Comparative analysis of antifibrinolytic medications in pediatric heart surgery

J Thorac Cardiovasc Surg. 2012 Mar;143(3):550-7. doi: 10.1016/j.jtcvs.2011.06.048. Epub 2012 Jan 20.

Abstract

Objectives: Recent studies suggest adverse events associated with aprotinin in adults may not occur in children, and there is interest in further pediatric study of aprotinin. However, there are limited contemporary data comparing aprotinin with other available antifibrinolytics (aminocaproic acid [ACA] and tranexamic acid [TXA]) to guide current practice and aid in potential trial design. We performed a comparative analysis in a large multicenter cohort.

Methods: The Society of Thoracic Surgeons Congenital Heart Surgery Database (2004-2008) was linked to medication data from the Pediatric Health Information Systems Database. Efficacy and safety outcomes were evaluated in multivariable analysis adjusting for patient and center factors overall and in neonates and those undergoing redo sternotomy.

Results: A total of 22,258 patients (25 centers) were included: median age, 7.6 months (interquartile range, 2.6-43.4 months). Aprotinin (vs no drug) was associated with a significant reduction in combined hospital mortality/bleeding requiring surgical intervention overall (odds ratio [OR], 0.81; 95% confidence intervals [CI], 0.68-0.91) and in the redo sternotomy subgroup (OR, 0.57; 95% CI, 0.40-0.80). There was no benefit in neonates and no difference in renal failure requiring dialysis in any group. In comparative analysis, there was no difference in outcome in aprotinin versus ACA recipients. TXA (vs aprotinin) was associated with significantly reduced mortality/bleeding requiring surgical intervention overall (OR, 0.47; 95% CI, 0.30-0.74) and in neonates (OR, 0.30; 95% CI, 0.15-0.58).

Conclusions: These observational data suggest aprotinin is associated with reduced bleeding and mortality in children undergoing heart surgery with no increase in dialysis. Comparative analyses suggest similar efficacy of ACA and improved outcomes associated with TXA.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminocaproates / therapeutic use
  • Antifibrinolytic Agents / adverse effects
  • Antifibrinolytic Agents / therapeutic use*
  • Aprotinin / therapeutic use
  • Cardiac Surgical Procedures* / adverse effects
  • Cardiac Surgical Procedures* / mortality
  • Chi-Square Distribution
  • Child, Preschool
  • Female
  • Heart Defects, Congenital / blood
  • Heart Defects, Congenital / surgery*
  • Hospital Mortality
  • Humans
  • Infant
  • Infant Mortality
  • Linear Models
  • Male
  • Odds Ratio
  • Postoperative Hemorrhage / chemically induced
  • Postoperative Hemorrhage / surgery
  • Registries
  • Renal Dialysis
  • Renal Insufficiency / etiology
  • Renal Insufficiency / therapy
  • Reoperation
  • Risk Assessment
  • Risk Factors
  • Sternotomy
  • Time Factors
  • Tranexamic Acid / therapeutic use
  • Treatment Outcome
  • United States

Substances

  • Aminocaproates
  • Antifibrinolytic Agents
  • Tranexamic Acid
  • Aprotinin