Study Ties Long-Term Proton Pump Inhibitor Use to Esophageal Cancer

Published on March 6, 2018 by Sandy Liebhard

Patients prescribed proton pump inhibitors, such as Nexium, Prilosec and PrevAcid, for extended periods of time may be more likely to develop esophageal cancer, according to a new study.

How Was the Study Conducted?

The research, which was published online last month in Cancer Epidemiology, utilized four Swedish registries to identify796,492 patients without a history of cancer who were exposed to maintenance proton pump inhibitor therapy between 2005 and 2014.

Most were female (58.5%), and 34.0% were age 70 years or older. They were taking proton pump inhibitors for a variety of indications, including:

• Maintenance therapy with aspirin (34.8%)
• Maintenance therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) (30.4%)
• Gastroesophageal reflux disease (GERD) (25.3%)
• Gastroduodenitis (13.2%)
• Peptic ulcer disease (10.0%)
• Other (<10%)

The authors of the study then compared this cohort to adults in the general population matched for sex and age over the same period.

What Did the Findings Suggest?

Among all individuals using maintenance proton pump inhibitor therapy, the overall standardized incident ration (SIR) of esophageal adenocarcinoma was 3.93.  The SIRs of adenocarcinoma were also higher among individuals without GERD who used the drugs for indications not associated with any increased cancer risk. For example, the SIRs among participants using proton pump inhibitors in conjunction with NSAIDs and aspirin maintenance therapy were 2.74 and 2.06, respectively.

The SIRS of esophageal squamous cell carcinoma were increased for most investigated indications, but to a lesser degree than for esophageal adenocarcinoma.

“In conclusion, the long-term use of PPIs is associated with increased risk of esophageal adenocarcinoma in the absence of other risk factors. Long term use of PPIs should be addressed with caution,” the study authors concluded.

Other Side Effects Linked to Long-Term Proton Pump Inhibitor Use

Proton pump inhibitors, including Nexium, Prilosec, and PrevAcid, are indicated for the short-term treatment of GERD and other gastric disorders related to the excess production of stomach acid. While more than 15 million Americans used prescription proton pump inhibitors in 2013, it has been estimated that between 25% and 70% of these prescriptions have no appropriate indication.

Because they have become so ubiquitous, most people give little thought to the side effects potentially associated with these popular heartburn medications. However, this study is not the first to raise concerns about long-term proton pump inhibitor use. In fact, previous research has linked extended treatment to an increased risk for gastric cancer, certain bone fractures, heart attacks, dementia, B12 deficiency, low magnesium levels, kidney complications, C. diff infections and pneumonia.

Hundreds of people are currently pursuing proton pump inhibitor lawsuits for life-threatening kidney problems – including kidney failure, chronic kidney disease, acute interstitial nephritis, and acute kidney injury – allegedly connected with the long-term use of Nexium and other drugs in this class. Plaintiffs accuse proton pump inhibitor manufacturers of concealing information linking their products to serious kidney complications and assert that their injuries could have been avoided had proper warnings been provided to patients and doctors.