title: Mortality associated with aprotinin during 5 years following coronary artery bypass graft surgery.
abstract: BACKGROUND
  Acute safety concerns have been raised recently regarding certain hemorrhage-sparing medications commonly used in cardiac surgery. However, no comprehensive data exist regarding their associations with long-term mortality.
  
  
  OBJECTIVE
  To contrast long-term all-cause mortality in patients undergoing coronary artery bypass graft (CABG) surgery according to use of 2 lysine analog antifibrinolytics (aminocaproic acid and tranexamic acid), the serine protease inhibitor aprotinin, or no antibleeding agent.
  
  
  METHODS
  Observational study of mortality conducted between November 11, 1996, and December 7, 2006. Following index hospitalization (4374 patients; 69 medical centers), survival was prospectively assessed at 6 weeks, 6 months, and annually for 5 years after CABG surgery among 3876 patients enrolled in a 62-center international cohort study. The associations of survival with hemorrhage-sparing medications were compared using multivariable analyses including propensity adjustments.
  
  
  METHODS
  Death (all-cause) over 5 years.
  
  
  RESULTS
  Aprotinin treatment (223 deaths among 1072 patients [20.8% 5-year mortality]) was associated with significantly increased mortality compared with control (128 deaths among 1009 patients [12.7%]; covariate adjusted hazard ratio for death, 1.48; 95% confidence interval, 1.19-1.85), whereas neither aminocaproic acid (132 deaths among 834 patients [15.8%]; adjusted hazard ratio for death, 1.03; 95% confidence interval, 0.80-1.33) nor tranexamic acid (65 deaths among 442 patients [14.7%]; adjusted hazard ratio for death, 1.07; 95% confidence interval, 0.80-1.45) was associated with increased mortality. In multivariable logistic regression, either with propensity adjustment or without, aprotinin was independently predictive of 5-year mortality (adjusted odds ratio with propensity adjustment, 1.48; 95% confidence interval, 1.13-1.93; P = .005) among patients with diverse risk profiles, as well as among those surviving their index hospitalization. Neither aminocaproic nor tranexamic acid was associated with increased risk of death.
  
  
  CONCLUSIONS
  These findings indicate that in addition to the previously reported acute renal and vascular safety concerns, aprotinin use is associated with an increased risk of long-term mortality following CABG surgery. Use of aprotinin among patients undergoing CABG surgery does not appear prudent because safer and less expensive alternatives (ie, aminocaproic acid and tranexamic acid) are available.
authors.affiliation: Ischemia Research and Education Foundation, San Bruno, Calif 94066 , USA. dtb@iref.org
authors.forename: Dennis T
authors.initials: DT
authors.lastname: Mangano
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Miao
authors.forename: Alain
authors.initials: A
authors.lastname: Vuylsteke
authors.forename: Iulia C
authors.initials: IC
authors.lastname: Tudor
authors.forename: Rajiv
authors.initials: R
authors.lastname: Juneja
authors.forename: Daniela
authors.initials: D
authors.lastname: Filipescu
authors.forename: Andreas
authors.initials: A
authors.lastname: Hoeft
authors.forename: Manuel L
authors.initials: ML
authors.lastname: Fontes
authors.forename: Zak
authors.initials: Z
authors.lastname: Hillel
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ott
authors.forename: Tatiana
authors.initials: T
authors.lastname: Titov
authors.forename: Cynthia
authors.initials: C
authors.lastname: Dietzel
authors.forename: Jack
authors.initials: J
authors.lastname: Levin
mesh_terms: D000368:Aged; D000614:Aminocaproates / Q000627:therapeutic use; D000933:Antifibrinolytic Agents / Q000627:therapeutic use; D007611:Aprotinin / Q000009:adverse effects* / Q000627:therapeutic use; D002315:Cardiopulmonary Bypass; D001026:Coronary Artery Bypass / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006490:Hemostatics / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D016015:Logistic Models; D008239:Lysine / Q000031:analogs & derivatives; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012306:Risk; D015842:Serine Proteinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D016019:Survival Analysis; D014148:Tranexamic Acid / Q000627:therapeutic use
chemical_list: D000614:Aminocaproates; D000933:Antifibrinolytic Agents; D006490:Hemostatics; D015842:Serine Proteinase Inhibitors; D014148:Tranexamic Acid; D007611:Aprotinin; D008239:Lysine