06/15/11





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TAMPA – There is no question that proton pump inhibitors are useful, effective, and properly prescribed in many elderly people, professor of geriatrics David R. Thomas, MD, CMD, said at the AMDA annual meeting. said.

"On the other hand, there are a whole bunch of questions about adverse events and drug interactions," Dr. Thomas said at the AMDA annual meeting. "That is the dark side of PPIs."

Courtesy Craig Huey Photography
David R. Thomas, MD, CMD, reviewed adverse events and drug interactions with proton pump inhibitors.David R. Thomas, MD, CMD, reviewed adverse events and drug interactions with proton pump inhibitors.

More research is needed to evaluate this risk in the setting of cardiovascular disease, Dr. Thomas said.Concerns about administering the PPI omeprazole with clopidogrel (Plavix) include an interaction that can inhibit the pharmacologic activity of clopidogrel in some patients, Dr. Thomas said.

There is a clear in vitro effect of omeprazole on platelet aggregation that begins at day seven, he noted. Until data are more conclusive, "you should probably avoid this combination," said Dr. Thomas, professor of internal medicine and geriatric medicine at St. Louis University. However, he added, no such association has been found for the PPI pantoprazole, "so it may not be a class effect."

Another study of the PPI-clopidogrel combination suggested increased cardiovascular events among patients with coronary artery disease. For example, the 90-day readmission rate for an acute myocardial infarction was 27% greater among patients discharged on clopidogrel plus a PPI than in patients discharged on clopidogrel alone (Clin. Cardiol. 2010;33:168-71). The researchers followed 734 patients hospitalized for an initial acute myocardial infarction and stent placement.

However, a PPI trial with 3,751 patients prescribed clopidogrel and aspirin showed no significant difference in cardiovascular disease events between those also prescribed omeprazole (4.9% of that group had events) and those getting a placebo (5.7%) (N. Engl. J. Med. 2010;363:1909-17). Investigators also found a benefit in the PPI group: less gastrointestinal bleeding with omeprazole (1.1% of that group), compared with than in people getting placebo (2.9%).

 

PPI use was associated with higher rates of community-acquired pneumonia during patients’ first year of treatment with acid suppressors (Epidemiology 2009;20:800-6). The same report cleared H₂-receptor antagonists of any such association, Dr. Thomas said. This research confirmed earlier, similar findings of greater risk for pneumonia shortly after initiation of PPI therapy (odds ratio, 1.5) but not after initiation of H2-receptor antagonists (OR, 1.10) (Arch. Intern. Med. 2007;167:950-55).

"For community-acquired pneumonia, when you start taking [a PPI] can make a difference," Dr. Thomas said. "This makes sense. The first line of defense against infection is stomach acid. Most common bacteria will not live at the pH in the stomach. When you suppress that stomach acid, you get overgrowth ... and when you aspirate, you get pneumonia."

Dr. Thomas emphasized, however, that studies to date suggest an association and not causation.

Another study "adds to the confusion" about PPIs because the researchers did not find any difference in pneumonia rates with esomeprazole when they pooled data from multiple studies (Drug Saf. 2008;31:627-36). Different exclusion criteria may explain the null finding, said Dr. Thomas, who also noted that the authors were employees of AstraZeneca, the study’s sponsor.

Researchers have also looked at the risk of bone fractures with PPIs. Use of a PPI within the past year was associated with an increased fracture risk in one study (OR, 1.18) (Calcif. Tissue Int. 2006;79:76-83). This paper revealed a decrease in fractures in patients who had taken H₂-receptor antagonists in the past 12 months (OR, 0.88).

Fracture risk may be elevated particularly with longer use of a PPI, Dr. Thomas said. Exposure of 7 years or longer was associated with higher likelihood of an osteoporosis-related fracture (adjusted odds ratio, 1.92) in a case-control study (CMAJ 2008;179:319-26). "So there is a clear association with duration and increased risk of fracture," he noted.

Other researchers have suggested an association between acid suppression therapy and Clostridium difficile infection (Am. J. Gastroenterol. 2007;102:2047-56). One group reviewed 12 papers with a total of 2,948 patients with C. difficile infection and found a higher likelihood that these patients were on PPI therapy (OR, 1.96) or H₂-receptor antagonists (OR, 1.40).

"C. difficile is a spore, and [infection] probably has to do with acid suppression," Dr. Thomas said. Less stomach acid may mean a greater likelihood of a favorable environment for the spores to germinate. The effect was not as great in patients taking H₂-receptor antagonists.

Other investigators found that PPI use was a significant risk factor for C. difficile–associated disease in nursing home patients (J. Am. Med. Dir. Assoc. 2005;6:105-8). About 60% of patients with C. difficile–associated disease were on PPI therapy vs. 32% of controls.

"You can still treat whatever you are treating – indigestion and heart burn – using H₂-receptor blocking agents," Dr. Thomas said. He reported having no relevant financial conflicts of interest.

Damian McNamara is with the Miami bureau of Else;ier Global Medical News.