Francis K L Chan1, Moe Kyaw2, Tetsuya Tanigawa3, Kazuhide Higuchi4, Kazuma Fujimoto5, Pui Kuan Cheong2, Vivian Lee6, Yoshikazu Kinoshita7, Yuji Naito8, Toshio Watanabe3, Jessica Y L Ching2, Kelvin Lam2, Angeline Lo2, Heyson Chan2, Rashid Lui2, Raymond S Y Tang2, Yasuhisa Sakata5, Yee Kit Tse2, Toshihisa Takeuchi4, Osamu Handa8, Hiroko Nebiki9, Justin C Y Wu2, Takashi Abe10, Tsuyoshi Mishiro7, Siew C Ng2, Tetsuo Arakawa3. 1. Department of Medicine and Therapeutics, Institute of Digestive Disease, The Chinese University of Hong Kong. Electronic address: fklchan@cuhk.edu.hk. 2. Department of Medicine and Therapeutics, Institute of Digestive Disease, The Chinese University of Hong Kong. 3. Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan. 4. Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan. 5. Department of Internal Medicine and Gastroenterology, Saga Medical School, Saga, Japan. 6. School of Pharmacy, The Chinese University of Hong Kong. 7. Second Department of Internal Medicine, Shimane University Faculty of Medicine, Izumo, Japan. 8. Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan. 9. Department of Gastroenterology, Osaka City General Hospital, Osaka, Japan. 10. Department of Gastroenterology, Takarazuka Municipal Hospital, Hyogo, Japan.
Abstract
BACKGROUND & AIMS: It is not clear whether H2-receptor antagonists (H2RAs) reduce the risk of gastrointestinal (GI) bleeding in aspirin users at high risk. We performed a double-blind randomized trial to compare the effects of a proton pump inhibitor (PPI) vs a H2RA antagonist in preventing recurrent upper GI bleeding and ulcers in high-risk aspirin users. METHODS: We studied 270 users of low-doseaspirin (≤325 mg/day) with a history of endoscopically confirmed ulcer bleeding at 8 sites in Hong Kong and Japan. After healing of ulcers, subjects with negative results from tests for Helicobacter pylori resumed aspirin (80 mg) daily and were assigned randomly to groups given a once-daily PPI (rabeprazole, 20 mg; n = 138) or H2RA (famotidine, 40 mg; n = 132) for up to 12 months. Subjects were evaluated every 2 months; endoscopy was repeated if they developed symptoms of upper GI bleeding or had a reduction in hemoglobin level greater than 2 g/dL and after 12 months of follow-up evaluation. The adequacy of upper GI protection was assessed by end points of recurrent upper GI bleeding and a composite of recurrent upper GI bleeding or recurrent endoscopic ulcers at month 12. RESULTS: During the 12-month study period, upper GI bleeding recurred in 1 patient receiving rabeprazole (0.7%; 95% confidence interval [CI], 0.1%-5.1%) and in 4 patients receiving famotidine (3.1%; 95% CI, 1.2%-8.1%) (P = .16). The composite end point of recurrent bleeding or endoscopic ulcers at month 12 was reached by 9 patients receiving rabeprazole (7.9%; 95% CI, 4.2%-14.7%) and 13 patients receiving famotidine (12.4%; 95% CI, 7.4%-20.4%) (P = .26). CONCLUSIONS: In a randomized controlled trial of users of low-dose aspirin at risk for recurrent GI bleeding, a slightly lower proportion of patients receiving a PPI along with aspirin developed recurrent bleeding or ulcer than of patients receiving an H2RA with the aspirin, although this difference was not statistically significant. ClincialTrials.gov no: NCT01408186.
RCT Entities:
BACKGROUND & AIMS: It is not clear whether H2-receptor antagonists (H2RAs) reduce the risk of gastrointestinal (GI) bleeding in aspirin users at high risk. We performed a double-blind randomized trial to compare the effects of a proton pump inhibitor (PPI) vs a H2RA antagonist in preventing recurrent upper GI bleeding and ulcers in high-risk aspirin users. METHODS: We studied 270 users of low-dose aspirin (≤325 mg/day) with a history of endoscopically confirmed ulcer bleeding at 8 sites in Hong Kong and Japan. After healing of ulcers, subjects with negative results from tests for Helicobacter pylori resumed aspirin (80 mg) daily and were assigned randomly to groups given a once-daily PPI (rabeprazole, 20 mg; n = 138) or H2RA (famotidine, 40 mg; n = 132) for up to 12 months. Subjects were evaluated every 2 months; endoscopy was repeated if they developed symptoms of upper GI bleeding or had a reduction in hemoglobin level greater than 2 g/dL and after 12 months of follow-up evaluation. The adequacy of upper GI protection was assessed by end points of recurrent upper GI bleeding and a composite of recurrent upper GI bleeding or recurrent endoscopic ulcers at month 12. RESULTS: During the 12-month study period, upper GI bleeding recurred in 1 patient receiving rabeprazole (0.7%; 95% confidence interval [CI], 0.1%-5.1%) and in 4 patients receiving famotidine (3.1%; 95% CI, 1.2%-8.1%) (P = .16). The composite end point of recurrent bleeding or endoscopic ulcers at month 12 was reached by 9 patients receiving rabeprazole (7.9%; 95% CI, 4.2%-14.7%) and 13 patients receiving famotidine (12.4%; 95% CI, 7.4%-20.4%) (P = .26). CONCLUSIONS: In a randomized controlled trial of users of low-dose aspirin at risk for recurrent GI bleeding, a slightly lower proportion of patients receiving a PPI along with aspirin developed recurrent bleeding or ulcer than of patients receiving an H2RA with the aspirin, although this difference was not statistically significant. ClincialTrials.gov no: NCT01408186.
Authors: Alan N Barkun; Majid Almadi; Ernst J Kuipers; Loren Laine; Joseph Sung; Frances Tse; Grigorios I Leontiadis; Neena S Abraham; Xavier Calvet; Francis K L Chan; James Douketis; Robert Enns; Ian M Gralnek; Vipul Jairath; Dennis Jensen; James Lau; Gregory Y H Lip; Romaric Loffroy; Fauze Maluf-Filho; Andrew C Meltzer; Nageshwar Reddy; John R Saltzman; John K Marshall; Marc Bardou Journal: Ann Intern Med Date: 2019-10-22 Impact factor: 25.391