Proton Pump Inhibitor Therapy Reduces Peptic Ulcer Bleeding

March 13, 2007 — Proton pump inhibitors (PPIs) reduce incidence of peptic ulcer bleeding and the need for surgery, according to the results of a Cochrane meta-analysis of randomized controlled trials reported in the March issue of the Mayo Clinic Proceedings.

"In our original Cochrane Collaboration systematic review and meta-analysis, we found that proton pump inhibitor (PPI) treatment reduced rates of rebleeding and surgical intervention after peptic ulcer bleeding but did not reduce all-cause mortality," write Grigoris I. Leontiadis, MD, PhD, from the Democritus University of Thrace School of Medicine in Alexandroupolis, Greece, and colleagues. "We have updated our original review with the inclusion of more recent randomized controlled trials (RCTs). Our aim was to evaluate the overall benefit of PPI treatment in the management of ulcer bleeding since this is an important clinical issue with major associated health care costs."

By searching MEDLINE, EMBASE, CENTRAL, Cochrane Library, and metaRegister of Controlled Trials databases and published proceedings of major meetings through November 2004, the investigators identified 24 trials (4373 participants) that compared oral or intravenous PPIs with placebo or a histamine2-receptor antagonist for peptic ulcer bleeding. They also contacted pharmaceutical companies and other experts, and they performed data extraction and assessment of study validity independently in duplicate.

Evaluated outcomes were 30-day all-cause mortality, rebleeding, surgery, and repeated endoscopic treatment. Subgroup analyses and meta-regression were used to determine influence of study characteristics on outcomes.

Statistical heterogeneity was apparent only for rebleeding. Although PPI treatment had no significant effect on mortality (odds ratio [OR], 1.01; 95% confidence interval [CI], 0.74 - 1.40; number needed to treat [NNT], incalculable), PPI use was associated with significantly reduced rebleeding (OR, 0.49; 95% CI, 0.37 - 0.65; NNT, 13) and the need for surgery (OR, 0.61; 95% CI, 0.48 - 0.78; NNT, 34) and repeated endoscopic treatment (OR, 0.32; 95% CI, 0.20 - 0.51; NNT, 10).

When analysis was confined to blinded trials, results were similar. PPI treatment was associated with significantly reduced mortality in Asian trials (OR, 0.35; 95% CI, 0.16 - 0.74; NNT, 34) and in patients with active bleeding or a nonbleeding visible vessel (OR, 0.53; 95% CI, 0.31 - 0.91; NNT, 50).

"In ulcer bleeding, PPIs reduce rebleeding and the need for surgery and repeated endoscopic treatment," the authors write. "They improve mortality among patients at highest risk."

Study limitations include those inherent in a meta-analysis, lack of detailed information on comorbidity in Asian patients, lack of data on transfusion requirements in the additional trials included in the current updated meta-analysis, publication bias, large number of subgroup analyses, and heterogeneity among included trials.

"The main clinical implication of our findings is that PPI treatment should be initiated as soon as practicable in patients with ulcer bleeding," the authors conclude. "It reduces rebleeding and the requirements for surgical intervention and additional endoscopic hemostatic treatment. When appropriately combined with endoscopic hemostatic treatment, PPI treatment also improves mortality among patients with the highest-risk endoscopic findings."

Some of the authors have disclosed various financial relationships with AstraZeneca Pharmaceuticals LP, Janssen-Cilag, GlaxoSmithKline, Sanofi-Aventis, TAP Pharmaceutical Products Inc, Altana, Santarus, Inc, Schwarz Pharma, NEGMA-GILD, Allergan Inc, Novartis Consumer Health, Takeda Pharmaceuticals America, Inc, and Valeant Pharmaceuticals International, Takeda (Japan), Takeda (Austria), Abbott (Canada), Wyeth (US), and/or Wyeth (Ireland).

Mayo Clin Proc. 2007;82:286-296.

Source: http://www.medscape.com/viewarticle/553525?src=mp