title: Similar Efficacy of Proton-Pump Inhibitors vs H2-Receptor Antagonists in Reducing Risk of Upper Gastrointestinal Bleeding or Ulcers in High-Risk Users of Low-Dose Aspirin.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.affiliation: Department of Medicine and Therapeutics, Institute of Digestive Disease, The Chinese University of Hong Kong. Electronic address: fklchan@cuhk.edu.hk.
authors.forename: Francis K L
authors.initials: FK
authors.lastname: Chan
authors.affiliation: Department of Medicine and Therapeutics, Institute of Digestive Disease, The Chinese University of Hong Kong.
authors.forename: Moe
authors.initials: M
authors.lastname: Kyaw
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tanigawa
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Higuchi
authors.affiliation: Department of Internal Medicine and Gastroenterology, Saga Medical School, Saga, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Fujimoto
authors.affiliation: Department of Medicine and Therapeutics, Institute of Digestive Disease, The Chinese University of Hong Kong.
authors.forename: Pui Kuan
authors.initials: PK
authors.lastname: Cheong
authors.affiliation: School of Pharmacy, The Chinese University of Hong Kong.
authors.forename: Vivian
authors.initials: V
authors.lastname: Lee
authors.affiliation: Second Department of Internal Medicine, Shimane University Faculty of Medicine, Izumo, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kinoshita
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naito
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Medicine and Therapeutics, Institute of Digestive Disease, The Chinese University of Hong Kong.
authors.forename: Jessica Y L
authors.initials: JY
authors.lastname: Ching
authors.affiliation: Department of Medicine and Therapeutics, Institute of Digestive Disease, The Chinese University of Hong Kong.
authors.forename: Kelvin
authors.initials: K
authors.lastname: Lam
authors.affiliation: Department of Medicine and Therapeutics, Institute of Digestive Disease, The Chinese University of Hong Kong.
authors.forename: Angeline
authors.initials: A
authors.lastname: Lo
authors.affiliation: Department of Medicine and Therapeutics, Institute of Digestive Disease, The Chinese University of Hong Kong.
authors.forename: Heyson
authors.initials: H
authors.lastname: Chan
authors.affiliation: Department of Medicine and Therapeutics, Institute of Digestive Disease, The Chinese University of Hong Kong.
authors.forename: Rashid
authors.initials: R
authors.lastname: Lui
authors.affiliation: Department of Medicine and Therapeutics, Institute of Digestive Disease, The Chinese University of Hong Kong.
authors.forename: Raymond S Y
authors.initials: RS
authors.lastname: Tang
authors.affiliation: Department of Internal Medicine and Gastroenterology, Saga Medical School, Saga, Japan.
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Sakata
authors.affiliation: Department of Medicine and Therapeutics, Institute of Digestive Disease, The Chinese University of Hong Kong.
authors.forename: Yee Kit
authors.initials: YK
authors.lastname: Tse
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan.
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Takeuchi
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Handa
authors.affiliation: Department of Gastroenterology, Osaka City General Hospital, Osaka, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nebiki
authors.affiliation: Department of Medicine and Therapeutics, Institute of Digestive Disease, The Chinese University of Hong Kong.
authors.forename: Justin C Y
authors.initials: JC
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, Takarazuka Municipal Hospital, Hyogo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Abe
authors.affiliation: Second Department of Internal Medicine, Shimane University Faculty of Medicine, Izumo, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Mishiro
authors.affiliation: Department of Medicine and Therapeutics, Institute of Digestive Disease, The Chinese University of Hong Kong.
authors.forename: Siew C
authors.initials: SC
authors.lastname: Ng
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Arakawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects*; D004311:Double-Blind Method; D015738:Famotidine / Q000627:therapeutic use*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010437:Peptic Ulcer / Q000517:prevention & control*; D010438:Peptic Ulcer Hemorrhage / Q000097:blood / Q000517:prevention & control*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D064750:Rabeprazole / Q000627:therapeutic use*; D012008:Recurrence; D012307:Risk Factors; D055502:Secondary Prevention
chemical_list: D006454:Hemoglobins; D006635:Histamine H2 Antagonists; D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D064750:Rabeprazole; D015738:Famotidine; D001241:Aspirin
keywords: ASA; Acid-Suppressive Drugs; Antiplatelet; Hemorrhage