Professor Vivien Chen.

A major international trial showing apixaban more than halves the bleeding risk in patients being treated for blood clots compared to rivaroxaban will change prescribing practices around the world, its lead Australian investigator says.

First presented at a late breakthrough session at the ISTH 2025 Congress and now published in full in the New England Journal of Medicine [link here], the head-to-head trial addresses a longstanding evidence gap on the preferred direct oral anticoagulant (DOAC) for treating acute venous thromboembolism (VTE).

Sydney haematologist Professor Vivien Chen, who spearheaded the Australian arm of the trial, expected guidelines would be re-evaluated on the back of these results, adding that the Thrombosis & Haemostasis Society of Australia and New Zealand (THANZ) was already updating its guidance on VTE management.

“I think that this will influence our practice very quickly,” she told the limbic.

What the study found

The COBRRA (Comparison of Bleeding Risk with Rivaroxaban versus Apixaban) trial, led by researchers at The Ottawa Hospital in Canada with Australian and Irish colleagues, involved 2,760 patients (mean age 58, 44% female) with acute symptomatic pulmonary embolism or proximal deep-vein thrombosis from 32 centres across the three countries.

Participants were randomly assigned 1:1 to either standard-of-care DOAC, apixaban (10 mg twice daily for 7 days followed by 5 mg twice daily) or rivaroxaban (15 mg twice daily for 21 days followed by 20 mg daily) for 3 months.

Treatment with apixaban led to a significant reduction in clinically relevant bleeding risk, defined as a composite of major bleeding or clinically relevant non-major bleeding, during the study period (relative risk 0.46; 95% CI 0.33-0.65; P<0.001).

Specifically, 3.3% of patients receiving apixaban experienced clinically relevant bleeding versus 7.1% of patients receiving rivaroxaban.

Both major bleeding (0.4% vs 2.4%; relative risk 0.16; 95% CI, 0.06 to 0.40)  and clinically relevant non-major bleeding (2.9% vs 4.9%; relative risk 0.59; 95% CI, 0.40 to 0.86) were also independently assessed, with results favouring apixaban.

There were no deaths from bleeding or recurrent VTE in either group and no apparent difference in the risk of recurrent symptomatic VTE between the groups, although the study was not powered to detect this finding, the researchers said.

‘A transformational result for patient safety’

Speaking to the limbic, Professor Chen said the pragmatic nature of the trial, which was investigator-initiated and had no drug company involvement, made the results “very applicable to everyday practice” and could be adopted straight away.

The impacts would likely be wide-ranging, potentially improving patient outcomes and producing significant cost-savings, she said.

“We know that anticoagulation-related bleeding events are the most disruptive of the complications. Not only does it lead to hospitalisation, it leads to interruption in treatment, which is suboptimal for the long-term outcomes of the individuals,” said Professor Chen, the thrombosis lead haematologist at Concord Hospital and a professor of medicine at the University of Sydney.

The data could also be useful for informing discussions with patients who often asked questions about which anticoagulant was best for them, she added.

“This allows us to use hard data. It’s always a joint decision between a patient and the physician, but we’ll be able to tell them in very clear terms about the relative bleeding risks of one versus the other therapy, and that we have not seen a signal for any difference in thrombotic rate,” she said.

She stressed the findings were not applicable to the cancer-associated thrombosis population, patients with hospital-acquired VTE, those weighing more than 120 kg or those with significant renal impairment, all of whom were excluded from the trial.

“It’s really for those ambulant community-acquired blood clots, which make up the vast majority of thrombosis within the Australian community,” she said.

“This is the kind of research that we love, being able to do things that make a practical difference to the patients that we’re managing every day.”

The results could also have “a huge impact on access” to apixaban in New Zealand, which was currently not subsidised, Professor Chen said. Her New Zealand colleagues have already submitted a funding application using the data.

She added there was more to come from the COBRRA trial.

Future studies included health economics analyses and a biomarker substudy within the Australian arm to determine whether biomarkers could be used to predict bleeding or clotting risk in patients for more personalised treatment.

THANZ president Dr Danny Hsu said THANZ had been a critical partner in the trial, with its Clinical Trials Group’s coordination of the Australian sites highlighting how the community could execute practice-changing, global research.

“This landmark study, spearheaded by Professor Chen in Australia, is a testament to what we can achieve when we unite our national expertise to answer the most critical questions in clinical thrombosis,” he said.