Thursday, 15 September 2011

THE APROTININ STORY - HAVE WE GOT IT WRONG?

In the 1990s and early 2000s ,  Aprotinin was used very frequently in cardiac surgical operations to diminish bleeding. In addition, every issue of most cardiothoracic journals had articles showing how good Aprotinin was in minimizing end organ damage after cardiac surgery. Aprotinin was cardiac surgery's Statins - it could do no wrong. It was definitely very effective at doing the job set out on the tin i.e. control bleeding.
Aprotinin was first introduced by Bayer in the 1970s as a treatment for acute pancreatitis. It was in the late 1980s that research performed at the Hammersmith and Harefied Hospitals in London confirmed the efficacy of the drug at controlling bleeding associated with post cardiac surgery coagulopathy.
In 2006, a large observational study performed by a group  led by Dennis Mangano suggested increased rates of thromboses and deaths associated with the use of the drug. Mangano then started a single minded campaign to get the drug banned. It came to a point when googling Aprotinin produced details of dozens of American legal firms who were prepared to sue institutions carrying out cardiac surgery. Most of the anti Aprotinin drug studies seemed to be published in the New England Journal of Medicine including the BART study. This was a properly conducted randomised study from centres in Canada. This showed an excess of deaths in patients undergoing complex cardiac surgery (valve and CABG valve cases). Based on this ONE study, Aprotinin use dwindled around the world - from HERO status to ZERO in 18 short months. The drug is still available but you REALLYhave to justify using it and you have to get a separate informed consent from the patient. Many surgeons now just don't bother.
Thrombosis is  bad for cardiovascular interventions. Cardiologists do everything to bash the clotting cascade and platelet function. In cardiovascular surgery, we face the opposite problem in the immediate postoperative period i.e. bleeding which itself can be fatal - so we promote thrombosis early on and reverse it soon after. Getting a balance can be difficult. In the post Aprotinin era, we use alot more blood products (which are costly and carry risk of their own) and newer even costlier drugs such as Novo 7. Any systemic drug (including blood products such as plasma and donor platelets) which controls bleeding will also increase the chances of intravascular thrombosis and associated morbidity. The surgeon has to decide on the relative risks.   This study published in the Circulation Journal confirm what many cardiac surgeons have perceived for themselves. I think we have shot ourselves in the foot and patients (and health service finances) pay the price.
 (ps next to the image of trasylol on google, I found an advert for the UK National Accident Helpline and first4 lawyers .co.uk!!)