Concerns that the antifibrinolytic agent tranexamic acid may raise the risk of MI and stroke in patients undergoing cardiac surgery have been quashed after findings from a 10-year long trial finds no evidence to support these fears.
Researchers from The Alfred in Melbourne who conducted the trial involving more than 4000 patients say theirs is the first large randomised controlled trial to provide robust safety data about the drug for patients in cardiac surgery settings.
“We had no safety data about this drug – nowhere in the world. No one else has tried to undertake the challenge of doing a trial like this to really find out what the true benefits and risks are for this particular medication” said study lead and director of Anaesthesia and Perioperative Medicine at the Alfred, Professor Paul Myles in an interview with the limbic.
The team say their findings are the first to show the drug carries no thrombotic risk. They also claim the benefits of reducing bleeding complications by using the drug are greater than anyone had previously thought – patients in the study who had been given tranexamic acid had a lower risk of blood loss, blood transfusion, and reoperation compared to the placebo group, Professor Myles said.
“We showed absolutely clearly that there is no excess or safety risk at all for heart attack or stroke … this is really valuable information it means that heart surgery teams around the world can use this drug much more freely and probably at a higher dose.”
However, the researchers did report that the drug was associated with a small but higher risk of postoperative seizure.
In the study carried out between 2006 and 2015 some 4630 patients undergoing cardiac surgery were randomised to receive tranexamic acid or a placebo.
The primary outcome, a composite of death or thrombotic complications occurred within the first 30 days after surgery in 386 patients (16.7%) in the tranexamic acid group and in 420 patients (18.1%) in the placebo group.
Myocardial infarction was detected within the first 30 days after surgery in 269 patients (11.6%) in the tranexamic acid group and in 300 patients (12.9%) in the placebo group. The rates of death, stroke, pulmonary embolism, renal failure, and bowel infarction were similar across the two groups, Professor Myles said.
Major haemorrhage or cardiac tamponade leading to reoperation occurred in 1.4% of the patients in the tranexamic acid group and in 2.8% of the patients in the placebo group (P = 0.001).
The results were consistent among patients who were being treated with aspirin and those who were not.
According to Professor Myles patients in the tranexamic acid group received 46% fewer units of blood products than did those in the placebo group.
“In a cardiac surgical practice similar to the practices in which our trial population was treated, the use of tranexamic acid would save approximately 57 units of blood products for every 100 patients treated.”
Meanwhile, Professor Myles said that while the risk of postoperative seizure associated with the drug is small – occurring in 15 people (0.7%) in the treatment group and two (0.1%) in the placebo group – the study does clearly show for the first time that the link is causal although, based on their findings, it’s unlikely to be dose dependent.
“There’s no doubt that patients getting this drug are at risk of seizures, albeit rare, and we don’t know the clinical importance of this.
“The fact that someone has a seizure usually in the first 24 hours after surgery is obviously distressing and worrying but there’s no evidence that, in and of itself, causes any long term harm – it certainly doesn’t lead to epilepsy or other seizures so it might just be a transient phenomenon.”
He also noted that the risk for seizure appeared to be ‘almost exclusively’ seen in the patients undergoing open chamber surgery.
“So we can now consider whether we use a lower dose in patients undergoing valve surgery but more importantly for all those others that are having standard bypass surgery we can freely use it really with no particular concern at all.”