High-Dose Proton Pump Inhibitors May Be No More Effective Than Lower Doses for Bleeding Peptic Ulcer
By Laurie Barclay, MD
Medscape Medical News
May 11, 2010 — High-dose proton pump inhibitors (PPIs) may be no more effective than lower doses for bleeding peptic ulcer, according to the results of a systematic review reported in the May 10 issue of the Archives of Internal Medicine. The article describing this systematic review and meta-analysis of randomized controlled trials is part of a series about PPIs published in the Archives of Internal Medicine entitled "Less Is More."
"High-dose...PPIs (80-mg bolus, followed by 8-mg/h continuous infusion for 72 hours) have been widely studied and used," write Chih-Hung Wang, MD, from National Taiwan University Hospital and National Taiwan University College of Medicine in Taipei, and colleagues. "However, to date no concrete evidence has shown that high-dose PPIs are more effective than non–high-dose PPIs."
The reviewers searched the literature for randomized controlled trials comparing rebleeding, surgical intervention, and mortality seen with the use of high-dose PPIs vs non–high-dose PPIs in patients with bleeding peptic ulcer. A meta-analysis of 1157 patients from 7 high-quality randomized studies combined outcomes data, which were reported as odds ratios (ORs).
Compared with non–high-dose PPIs, high-dose PPIs had statistically similar effects on rates of rebleeding (7 studies enrolling a total of 1157 patients; OR, 1.30; 95% confidence interval [CI], 0.88 - 1.91), surgical intervention (6 studies enrolling a total of 1052 patients; OR, 1.49; 95% CI, 0.66 - 3.37), and mortality (6 studies enrolling a total of 1052 patients; OR, 0.89; 95% CI, 0.37 - 2.13). Severity of signs of recent hemorrhage at initial endoscopy, route of PPI administration, or PPI dose did not affect summary outcome measures, according to the results of post hoc subgroup analyses.
"Compared with non–high-dose PPIs, high-dose PPIs do not further reduce the rates of rebleeding, surgical intervention, or mortality after endoscopic treatment in patients with bleeding peptic ulcer," the study authors write.
Limitations of this study include failure to use the intent-to-treat principle for data synthesis; lack of funnel plots to detect publication biases; and inclusion of only 7 studies, most of which enrolled few patients.
Editorial: Consider Other Treatments
In an accompanying editorial, Mitchell H. Katz, MD, from the San Francisco Department of Public Health, San Francisco, California, describes this systematic review as well as the other studies described in the series, "Less Is More."
"For most patients the adverse effects of PPIs outweigh the benefits," Dr. Katz writes. "Reducing the unnecessary use of these medications will require action by both physicians and patients. As physicians, we should offer treatments other than PPIs for functional dyspepsia, prescribe short courses of PPI treatment (after disclosure of possible risks and benefits), and consider a trial of discontinuing PPI therapy in patients who are asymptomatic."
The study authors have disclosed no relevant financial relationships.
Dr Katz is an independent consultant for Health Management Associates.