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Angiotensin receptor blockers are not carcinogenic in rodents (1049.4)
Author(s) -
De Felice Albert,
Link William,
Gatti Philip
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1049.4
Subject(s) - medicine , lung cancer , carcinogen , placebo , clinical trial , oncology , dose , lung , cancer , pharmacology , pathology , biology , genetics , alternative medicine
A published meta‐analysis (Sipahi, 2010) of several clinical trials of three angiotensin receptor blockers (ARBs) showed an 8% excess (95% CI of 1‐15%) in new diagnosed cancer, and 25% excess in lung cancer (95% CI of 5‐49%). Despite numerous acknowledged shortcomings of that analysis, and no difference in cancer death, FDA's Division of Cardiovascular and Renal Products re‐visited all 19 FDA‐mandated rodent carcinogenicity trials of nine ARBs: 16 lifetime(2 year) trials in standard mice and rat strains, and 3 six mo. trials in transgenic mice(2 inTgrasH2 and 1 in p‐53 +/‐ ). Regression analysis of placebo‐controlled mouse lung tumor incidence collapsed across strains , gender, and ARBs vs. multiples of maximum human exposure revealed no tumor excess at dosages up to 20‐200X that in humans(R 2 =0.01). Regression analysis was confined to data from the mice since both control and treated rats were devoid of lung tumors in lifetime trials. Accordingly, and regardless of strain, ARBs neither promoted nor initiated lung tumors in mice or rats, respectively. This finding is consistent with prior formal survival‐adjusted statistical analyses of individual rodent carcinogenicity trials submitted to this Division over the last several decades. Such trials were uniformly judged to be negative for excess lung or any other site‐specific tumors by FDA's executive carcinogenicity assessment committee per p‐values selected to allow no more than a 10% false positive rate in a standard test battery( 2‐yr rat and mice), or the ICH battery(2 yr rat and 6‐mo.transgenic mouse). FDA's own comprehensive study‐level meta‐analysis of 31 clinical trials of 6 ARBs vs non‐ARBs also absolved them of excess lung or other site‐specific tumor and of excess cancer death (FDA safety announcement,2011)