title: A comparison of aprotinin and lysine analogues in high-risk cardiac surgery.
abstract: BACKGROUND
  Antifibrinolytic agents are commonly used during cardiac surgery to minimize bleeding and to reduce exposure to blood products. We sought to determine whether aprotinin was superior to either tranexamic acid or aminocaproic acid in decreasing massive postoperative bleeding and other clinically important consequences.
  
  
  METHODS
  In this multicenter, blinded trial, we randomly assigned 2331 high-risk cardiac surgical patients to one of three groups: 781 received aprotinin, 770 received tranexamic acid, and 780 received aminocaproic acid. The primary outcome was massive postoperative bleeding. Secondary outcomes included death from any cause at 30 days.
  
  
  RESULTS
  The trial was terminated early because of a higher rate of death in patients receiving aprotinin. A total of 74 patients (9.5%) in the aprotinin group had massive bleeding, as compared with 93 (12.1%) in the tranexamic acid group and 94 (12.1%) in the aminocaproic acid group (relative risk in the aprotinin group for both comparisons, 0.79; 95% confidence interval [CI], 0.59 to 1.05). At 30 days, the rate of death from any cause was 6.0% in the aprotinin group, as compared with 3.9% in the tranexamic acid group (relative risk, 1.55; 95% CI, 0.99 to 2.42) and 4.0% in the aminocaproic acid group (relative risk, 1.52; 95% CI, 0.98 to 2.36). The relative risk of death in the aprotinin group, as compared with that in both groups receiving lysine analogues, was 1.53 (95% CI, 1.06 to 2.22).
  
  
  CONCLUSIONS
  Despite the possibility of a modest reduction in the risk of massive bleeding, the strong and consistent negative mortality trend associated with aprotinin, as compared with the lysine analogues, precludes its use in high-risk cardiac surgery. (Current Controlled Trials number, ISRCTN15166455 [controlled-trials.com].).
authors.affiliation: Ottawa Health Research Institute, Ottawa, Canada.
authors.forename: Dean A
authors.initials: DA
authors.lastname: Fergusson
authors.forename: Paul C
authors.initials: PC
authors.lastname: Hébert
authors.forename: C David
authors.initials: CD
authors.lastname: Mazer
authors.forename: Stephen
authors.initials: S
authors.lastname: Fremes
authors.forename: Charles
authors.initials: C
authors.lastname: MacAdams
authors.forename: John M
authors.initials: JM
authors.lastname: Murkin
authors.forename: Kevin
authors.initials: K
authors.lastname: Teoh
authors.forename: Peter C
authors.initials: PC
authors.lastname: Duke
authors.forename: Ramiro
authors.initials: R
authors.lastname: Arellano
authors.forename: Morris A
authors.initials: MA
authors.lastname: Blajchman
authors.forename: Jean S
authors.initials: JS
authors.lastname: Bussières
authors.forename: Dany
authors.initials: D
authors.lastname: Côté
authors.forename: Jacek
authors.initials: J
authors.lastname: Karski
authors.forename: Raymond
authors.initials: R
authors.lastname: Martineau
authors.forename: James A
authors.initials: JA
authors.lastname: Robblee
authors.forename: Marc
authors.initials: M
authors.lastname: Rodger
authors.forename: George
authors.initials: G
authors.lastname: Wells
authors.forename: Jennifer
authors.initials: J
authors.lastname: Clinch
authors.forename: Roanda
authors.initials: R
authors.lastname: Pretorius
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000614:Aminocaproates / Q000009:adverse effects / Q000627:therapeutic use*; D000933:Antifibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007611:Aprotinin / Q000009:adverse effects / Q000627:therapeutic use*; D001803:Blood Transfusion / Q000706:statistics & numerical data; D006348:Cardiac Surgical Procedures / Q000401:mortality; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007902:Length of Stay; D008239:Lysine / Q000031:analogs & derivatives*; D008297:Male; D008875:Middle Aged; D019106:Postoperative Hemorrhage / Q000453:epidemiology / Q000517:prevention & control*; D014148:Tranexamic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000614:Aminocaproates; D000933:Antifibrinolytic Agents; D014148:Tranexamic Acid; D007611:Aprotinin; D008239:Lysine