Ability of Rabeprazole to Prevent Gastric Mucosal Damage From Clopidogrel and Low Doses of Aspirin Depends on CYP2C19 Genotype  Takahiro Uotani, Mitsushige Sugimoto, Masafumi Nishino, Chise Kodaira, Mihoko Yamade, Shu Sahara, Takanori Yamada, Satoshi Osawa, Ken Sugimoto, Tatsuo Tanaka, Kazuo Umemura, Hiroshi Watanabe, Hiroaki Miyajima, Takahisa Furuta  Clinical Gastroenterology and Hepatology  Volume 10, Issue 8, Pages 879-885.e2 (August 2012) DOI: 10.1016/j.cgh.2012.04.016 Copyright © 2012 AGA Institute Terms and Conditions

Figure 1 MLS system of gastric mucosal damage on days 3 and 7 in controls and the 4 treatment regimens in H pylori–negative (B) and –positive subjects (C) in study 1. (A) Representative endoscopic findings of gastric mucosal injury with different MLSs.15,16 (B) On days 3 and 7, significant gastric mucosal damages were observed with the A, C, and AC regimens in H pylori–negative subjects. For the ACR regimen, MLSs on days 3 and 7 were lowest apart from the controls. (C) On days 3 and 7, significant gastric mucosal damages were observed with the A, C, and AC regimens in H pylori–positive subjects. For the ACR regimen, the MLSs on days 3 and 7 were lowest apart from the controls. *P < .05. Clinical Gastroenterology and Hepatology 2012 10, 879-885.e2DOI: (10.1016/j.cgh.2012.04.016) Copyright © 2012 AGA Institute Terms and Conditions

Figure 2 Median 24-hour intragastric pH (A) and percent time with pH <4 (B) on day 7 in study 1. (A) The median 24-hour pH for the ACR regimen was significantly higher than those for other regimens (all P = .005), especially in H pylori–positive subjects. The 24-hour pH in regimen ACR was significantly higher in H pylori–positive subjects in comparison with that in H pylori–negative subjects. (B) The percentage time for pH <4 in the ACR regimen was significantly shorter than those for other regimens (all P = .005), especially in H pylori–positive subjects. The percentage time for pH <4 in regimen ACR was significantly shorter in H pylori–positive subjects in comparison with that in H pylori–negative subjects. *P < .05. Clinical Gastroenterology and Hepatology 2012 10, 879-885.e2DOI: (10.1016/j.cgh.2012.04.016) Copyright © 2012 AGA Institute Terms and Conditions

Figure 3 Effect of CYP2C19 genotype status (RM or IM/PM) on median 24-hour pH and gastric mucosal injury assessed by MLS with different regimens in H pylori–negative and –positive subjects in study 1. (A) The median pH in RMs was significantly lower than that in IM/PM groups with the ACR regimen in H pylori–negative subjects. (B) For the ACR regimen, the median MLS in RMs on day 7 was significantly higher than that in the IM/PM group in H pylori–negative subjects.*P < .05. Clinical Gastroenterology and Hepatology 2012 10, 879-885.e2DOI: (10.1016/j.cgh.2012.04.016) Copyright © 2012 AGA Institute Terms and Conditions

Figure 4 Ulcer/erosion-based (A) and hemorrhage-based (B) MLSs in control and 4 regimens on days 3 and 7. A significant increase in both ulcer/erosion and hemorrhage scores was observed in all of the regimens in comparison with controls on days 3 and 7. The ACR regimen significantly reduced hemorrhage score attained with the A, AC, and AC regimens. Although the A regimen increased both scores, the hemorrhage score in the C regimen was higher than that in ulcer/erosion score. *P < .05. Clinical Gastroenterology and Hepatology 2012 10, 879-885.e2DOI: (10.1016/j.cgh.2012.04.016) Copyright © 2012 AGA Institute Terms and Conditions

Figure 5 The effect of CYP2C19 genotype status on IPA by aspirin (A) and clopidogrel (B) and MLSs with AC regimen in study 2. (A) IPAs by aspirin increased from day 3 to day 7. IPAs by aspirin did not differ among CYP2C19 genotype groups. (B) IPA by clopidogrel significantly differed among the 3 CYP2C19 genotype groups. (C) MLS was increased from day 3 to day 7. However, MLSs did not differ among CYP2C19 genotype groups on days 3 and 7. *P < .05. Clinical Gastroenterology and Hepatology 2012 10, 879-885.e2DOI: (10.1016/j.cgh.2012.04.016) Copyright © 2012 AGA Institute Terms and Conditions