Among patients on low-dose aspirin at risk for recurrent GI bleeding, there were slightly fewer GI bleeds or ulcers when patients were on the proton pump inhibitor rabeprazole (Aciphex) instead of the histamine2-receptor antagonist famotidine (Pepcid), but the difference was not statistically significant according to a study reported in the January issue of Gastroenterology.
In a 270-subject, double-blind, randomized trial in Hong Kong and Japan led by Francis Chan, MD, of the Chinese University of Hong Kong, investigators found, “Among high-risk aspirin users, the incidence of recurrent bleeding is comparable with either use of PPI [proton pump inhibitor] or H2RA [H2-receptor antagonist].” However, “since a small difference in efficacy cannot be excluded, PPI probably remains the preferred treatment for long-term protection against upper GI bleeding in high-risk aspirin users” (Gastroenterology. 2016 Sep 15. doi: 10.1053/j.gastro.2016.09.006 ).
Even so, “our findings suggest that famotidine may be a reasonable alternative option for aspirin users who disfavor long-term PPI therapy,” they said.
Because of concerns about the long-term safety of PPIs, including the association between PPIs and increased risk of serious cardiovascular events in patients on clopidogrel (Plavix), clinicians have been looking for alternatives. The findings reassure that H2RAs are a reasonable choice; many clinicians have already turned to them.
All 270 subjects had previously had endoscopically confirmed ulcer bleeding while on low-dose aspirin (325 mg or less per day). “Considering clinicians will be most concerned with the adequacy of gastroprotective treatment effect in aspirin users with the highest risk, we exclusively enrolled patients with endoscopy-proven upper GI bleeding,” Dr. Chan and his colleagues said.
After the ulcers healed, the subjects resumed aspirin (80 mg) daily and were randomized to either famotidine 40 mg once daily (n = 132) or rabeprazole 20 mg daily (n = 138) for up to 12 months. Helicobacter pylori was eradicated prior to randomization in patients who tested positive. Subjects were evaluated every 2 months, with repeat endoscopy for symptoms of upper GI bleeding or significant drops in hemoglobin, as well as at the end of the study.
During the 12-month study period, upper GI bleeding recurred in one patient receiving rabeprazole (0.7%) and four receiving famotidine (3.1%; P = .16). The composite endpoint of recurrent bleeding or endoscopic ulcers at month 12 was reached by nine patients in the rabeprazole group (7.9%) and 13 receiving famotidine (12.4%; P = .26).
“Our findings indicate that both treatments are comparable in preventing recurrent upper GI bleeding in high-risk aspirin users, although a small difference in efficacy cannot be excluded,” the investigators said.
Over two-thirds of the subjects were men, and the mean age was 73 years. About a quarter in the PPI group and almost 40% in the H2RA group had H. pylori cleared before randomization.
The Research Grant Council of Hong Kong funded the work. Dr. Chan has served as a consultant to Pfizer, Eisai, Takeda, and Otsuka, and has received research grants from Pfizer and lecture fees from Pfizer, AstraZeneca, and Takeda. Several other authors reported similar industry disclosures.