For ICU patients at risk for gastrointestinal bleeding, prophylaxis with a proton-pump inhibitor (PPI) was not associated with any difference in the risk of death in 90 days compared to placebo, a study found.
The multicenter European trial included 3,298 patients who had been admitted to the ICU for an acute condition and were considered at risk for gastrointestinal bleeding, based on a history of liver disease, coagulopathy, shock, treatment with anticoagulant agents, renal replacement therapy, or mechanical ventilation expected to last more than 24 hours. Patients were randomized to either 40 mg of IV pantoprazole (n=1,645) or placebo (n=1,653) daily. Results were published by the New England Journal of Medicine on Oct. 24.
Data on the primary outcome, 90-day mortality, were available for 3,282 patients, and rates were similar between groups: 31.3% on pantoprazole versus 30.4% on placebo (relative risk, 1.02; 95% CI, 0.91 to 1.13; P=0.76). The groups were also similar for the secondary outcome, a composite of clinically important events during the ICU stay (gastrointestinal bleeding, pneumonia, Clostridium difficile infection, and myocardial ischemia): 21.9% on pantoprazole versus 22.6% on placebo (relative risk, 0.96; 95% CI, 0.83 to 1.11). Clinically important gastrointestinal bleeds were less common with pantoprazole than placebo (2.5% vs. 4.2%), but infections and serious adverse reactions were similar in both groups.
The finding that prophylaxis with a PPI was not associated with any change in rates of death or infectious complications supports a recent meta-analysis but differs from observational trials that have suggested increased risk of infectious complications and myocardial ischemia with PPIs, the authors said. They noted that their study did find a suggestion of higher mortality in patients with more severe disease who received pantoprazole and said this finding should be further investigated.
A strength of the trial was its size, but limitations included lack of assessment of other medical interventions, limited power, and no data on whether patients used acid suppressants before ICU admission or received enteral nutrition, the authors said. An accompanying editorial described the study's secondary outcome findings as difficult to interpret but noted that the study highlights the low prevalence of gastrointestinal bleeding in modern ICUs.
“In our view, the take-home message from this trial is that, given the low incidence of clinically important upper gastrointestinal bleeding in the ICU, prophylaxis with a PPI, if initiated, should be reserved for seriously ill patients who are at high risk for this complication,” the editorialists wrote.