Safety of Perioperative Aprotinin Administration During Isolated Coronary Artery Bypass Graft Surgery: Insights From the ART (Arterial Revascularization Trial)

J Am Heart Assoc. 2018 Mar 3;7(5):e007570. doi: 10.1161/JAHA.117.007570.

Abstract

Background: There is still uncertainty about the safety of aprotinin for coronary artery bypass graft surgery. The ART (Arterial Revascularization Trial) was designed to compare survival after bilateral versus single internal thoracic artery grafting. Many of the ART patients (≈30%) received perioperative aprotinin. We investigated the association between perioperative aprotinin administration and short-term (in-hospital) and long-term outcomes by performing a post hoc analysis of the ART.

Methods and results: Among patients enrolled in the ART (n=3102) from 2004 to 2007, we excluded those who did not undergo surgery (n=18) and those with no information about use of perioperative aprotinin (n=9). Finally, 836 of 3076 patients (27%) received aprotinin. Propensity matching was used to select 536 pairs for final comparison. Aprotinin was also associated with an increased risk of hospital mortality (9 [1.7%] versus 1 [0.2%]; odds ratio, 9.12; 95% confidence interval [CI], 1.15-72.2; P=0.03), intra-aortic balloon pump insertion (37 [6.9%] versus 17 [3.2%]; odds ratio, 2.26; 95% CI, 1.26-4.07; P=0.006), and acute kidney injury (102 [19.0%] versus 76 [14.2%]; odds ratio, 1.42; 95% CI, 1.03-1.97; P=0.03). Aprotinin was not associated with a lower incidence of transfusion (37 [6.9%] versus 28 [5.2%]; odds ratio, 1.34; 95% CI, 0.81-2.23; P=0.25) and reexploration (26 [4.9%] versus 19 [3.5%]; hazard ratio, 1.39; 95% CI, 0.76-2.53; P=0.28). At 5 years, all-cause mortality was significantly increased in the aprotinin group (56 [10.6%] versus 38 [7.3%]; hazard ratio, 1.51; 95% CI, 1.0-2.28; P=0.045).

Conclusions: In the present post hoc ART analysis, aprotinin was associated with a significantly increased risk of early and late mortality.

Clinical trial registration: URL: http://www.isrctn.com. Unique identifier: ISRCTN46552265.

Keywords: Surgery; aprotinin; coronary artery bypass graft surgery; outcomes; propensity score matching.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aprotinin / administration & dosage*
  • Aprotinin / adverse effects
  • Blood Loss, Surgical / mortality
  • Blood Loss, Surgical / prevention & control*
  • Coronary Artery Bypass* / adverse effects
  • Coronary Artery Bypass* / mortality
  • Coronary Artery Disease / mortality
  • Coronary Artery Disease / surgery*
  • Drug Administration Schedule
  • Female
  • Hemostatics / administration & dosage*
  • Hemostatics / adverse effects
  • Hospital Mortality
  • Humans
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Perioperative Care / adverse effects
  • Perioperative Care / methods*
  • Perioperative Care / mortality
  • Postoperative Hemorrhage / etiology
  • Postoperative Hemorrhage / mortality
  • Postoperative Hemorrhage / prevention & control*
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Hemostatics
  • Aprotinin

Associated data

  • ISRCTN/ISRCTN46552265