Pantoprazole reduces upper gastrointestinal bleeding risk in ventilated patients

Key takeaways:

• Across several subgroups, pantoprazole decreased clinically important upper gastrointestinal bleeding more than placebo.
• A similar proportion of patients receiving pantoprazole vs. placebo died by day 90.

Fewer ventilated patients who received pantoprazole, a widely available proton-pump inhibitor, experienced clinically important upper gastrointestinal bleeding, according to research published in the New England Journal of Medicine.

“Physicians, nurses and pharmacists working in the ICU setting will use this information in practice right away, and the trial results ... will be incorporated into international practice guidelines,” Deborah Cook, MD, FRCPC, MSc, professor in the department of medicine at McMaster University, said in a press release.

In the international, randomized REVISE trial, Cook and colleagues evaluated 4,821 ICU patients (mean age, 58.2 years; 36.3% women; mean Acute Physiology and Chronic Health Evaluation [APACHE] II score, 21.7) undergoing invasive ventilation to assess the impact of 40 mg daily intravenous pantoprazole vs. a matching placebo on 90-day clinically important gastrointestinal (GI) bleeding and mortality.

Notably, researchers defined clinically important GI bleeding as “overt gastrointestinal bleeding with evidence of hemodynamic compromise or leading to therapeutic interventions in the ICU (or resulted in readmission to the ICU during the index hospital stay).”

In this patient population, 2,417 patients (mean age, 58.2 years; 36.5% women; APACHE II, 21.8) received pantoprazole, and 2,404 (mean age, 58.3 years; 36.2% women; APACHE II, 21.7) received placebo.

The median treatment period for both groups was 5 days, according to researchers.

Data on 90-day upper GI bleeding were available for 2,385 patients in the pantoprazole group and 2,377 patients in the placebo group.

Fewer patients in the pantoprazole group experienced clinically important upper GI bleeding than the placebo group at day 90 (1% vs. 3.5%), signaling a reduced risk for this outcome with pantoprazole (HR = 0.3; 95% CI, 0.19-0.47; P < .001).

Pantoprazole continued to be linked to a decreased risk for clinically important upper GI bleeding in several subgroups: sex, acid suppression use prior to hospitalization, APACHE II score (< 25 vs. 25), diagnosis at ICU admittance (surgical/trauma vs. medical) and SARS-CoV-2 status.

In contrast, 90-day mortality did not significantly differ between patients receiving pantoprazole and patients receiving placebo (29.1% vs. 30.9%). This result was found in all the above subgroups.

Further, ICU mortality and in-hospital mortality in the pantoprazole and placebo groups did not significantly differ.

Researchers also compared ventilator-associated pneumonia, Clostridioides difficile infection and patient-important bleeding between the two groups after adjusting for multiplicity.

When compared with patients receiving placebo, fewer patients receiving pantoprazole had patient-important GI bleeding, which researchers noted “was defined according to the ICU experience of patients and their families” (1.5% vs. 4.2%; HR = 0.36; 95% CI, 0.25-0.53; P < .001).

Within the pantoprazole and placebo groups, researchers found similar proportions of patients who experienced ventilator-associated pneumonia (23.2% vs. 23.8%) and a C. difficile infection (1.2% vs. 0.7%).

“It is unclear whether these trial results would apply to patients with unassisted breathing,” Cook and colleagues wrote.

Reference:

• Global trial confirms benefits of antacids on bleeding prevention for ventilated patients. https://www.eurekalert.org/news-releases/1048055. Published June 14, 2024. Accessed June 14, 2024.