Aprotinin And ACE Inhibitors Associated With Postoperative Renal Dysfunction During Off-Pump Cardiac Surgery

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Main Category: Cardiovascular / Cardiology
Also Included In: Clinical Trials / Drug Trials;  Pharmacy / Pharmacist;  Blood / Hematology
Article Date: 08 Feb 2008 - 0:00 PDT

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When used during on-pump cardiac surgery, the blood-conserving drug aprotinin appears to be safe. However, when used in combination with angiotensin-converting enzyme (ACE) inhibitors during off-pump cardiac surgery, it has been associated with a significant risk of renal dysfunction in the postoperative phase. This is the conclusion of authors Mouton, Finch, Davies, Binks and Zacharowski in an article published in the February 8, 2008 edition of The Lancet.

Aprotinin is a drug routinely used to save blood during cardiac surgery. A serine protease inhibitor, it has anti-inflammatory effects and helps to prevent the breakdown of clotting fibrous blood. Many randomized control trials have shown that it reduces bleeding for the entire perioperative period, thus reducing the need for blood transfusion during cardiac surgery. Unfortunately, other studies have shown a link between aprotinin and renal failure. In fact, the license holder for aprotinin, Bayer plc, UK, voluntarily suspended the worldwide marketing of the drugs following preliminary findings that suggested it increased mortality in a Canadian study known as the BART analysis.

The authors performed a retrospective study of the effects aprotinin had on renal dysfunction, with a specific focus on on-pump versus off-pump cardiac surgery, as well as potential co-medication with ACE inhibitors. This study included 9875 patients undergoing cardiac surgery between January of 2000 and September of 2007. They then examined the incidence of renal dysfunction in patients receiving a number of antifibrinolytic treatments including aprotinin, and tranexamic acid, in conjuntion with the presence or absence of pre-operative ACE inhibitor treatment for both on-pump and off-pump surgical techniques.

"On-pump surgery" refers to cardiac surgery performed with the patient on a bypass pump. Most of this study was composed of patients who had undergone surgery of this type. However, today, an alternative technique is often used where surgeons operate on a beating heart, so patients never go on a bypass machine. This is referred to as "off pump" cardiac surgery.

In the 5434 patients who had undergone on-pump surgery, there was no significant correlation between aprotinin and postoperative renal dysfunction, regardless of the use of ACE inhibitors. For the 848 patients taking ACE inhibitors and undergoing off-pump surgery, a two-fold increase in risk of renal dysfunction was associated with the use of aprotinin.

"We recommend that it might be beneficial for patients to discontinue any use of an ACE inhibitor before elective off-pump surgery, particularly patients with a history of renal impairment." The authors state. "The international communities of cardiac anaesthesia and surgery face controversy regarding the use of aprotinin. In the UK, the CHM is awaiting the decision of the European Commission which is undertaking a full review for the risks and benefits of aprotinin. In our study, we recorded little association between use of aprotinin and the occurrence of renal dysfunction in patients undergoing on-pump cardiac surgery, irrespective of ACE inhibitor use."

In an attending Comment in the same issue of The Lancet, Dr Derek Hausenloy, The Hatter Cardiovascular Institute, University College London Hospital and Medical School, London, UK, and colleagues, said: "The [full] outcome of the BART analysis will not be known for some time -- will the results support or refute the findings of 64 randomised trials? While waiting for that analysis, the use of aprotinin in the US and in some European countries has been necessarily restricted, with the consequence that some high-risk patients having cardiac surgery might not receive optimum therapy."

Effect of aprotinin on renal dysfunction in patients undergoing on-pump and off-pump cardiac surgery: a retrospective observational study
Ronelle Mouton, David Finch, Ian Davies, Andrea Binks, Kai Zacharowski
The Lancet, Volume 371, Number 9611, 9 February 2008
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Written by Anna Sophia McKenney
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