Parker Waichman LLP is investigating potential lawsuits on behalf of individuals who were diagnosed with pancreatic cancer or who died following treatment with a proton pump inhibitor.
What Are PPIs?
According to MedicineNet, proton pump inhibitors are used in the prevention and treatment of acid-related conditions such as esophageal duodenal and stomach ulcers, nonsteroidal anti-inflammatory drugs- (NSAIDs) associated ulcer, ulcers, gastroesophageal reflux disease (GERD), and Zollinger-Ellison syndrome. PPIs are also used along with antibiotics in patients diagnosed with helicobacter pylori, which is a bacterium that, with acid, causes ulcers of the stomach and duodenum.
PPIs are associated with serious side effects, including erythema mulitorme, ancreatitis, reduced kidney function, reduced liver function, serious allergic reactions Stevens-Johnson sSyndrome (SJS), and Toxic Epidermal Necrolysis (TEN)
A list, in part, of PPIs includes:
- Aciphex, Aciphex Sprinkle (rabeprazole)
- Dexilent, Dexilent Solutab (dexlansoprazole) [The brand name Kapidex was changed to Dexilent]
- Nexium, Nexium IV, Nexium 24 HR (esomeprazole)
- Prevacid, Prevacid IV, Prevacid 24-Hour (lansopraozole)
- Prilosec, Prilosec OTC (omeprazole)
- Protonix (pantoprazole)
- Vimovo (esomeprazole magnesium/naproxen)
- Yosprala (aspirin and omeprazole)
- Zegerid, Zegerid OTC (omeprazole/sodium bicarbonate)
2017 Research Reveals Association Between Proton Pump Inhibitors and Pancreatic Cancer, Death
Recent data question the safety of proton pump inhibitors. For example, a study published in a 2017 Digestive Disease Week revealed that researchers at the University of Pennsylvania discovered that proton pump inhibitors (PPI) were associated with an increased risk for patients developing pancreatic cancer. A second study published in BMJ Open revealed that military veterans who used PPIs experienced what Gastroenterology & Endoscopy News described as a small but significantly increased risk for premature death when compared with individuals who took other reflux medication or no therapy for reflux.
“There’s a lot of laboratory data to suggest links between the trophic hormone gastrin and abnormal cell growth of various types, and one key medication known to cause gastrin elevation is [the] PPI,” said Malcolm Kearns, MD, a resident in internal medicine at the Hospital of the University of Pennsylvania, in Philadelphia. Dr. Kearns helped conduct the study that reviewed PPIs and pancreatic cancer. “The number of prescriptions for PPIs has skyrocketed in recent years—many are started and continued without appropriate indications or regular evaluation. So we wanted to examine, at a population level, whether there was an association between pancreatic cancer and PPIs,” he said, according to Gastroenterology & Endoscopy News.
PPIs are known to cause hypergastrinemia (excess blood gastrin levels), which has been associated with gastrointestinal malignancies in experimental models. The Penn researchers worked to evaluate the relationship between PPIs and pancreatic cancer and survival following diagnosis. For their research, the team used the Health Improvement Network, which is a medical records database representative of the United Kingdom (U.K.) population.
The team conducted a nested case–control study and a retrospective cohort study. The case–control study matched patients diagnosed with incident pancreatic cancer with up to four controls that were based on age, sex, practice site, and duration and calendar time of follow-up. The researchers estimated the odds ratios (OR) and confidence intervals for the association between use of PPI medications and pancreatic cancer. Gastroenterology & Endoscopy News also reported that, in the retrospective cohort study, researchers compared pancreatic cancer patient survival based on how long the patients had been taking PPIs at the time of their diagnosis.
