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- Title
Ranitidine Use and Incident Cancer in a Multinational Cohort.
- Authors
You, Seng Chan; Seo, Seung In; Falconer, Thomas; Yanover, Chen; Duarte-Salles, Talita; Seager, Sarah; Posada, Jose D.; Shah, Nigam H.; Nguyen, Phung-Anh; Kim, Yeesuk; Hsu, Jason C.; Van Zandt, Mui; Hsu, Min-Huei; Lee, Hang Lak; Ko, Heejoo; Shin, Woon Geon; Pratt, Nicole; Park, Rae Woong; Reich, Christin G.; Suchard, Marc A.
- Abstract
Key Points: Question: Is use of ranitidine associated with higher risk for incident cancer compared with other histamine-2 (H2) receptor antagonists (H2RAs)? Findings: In this cohort study including 1 183 999 individuals from 11 large databases across Europe, North America, and Asia, risk of cancer among ranitidine users did not differ from users of other H2RAs. Ranitidine use was not associated with an increased risk of esophageal, stomach, or colorectal cancer, or 13 other subtypes of cancer. Meaning: These findings suggest that a history of ranitidine use is not associated with an increased risk of cancer compared with use of other H2 receptor antagonists, but further research is needed on the long-term effects of ranitidine on cancer development. This cohort study examines the comparative risk of cancer associated with the use of ranitidine vs other histamine-2 receptor antagonists. Importance: Ranitidine, the most widely used histamine-2 receptor antagonist (H2RA), was withdrawn because of N-nitrosodimethylamine impurity in 2020. Given the worldwide exposure to this drug, the potential risk of cancer development associated with the intake of known carcinogens is an important epidemiological concern. Objective: To examine the comparative risk of cancer associated with the use of ranitidine vs other H2RAs. Design, Setting, and Participants: This new-user active comparator international network cohort study was conducted using 3 health claims and 9 electronic health record databases from the US, the United Kingdom, Germany, Spain, France, South Korea, and Taiwan. Large-scale propensity score (PS) matching was used to minimize confounding of the observed covariates with negative control outcomes. Empirical calibration was performed to account for unobserved confounding. All databases were mapped to a common data model. Database-specific estimates were combined using random-effects meta-analysis. Participants included individuals aged at least 20 years with no history of cancer who used H2RAs for more than 30 days from January 1986 to December 2020, with a 1-year washout period. Data were analyzed from April to September 2021. Exposure: The main exposure was use of ranitidine vs other H2RAs (famotidine, lafutidine, nizatidine, and roxatidine). Main Outcomes and Measures: The primary outcome was incidence of any cancer, except nonmelanoma skin cancer. Secondary outcomes included all cancer except thyroid cancer, 16 cancer subtypes, and all-cause mortality. Results: Among 1 183 999 individuals in 11 databases, 909 168 individuals (mean age, 56.1 years; 507 316 [55.8%] women) were identified as new users of ranitidine, and 274 831 individuals (mean age, 58.0 years; 145 935 [53.1%] women) were identified as new users of other H2RAs. Crude incidence rates of cancer were 14.30 events per 1000 person-years (PYs) in ranitidine users and 15.03 events per 1000 PYs among other H2RA users. After PS matching, cancer risk was similar in ranitidine compared with other H2RA users (incidence, 15.92 events per 1000 PYs vs 15.65 events per 1000 PYs; calibrated meta-analytic hazard ratio, 1.04; 95% CI, 0.97-1.12). No significant associations were found between ranitidine use and any secondary outcomes after calibration. Conclusions and Relevance: In this cohort study, ranitidine use was not associated with an increased risk of cancer compared with the use of other H2RAs. Further research is needed on the long-term association of ranitidine with cancer development.
- Subjects
UNITED States; UNITED Kingdom; SPAIN; FRANCE; TAIWAN; SOUTH Korea; GERMANY; TUMOR risk factors; RESEARCH; CONFIDENCE intervals; RANITIDINE; ANTIHISTAMINES; RISK assessment; COMPARATIVE studies; RESEARCH funding; DESCRIPTIVE statistics; TUMORS; LOGISTIC regression analysis; DATA analysis software; LONGITUDINAL method; PROPORTIONAL hazards models; ADULTS
- Publication
JAMA Network Open, 2023, Vol 6, Issue 9, pe2333495
- ISSN
2574-3805
- Publication type
Article
- DOI
10.1001/jamanetworkopen.2023.33495