Intermittent PPI Therapy Effective for High-Risk Bleeding Ulcers

By Will Boggs MD

September 12, 2014

NEW YORK (Reuters Health) - Intermittent proton pump inhibitor (PPI) therapy is as effective as continuous PPI therapy for high-risk bleeding ulcers, according to a systematic review and meta-analysis.

Current guidelines recommend an IV bolus followed by a continuous infusion after endoscopic treatment of bleeding ulcers with high-risk findings. Although other trials and meta-analyses have addressed the issue of whether intermittent PPI therapy can be substituted for continuous infusion, they have not proven that such therapy in noninferior.

Dr. Loren Laine from Yale School of Medicine, New Haven, Connecticut and colleagues performed a systematic review and meta-analysis of 13 randomized clinical trials to assess the clinical efficacy of intermittent PPI regimens vs the standard bolus plus continuous-infusion regimen after successful endoscopic therapy in patients with bleeding ulcers.

Ten trials addressed recurrent bleeding within seven days of treatment; in these, the risk of recurrent rebleeding was 28% lower for intermittent PPI therapy, according to a report online September 8th in JAMA Internal Medicine.

Results were similar in the nine trials that reported recurrent bleeding at three days and in the 13 trials that reported recurrent bleeding within 30 days, with both analyses demonstrating noninferiority of intermittent PPI therapy.

Moreover, intermittent PPI therapy was associated with similar rates of mortality, surgery/radiologic intervention, urgent intervention, red blood cell transfusions, and hospital length of stay.

"Our review does not allow us to determine the reason that the efficacy of intermittent administration of a PPI is similar to a continuous infusion in patients with bleeding ulcers," the researchers say.

"Given the greater ease of use and lower cost and resource utilization, intermittent PPI therapy should be the regimen of choice after endoscopic therapy in such patients," they conclude. "Current national and international guidelines should be revised to incorporate this new information and recommend intermittent PPI therapy."

Dr. Laine did not respond to a request for comments.

Dr. Angel Lanas from the University of Zaragoza School of Medicine in Spain has also reported on the use of PPI therapy for peptic ulcer bleeding. He told Reuters Health by email, "In fact, in many hospitals around the world, where no peristaltic pump for continuous infusion can be used, intermittent therapy with PPI bolus was the rule. We have data that suggest that gastric pH control may be also be effective."

"PPI still is essential and should be administered in sufficient doses to achieve gastric pH control; this can be obtained by different routes and ways (continuous, bolus, oral), although endoscopy therapy still is the main action to control peptic ulcer bleeding," Dr. Lanas concluded.

In the same issue of JAMA Internal Medicine, Dr. Michael E. Johansen from Ohio State University, Columbus, Ohio and colleagues report in a research letter that the use of high-cost PPIs results in $47.1 billion in excess expenditures between 2007 and 2011, compared with low-cost, therapeutically equivalent PPIs.

Increased use of high-cost PPIs was associated with decreasing age, female sex, private insurance, region (Northeast or South), and the highest income category.

Dr. Johansen told Reuters Health by email, "I had expected that there would be large levels of excess expenditure, but the level of excess was dramatically higher than I had expected."

"On a local level, I am optimistic that creative people will find ways to improve the efficiency of prescribing and healthcare in general," Dr. Johansen said. "On a national policy level, change will be harder to achieve."

"We need to be good stewards of healthcare resources," Dr. Johansen said. "Writing a prescription for an expensive drug to a few patients does not seem like a big deal, but on a societal level the ramifications are enormous."


JAMA Intern Med 2014.


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