How and when to use aprotinin for patients at high risk of bleeding undergoing isolated CABG: Mr Dumbor Ngaage
Aprotinin is indicated to reduce blood loss and transfusion requirements in patients at high risk of major bleeding, undergoing isolated coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass (i.e. coronary artery bypass graft surgery that is not combined with other cardiovascular surgery). Aprotinin should only be used after careful consideration of the benefits and risks, and the consideration that alternative treatments are available.1 A regulatory review of pooled analyses concluded that the overall data for aprotinin have consistently shown a reduction in the incidence of massive post-operative bleeding and the need for transfusion, compared with other haemostatic agents.2 Mr Dumbor Ngaage, a Consultant Cardiac Surgeon at the Hull University Teaching Hospitals NHS Trust answers questions on his experience with aprotinin and where he sees it offering a benefit for patients at high risk of bleeding undergoing isolated CABG.
Dumbor Ngaage, Consultant Cardiac Surgeon, Hull University Teaching Hospitals NHS Trust
Mr Ngaage obtained his primary medical degree (MB.BS) from the University of Benin, Nigeria, and postgraduate degrees in General Surgery; FWACS (Fellow of the West African College of Surgeons) in Nigeria, and FRCSED, in the UK. He obtained FRCS (C-Th), FETCS in cardiovascular surgery, FETCS in thoracic surgery, and a MS in clinical research from The Mayo Graduate School, USA. Mr Ngaage is on the editorial board of cardiothoracic and intensive care journals, and has published high impact research in blood conservation strategies in cardiac surgery.
Mr Ngaage is the Chief Investigator for FARSTER, an NIHR-funded multi-centre RCT of post-operative recovery after cardiac surgery.
When carrying out an isolated CABG procedure, how do you determine which patients may benefit from aprotinin?
Aprotinin is usually not required for most elective isolated first-time CABG procedures.
I consider using aprotinin in patients at high risk of post-operative bleeding, namely in patients:
• Undergoing CABG with continued dual antiplatelet therapy* (DAPT) or recent loading with DAPT
• Pre-operative anaemia
• Acute coronary syndrome/NSTEMI/STEMI requiring urgent surgery.
I also consider using aprotinin in patients that will not, or cannot, be transfused, such as Jehovah’s witnesses and those with rare antibodies.
Post-operative bleeding can lead to increased blood transfusions and re-operation for bleeding/tamponade – I describe this as “the triple jeopardy of cardiac surgery”.
Patients who are more vulnerable to the dire consequences of this triple jeopardy include octogenarians, heart failure patients and those with low body mass index.
Aprotinin could play a role in the haemostatic strategy for some of these patients.
If a patient requires an emergency or urgent CABG and has received DAPT within the last 5 days, is aprotinin appropriate in this scenario?
About 35% of patients at my institution who are awaiting a CABG procedure are taking DAPT. Often, these patients do not stop DAPT in sufficient time for surgery, especially if the procedure is non-elective. Aprotinin may be considered for these patients, and its potent anti-inflammatory and haemostatic effects may enable CABG to be performed effectively in this scenario. This has been demonstrated in the study by van der Linden et al. 2005 which compared the use of aprotinin vs placebo in patients who received clopidogrel five days before CABG.3 It should be noted that aprotinin is not heparin-sparing and adequate anticoagulation needs to be maintained during aprotinin therapy, in line with the aprotinin label.1
When would you choose aprotinin instead of tranexamic acid (TXA) on isolated CABG?
In high risk patients, compared to TXA, patients taking aprotinin have less post-operative blood loss, a lower need for transfusions, and shorter stays in the ICU.4
*DAPT = aspirin and clopidogrel or ticagrelor or prasugrel
References: 1. Medicines.org.uk. (2017). Aprotinin 10,000 KIU/ml Injection BP – Summary of Product Characteristics (SPC) – (eMC). [online] Available at: https://www.medicines.org.uk/emc/product/2472/smpc. 2. European Medicines Agency. Assessment report: Antifibrinolytics containing aprotinin, aminocaproic acid and tranexamic acid. Available at: https://www.ema.europa.eu/en/documents/referral/assessment-report-antifibrinolytic-medicines-aprotinin_en.pdf. 3. Van der Linden J, Lindvall G, Sartipy U. Aprotinin Decreases Postoperative Bleeding and Number of Transfusions in Patients on Clopidogrel Undergoing Coronary Artery Bypass Graft Surgery. Circulation. 2005;112:I276–80. 4. Deloge E, Amour J, Provenchere S, Rozec B, Scherrer B, Ouattara A. Aprotinin vs. tranexamic acid in isolated coronary artery bypass surgery: A multicentre observational study. Eur J Anaesthesiol. 2017 May;34(5):280–87.
