The first clinical trial to compare two commonly used drugs head-to-head for venous thrombosis treatment has found a clear winner: while both drugs work well to prevent recurrent blood clots, apixaban is safer than rivaroxaban, with fewer bleeding complications.
Venous thrombosis occurs when a blood clot lodges in the veins of the legs or lungs. It is the third leading cause of cardiovascular death after heart attack and stroke and is the most common preventable cause of death in hospitalized patients.
Clinical guidelines currently recommend that patients recovering from venous thrombosis take an anticoagulant such as apixaban or rivaroxaban for three months to prevent further clots. While these drugs are effective in preventing blood clots, serious bleeding can be a side effect.
The COBRRA trial, led by researchers at The Ottawa Hospital in Canada, aimed to directly compare bleeding with apixaban and rivaroxaban in venous thrombosis patients. The trial enrolled 2,760 participants from 32 sites across Canada, Australia and Ireland.
Results highlight major difference in bleeding risk
Results showed that 7.1 per cent of participants who received rivaroxaban experienced clinically relevant bleeding after three months compared to 3.3 per cent of participants who received apixaban, representing more than double the risk of bleeding with rivaroxaban. There was no significant difference in the risk of recurrent blood clots.
“These results clearly show that apixaban is the safer option for treating venous thrombosis,” said lead author Dr. Lana Castellucci , senior scientist and thrombosis physician at The Ottawa Hospital and professor at the University of Ottawa. “This trial provides highly anticipated evidence for physicians and should bring real peace of mind to venous thrombosis patients, who often live with the dual fear of blood clot recurrence and bleeding.”
“This practice-changing trial and its findings exemplify the powerful impact of academically led, government-funded clinical research in addressing questions that truly matter to patients,” said senior author Dr. Marc Rodger , Physician-in-Chief at the McGill University Health Centre (MUHC), senior scientist at the Research Institute of the MUHC, and affiliate senior scientist at The Ottawa Hospital.
Dr. Vivien Chen , Thrombosis Lead Haematologist at Concord Hospital and professor of medicine at University of Sydney, highlighted the value of international participation.
“Because this was a real world, standard of care trial conducted across three countries, the findings have strong global relevance,” she said. “Patients in Australia, Canada and Ireland were treated according to routine clinical practice, making the findings broadly applicable to diverse health systems and patient populations.”
Significant impact for patients
Clinical trial participant Jonathan Love agrees that the results are important for patients. The retired Ottawa resident enrolled in the trial in January 2025 after being diagnosed with venous thrombosis.
“I went to the hospital emergency department because of swelling in one leg and after some scans, the doctors found a pretty significant blood clot in my leg, as well as multiple major clots in my lungs,” said Love. “I was worried of course, but I knew I was in good hands. My treatment was a success and it feels good to know that I played a small part in this study that will help many others.”
Funding and acknowledgements: The COBRRA trial was funded by the Canadian Institutes of Health Research and Medical Research Future Fund in Australia with in-kind support from Royal College of Surgeons in Ireland and the International Network of Venous Thromboembolism Clinical Research Networks. Core support was provided by the Ottawa Methods Centre. The pilot trial was funded by the CanVECTOR network.
The Ottawa Hospital (TOH) is one of Canada’s top learning and research hospitals where we are guided by our vision to provide the world-class and compassionate care we would all want for our loved ones. Our multi-campus hospital, affiliated with the University of Ottawa, is home to the Regional Trauma Centre and Cancer Centre, and to discoveries that are adopted globally. Backed by generous support from the community, we are focused on reshaping the future of health care to improve the health of our diverse population of patients from Eastern Ontario, Western Quebec, and Nunavut. For more information about research at The Ottawa Hospital, visit ohri.ca .
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Jenn Ganton
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Ottawa Hospital Research Institute
613-614-5253
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New England Journal of Medicine
Randomized controlled/clinical trial
People
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