Antifibrinolytic agents and angiotensin-converting enzyme inhibitors: the effect on postoperative renal dysfunction in cardiac surgery

Objective

To investigate the effect of the antifibrinolytic agents aprotinin and tranexamic acid on the occurrence of acute postoperative renal dysfunction in cardiac surgery on patients treated preoperatively with angiotensin-converting enzyme (ACE) inhibitors.

Methods

A total of 7,420 patients who had undergone nonemergency coronary artery bypass graft or valve surgery in the Bristol Royal Infirmary from January 2000 until end of March 2006 were included in a retrospective observational study. The incidence of postoperative renal dysfunction was compared in patients given aprotin, tranexamic acid or no antifibrinolytic agent, using propensity-adjusted multivariable logistic regression. Further analysis was performed comparing patients taking ACE inhibitors preoperatively with those not taking ACE inhibitors. Renal dysfunction was defined as creatinine higher than 200 μmol/l and/or renal dialysis. Patients with a previous history of renal dysfunction were excluded from the study.

Results

Using propensity-adjusted multivariable logistic regression (C-index, 0.82), the use of aprotinin in patients taking ACE inhibitors was associated with more than doubling the risk of acute postoperative renal failure in patients undergoing nonemergency cardiac surgery (odds ratio 2.64; confidence interval 1.32–5.27). Tranexamic acid was also associated with a significant increase in the risk of renal failure (odds ratio 1.59; confidence interval 1.09–2.31) in patients taking ACE inhibitors. However, in this study, there was no association between either aprotinin (odds ratio 1.01) or tranexamic acid (odds ratio 1.19) and postoperative renal failure in patients not taking ACE inhibitors.

Conclusion

In cardiac surgery, there is a significant association between use of the antifibrinolytic drugs aprotinin and tranexamic acid and the occurrence of acute postoperative renal dysfunction, in patients taking ACE inhibitors. The potential blood-saving benefits of antifibrinolytic drugs should be weighed up against this serious postoperative complication.