Long-term PPI Use and Increased Esophageal CA Risk
By Kristin Jenkins, Medscape
Long-term maintenance therapy with proton-pump inhibitors (PPIs) was shown to be associated with an increased risk for esophageal cancer, even in patients taking PPIs for indications not previously associated with this cancer risk, according to results from a new study from Sweden.
The authors call for "a more restrictive attitude towards maintenance use of PPIs."
However, this "surprising" observation comes from a single cohort study that lacks the evidence to demonstrate a causal relationship, warn experts approached for comment. They say that clinicians shouldn't stop prescribing PPIs as recommended by current guidelines.
The new study was published online February 22 in Cancer Epidemiology by a team led by Nele Brusselaers, MD, PhD, associate professor of clinical epidemiology at the Karolinska Institutet and the Karolinska University Hospital in Stockholm.
In the study, data from four national registers in Sweden were used to identify 796,492 patients without a history of cancer who were exposed to maintenance PPI therapy between 2005 and 2014. Most were female (58.5%), and 34.0% were age 70 years or older.
The indications for PPI use included maintenance therapy with aspirin (34.8%), nonsteroidal anti-inflammatory drugs (NSAIDs) (30.4%), gastroesophageal reflux disease (GERD) (25.3%), gastroduodenitis (13.2%), and peptic ulcer disease (10.0%). Less than 10% of participants were taking PPIs for other indications.
The team compared this cohort of nearly 800,000 patients taking PPIs to adults in the general population matched for sex and age over the same period.
They found that the overall standardized incidence ratio (SIR) for esophageal adenocarcinoma (EAC) in PPI users was 3.93, and the overall SIR for esophageal squamous cell carcinoma (SCC) was 2.77.
The study also showed that in patients without GERD who were taking PPI maintenance therapy with NSAIDs or aspirin, the SIR for EAC was 2.74 and 2.06, respectively.
To evaluate confounding by indication, stratified analyses were performed for each indication not associated with an increased risk for EAC. This separate analysis was one of the study's chief strengths because it minimized the risk for confounding by indication that has limited previous research, Brusselaers and colleagues say. However, they were unable to identify the indication for PPI therapy in 25% of the cohort.
Increase in Cancer Not Seen With H2-Antagonists
A comparative analysis in 20,177 patients taking only histamine-2 receptor (H2) antagonists (such as ranitidine) found no increased risk for EAC (SIR, 0.39) or SCC (SIR, 0.50).
This finding "lends support to the hypothesis that this association may be due to PPI medication per se, and not related to other factors that predispose to using anti-acidic medications," the study authors say.