Nigam H. Shah, MBBS, PhD, assistant professor of medicine, Stanford Center for Biomedical Research, Stanford University, California. His study was published in PLOS One
Quick relief from acute heartburn and its chronic cousin GERD is a good thing. But is it worth risking a heart attack?
That’s the devil’s choice that millions of Americans may be making without realizing it. A large new “big data” study finds a strong statistical link between proton pump inhibitors (PPIs) such as Prilosec, Prevacid and Nexium (and their generic versions) and heart attacks. It’s big news because PPIs are the third most popular prescription drugs and the second most popular over-the-counter drugs in the country…used by 21 million Americans. And the increased risk for heart attacks is not just to people with heart conditions or those taking certain medications, but to everyone, healthy or sick, young or old.
PPIs, which temporarily turn off the body’s ability to make stomach acid, reducing symptoms of gastroesophageal reflux disease (GERD) and other medical conditions, have been raising safety concerns for years. They interfere with the body’s ability to absorb nutrients, increase the risk for fractures and make it difficult to treat gastrointestinal infections such as C. difficile.
There has been ongoing concern about PPIs and the heart, too, but mostly for people who already have heart disease. Doctors have known for a long time that people who take both the blood thinner clopidogrel (Plavix) and PPIs are at higher risk for heart attacks and stroke. They suspected that PPIs blocked an enzyme that allows clopidogrel to do its job.
But other researchers worried that the heart risks were broader. There was a whisper in the data that suggested that even people not taking blood thinners were at increased heart risk. So the researchers designed the latest study. And what has come back from the data was less like a whisper and more like…a roar.
This new study was conducted using a “data-mining” method to search through two large databases that contained the medical records of more than three million patients. These included patients treated in doctor’s offices around the country as well as patients treated at Stanford University Medical Center.
First, they identified adults diagnosed with GERD. Then they examined their medical records to see whether they had received one of two main types of acid-suppressing medication. Some are by prescription only, others over-the-counter, and some are available both ways…
• PPIs: Omeprazole (such as Prilosec), lansoprazole (Prevacid), pantoprazole (Protonix), esomeprazole (Nexium), rabeprazole (AcipHex) and dexlansoprazole (Kapidex).
• Histamine blockers: Cimetidine (such as Tagamet), famotidine (Pepcid), nizatidine (Axid) and ranitidine (Zantac).
They excluded anyone taking the blood thinner clopidogrel. Then they compared the patients with others who had GERD but did not take either of these two classes of medication. These controls were matched to the drug takers based on age, gender, length of follow-up and other variables. Finally, the researchers looked for diagnosis codes in the medical records of both GERD patients and controls indicating that they had had heart attacks sometime after starting either sort of medication.
The researchers used two different databases, but each one showed a similar result—PPIs increased heart attack risk substantially….
• PPI use overall was associated with 16% to 19% greater chance of heart attack.
• PPI use by people 55 or younger was associated with 25% to 40% increased risk.
• Among all the drugs, pantoprazole had the strongest association with increased heart attack risk, a 34% higher risk when averaged across age groups.
• Esomeprazole had the weakest association with increased heart attack risk—8% higher risk.
• Histamine blocker use was not associated with increased heart attack risk in either set of data.
Then the researchers looked at the data from the other side. Instead of looking at people who took these GERD drugs, they looked at those who had had coronary angiograms after having abnormal cardiac stress tests, chest pain or shortness of breath—indicating the probability of heart disease. Amongst these cardiac patients, after adjusting for all known risk factors, those who had used PPIs had double the risk of dying from a cardiovascular cause such as a heart attack, heart failure or stroke compared with cardiac patients who hadn’t used PPIs. Again in this case, histamine blockers were not associated with increased risk.
All of these results, whether reached by looking first for people who took PPIs or first for people who had heart trouble, look like very bad news for the safety of PPIs!
How might PPIs damage the cardiovascular system? The researchers note that these drugs suppress an enzyme needed for the body to make nitric acid, which relaxes and protects arteries and veins. In short, PPIs may lead to constriction of blood vessels, causing heart disease.
It’s not proof, to be sure. Like any statistical study, even this large study can show only an association. The researchers acknowledged that their analysis didn’t account for several factors, including use of other types of over-the-counter drugs and the presence of other medical conditions, that could contribute to risk for heart attacks. They note that future epidemiological studies may find different risk percentages, so comparing one PPI to another isn’t an exact science. But they emphasize that their analysis indicates that there is 97.5% chance that the PPI/heart attack association they identified is real.
Some day, a large, randomized, placebo-controlled study with thousands of patients may be powerful enough to prove (or disprove) that PPIs cause heart attacks. But you don’t have to wait to protect yourself whether you have GERD or are using a PPI for any other condition. PPIs are effective for many conditions besides heartburn, such as stomach ulcers, including those caused by H. pylori bacteria and those brought on by chronic use of nonsteroidal anti-inflammatories (for arthritis pain, for example)…Crohn’s disease…and complications of certain gastrointestinal cancers such as Zollinger-Ellison syndrome. If your doctor has prescribed a PPI to you for a specific medical condition other than GERD, make it a point to have a discussion about whether there are alternate approaches worth exploring now.
If it’s GERD, there are safer ways to get relief. Even before this study, the official advice was to use PPIs for no more than two weeks at a time or for more than three times in a year. But once you stop taking them, your stomach may respond by temporarily making even more acid than before, so your symptoms might get worse. In other words, it’s easy to get hooked. It’s also possible that your GERD got worse while you were on PPIs for a long time—they don’t cure GERD or stop its progression. The good news about acid rebound is that it doesn’t happen with everyone, and when it does, it lasts only two or three weeks.
Whether you have taken PPIs or not, a lifestyle approach to managing GERD is key…
• Cut back on coffee and other sources of caffeine.
• Cut back on fatty foods.
• Eat smaller, more frequent meals rather than a few one large ones
• Cut back on alcohol.
• Wait three hours after eating and drinking before lying down.
• Elevate the head of your bed so that gravity keeps stomach acid in your stomach.
• Lose weight if you need to.
• Don’t smoke.
You can learn much more about the anti-GERD lifestyle in the Bottom Line Guide to Drug-Free Heartburn Relief.
If you do go the pharmaceutical route, histamine blockers appear to be the safer choice. They are sold with and without prescription in generic formulas and as the brand names Tagamet, Pepcid, Axid and Zantac. Regular antacids, such as Tums, also are safe choices.
But even these should be used only for short-term treatment of your GERD symptoms. A healthy body needs strong stomach acid to properly digest food, after all.