title: Congestive heart failure risk in cancer patients treated with vascular endothelial growth factor tyrosine kinase inhibitors: a systematic review and meta-analysis of 36 clinical trials.
abstract: OBJECTIVE
  Congestive heart failure (CHF) associated with vascular endothelial growth factor tyrosine-kinase inhibitors (VEGFR-TKIs) has emerged as a relevant problem in clinical and scientific communities. We performed an up-to-date, comprehensive meta-analysis to determine the overall incidence and risk of CHF in cancer patients receiving VEGFR-TKIs.
  
  
  METHODS
  The databases of PubMed, Web of Science and abstracts presented at the American Society of Clinical Oncology up to August 31 2013 were searched for relevant articles. Statistical analyses were conducted to calculate the summary incidence, odds ratio (OR) 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 10 553 patients from 36 clinical trials were included. The overall incidence of all grade and high grade CHF associated with VEGFR-TKIs was 3.2% (95% CI 1.8%, 5.8%) and 1.4% (95% CI 0.9%, 2.3%), respectively. The use of VEGFR-TKIs significantly increased the risk of developing all grade (OR 2.37, 95% CI 1.76, 3.20, P < 0.001) and high grade (OR 3.51, 95% CI 1.74, 7.05, P < 0.001) CHF. In subgroup analyses, the risk of CHF did not significantly vary with tumour types (P = 0.071 for all grade; P = 0.72 for high grade) and VEGFR-TKIs (P = 0.55 for all grade; P = 0.99 for high grade). Meta-regression indicated that CHF might possibly occur early in the treatment of VEGFR-TKIs. No evidence of publication bias was observed.
  
  
  CONCLUSIONS
  The use of VEGFR-TKIs is associated with a significantly increased risk of developing congestive heart failure in cancer patients. Clinicians should be aware of this risk and provide close monitoring in patients receiving these therapies.
authors.affiliation: Department of Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, no. 600, Yishan Road, Shanghai, 200233, China.
authors.forename: Wei-Xiang
authors.initials: WX
authors.lastname: Qi
authors.forename: Zan
authors.initials: Z
authors.lastname: Shen
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Tang
authors.forename: Yang
authors.initials: Y
authors.lastname: Yao
mesh_terms: D002986:Clinical Trials as Topic; D006333:Heart Failure / Q000139:chemically induced*; D006801:Humans; D009369:Neoplasms; D016017:Odds Ratio; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D017594:Publication Bias; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D012306:Risk
chemical_list: D047428:Protein Kinase Inhibitors; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: VEGFR-TKIs; congestive heart failure; meta-analysis