Long-term use of acid reflux drugs weighed

Washington -- Two new studies on proton pump inhibitors are uncovering added benefits and risks associated with the popular prescription and over-the-counter medications used to treat acid reflux.

One study reinforced the drugs' cost-effectiveness when used to reduce the risk for upper gastrointestinal bleeding that may result from long-term aspirin therapy. The other found long-term use may heighten the risk of osteoporosis-related fractures.

A large observational study in the Aug. 12 Canadian Medical Assn. Journal determined that patients who used proton pump inhibitors for seven or more years had a significantly greater risk for fractures.

It mirrored findings published in the Dec. 27, 2006, Journal of the American Medical Association, which also showed long-term PPI use, particularly at higher doses, was associated with increased risk of hip fractures.

Osteoporosis and its accompanying fracture risk is a major health threat for an estimated 44 million Americans, or 55% of people 50 and older, according to the National Osteoporosis Foundation.

However, the evidence is not yet strong enough to change the current risk-benefit calculation that favors the use of the medications to treat acid reflux, said Laura Targownik, MD, the lead author of the Canadian study and an assistant professor of internal medicine at the University of Manitoba in Winnipeg.

"What I advise my patients at this point is, if they are on [proton pump inhibitors] for a solid indication, like severe reflux that can't be managed in any other way, or they are on nonsteroidal anti-inflammatory drugs and have a risk of ulcer complications, I would probably keep them on PPIs."

However, as a precaution, Dr. Targownik noted, she also would ensure that patients take adequate calcium and vitamin D and have regular bone density scans.

The lead author of the 2006 JAMA study agreed the evidence tying the medication to osteoporosis is not yet solid enough to change prescribing habits.

Other variables may be at work, said Sameer Dev Saini, MD, a clinical lecturer at the University of Michigan Medical School in Ann Arbor. He noted that none of the studies was able to control for calcium intake or vitamin D intake. "We don't fully know if the effects we see in the papers are from the proton pump inhibitor or some other confounding factor."

But the advantages also should not be discounted. "On the flip side, we have very strong evidence that PPIs are very helpful for patients who have had ulcer bleeding in the past," he said. "In those patients there is a very strong protective effect of PPIs."

Medications for the long term

Although medical guidelines recommend that patients with cardiovascular disease take low-dose aspirin, long-term aspirin use poses a risk for upper gastrointestinal bleeding. "The stomach normally has a protective coating to prevent acid-related injury, but aspirin and other NSAIDs impair the stomach's ability to form this barrier coating, potentially leading to ulcer formation," said Dr. Saini. "Furthermore, these drugs may themselves cause injury directly to the stomach cells and can impair the ability of platelets to form a plug in the event of bleeding."

Dr. Saini and colleagues found that at OTC prices, PPIs are cost-effective for patients older than 65 who are taking low-dose aspirin and may be cost-effective for patients as young as 50. Their study is in the Aug. 11/25 Archives of Internal Medicine.

The fact the medications involved, aspirin and proton pump inhibitors, are recommended for long-term use also is raising concerns. "And it should," said Dr. Saini. "If there is a long term effect like bone loss, I think that will be very important to know."

Dr. Targownik and colleagues are continuing to explore that link. "We are looking prospectively to see if people develop osteoporosis over time." This time, dietary factors such as calcium and vitamin D will also be considered, she added.