SAN DIEGO – New research suggests histamine-2 receptor antagonists aren’t a viable alternative to proton pump inhibitors to prevent recurrence of bleeding peptic ulcers in clopidogrel users.
U.S. and European agencies have warned of interactions between proton pump inhibitors (PPIs) and clopidogrel. But a study presented at the annual Digestive Disease Week finds significant upper GI events were much more common in patients who took famotidine (Protonix), a histamine-2 receptor antagonist (H2RA), compared with those who took pantoprazole (Pepcid), a PPI, as a preventive treatment.
Dr. Ping-I Hsu
“The findings will change the practice of some physicians who prescribe H2RA to prevent UGI [upper GI] events in clopidogrel users,” said study lead author Dr. Ping-I Hsu, chief of gastroenterology at Kaohsiung Veterans General Hospital and professor of medicine at National Yang-Ming University, both in Taiwan.
Currently, Dr. Hsu said, “physicians often use PPIs to prevent ulcer complications in clopidogrel users because it is the only drug proven useful in the prevention of peptic ulcers and ulcer complications in clopidogrel users.”
But “both the U.S. Food & Drug Administration and the European Medicines Agency have posted safety warnings and discourage the use of PPIs with clopidogrel unless absolutely necessary,” he said.
Enter the prospect of H2RA medications as an alternative. The new study, Dr. Hsu said, is the first to explore the GI protection effect and safety of H2RAs in patients on clopidogrel monotherapy.
The randomized prospective study followed 120 patients with a history of peptic ulcer bleeding (but not at initial endoscopy) and atherosclerosis. All long-term users of ADP receptor antagonists, they were assigned to pantoprazole (40 mg daily) or famotidine (40 mg daily) for 48 weeks.
Patients were examined via endoscopy when they experienced events like severe epigastric discomfort.
The famotidine group had more significant upper GI events (13.3%) than the pantoprazole group (1.7%). Diarrhea was equal in both groups (1.7%). Pneumonia was comparable (0% and 1.7% for pantoprazole and famotidine, respectively), as was fracture (1.7% and 0%).
Wider differences were found in acute myocardial infarction (1.5% and 4.5%), and cerebral vascular accident (0% and 3.4%) for pantoprazole and famotidine, respectively.
According to Dr. Hsu, three earlier studies linked concurrent use of PPIs and clopidogrel to significant increases in cardiovascular events. But this study linked a higher cardiac risk to the H2RA medication.
The researchers found no differences between the drugs in sequential changes of serum magnesium levels and bone mineral densities.
Dr. Hsu made this recommendation to physicians: “Please don’t use H2RAs to prevent peptic ulcer or ulcer complications in clopidogrel users. It is ineffective to prevent UGI [upper GI] events in clopidogrel users who have a history of ulcer bleeding. PPIs can effectively prevent UGI events in clopidogrel users with a history of ulcer bleeding.”
In addition, he said, the risk of thrombotic events is lower on a PPI.