PMID- 37292205
OWN - NLM
STAT- MEDLINE
DCOM- 20230612
LR  - 20230614
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 14
DP  - 2023
TI  - Cardiovascular toxicity profiles of immune checkpoint inhibitors with or without 
      angiogenesis inhibitors: a real-world pharmacovigilance analysis based on the 
      FAERS database from 2014 to 2022.
PG  - 1127128
LID - 10.3389/fimmu.2023.1127128 [doi]
LID - 1127128
AB  - BACKGROUND: Immune checkpoint inhibitors (ICIs) combined with angiogenesis 
      inhibitors (AGIs) have become increasingly available for multiple types of 
      cancers, although the cardiovascular safety profiles of this combination therapy 
      in real-world settings have not been elucidated to date. Therefore, we aimed to 
      comprehensively investigate the cardiovascular toxicity profiles of ICIs combined 
      with AGIs in comparison with ICIs alone. METHODS: The Food and Drug 
      Administration Adverse Event Reporting System (FAERS) database from the 1(st) 
      quarter of 2014 to the 1(st) quarter of 2022 was retrospectively queried to 
      extract reports of cardiovascular adverse events (AEs) associated with ICIs 
      alone, AGIs alone and combination therapy. To perform disproportionality 
      analysis, the reporting odds ratios (RORs) and information components (ICs) were 
      calculated with statistical shrinkage transformation formulas and a lower limit 
      of the 95% confidence interval (CI) for ROR (ROR(025)) > 1 or IC (IC(025)) > 0 
      with at least 3 reports was considered statistically significant. RESULTS: A 
      total of 18 854 cardiovascular AE cases/26 059 reports for ICIs alone, 47 168 
      cases/67 595 reports for AGIs alone, and 3 978 cases/5 263 reports for 
      combination therapy were extracted. Compared to the entire database of patients 
      without AGIs or ICIs, cardiovascular AEs were overreported in patients with 
      combination therapy (IC(025)/ROR(025) = 0.559/1.478), showing stronger signal 
      strength than those taking ICIs alone (IC(025)/ROR(025) = 0.118/1.086) or AGIs 
      alone (IC(025)/ROR(025) = 0.323/1.252). Importantly, compared with ICIs alone, 
      combination therapy showed a decrease in signal strength for noninfectious 
      myocarditis/pericarditis (IC(025)/ROR(025) = 1.142/2.216 vs. IC(025)/ROR(025) = 
      0.673/1.614), while an increase in signal value for embolic and thrombotic events 
      (IC(025)/ROR(025) = 0.147/1.111 vs. IC(025)/ROR(025) = 0.591/1.519). For outcomes 
      of cardiovascular AEs, the frequency of death and life-threatening AEs was lower 
      for combination therapy than ICIs alone in noninfectious myocarditis/pericarditis 
      (37.7% vs. 49.2%) as well as in embolic and thrombotic events (29.9% vs. 39.6%). 
      Analysis among indications of cancer showed similar findings. CONCLUSION: 
      Overall, ICIs combined with AGIs showed a greater risk of cardiovascular AEs than 
      ICIs alone, mainly due to an increase in embolic and thrombotic events while a 
      decrease in noninfectious myocarditis/pericarditis. In addition, compared with 
      ICIs alone, combination therapy presented a lower frequency of death and 
      life-threatening in noninfectious myocarditis/pericarditis and embolic and 
      thrombotic events.
CI  - Copyright (c) 2023 Wang, Cui, Deng, Wang and Ren.
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 - Deng, Lei
AU  - Deng L
AD  - Department of Radiation 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 - Wang, Lin
AU  - Wang L
AD  - Department of Medical 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 - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230524
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Immune Checkpoint Inhibitors)
RN  - 0 (Angiogenesis Inhibitors)
SB  - IM
MH  - United States
MH  - Humans
MH  - Immune Checkpoint Inhibitors/adverse effects
MH  - Pharmacovigilance
MH  - Angiogenesis Inhibitors/adverse effects
MH  - *Myocarditis/drug therapy
MH  - United States Food and Drug Administration
MH  - Retrospective Studies
MH  - *Neoplasms/drug therapy
MH  - *Pericarditis/drug therapy
PMC - PMC10244526
OTO - NOTNLM
OT  - FAERS database
OT  - angiogenesis inhibitor
OT  - cardiovascular toxicity
OT  - combination therapy
OT  - disproportionality analysis
OT  - immune checkpoint inhibitor
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- 2023/06/09 06:42
MHDA- 2023/06/12 06:42
PMCR- 2023/01/01
CRDT- 2023/06/09 04:19
PHST- 2023/02/07 00:00 [received]
PHST- 2023/05/15 00:00 [accepted]
PHST- 2023/06/12 06:42 [medline]
PHST- 2023/06/09 06:42 [pubmed]
PHST- 2023/06/09 04:19 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2023.1127128 [doi]
PST - epublish
SO  - Front Immunol. 2023 May 24;14:1127128. doi: 10.3389/fimmu.2023.1127128. 
      eCollection 2023.