Got Heartburn? A Caution About Your Proton Pump Inhibitor

Prolonged use of these drugs carries a risk of osteoporosis and heart problems.

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Heartburn is ailing the masses. By one estimate, 20 percent of the Western population experiences acid reflux at least once a week. And we're shelling out buckets of cash—$25.6 billion worldwide in 2008—to alleviate those hot, sour, acidic pains in the chest. For many, the use of a proton pump inhibitor like Nexium, Prilosec, or Prevacid is extremely effective in treating symptoms of acid reflux or a peptic ulcer. Available for about two decades now, PPIs are perceived to be very safe. But research over the last four to five years has suggested patients and doctors shouldn't get complacent about this prescription—particularly over the long term.

John Clarke, assistant professor of medicine and director of esophageal motility at Johns Hopkins University, discussed the finer points of proton pump inhibitor therapy with U.S. News. Below are some excerpts from the conversation.

What should people taking PPIs over the long term consider?


The thing I'm most worried about is the risk of osteoporosis. Physiologically it makes sense; if you decrease your gastric acid [by taking a PPI], you're likely to absorb less calcium. Gastric acid can help cleave calcium from food, and suppression of gastric acid may lead to relative malabsorption. Research has shown that the rates of fractures appear to correspond to both the length of time that you're on the PPI as well as dose. Who should be concerned about this correlation?


I see a lot of patients in their 20s or 30s who take PPIs. To think they may be on these meds indefinitely kind of raises a red flag about their bone density down the road. Attempts should really be made to limit PPIs to a finite length of time. If long-term use is necessary, there are ways to be proactive in addressing issues of bone density. Take calcium and Vitamin D and a bisphosphonate, which can be done as infrequently as once a year. If someone has osteopenia [lower than normal bone mineral density but not full-blown osteoporosis], sometimes I'm a little more aggressive about starting a bisphosphonate early. Who does need PPIs over the long-term?


Indication for chronic use of a PPI is if you have erosive esophagitis or any complication like Barrett's esophagus. Also, patients who need daily aspirin and have a somewhat significant GI-risk profile. And how about heart attack patients taking PPIs and Plavix, the blood thinner? Research in a March issue of the Journal of the American Medical Association found that nearly 30 percent of patients taking both Plavix and a PPI died or were rehospitalized, compared with nearly 21 percent of patients taking only Plavix.


There's a body of literature that's emerging that appears to show that patients on acid suppressants and on Plavix seem to have more cardiac effects—and the combination may result in Plavix being less effective. It's a bit unclear if this is a drug-class effect, of all acid-suppressant therapies, or if it is limited to certain drugs. Omeprazole and espmeprazole, one or the other of which is in Prilosec, Nexium, and Zegerid, appear to be most associated with this effect. But we're still waiting for data. It may be better to switch to one of the agents that doesn't contain omeprazole or esomeprazole.

Should people taking Plavix stop taking their PPIs?


I wouldn't stop, but patients may want to discuss the issue with their doctor. People on daily, long-term aspirin therapy and Plavix really do need the acid-suppressant therapy. Even a daily baby aspirin can cause a GI bleed or an ulcer bleed. If you have any erosive esophagitis, it can lead to esophageal cancer. Taking an acid-suppressant may limit the rate at which cancer forms. And what about PPIs and higher rates of infection? Studies have found that hospital patients on PPIs, at least, are at some increased risk of both pneumonia and Clostridium difficile infection.


For most people, I don't think this is a significant concern. Gastric acid has a barrier function toward certain types of infection, and PPI meds block acid—they're really very effective—so if you don't have gastric acid, an infection can be viable beyond the stomach. It has been shown that the average person gets about 3.3 infections per year, but if you take an acid suppressant, it goes to 4.1.