The availability of an anticoagulant reversal agent in Australia has changed the conversation about treatment choices for patients and removed a concern for clinicians, a cardiologist says.

Speaking to the limbic following a breakfast symposium, held at the recent Cardiology Society of Australia and New Zealand annual conference in Adelaide, Professor John Amerena a cardiologist at Geelong Private Hospital in Victoria said the availability of the reversal agent idarucizumab (Praxbind) was a reassurance for all clinicians, particularly GPs.

“The biggest issue for GPs when contemplating using new anticoagulants has been the lack of a reversal agent… Now we have something that can reverse dabigatran (Pradaxa) we assume a lot of that hesitation will diminish,” he said.

Idarucizumab: a specific reversal agent for dabigatran

Idarucizumab is a humanized Fab fragment that binds to dabigatran with high affinity and is excreted by the kidney, delegates attending the breakfast symposium at the CSANZ annual conference in Adelaide were told.

It also has a short half-life, no intrinsic pro-coagulant or anticoagulant activity and did not interact with other drugs. Delegates were reminded that dabigatran (Praxbind) does not reverse the other direct oral anticoagulants.

RE–VERSE AD ¹ was the main trial published in the New England Journal of Medicine as an interim analysis earlier this year.

The multicentre single arm open label phase 3 trial involved two groups of patients taking dabigatran – Group A who came into hospital with uncontrolled bleeding and Group B who required emergency surgery or a procedure.

Patients were given 5mg of intravenous idarucizumab as two sequential 2.5g doses. The primary end point was the median percentage reversal of the drug (dabigatran) as determined by blood measures.

Clotting tests were performed on blood taken at baseline, 10 and 30 minutes, and then at 1, 2, 4, 12 and 24 hours, but the results were not available to clinicians when they made the decision to treat.

Among patients with clotting tests suggestive of active dabigatran, idarucizumab normalised the results in 88-98% of cases, an effect was evident within minutes.

Reassurance of anticoagulation reversal

According to Professor Amerena the biggest fear for most practitioners was causing a problem for their patients.

“Physicians often feel that if we give a drug and the patient bleeds it’s our fault because we prescribed it, whereas if they have a stroke it’s because of the patient’s underlying condition,” he explained.

“We’re trying to reverse that strategy to say there are a lot of patients who would benefit from anticoagulation and that clinicians should err on the side of giving anticoagulation to reduce the risk of stroke and accept that there’s a small risk of bleeding.”

For patients the clinical consequences of having a stroke are far greater than the risks associated with bleeding, he said.

“We explain to patients that the risk of bleeding is reduced with these newer oral anticoagulants compared with warfarin, and can now say that if they are unlucky enough to have a bleed while taking dabigatran (Pradaxa) the anticoagulant effect can be reversed straight away with Idarucizumab (Praxbind).”

Professor Amerena also said that a potentially bigger group of patients who could need reversal were those who required emergency surgery. “If a patient comes in with appendicitis, trauma from a car accident or sepsis you can’t just wait for 24 to 48 hours for it to wear off – this is a potentially bigger group of patients who require immediate reversal,” he said. This type of patient was also studied in RE–VERSE AD ¹ and bleeding at the time of surgery was judged to be normal in >90% of patients after Praxbind was administered.

References

• New England Journal of Medicine 2015; 373: 511-520.
• PBS Drug-Utilisation Sub Committee: Novel oral anticoagulants for non-atrial fibrillation indications: utilisation analysis; October 2014.
• International Journal of Cardiology 2016; 203: 746-752.