Studies confirm that this proton pump inhibitor in patients taking low-dose aspirin or NSAIDs is highly effective in preventing upper GI ulcers or bleeding.
Two studies confirm that the proton pump inhibitor (PPI) rabeprazole is highly effective in preventing upper GI ulcers or bleeding in patients taking low-dose aspirin (ASA) or NSAIDs. Researchers from Hong Kong and Japan reported on their pair of well-designed randomized studies at Digestive Disease Week 2014 in Chicago.
An aspirin study conducted by Chan and colleagues at Chinese University of Hong Kong and Osaka City University in Japan went beyond others that simply demonstrate that protective concurrent antacid treatment prevents ulceration. Here the end point was the more serious consequence of bleeding. Of note, the aspirin study found that rabeprazole and famotidine are equally protective.
The other study was a 12-week, double-blind, randomized, placebo-controlled trial in patients who had osteoarthritis, rheumatoid arthritis, or other musculoskeletal pain and required regular use of NSAIDs and tested negative for Helicobacter pylori. Patients were excluded if they had a history of GI bleeding in the previous year; had previous gastric or duodenal surgery, erosive esophagitis, or gastric outlet obstruction; used cyclooxygenase-2 inhibitors, anticoagulants, dual antiplatelet therapy, disease-modifying antirheumatic drugs, or corticosteroids (dose equivalent of prednisolone/prednisone, more than 10-mg daily stable dose); or regularly used gastroprotective agents (more than 3 days per week).
Participants were randomized to rabeprazole, 20 mg once daily, or placebo. The primary end point was the 12-week cumulative incidence of gastric/duodenal ulcer, more than 10 erosions, or severe dyspepsia. Ninety-nine patients completed the trial (49 rabeprazole, 50 placebo) and underwent esophagogastroduodenoscopy. The demographic characteristics of the two groups were comparable. Eight patients (16%) receiving rabeprazole and 19 (38%) receiving placebo met the criteria for the primary end point (odds ratio = 0.318; 95% CI, 0.123-0.822; P = .015).
The investigators concluded that rabeprazole is effective in preventing dyspepsia and gastroduodenal injury associated with NSAIDs. The risk of bleeding observed in patients who did not receive rabeprazole was more than twice as great as in those who did.
The aspirin study went further still, comparing rabeprazole with the histamine-2 receptor antagonist (H2RA) famotidine in preventing recurrent upper GI bleeding in a 12-month, double-blind, randomized trial involving 163 Helicobacter-negative patients taking 80 mg of ASA daily. After healing of the initial ulcer, patients were assigned to receive 20 mg of rabeprazole once daily (84 patients) or 40 mg of famotidine once daily (79 patients) for 12 months or until recurrent bleeding occurred. Endoscopy was repeated if they developed symptoms of recurrent GI bleeding, had a drop in hemoglobin level of more than 2 g/dL, withdrew early because of severe dyspepsia, or completed 12 months of follow-up.
The primary end point was recurrent upper GI bleeding as determined by an independent adjudication committee. Secondary end points included recurrent endoscopic ulcers or multiple erosions (more than 10) at 12 months and lower GI bleeding.
Fifteen patients terminated early for suspected recurrent bleeding (9 in the PPI rabeprazole group and 6 in the famotidine group). The adjudication committee confirmed that 1 patient (1.2%) in the rabeprazole group and 3 (3.8%) in the famotidine group had recurrent upper GI bleeding (P = .29). Eight patients (9.5%) receiving rabeprazole and 3 (3.8%) receiving famotidine had lower GI bleeding (P = .17). At 12 months, recurrent endoscopic ulcers/multiple erosions were found in 6 patients (7.1%) receiving rabeprazole and 7 (8.9%) receiving famotidine (P = .62). Among ASA users with a history of upper GI bleeding, this analysis did not show a significant difference in recurrent upper GI bleeding between patients receiving rabeprazole and those receiving famotidine.
The studies clearly show that this particular PPI is effective in reducing GI bleeding in patients receiving NSAIDs or aspirin. But, interestingly, rigorous study cannot demonstrate a difference between the PPI and an old-reliable H2RA, famotidine.