PMID- 36312283
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221102
IS  - 2297-055X (Print)
IS  - 2297-055X (Electronic)
IS  - 2297-055X (Linking)
VI  - 9
DP  - 2022
TI  - Cardiovascular toxicity associated with angiogenesis inhibitors: A comprehensive 
      pharmacovigilance analysis based on the FDA Adverse Event Reporting System 
      database from 2014 to 2021.
PG  - 988013
LID - 10.3389/fcvm.2022.988013 [doi]
LID - 988013
AB  - BACKGROUND: The profiles of cardiovascular toxicity associated with angiogenesis 
      inhibitors, including intravenous monoclonal antibodies (mAbs) and oral tyrosine 
      kinase inhibitors (TKIs), targeting vascular endothelial growth factor (VEGF) 
      remain poorly elucidated in real-world settings. This pharmacovigilance analysis 
      aimed to comprehensively investigate the frequency, spectrum, timing, and 
      outcomes of cardiovascular toxicities associated with angiogenesis inhibitors and 
      to explore the differences in such patterns between mAbs and TKIs. METHODS: 
      Disproportionality analysis was performed by leveraging reports from the FDA 
      Adverse Event Reporting System (FAERS) database from 2014 to 2021. Cardiovascular 
      adverse events (AEs) were grouped into nine narrow categories using the 
      Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries 
      (SMQs). Reporting odds ratio (ROR) and information components (ICs) were 
      calculated with statistical shrinkage transformation formulas and a lower limit 
      of 95% confidence interval (CI) for ROR (ROR(025)) > 1 or IC (IC(025)) > 0, with 
      at least three reports being considered statistically significant. RESULTS: A 
      total of 757,577 reports of angiogenesis inhibitors and 70,668 (9.3%) reports of 
      cardiovascular AEs were extracted. Significant disproportionality was detected in 
      angiogenesis inhibitors for cardiovascular AEs (IC(025)/ROR(025) = 0.35/1.27). 
      Bevacizumab (31.8%), a mAb, presented the largest number of reports, followed by 
      sunitinib (12.4%), a TKI. Hypertension (SMQ) was detected with the strongest 
      signal value (IC(025)/ROR(025) = 1.73/3.33), followed by embolic and thrombotic 
      events (SMQ) (IC(025)/ROR(025) = 0.32/1.26). Hypertension showed the shortest 
      time to onset with a median (interquartile range) value of 23 (8, 69) days, while 
      embolic and thrombotic events had the longest value of 51 (16, 153) days. 
      Notably, hypertension presented the lowest proportions of death and 
      life-threatening events (10.9%), whereas embolic and thrombotic events posed the 
      highest (29.3%). Furthermore, both mAbs (IC(025)/ROR(025) = 0.47/1.39) and TKIs 
      (IC(025)/ROR(025) = 0.30/1.23) showed increased cardiovascular AEs. Hypertension 
      was detected in both agents (IC(025)/ROR(025) = 1.53/2.90 for mAbs and 
      IC(025)/ROR(025) = 1.83/3.56 for TKIs) with a shorter time to onset of 17 (6, 48) 
      days for TKIs than mAbs of 42 (14, 131) days. By contrast, embolic and thrombotic 
      events were detected for mAbs (IC(025)/ROR(025) = 0.90/1.87) without TKI 
      (IC(025)/ROR(025) = -0.08/0.95). CONCLUSION: Angiogenesis inhibitors were 
      associated with increased cardiovascular toxicity with a discrepancy between 
      intravenous mAbs and oral TKIs, deserving distinct monitoring and appropriate 
      management.
CI  - Copyright (c) 2022 Wang, Cui, Ren, Dong and Cui.
FAU - Wang, YanFeng
AU  - Wang Y
AD  - Department of Comprehensive Oncology, National Cancer Center/National Clinical 
      Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences 
      and Peking Union Medical College, Beijing, China.
FAU - Cui, Chanjuan
AU  - Cui C
AD  - Department of Laboratory Medicine, National Cancer Center/National Clinical 
      Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences 
      and Peking Union Medical College, Beijing, China.
FAU - Ren, Xiayang
AU  - Ren X
AD  - Department of Pharmacy, National Cancer Center/National Clinical Research Center 
      for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing, China.
FAU - Dong, Xinran
AU  - Dong X
AD  - School of Electronics Engineering and Computer Science, Peking University, 
      Beijing, China.
FAU - Cui, Wei
AU  - Cui W
AD  - Department of Laboratory Medicine, National Cancer Center/National Clinical 
      Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences 
      and Peking Union Medical College, Beijing, China.
LA  - eng
PT  - Journal Article
DEP - 20221013
PL  - Switzerland
TA  - Front Cardiovasc Med
JT  - Frontiers in cardiovascular medicine
JID - 101653388
PMC - PMC9606330
OTO - NOTNLM
OT  - FAERS database
OT  - angiogenesis inhibitors
OT  - cardiovascular toxicity
OT  - disproportionality analysis
OT  - pharmacovigilance analysis
OT  - real-world study
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/11/01 06:00
MHDA- 2022/11/01 06:01
PMCR- 2022/01/01
CRDT- 2022/10/31 04:37
PHST- 2022/07/06 00:00 [received]
PHST- 2022/09/14 00:00 [accepted]
PHST- 2022/10/31 04:37 [entrez]
PHST- 2022/11/01 06:00 [pubmed]
PHST- 2022/11/01 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fcvm.2022.988013 [doi]
PST - epublish
SO  - Front Cardiovasc Med. 2022 Oct 13;9:988013. doi: 10.3389/fcvm.2022.988013. 
      eCollection 2022.