SCTS Conference News spoke with Professor Mahmoud Loubani (Consultant Cardiothoracic Surgeon and Honorary Professor of Cardiothoracic Surgery at Castle Hill Hospital (CHH), Co-Chair SCTS Academic and Research Subcommittee, Yorkshire and Humber NIHR CRN Lead for Cardiothoracic Surgery) who outlined the rationale, indications and outcomes when his centre reintroduced aprotinin for patients undergoing isolated-CABG.

Aprotinin is indicated for prophylactic use to reduce blood loss and blood transfusion in adult patients at high risk of major blood loss undergoing isolated cardiopulmonary bypass graft surgery. Aprotinin should only be used after careful consideration of the benefits and risks, and alternative treatments⁴

Prior to the re-launching aprotinin for patients undergoing isolated-CABG, how did you manage without aprotinin and what were the subsequent challenges due to not having this drug available?

Aprotinin was used for several years to reduce bleeding during and after surgery and was used very widely during my training period. However, several papers were published reporting increased morbidity and mortality of its use and subsequently, many units stopped using it. This meant we now had limited choices to reduce intra – and post-operative bleeding in patients who were at high-risk from bleeding. We used alternatives such as tranexamic acid, but this was not as effective as aprotinin in patients at high risk, and had its own side-effects.¹ As a result, we had to be very cautious when operating on patients with bleeding tendencies, often resulting in a delay in surgery and increased hospital stay. Therefore, there was an urgent need to either use aprotinin or find a suitable alternative. Over time, more papers were published supporting the use of aprotinin and questioning the findings of previous publications. This resulted in more surgical units beginning to use aprotinin with positive results. In addition to the clinical literature, there were also positive outcomes demonstrated from the Nordic Aprotinin Patient Registry (NAPaR) in isolated-CABG patients.²

What criteria do you use for identifying patients requiring aprotinin?

We identify patients who would be suitable for treatment with aprotinin based on their characteristics that put them at increased risk of perioperative bleeding.

For patients undergoing isolated-CABG, these characteristics included:

• Previous cardiac surgery
• Hepatic dysfunction affecting clotting
• Inherited or acquired abnormalities
• Low platelet count <150
• Documented hepatic dysfunction affecting clotting dysfunction
• Dual antiplatelet therapy
• Oral anticoagulant therapy
• Jehovah’s Witness or another reason to refuse blood transfusion.

It is important to refer to the aprotinin summary of product characteristics to identify patients for whom aprotinin is not suitable, including patients who are hypersensitive or have been exposed. to aprotinin in the previous 12 months.

When and why did you start using aprotinin for patients undergoing isolated CABG at CHH?

Isolated-CABG patients are not the typical group of patients we would have thought were the ideal patients for aprotinin. However, isolated-CABG patients can be at an increased risk of bleeding, especially in the current era where we are operating on a lot of urgent cases, who present with a non-ST-elevation myocardial infarction (NSTEMI) and are placed on dual antiplatelet therapy, and then referred for surgery. There is good evidence that we should continue with the dual antiplatelet therapy but that would put them at an increased risk of bleeding once we operate on them and when restarting dual antiplatelet therapy post-surgery.³ All these considerations made us think again about aprotinin. In 2018, we had a number of consultations and discussions about reinstating aprotinin on our formulary. It was particularly helpful to receive the latest information and data from the Nordic Aprotinin Patient Registry (NAPaR)² and the approved indications for aprotinin in isolated-CABG patients.⁴ We developed a standard operating procedure for the use of aprotinin in this group of patients, which was widely consulted on and included all the stakeholders, from surgeons and perfusionists to anaesthesiologists. We were subsequently granted approval by the drugs and therapeutics committee in May 2019.

Would you be happy to help share your experiences with aprotinin for patients undergoing isolated-CABG with other centres?

There is a reluctance among some surgeons to consider using aprotinin for patients undergoing isolated-CABG under its current licence. The important message to other centres and surgeons is that although we want to use aprotinin for the more complex procedures, there are a cohort of isolated-CABG patients that do benefit from aprotinin. Aprotinin has been proven to be an effective drug at reducing blood loss¹ . It is very helpful to have it in the armamentarium of the cardiac surgeon to deal with the very common problem of bleeding during and after cardiac surgery. We need every tool at our disposal and aprotinin is one we can use to help improve our outcomes. I would be happy to share my experience with aprotinin in isolated-CABG patients to outline the positive outcomes for the hospital and patient.