study protocol: Marker, et al 2017 in Systematic Reviews.