Since their introduction in 1990, the drugs collectively known as proton pump inhibitors (common brand names: (Nexium, Prevacid, Prilosec) have become among the most frequently prescribed in the country; they are also available over the counter. They suppress stomach acid more effectively than a previous class of drugs called H2 blockers (Zantac, Tagamet, Pepcid).
They have also given users reason to be wary. In recent years, scores of studies have reported associations between prescription P.P.I. use and an array of health problems, including
- bone fractures,
- low magnesium levels,
- kidney injuries and
- possibly cardiovascular drug interactions.
They are also linked to infections, like the stubborn Clostridium difficile and pneumonia. Reducing the acidity of the stomach, researchers believe, allows bacteria to thrive and then spread to other organs like the lungs and intestines.
The latest findings, published last month in JAMA Internal Medicine, point to increased risk of chronic kidney disease among users, which is particularly worrisome.
“You can treat and hopefully cure infections,” said Dr. Adam Schoenfeld, an internal medicine resident at the University of California, San Francisco, and co-author of an accompanying editorial on the drugs’ adverse effects. “Fractures can heal, though they can be catastrophic events for older people. But chronic kidney disease doesn’t go away.”
The new study, by a Johns Hopkins team, compiled years of data from two sources, a community sample of 10,482 adults in four communities
Those who took prescription proton pump inhibitors were 20 percent to 50 percent more likely to develop chronic kidney disease than nonusers
Like the rest of these drug studies, this one demonstrated an association, not a direct cause.
a dose effect: The risk of chronic kidney disease rose 15 percent among those taking the drug once a day, but 46 percent in those taking it twice daily, compared with nonusers. “That leads us to believe there’s a causal effect,” Dr. Grams said.
Relative risk statistics sometimes seem to exaggerate the dangers of a drug or an illness, if they were low to begin with.
This is easily demonstrated by the recent biased numbers in the CDC guidelines, which always use the relative dangers to compare because it looks so much scarier:
If the absolute risk of an adverse effect is only 1% to begin with, what sounds like a dramatic relative risk increase of 150% raises the absolute risk to only 2.5%,
An increase in absolute risk to 2.5% is still a very low absolute risk, but an increase of 150% in relative risk sounds huge, so the anti-opioid folks are broadcasting the scarier numbers.
In scientific circles, these the relative risk numbers are known to be misleading and are therefore rarely used, evidence that the supposedly neutral studies were designed and written to be appealing to the public, not to scientists.
“When you have 15 million people using these drugs, even relatively rare adverse effects can affect a lot of people.”
Older people should probably pay special heed. They are more likely to experience reflux, Dr. Semla explained, in part because the muscle that prevents stomach acid from rising into the esophagus weakens with age. Older adults are therefore more likely to take these drugs, and also more vulnerable to the diseases and disorders associated with them, especially with long-term use.
All of this led an American Geriatrics Society panel last year to add proton pump inhibitors to the list called the Beers Criteria for Potentially Inappropriate Medication Use in Older Adults, citing the risk of bone loss and fractures and C. diff infection.
The Food and Drug Administration has also issued several safety announcements about these drugs’ association with C. diff, fracture risk and low magnesium, linked to kidney disease and other ailments.
So you’d think use of proton pump inhibitors would be declining. It’s not.“Despite this information, those drugs are extremely overprescribed,” Dr. Schoenfeld said.
From 1999 to 2002, 9 percent of people ages 55 to 64 reported using a prescription gastric reflux drug (including non-P.P.I.s) in the previous 30 days, the Centers for Disease Control and Prevention has reported.Ten years later, the proportion had risen to 16 percent. Among prescription medications, only cardiac and cholesterol drugs were more commonly used by adults ages 55 to 64.
Proton pump inhibitors can be crucial medications, doctors hasten to point out, for those with peptic ulcers or for intensive care patients, among others. They’re also the most effective option for severe reflux. But whether over the counter or prescribed (prescriptions can involve higher doses), they are usually recommended for short-term use
Dr. Semla suggests raising the head of your bed, so stomach acid has a harder time climbing upward.
Moreover, “if people eat a lot of fatty, greasy foods or drink a lot of alcohol or caffeine, those are all triggers for heartburn,” Dr. Schoenfeld said. It probably also helps — “people are going to hate me” — to cut back on chocolate.
“With time or with dietary changes,” he said, “a lot of these symptoms would go away on their own.”