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Dosage Effects of Histamine-2 Receptor Antagonist on the Primary Prophylaxis of Non-Steroidal Anti-Inflammatory Drug (NSAID)-Associated Peptic Ulcers: A Retrospective Cohort Study

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Abstract

Background

A histamine-2 receptor antagonist (H2RA) is one of the common gastroprotective co-therapies used with non-steroidal anti-inflammatory drugs (NSAIDs) for the prevention or treatment of peptic ulcers (PUs). To date, no study has directly compared the prophylactic effectiveness between high-dose and low-dose H2RA.

Objective

Our objective was to compare the effectiveness of high-dose versus low-dose H2RAs in the primary prophylaxis of PUs among short-term NSAID users.

Methods

A retrospective cohort study was conducted using the Clinical Data Analysis and Reporting System (CDARS) in Hong Kong. Patients aged 18 years or above who received a single prescription of oral NSAID with oral H2RA were identified within the study period (1 January 2009–31 December 2012). Patients with a history of or risk factors for PU in the corresponding 2 years prior to the index date (of the first NSAID prescription) were excluded. Log binomial regression analysis was used to calculate the relative risk of PU among NSAID users with high-dose H2RA versus low-dose H2RA exposure.

Results

Among the NSAID cohort (n = 102,042), 77,509 (76 %) were on low-dose H2RA and 24,533 (24 %) were on high-dose H2RA. Of the total 69 PU cases identified during the drug exposure period, 64 (0.08 %) received low-dose-H2RA and five (0.02 %) received high-dose H2RA. The overall absolute risk of PUs for NSAID users whilst on H2RA was approximately 1 per 1,479 patients. The adjusted relative risk for NSAID users receiving high-dose H2RA versus low-dose H2RA was 0.32 (95 % confidence interval [CI] 0.13–0.79). Patients aged ≥65 years, receiving a longer duration of treatment, or with concomitant use of antiplatelet agents were found to be at higher risk of PU.

Conclusion

High-dose H2RA showed greater effectiveness than low-dose H2RA in the primary prophylaxis of NSAID-associated PUs in short-term new users.

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Acknowledgments

The authors thank Dr. Vincent C.C. Cheng for his support on the verification of ICD-9-CM codes for related diagnosis/procedures in this study. We also thank Lisa Wong for proofreading and editing the manuscript.

Declaration of funding interests

None to declare.

Declaration of competing interest

Ying He, Esther W. Chan, Kenneth K.C. Man, Wallis C.Y. Lau, Wai K. Leung, Lai M. Ho, and Ian C.K. Wong declare no support from any organization for the submitted work; no financial relationships with any organization that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work.

Ethical approval

The study protocol was approved by Institutional Review Board of the University of Hong Kong/HA Hong Kong West Cluster (IRB reference number: UW 12-196).

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Authors and Affiliations

  1. Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China

    Ying He, Esther W. Chan, Kenneth K. C. Man, Wallis C. Y. Lau & Ian C. K. Wong

  2. Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China

    Wai K. Leung

  3. Division of Epidemiology and Biostatistics, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China

    Lai M. Ho

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  1. Ying He
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Correspondence to Ian C. K. Wong.

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He, Y., Chan, E.W., Man, K.K.C. et al. Dosage Effects of Histamine-2 Receptor Antagonist on the Primary Prophylaxis of Non-Steroidal Anti-Inflammatory Drug (NSAID)-Associated Peptic Ulcers: A Retrospective Cohort Study. Drug Saf 37, 711–721 (2014). https://doi.org/10.1007/s40264-014-0209-0

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