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1. Clin Gastroenterol Hepatol. 2012 Apr 25. [Epub ahead of print]

Ability of Rabeprazole to Prevent Gastric Mucosal Damage from Clopidogrel and Low
Doses of Aspirin Depends on CYP2C19 Genotype.

Uotani T, Sugimoto M, Nishino M, Kodaira C, Yamade M, Sahara S, Yamada T, Osawa
S, Sugimoto K, Tanaka T, Umemura K, Watanabe H, Miyajima H, Furuta T.

Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu,
JAPAN.

BACKGROUND & AIMS: Low doses of aspirin can injure the gastric mucosa. It is not
clear if other drugs, such as the anti-platelet agent, clopidogrel, also cause
gastric mucosal injury or exacerbate aspirin-induced injury, or if proton-pump
inhibitors prevent damage. METHODS: Twenty Japanese subjects with different
CYP2C19 genotypes were randomly assigned to groups that were given a low dose of
aspirin (100 mg; A), clopidogrel (75 mg; C), the low dose of aspirin and
clopidogrel (AC), or the low dose of aspirin in combination with clopidogrel and
rabeprazole (10 mg; ACR), once daily for 7 days. Subjects underwent
gastroduodenoscopy and platelet tests on days 3 and 7; gastric mucosal damage was
assessed using the modified LANZA score (MLS). We performed 24 h intragastric pH
monitoring on day 7 of each regimen. We also analyzed the effects of the AC
regimen on 30 patients with different CYP2C19 genotypes. RESULTS: Subjects in
groups A, C, and AC had significantly higher levels of gastric mucosal damage
days 3 and 7, compared with baseline. The median MLS for the AC group was similar
to that of the A group. Helicobacter pylori -negative subjects in the ACR group
with different CYP2C19 genotypes had significant differences in MLSs,
intragastric pH, and platelet function. Gastric mucosal injury was inhibited
equally among H pylori -positive subjects in the ACR group. Rabeprazole did not
appear to affect platelet function or intragastric pH in patients given
clopidogrel. CONCLUSIONS: Clopidogrel and low doses of aspirin cause a similar
degree of gastric mucosal damage. Rabeprazole prevented this damage without
reducing the anti-platelet function of clopidogrel. However, its prophylactic
effect varies with CYP2C19genotype in H pylori-negative subjects.

Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

PMID: 22542748 [PubMed - as supplied by publisher]