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High-dose intravenous PPI regimen no better than standard-dose regimen in preventing recurrent bleeding after endoscopic hemostasis of bleeding ulcers, researchers report

Friday, December 12 2008 | Comments

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What's This? Standard-dose proton pump inhibitor (PPI) infusion appears to be as effective as a high-dose regimen in reducing the risk of recurrent bleeding following endoscopic hemostasis of bleeding ulcers, according to data from a prospective, head-to-head study.

"Once primary hemostasis is achieved by endoscopic therapy, clinical trials show that a high-dose PPI infusion is superior to placebo; however, when the comparator is a standard-dose PPI regimen, 4 prospective trials and a meta-analysis report no difference in the magnitude of risk reduction between the intensive- and the low-dose regimens," the authors of the study wrote.

To compare the effectiveness of high- and standard-dose PPI regimens on the risk of recurrent bleeding, 474 patients with actively bleeding ulcers, nonbleeding visible vessels, or adherent clots were treated with epinephrine injection and/or thermal coagulation and were then randomized to receive intravenous PPI therapy according to an intensive regimen (80 mg bolus followed by 8 mg/hr for 72 hrs as a continuous infusion; n=238) or a standard regimen (40 mg bolus daily followed by saline infusion for 72 hrs; n=236) on a double-blind basis. All of the patients received oral PPIs at a dosage of 20 mg twice daily after the infusion.

Repeat bleeding--the primary endpoint--occurred in 28 patients (11.8%) in the high-dose group and in 19 patients (8.1%) in the standard-dose group, which translated to a nonsignificant between-group difference of 3.8%. Recurrent bleeding most commonly occurred during the period of intravenous administration; specifically, 16 patients (6.7%) in the high-dose group and 22 patients (9.3%) in the standard-dose group experienced rebleeding within the first 3 days.

Between-group rebleeding rates were similar for gastric and duodenal ulcers and for ulcer size smaller or larger than 2 cm. However, rebleeding was significantly more common in the patients with bleeding ulcers (29 of 205 patients) than in those with nonbleeding lesions (18 of 269 patients; P=.007).

Furthermore, a significantly larger proportion of the patients in the high-dose group required prolonged (>5 days) hospitalization relative to the standard-dose group (P=.03).

In a multivariate analysis, independent predictors of rebleeding included a Rockall score of >=6 at presentation (HR, 2.14; 95% CI, 1.15-3.98; P=.017) and active index bleeding (HR, 1.88; 95% CI, 1.02-3.49; P=.043).

"In conclusion, in patients with bleeding peptic ulcers with successful endoscopic hemostasis, the high-dose intensive PPI regimen had no advantage with respect to in-hospital rates of rebleeding ..., transfusion requirements, need for surgery, length of hospital stay or death," the authors wrote. (Andriulli A, et al. Am J Gastroenterol 2008;103:3011-3018.)

"It is unlikely that we will soon see a study of equivalent or superior quality addressing this specific research question in the short term, and thus, this study likely represents the best evidence available," wrote Dr. Laura Targownik and Peter Thomson of the University of Manitoba in an accompanying editorial. "Clearly, any decision to utilize the lower-intensity PPI regimen in any practice should be accompanied by an intensive surveillance for evidence of an increased rate of rebleeding and other complications." (Am J Gastroenterol 2008;103:3019-3021.)

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