PMID- 34380327
OWN - NLM
STAT- MEDLINE
DCOM- 20211027
LR  - 20211027
IS  - 1941-7705 (Electronic)
IS  - 1941-7713 (Linking)
VI  - 14
IP  - 8
DP  - 2021 Aug
TI  - Neoplasm Reports in Food and Drug Administration Adverse Event Reporting System 
      Following Angiotensin Receptor Blocker Recalls.
PG  - e007476
LID - 10.1161/CIRCOUTCOMES.120.007476 [doi]
AB  - 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.
FAU - Cohen Sedgh, Robert
AU  - Cohen Sedgh R
AD  - Western University of Health Sciences, Pomona, CA (R.C.S., J.M., C.A.J.).
FAU - Moon, Jungyeon
AU  - Moon J
AD  - Western University of Health Sciences, Pomona, CA (R.C.S., J.M., C.A.J.).
FAU - Jackevicius, Cynthia A
AU  - Jackevicius CA
AD  - Western University of Health Sciences, Pomona, CA (R.C.S., J.M., C.A.J.).
AD  - VA Greater Los Angeles Healthcare System, CA (C.A.J.).
AD  - Institute for Clinical Evaluative Sciences, Toronto, Canada (C.A.J.).
AD  - Institute of Health Policy, Management and Evaluation, University of Toronto, 
      Canada (C.A.J.).
LA  - eng
PT  - Journal Article
DEP - 20210812
PL  - United States
TA  - Circ Cardiovasc Qual Outcomes
JT  - Circulation. Cardiovascular quality and outcomes
JID - 101489148
RN  - 0 (Angiotensin Receptor Antagonists)
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Antihypertensive Agents)
SB  - IM
MH  - Angiotensin Receptor Antagonists/adverse effects
MH  - Angiotensin-Converting Enzyme Inhibitors
MH  - Antihypertensive Agents/therapeutic use
MH  - Cross-Sectional Studies
MH  - Humans
MH  - *Hypertension/drug therapy
MH  - *Neoplasms/chemically induced/diagnosis/drug therapy
MH  - Retrospective Studies
MH  - United States/epidemiology
MH  - United States Food and Drug Administration
OTO - NOTNLM
OT  - angiotensin receptor blockers
OT  - drug recalls
OT  - irbesartan
OT  - losartan
OT  - neoplasms
OT  - valsartan
EDAT- 2021/08/13 06:00
MHDA- 2021/10/28 06:00
CRDT- 2021/08/12 05:26
PHST- 2021/08/13 06:00 [pubmed]
PHST- 2021/10/28 06:00 [medline]
PHST- 2021/08/12 05:26 [entrez]
AID - 10.1161/CIRCOUTCOMES.120.007476 [doi]
PST - ppublish
SO  - Circ Cardiovasc Qual Outcomes. 2021 Aug;14(8):e007476. doi: 
      10.1161/CIRCOUTCOMES.120.007476. Epub 2021 Aug 12.