Increased perioperative mortality following aprotinin withdrawal: a real-world analysis of blood management strategies in adult cardiac surgery

Graham J. Walkden, Veerle Verheyden, Rosalind Goudie, Gavin J. Murphy*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

20 Citations (Scopus)


To evaluate the effect of aprotinin withdrawal in 2008 on patient outcomes, to assess the likely risks and benefits of its re-introduction, and to consider the relevance of existing evidence from clinical trials to 'real-world' practice.

We performed a nested case-control study of two cohorts undergoing adult cardiac surgery in a single tertiary centre. The first group underwent surgery between 1 January 2005 and 30 July 2007 (n = 3,578), prior to aprotinin withdrawal; the second group underwent surgery between 1 January 2009 and 31 December 2010 (n = 3,030), after aprotinin withdrawal. Propensity matching was used to select patients matched for 24 covariates in both groups (n = 3,508). We also estimated the effect of aprotinin withdrawal on a subgroup of high-risk patients (n = 1,002). Results were expressed as adjusted odds ratios (OR) and 95 % confidence intervals (CI) for categorical data and hazard ratios (HR) for time-to-event data.

In propensity-matched cohorts, the withdrawal of aprotinin from clinical use was associated with more bleeding, higher rates of emergency re-sternotomy, OR 2.10 (1.04-4.25), and acute kidney injury (AKI), OR 1.86 (1.53-2.25). In high-risk patients, the increases in bleeding and AKI following aprotinin withdrawal were of a greater magnitude. Aprotinin withdrawal was also associated with a significant increase in 30-day mortality, HR 2.51 (1.00-6.29), in the high-risk group. The results were not altered by sensitivity analyses that adjusted for potential selection bias, time series bias and unmeasured confounders.

Aprotinin withdrawal was associated with increased complication rates and patient deaths following cardiac surgery. These real-world findings are at odds with those of randomised trials and cohort studies that have considered the clinical role of aprotinin.

Original languageEnglish
Pages (from-to)1808-1817
Number of pages10
JournalIntensive Care Medicine
Issue number10
Publication statusPublished - Oct 2013


  • Aprotinin
  • Cardiac surgery
  • Mortality
  • Blood management
  • RISK

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