The team analyzed 4,113 patients who were diagnosed with pancreatic cancer and 16,072 matched controls (individuals with similar background but who are not diagnosed with pancreatic cancer). The researchers discovered that cancer patients were likelier to be current PPI users at the time of the study. Although the patients were likelier to be obese, to smoke, to use alcohol, and to be diagnosed with diabetes, when compared to the controls, the duration of PPI use was significantly lower in pancreatic patients. After adjusting for body mass index (BMI), smoking, alcohol use, and diabetes, the researchers discovered that active and former PPI users experienced an increased risk for developing pancreatic cancer, according to Gastroenterology & Endoscopy News. The team discovered “a modest decrease” in survival following diagnosis of pancreatic cancer in short-term, active PPI users, who were defined as having received their first PPI prescription less than 12 months prior to the study’s start date. Former users were described as not having received a PPI prescription within six months of the study’s index date. Short-term active users received their first prescription less than one year before the index date. Intermediate-term users received their first prescription one and two years prior to the index date. Long-term active users received their first prescription more than two years prior to the index date.
Philip Katz, MD, director of Motility Laboratories for the Division of Gastroenterology at the Jay Monahan Center for Gastrointestinal Health at New York-Presbyterian Hospital/Weill Cornell Medicine, in New York City, described the research as “well done and thoughtful.” He also said that, “A shorter duration of PPI use had a stronger association with pancreatic cancer compared to a longer duration, which speaks against the PPI being the issue,” Dr. Katz said. “One would suspect a confounder such as GERD, or that the patients’ symptoms were suggestive of an acid-related problem, but were likely from the cancer instead,” he said. “What this really reinforces, as do many studies like it, is that we shouldn’t be prescribing these drugs without a solid indication.”
Dr. Kearns said, “What could have caused that increased odds ratio within six months [in short-term PPI users] could have been the symptoms of pancreatic cancer itself. But what we found compelling about our data was that the elevated OR was persistent even up to 24 months prior to diagnosis of pancreatic cancer.” He added that, “The reason that’s significant is that the mean survival following diagnosis of pancreatic cancer is around six months. So it would be unlikely that patients that were prescribed PPIs two years prior to diagnosis of pancreatic cancer were started on them because of symptoms of pancreatic cancer…. [PPIs] are a medication that’s often prescribed and continued without giving it a great deal of thought.” Dr. Kearns also noted that, “So I hope that our study at least makes somebody think twice about refilling a prescription, or think to ask their patient if they’re really benefiting from it or suggest trialing off of their PPI.”
In the BMJ study, researchers at Washington University School of Medicine in St. Louis, Missouri and the VA St. Louis Health Care System reviewed death rates among a very large cohort of male veterans. Of these, approximately 350,000 began taking a PPI or histamine H2 receptor antagonist between October 2006 and September 2008. Patients were on the medications for an average of about 5.7 years, according to Gastroenterology & Endoscopy News.
Men who took PPIs experienced a 15 percent increased risk of death during the study period when compared with those participants who did not use PPI drugs. The increase was 23 percent when compared without treatment of a PPI or an H2 blocker, the investigators noted, wrote Gastroenterology & Endoscopy News.
The mortality rate difference was higher for individuals who took a PPI without a recorded gastrointestinal condition, the researchers reported, and it seemed to increase with duration of PPI use, according to Gastroenterology & Endoscopy News. “The results suggest excess risk of death among PPI users; risk is also increased among those without gastrointestinal conditions and with prolonged duration of use. Limiting PPI use and duration to instances where it is medically indicated may be warranted,” the researchers concluded.
Amitabh Chak, MD, professor of medicine at Case Western Reserve School of Medicine, in Cleveland, Ohio and an expert in gastroesophageal reflux disease (GERD), said observational studies such as the published in BMJ Open “should always be taken with a grain of salt and interpreted cautiously. They can be provocative but the results may be confounded by unmeasured risk factors.” Meanwhile, Dr. Chak, whose group recently received a $6 million grant from the National Institutes of Health (NIH) to study Barrett’s esophagus (serious GERD complication), said, in part that the findings “should help generate hypotheses and reconsider practices. These studies need to also be replicated.” He also noted that, “So how should we interpret these results? PPIs clearly are beneficial in treating GERD, preventing bleeding from [nonsteroidal anti-inflammatory drugs], and eradicating Barrett’s esophagus in patients undergoing ablative therapy. We should use PPIs for patients who benefit from PPIs and need them. We should not use PPIs for patients who don’t benefit from their use,” Gastroenterology & Endoscopy News reported.