| アブストラクト | BACKGROUND: A worldwide voluntary recall of valsartan in July 2018 due to the potential carcinogen N-nitrosodimethylamine received extensive media and public attention. This was followed by more Food and Drug Administration (FDA) recalls regarding other contaminated ARB (angiotensin receptor blocker) products. Our study investigated the association between the FDA recalls and ARB neoplasm adverse events (AEs) reported to the FDA adverse event reporting system. METHODS: In this cross-sectional study, data were retrospectively collected from the FDA adverse event reporting system database from January 2015 to December 2019. Reporting odds ratios (RORs) were estimated to detect signals of association between ARBs (valsartan, irbesartan, and losartan) and reported neoplasm AEs using negative (amoxicillin and sertraline) and positive (omeprazole and ranitidine) control exposures. The chi(2) was used to compare categorical variables. RESULTS: A total of 2 181 524 AEs, including 10 461 nonmetastatic neoplasm AEs were analyzed. Monthly RORs (95% CI) of valsartan-associated neoplasms versus controls (ROR*: valsartan/negative exposures; RORdagger: valsartan/omeprazole; and RORdouble dagger: valsartan/ranitidine) showed the highest signals after the recall date in July 2018 (7.64 [4.78-12.19]*; 4.77 [3.36-6.79]dagger; 4.13 [2.50-6.84]double dagger) and August 2018 (7.87 [5.19-11.94]*; 5.65 [4.12-7.75]dagger; and 7.20 [4.46-11.63]double dagger). In contrast, the highest cancer signals for the irbesartan and losartan recalls detected in March 2019 (4.80*; 4.06dagger; and 3.38double dagger) and April 2019 (3.63*; 3.69dagger; and 2.52double dagger) respectively, were lower. One-year postrecall reported neoplasm AEs were approximately 2-fold higher for valsartan than irbesartan (OR, 1.77 [95% CI, 1.47-2.13], P<0.0001) and losartan (OR, 2.07 [95% CI, 1.85-2.32], P<0.0001). Although all ARBs had the same nitrosamine contamination, we found 1-year postrecall versus prerecall cancer signals for valsartan were 3-fold higher versus control exposures, while the changes in RORs for irbesartan and losartan were only 20-30% higher. CONCLUSIONS: Significantly more postrecall neoplasms were reported for valsartan, with higher valsartan-associated cancer signals compared with irbesartan and losartan, although they all contained the same carcinogenic contaminant. Extensive media coverage of the FDA valsartan recall may have alarmed patients and generated these abrupt, biologically infeasible cancer signals. |
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| 投稿日 | 2021/8/13 |
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| 投稿者 | Cohen Sedgh, Robert; Moon, Jungyeon; Jackevicius, Cynthia A |
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| ジャーナル名 | Circulation. Cardiovascular quality and outcomes |
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| 組織名 | Western University of Health Sciences, Pomona, CA (R.C.S., J.M., C.A.J.).;VA Greater Los Angeles Healthcare System, CA (C.A.J.).;Institute for Clinical Evaluative Sciences, Toronto, Canada (C.A.J.).;Institute of Health Policy, Management and Evaluation, University of Toronto,;Canada (C.A.J.). |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/34380327/ |
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