Aims: Oral and intravenous proton pump inhibitors (PPIs) are equipotent in raising gastric pH. However, it is not known whether oral PPIs can replace intravenous PPIs in patients with bleeding peptic ulcers. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials to compare oral and intravenous PPIs among patients with peptic ulcer bleeding. A search of all major databases and relevant journals from inception to April 2015, without a restriction on languages, was performed. Results: A total of 859 patients from seven randomized controlled trials were included in the meta-analysis. Similar pooled outcome measures were demonstrated between the two groups in terms of oral PPIs vs. intravenous PPIs in the rate of recurrent bleeding within the 30-day follow-up period [risk ratio = 0.90; 95% confidence interval (CI): 0.58, 1.39; P = 0.62; I2 = 0%). In terms of the rate of mortality, both oral and intravenous PPIs showed similar outcomes, and the pooled risk ratio was 0.88 (95% CI: 0.29, 2.71; P = 0.82; I2 = 0%). Likewise, no significant difference was detected in the need for blood transfusion and length of hospital stay; the pooled mean differences were -0.14 (95% CI: -0.39, 0.12; P = 0.29; I2 = 32%) and -0.60 (95% CI: -1.42, 0.23; P = 0.16; I2 = 79%), respectively. Conclusions: Our results suggest that oral PPIs are a feasible, safe alternative to intravenous PPIs in patients with bleeding peptic ulcers, and may be able to replace intravenous PPIs as the treatment of choice in these patients.
IMPORTANCE: Current guidelines recommend an intravenous bolus dose of a proton pump inhibitor (PPI) followed by continuous PPI infusion after endoscopic therapy in patients with high-risk bleeding ulcers. Substitution of intermittent PPI therapy, if similarly effective as bolus plus continuous-infusion PPI therapy, would decrease the PPI dose, costs, and resource use.
OBJECTIVE: To compare intermittent PPI therapy with the currently recommended bolus plus continuous-infusion PPI regimen for reduction of ulcer rebleeding.
DATA SOURCES: Searches included MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases through December 2013; US and European gastroenterology meeting abstracts from 2009 to 2013; and bibliographies of systematic reviews.
STUDY SELECTION: Randomized trials of patients with endoscopically treated high-risk bleeding ulcers (active bleeding, nonbleeding visible vessels, and adherent clots) comparing intermittent doses of PPIs and the currently recommended regimen (80-mg intravenous bolus dose of a PPI followed by an infusion of 8 mg/h for 72 hours).
DATA EXTRACTION AND SYNTHESIS: Duplicate independent data extraction and risk-of-bias assessment were performed. Data were pooled using a fixed-effects model or a random effects model if statistical heterogeneity was present.
MAIN OUTCOMES AND MEASURES: The primary outcome was rebleeding within 7 days; additional predefined outcomes included rebleeding within 3 and 30 days, need for urgent intervention, mortality, red blood cell transfusion, and length of hospital stay. The primary hypothesis, defined before initiation of the literature review, was that intermittent use of PPIs was noninferior to bolus plus continuous infusion of PPIs, with the noninferiority margin predefined as an absolute risk difference of 3%.
RESULTS: The risk ratio of rebleeding within 7 days for intermittent vs bolus plus continuous infusion of PPIs was 0.72 (upper boundary of 1-sided 95% CI, 0.97) and the absolute risk difference was -2.64% (upper boundary of 1-sided 95% CI, -0.28%, which is well below the predefined noninferiority margin of 3%). Risk ratios for rebleeding within 30 days and 3 days, mortality, and urgent interventions were less than 1 and mean differences for blood transfusion and hospital length of stay were less than 0, indicating that no summary estimate showed an increased risk with intermittent therapy. The upper boundaries of 95% CIs for absolute risk differences were less than 1.50% for all predefined rebleeding outcomes.
CONCLUSIONS AND RELEVANCE: Intermittent PPI therapy is comparable to the current guideline-recommended regimen of intravenous bolus plus a continuous infusion of PPIs in patients with endoscopically treated high-risk bleeding ulcers. Guidelines should be revised to recommend intermittent PPI therapy.
Aims: Oral and intravenous proton pump inhibitors (PPIs) are equipotent in raising gastric pH. However, it is not known whether oral PPIs can replace intravenous PPIs in patients with bleeding peptic ulcers. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials to compare oral and intravenous PPIs among patients with peptic ulcer bleeding. A search of all major databases and relevant journals from inception to April 2015, without a restriction on languages, was performed. Results: A total of 859 patients from seven randomized controlled trials were included in the meta-analysis. Similar pooled outcome measures were demonstrated between the two groups in terms of oral PPIs vs. intravenous PPIs in the rate of recurrent bleeding within the 30-day follow-up period [risk ratio = 0.90; 95% confidence interval (CI): 0.58, 1.39; P = 0.62; I2 = 0%). In terms of the rate of mortality, both oral and intravenous PPIs showed similar outcomes, and the pooled risk ratio was 0.88 (95% CI.: 0.29, 2.71; P = 0.82; I2 = 0%). Likewise, no significant difference was detected in the need for blood transfusion and length of hospital stay; the pooled mean differences were -0.14 (95% CI.: -0.39, 0.12; P = 0.29; I2 = 32%) and -0.60 (95% CI.: -1.42, 0.23; P = 0.16; I2 = 79%), respectively. Conclusions: Our results suggest that oral PPIs are a feasible, safe alternative to intravenous PPIs in patients with bleeding peptic ulcers, and may be able to replace intravenous PPIs as the treatment of choice in these patients.
Systematic Review Question»Systematic review of interventions
