As preventive, H2RA poses risk for patients on clopidogrel

Histamine-2 receptor antagonists may not be a viable alternative to proton pump inhibitors to prevent recurrence of bleeding peptic ulcers in clopidogrel users, a study showed.

US and European agencies have warned of interactions between proton pump inhibitors (PPIs) and clopidogrel. But a study presented at the annual Digestive Disease Week found significant upper GI events were much more common in patients who took a histamine-2 receptor antagonist (H₂RA), compared with those who took a PPI, as a preventive treatment.

“The findings will change the practice of some physicians who prescribe H₂RA to prevent UGI [upper GI] events in clopidogrel users,” said the study lead chief of gastroenterology at Kaohsiung Veterans General Hospital and professor of medicine at National Yang-Ming University in Taiwan.

Currently, “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 US Food and Drug Administration and the European Medicines Agency have posted safety warning and discourage the use of PPIs with clopidogrel unless absolutely necessary.”

Enter the prospect of H₂RA medications as an alternative. The new study is the first to explore the GI protection effect and safety of H₂RA 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 adenosine diphosphate receptor antagonists they were assigned to for 48 weeks.

Patients were examined via endoscopy when they experienced events like severe epigastric discomfort.

The group had more significant upper GI events (13.3 percent) than the group (1.7 percent). Diarrhea was equal in both groups (1.7 percent). Pneumonia was compatible (0 percent and 1.7 percent), respectively, as was fracture (1.7 percent and 0 percent).

Wider differences were found in acute myocardial infarction (1.5 percent and 4.5 percent), and cerebral vascular accident (0 percent and 3.4 percent) respectively.

According to a doctor, three earlier studies linked concurrent use of PPIs an 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.

A recommendation made to physicians: “Please don’t use H₂RA to prevent peptic ulcer or ulcer complications in clopidogrel users. It is ineffective to prevent UGI [upper GI] events in clopidogrel users have a history of ulcer bleeding. PPIs can effectively prevent UGI events in clopidogrel users with a history of ulcer bleeding.”

In addition, the risk of thrombotic events is lower on a PPI.