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 χ² 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; ROR†: valsartan/omeprazole; and ROR‡: 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]†; 4.13 [2.50–6.84]‡) and August 2018 (7.87 [5.19–11.94]*; 5.65 [4.12–7.75]†; and 7.20 [4.46–11.63]‡). In contrast, the highest cancer signals for the irbesartan and losartan recalls detected in March 2019 (4.80*; 4.06†; and 3.38‡) and April 2019 (3.63*; 3.69†; and 2.52‡) respectively, were lower. One-year postrecall reported neoplasm AEs were ≈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.

中文翻译：

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血管紧张素受体阻滞剂召回后食品和药物管理局不良事件报告系统中的肿瘤报告

背景：由于潜在致癌物 N-亚硝基二甲胺，缬沙坦于 2018 年 7 月在全球范围内自愿召回，受到了媒体和公众的广泛关注。随后，美国食品和药物管理局 (FDA) 对其他受污染的 ARB（血管紧张素受体阻滞剂）产品进行了更多召回。我们的研究调查了 FDA 召回与向 FDA 不良事件报告系统报告的 ARB 肿瘤不良事件（AE）之间的关联。 方法：在这项横断面研究中，数据是从 2015 年 1 月的 FDA 不良事件报告系统数据库中回顾性收集到 2019 年 12 月。估计报告比值比 (ROR) 以检测 ARB（缬沙坦、厄贝沙坦、和氯沙坦）和使用阴性（阿莫西林和舍曲林）和阳性（奥美拉唑和雷尼替丁）对照暴露报告的肿瘤 AE。χ²用于比较分类变量。结果：共分析2 181 524例AE，其中非转移性肿瘤AE 10 461例。缬沙坦相关肿瘤与对照组（ROR*：缬沙坦/阴性暴露；ROR†：缬沙坦/奥美拉唑；ROR‡：缬沙坦/雷尼替丁）的每月 ROR（95% CI）在 2018 年 7 月召回日期后显示出最高信号（ 7.64 [4.78–12.19]*；4.77 [3.36–6.79]†；4.13 [2.50–6.84]‡) 和 2018 年 8 月（7.87 [5.19–11.94]*；5.65 [4.12–7.12†；和 [.4.75]] ]‡)。相比之下，2019 年 3 月（4.80*；4.06†；和 3.38‡）和 2019 年 4 月（3.63*；3.69†；和 2.52‡）分别检测到厄贝沙坦和氯沙坦召回的最高癌症信号较低。一年后召回报告的肿瘤 AE 缬沙坦比厄贝沙坦高约 2 倍（OR，1.77 [95% CI，1.47-2.13]，P <0.0001）和氯沙坦（OR，2.07 [95% CI，1.85–2.32]，P <0.0001）。尽管所有 ARB 都具有相同的亚硝胺污染，但我们发现缬沙坦的 1 年召回后与召回前癌症信号比对照暴露高 3 倍，而厄贝沙坦和氯沙坦的 ROR 变化仅高 20-30%。结论：显着缬沙坦报告了更多的召回后肿瘤，与厄贝沙坦和氯沙坦相比，缬沙坦相关癌症信号更高，尽管它们都含有相同的致癌污染物。媒体对 FDA 缬沙坦召回的广泛报道可能使患者感到震惊，并产生了这些突然的、生物学上不可行的癌症信号。