The following is a summary of “Associated Mortality Risk of Proton Pump Inhibitor Therapy for the Prevention of Stress Ulceration in Intensive Care Unit Patients,” published in the July 2023 issue of the Clinical Gastroenterology by Reynolds et al.
The objective was to systematically assess the potential risks and benefits associated with using proton pump inhibitors (PPIs) for stress ulcer prophylaxis in patients who are critically ill. The potential impact of proton pump inhibitors (PPIs) on mortality in critically ill patients continues to be debated in the medical community. A comprehensive examination and synthesis of randomized controlled trials (RCTs) and cohort studies using trial sequential analysis, Bayesian sensitivity analysis, and fragility index analysis. Extensive research was conducted on 31 medical studies involving 78,009 adults who were critically ill and received proton pump inhibitors (PPIs) compared to other treatment options. The use of proton pump inhibitors (PPIs) was associated with an increased mortality risk in all the studies analyzed. The mortality rate was 19.6% for those using PPIs compared to 17.5% for the comparator group.
The relative risk (RR) was 1.10, with a 95% CI of 1.02-1.20 and a P-value of 0.01. This association was also observed in the subgroup of randomized controlled trials (RCTs), where the mortality rate was 19.4% for PPI users and 18.7% for the comparator group. The RR was 1.05, with a 95% CI of 1.0-1.09 and a p-value of 0.04. However, there was no significant association between PPI use and mortality risk in cohort studies. The mortality rate was 19.9% for PPI users and 16.7% for the comparator group. The RR was 1.12, with a 95% CI of 0.98-1.28 and a p-value of 0.09. The findings were sustained through Bayesian sensitivity analysis (RR: 1.13; 95% credible interval: 1.035-1.227) and a fragility index analysis but not through sequential analysis (P=0.16). Randomized controlled trials (RCTs) involving patients with a more severe baseline illness demonstrated a higher mortality risk associated with the use of proton pump inhibitors (PPIs) compared to the comparator group (32.1% PPI vs. 29.4% comparator; relative risk: 1.09; 95% CI: 1.04-1.14; P-value <0.001).
The use of proton pump inhibitors (PPIs) demonstrated a decrease in clinically significant bleeding in randomized controlled trials (RCTs) (1.4% PPI vs. 2.1% comparator; relative risk (RR): 0.67; 95% CI: 0.5-0.9; P=0.009). However, cohort studies showed increased bleeding events associated with PPI use (2.7% PPI vs. 1.2% comparator; RR: 2.05; 95% CI: 1.2-3.52; P=0.009). The utilization of proton pump inhibitors (PPIs) did not demonstrate a correlation with a decreased occurrence of medically significant hemorrhaging in comparison to histamine-2 receptor antagonists (1.3% vs. 1.9%; relative risk: 0.59; 95% CI: 0.28-1.25, P=0.09). This meta-analysis revealed a correlation between using proton pump inhibitors (PPIs) and heightened susceptibility to mortality.