Heartburn Drugs: Let Your Doctor Make Treatment Choices

Millions of Americans spend millions of dollars every year on heavily advertised drugs to treat heartburn - not just time-honored antacids like Tums, Gaviscon, Maalox, Mylanta or Rolaids, but also newer and more powerful drugs that impede acid production. These include the H2 blocker drugs introduced in the mid 1970s like Tagamet, Pepcid and Zantac, which were once available only by prescription but are now sold in over-the-counter strengths.

In the late 1980s, an even more powerful drug known as the proton pump inhibitor (PPI) was developed. When one of them - Prilosec - was made available over-the-counter in 2003, sales soared. In fact, for a few months, Prilosec OTC became so popular that users found store shelves empty for weeks.

But are these more powerful drugs safe, especially for routine use? In recent years, a number of articles, some of them based on small patient studies, raised serious concerns, claiming they could be linked to cancer, heart problems and bone fractures. In 2005, the Wall Street Journal ran a prominent article titled "The Hidden Dangers of Heartburn," which linked heartburn with sleep problems, chronic cough, asthma and "an aggressive esophageal cancer that few survive." (The esophagus carries food from the mouth to the stomach after swallowing.)

The article claimed that evidence was emerging that PPI drugs might "play a role in the rise of esophageal cancer," and quoted a California physician who feared that esophageal cancer, although rare today, might soon become an epidemic.

That's an unsubstantiated and extreme personal opinion, says Reza Shaker, MD, Medical College of Wisconsin Professor of Medicine and Chief of the Division of Gastroenterology and Hepatology. Dr. Shaker is heading up a new five-year, $6 million research effort recently awarded to the Medical College from the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK), part of the National Institutes of Health. It will study the mechanisms that govern the biological interaction between the esophagus and the airway, and their changes due to disease or injury.

Low Incidence of Esophageal Cancer
The incidence of esophageal cancer remains low compared to colon or breast cancer, notes Dr. Shaker, and statistics from the National Cancer Institute (NCI) and the American Cancer Society (ACS) back him up. They estimate that 15,560 new cases will have been diagnosed in 2007, and 13,900 new deaths would be recorded for the same year. By contrast, the most common US cancers, although declining somewhat, still claim vastly more patient cases a year - 213,380 for lung cancer, 178,480 for breast cancer 112,340 colorectal cancer. NCI's "Cancer Trends 2007" report does list a number of cancers whose incidences are rising, and esophageal cancer is among them. The report does not cite a cause or reason, except that esophageal cancer is often detected after the disease is well-advanced. And it does say that survival rates are improving.

It's true that, if left untreated, reflux can lead to problems when acids from the stomach back up and irritate the esophagus. The scarring from this tissue damage can narrow the esophagus and make swallowing difficult. Some people develop a condition called Barrett's esophagus, where cells in the esophageal lining take on an abnormal shape and color, which, over time, can lead to cancer. The longer the duration of reflux disease the higher the chance of developing Barrett`s esophagus. However only about 5% of patients with acid reflux heartburn develop this condition.

In its "Cancer Facts and Figures 2007," the ACS notes that in Western countries, the rate of esophageal cancer, mainly the squamous cell type, has been dropping among African-American men and women. However, the rate of another type, adenocarcinoma of the esophagus, has been increasing by about 2% a year in white men, but is unchanged in white women.

"Years ago," Dr. Shaker says, "most esophageal cancers were squamous cell, and it was thought that the condition was found more among smokers. Today about half the cases are squamous cell, and half are adenocarcinomas. We don't know why exactly." But epidemiologic research suggests that the problem is linked to reflux disease and its complication, Barrett's esophagus.

If the incidence of heartburn seems to be increasing and esophageal cancer is slightly increasing, Dr. Shaker says, it could be because patients complain of heartburn symptoms more often today than they did years ago. "It used to be ignored or regarded as an annoying but relatively minor problem. People with limited resources only sought medical care for serious conditions. Today, that's changed."

In addition, diagnosis of esophageal cancer can be done at an earlier stage, although many cases of esophageal cancer today are still not diagnosed until they are well-advanced.

Other Possible Concerns
In 2007, two small studies raised concerns that two PPIs, Prilosec and Nexium, were linked to heart attacks. In December, after three months of safety reviews involving 16 studies, the Food and Drug Administration announced that there were no heightened heart risks associated with long-term use of the drugs.

PPIs and H2 blockers are not without risk, however. In 2005, there were concerns that Prilosec, Nexium and another PPI, Prevacid, put users at a three-fold increased risk of contracting C. difficile, a powerful bug that can cause severe diarrhea, with a crampy intestinal inflammation called colitis. Those taking H2 blockers were found to have a two-fold risk of acquiring the infection. Although the patients studied were not hospital patients, C. difficile has become a growing problem in hospitals and nursing homes.

A researcher at the Centers for Disease Control said that if research proves there is an association between heartburn drugs and C. difficile, it wouldn't surprise him, "because everyone and their brother seems to be on them."

In 2006, a British study found a higher incidence of hip fractures among people 50 and older who took heartburn drugs (the average age was 77). Men in the study had a higher risk of hip fracture than women, possibly because women may be more aware of osteoporosis and may get more calcium in their diets, one of the researchers said. "Those studies were retrospective chart reviews," Dr. Shaker says. "They haven't been reproduced. It should also be cautioned, however, that these findings are associations and by no means definitive in terms of cause and effect relationship."

Is It Something We Ate?
It's tempting to suspect that the high-protein, high-fat, low-fiber western diet and lifestyle and the resulting obesity contributes to heartburn and reflux disease, Dr. Shaker says. People in countries like China, Japan and India whose diets were not like western diets rarely complained of heartburn symptoms as recently as 15 years ago. Today residents of Korea, Japan and eastern Europe are reporting more heartburn problems.

Bottom Line
Should people continue taking PPIs and H2 blockers to relieve heartburn?

"Never self-treat," Dr. Shaker says. "Just because a drug is sold over-the-counter doesn't mean it's without side effects and risks. Only take PPIs and H2 blockers when they're recommended by your doctor; let him or her make the diagnosis, based on your symptoms. And if those symptoms change, go back and discuss them with your doctor. You might need additional screening."

He agrees that some patients probably should not routinely take these powerful drugs; they have other options. "Although it may be difficult, many patients could find relief by losing weight, wearing looser clothing, eating lighter meals in the evening, not lying down until at least four hours after a meal, and avoiding foods and drinks that cause irritation. And quitting smoking is critical to keeping a healthy esophagus.

"Live healthy and eat healthy, and your chances of controlling reflux disease will be much easier," Dr. Shaker says.

Barbara Abel
HealthLink Contributing Writer

MCW Health News presents up-to-date information on patient care and medical research by the physicians of the Medical College of Wisconsin.