Intermittent and Continuous PPI Therapy Produce Similar Results for Treating Bleeding Ulcers

Chicago—After patients with bleeding ulcers underwent successful endoscopic hemostasis, there was no difference if they received intermittent or continuous proton pump inhibitor (PPI) therapy, according to a systematic review and meta-analysis of randomized controlled trials. The groups had similar rates of re-bleeding and death.

Hamita Sachar, MD, the study’s lead author, presented the results on Sunday during a scientific session at Digestive Disease Week. She said current guidelines for this population recommend continuous intravenous PPI therapy for patients who have an ulcer with active bleeding, a non-bleeding visible vessel, or an adherent clot.

However, she noted that intermittent PPI is less expensive, is easier to administer, and requires less resource utilization than continuous PPI. Thus, she suggested that healthcare professionals should choose intermittent PPI instead of continuous PPI and change the standard of care for these patients.

Dr. Sachar said the current guidelines are based on data from a previous meta-analysis of randomized controlled trials that showed using continuous infusion PPI therapy led to a lower risk of re-bleeding, surgery, and mortality compared to groups who received placebo or no treatment. Intermittent PPI therapy also led to a decreased risk for re-bleeding compared with a placebo or no treatment group.

In this analysis, the researchers searched 3 major electronic databases from their inception through December 2013 as well as relevant abstracts from 2009 to 2013 from major medical conferences such as Digestive Disease Week, United European Gastroenterology Week, and the American College of Gastroenterology annual meeting. They also looked at the reference lists of prior systematic reviews.

The researchers only included randomized controlled trials of patients with bleeding gastric or duodenal ulcers with high-risk features such as active bleeding, non-bleeding visible vessels, and adherent clots that required endoscopic therapy with hemostasis. Patients in the studies were given PPI in intermittent doses and were compared with the recommended continuous infusion of 80 mg bolus administered intravenously followed by continuous infusion of 8 mg per hour for 3 days.

Studies were considered for inclusion if they had any of the following outcomes: re-bleeding, mortality, need for urgent intervention, red blood cell transfusions, and length of hospitalization.

The primary outcome of this analysis was re-bleeding within 7 days. Before conducting their analysis, the researchers defined the non-inferiority margin as up to a 3% absolute risk difference for re-bleeding within 7 days when comparing intermittent and continuous PPI treatment. Dr. Sachar said the margin was based on clinical judgment and from a prior meta-analysis that compared continuous infusion with placebo or no treatment. The 3% margin referred to the upper bound of a 95% confidence interval of the absolute risk difference.

After identifying more than 2400 studies, the researchers reviewed 24 studies before narrowing the final analysis to 13 studies that included 1691 patients. Of the 13 studies, 9 administered PPI intravenously and 4 administered PPI orally. Most of the studies followed a twice-daily dosing schedule. The cumulative dose of intermittent PPI ranged from 120 mg to 560 mg.

Ten of the 13 studies reported on the primary outcome of re-bleeding within 7 days. Of the 10, only 1 showed a significant difference between continuous and intermittent therapy.

According to the pooled analysis, the relative risk of re-bleeding was 0.72 when comparing intermittent and continuous therapy, meaning there was a lower risk of re-bleeding with the intermittent regimen. The results were similar for a sensitivity analysis that evaluated the intention-to-treat population. The treatment effect remained consistent across all pre-defined sub-groups, as well. Re-bleeding within 3 and 30 days also was less in the intermittent group compared with the continuous group.

The analysis had some limitations, according to Dr. Sachar. Eight of the 13 studies were not blinded, and the quality of the trials varied. However, she noted that sub-group analysis showed no significant interaction between the risk of bias and the treatment effect. She also mentioned that the researchers were unable to determine the most appropriate intermittent PPI regimen because there were a variety of regimens in the study. Still, subgroup analyses did not show significant interactions of treatment with dose, frequency, or route of administration of the intermittent PPI regimens.

—Tim Casey