title: Bevacizumab increases the risk of severe congestive heart failure in cancer patients: an up-to-date meta-analysis with a focus on different subgroups.
abstract: OBJECTIVE
  Congestive heart failure (CHF) risk with bevacizumab in breast cancer has been previously investigated in a meta-analysis, but its incidence and the risk of CHF in other tumor types remain unclear. Thus, we performed this meta-analysis to gather current data and evaluate the risk of CHF with bevacizumab in cancer patients, with a focus on different subgroups.
  
  
  METHODS
  The databases of PubMed and abstracts presented at the American Society of Clinical Oncology up to 31 December 2013 were searched for relevant articles. Statistical analyses were conducted to calculate the summary incidence, relative risk (RR), and 95 % confidence intervals (CIs) by using either random-effects or fixed-effect models according to the heterogeneity of included studies.
  
  
  RESULTS
  A total of 16,962 patients from 19 RCTs were included. The use of bevacizumab significantly increased the risk of developing high-grade CHF in cancer patients (RR 1.98, 95 % CI 1.30-3.02, p = 0.002), but not for all-grade CHF (RR 1.14, 95 % CI 0.87-1.49, p = 0.33). Risk might vary with bevacizumab dose and tumor types. RRs for patients receiving bevacizumab at 5 and 2.5 mg/kg/week were 2.25 (95 % CI 1.43-3.56) and 1.00 (95 % CI 0.33-3.05), respectively. High risks were observed in patients with breast cancer (RR 2.43, 95 % CI 1.48-3.98), renal cell cancer (RR 3.66, 95 % CI 0.41-33.01), and glioblastoma (RR 4.90, 95 % CI 0.24-102.39). Additionally, bevacizumab in combination with taxanes significantly increased the risk of high-grade CHF (RR 2.15, 95 % CI 1.09-4.25, p = 0.027).
  
  
  CONCLUSIONS
  Bevacizumab treatment significantly increases the risk of developing high-grade CHF in cancer patients. The risk may vary with bevacizumab dose and tumor types. Clinicians should be aware of the risks of CHF with the administration of this drug in cancer patients.
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong'An Road, Shanghai, 200032, China, qiweixiang1113@163.com.
authors.forename: Wei-Xiang
authors.initials: WX
authors.lastname: Qi
authors.forename: Shen
authors.initials: S
authors.lastname: Fu
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xiao-Mao
authors.initials: XM
authors.lastname: Guo
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use; D000068258:Bevacizumab; D006333:Heart Failure / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D012306:Risk; D012720:Severity of Illness Index
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab
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