title: Tyrosine kinase-targeting drugs-associated heart failure.
abstract: BACKGROUND
  The impact of cancer therapies on cardiac disease in the general adult cancer survivor population is largely unknown. Our objective was to evaluate which tyrosine kinase-targeting drugs are associated with greater risk for new-onset heart failure (HF).
  
  
  METHODS
  A nested case-control analysis was conducted within a cohort of 27 992 patients of Clalit Health Services, newly treated with a tyrosine kinase-targeting, and/or chemotherapeutic drug, for a malignant disease, between 1 January 2005 and 31 December 2012. Each new case of HF was matched to up to 30 controls from the cohort on calendar year of cohort entry, age, gender, and duration of follow-up. Main outcome measure was odds ratio (OR) with 95% confidence interval (CI) of new-onset HF.
  
  
  RESULTS
  There were 936 incident cases of HF during 71 742 person-years of follow-up. Trastuzumab (OR 1.90, 95% CI 1.46-2.49), cetuximab (OR 1.72, 1.10-2.69), panitumumab (OR 3.01, 1.02-8.85), and sunitinib (OR 3.39, 1.78-6.47) were associated with increased HF risk. Comorbidity independently associated with higher risk in a multivariable conditional regression model was diabetes mellitus, hypertension, chronic renal failure, ischaemic heart disease, valvular heart disease, arrhythmia, and smoking.
  
  
  CONCLUSIONS
  Trastuzumab, cetuximab, panitumumab, and sunitinib are associated with increased risk for new-onset HF.
authors.affiliation: Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, 7 Michal Street, Haifa 3436212, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Gronich
authors.affiliation: Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, 7 Michal Street, Haifa 3436212, Israel.
authors.forename: I
authors.initials: I
authors.lastname: Lavi
authors.affiliation: Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, 7 Michal Street, Haifa 3436212, Israel.
authors.forename: O
authors.initials: O
authors.lastname: Barnett-Griness
authors.affiliation: Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, 7 Michal Street, Haifa 3436212, Israel.
authors.forename: W
authors.initials: W
authors.lastname: Saliba
authors.affiliation: Drug Safety Group, Office of Clinical Pharmacology, US Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Abernethy
authors.affiliation: Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, 7 Michal Street, Haifa 3436212, Israel.|Office of Chief Physician, Clalit Health Services, 101 Arlozorov Street, Tel Aviv 6209804, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Rennert
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D000068818:Cetuximab / Q000009:adverse effects; D015331:Cohort Studies; D006333:Heart Failure / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D007211:Indoles / Q000009:adverse effects; D007557:Israel / Q000453:epidemiology; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D016017:Odds Ratio; D000077544:Panitumumab; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011758:Pyrroles / Q000009:adverse effects; D012307:Risk Factors; D000077210:Sunitinib; D000068878:Trastuzumab / Q000009:adverse effects
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D000077544:Panitumumab; D000068878:Trastuzumab; D000068818:Cetuximab; D000077210:Sunitinib