New drugs used to treat serious blood clots, known as direct oral anticoagulants (DOACs), are associated with reduced risks of major bleeding compared with the older anti-clotting drug, warfarin, according to a new study by researchers at the University of Nottingham.
The findings, published in the BMJ, provide initial reassurance about the safety of DOACs as an alternative to warfarin for all new patients.
For many years, warfarin has been the main treatment for potentially fatal blood clots, known as venous thromboembolism (VTE). But DOACs are increasingly being used as an alternative to warfarin because patients don’t need regular tests to check if they have the right amount of drug in their bloodstream.
Clinical trials have shown a reduced or similar risk of major bleeding for DOACs compared with warfarin. But such trials involve only carefully selected patients, so bleeding rates often do not reflect those seen in everyday, ‘real world’ clinical practice.
In addition, most observational studies have included only patients with irregular heartbeat (atrial fibrillation or AF), creating an information gap for patients without this condition.
To fill this gap, researchers at the University’s Division of Primary Care, set out to investigate the risks and benefits associated with the three commonest types of DOACs (dabigatran, rivaroxaban, and apixaban) compared with warfarin in patients with and without AF. The study was funded by the National Institute for Health Research.
Using data from two large UK primary care databases, they identified 196,061 patients who started or restarted anticoagulants (after more than a 12-month gap) between 2011 and 2016.
A total of 132,231 patients were taking warfarin, 7,744 dabigatran, 37,863 rivaroxaban, and 18,223 apixaban. Overall 53% (103,270) were diagnosed with AF and 47% (92,791) were prescribed anticoagulants for other conditions.
Patients were monitored for major bleeds leading to hospital admission or death, ischaemic stroke, VTE, and death from any cause (“all-cause mortality”).
After taking acount of several known risk factors, the researchers found that apixaban was associated with a lower risk of major bleeding, particularly brain and gastric bleeds, in patients with and without AF, compared with warfarin.
They also found a lower risk of brain bleeds associated with use of dabigatran in patients with AF - and with use of rivaroxaban in patients without AF - compared with warfarin.
Rivaroxaban and low dose apixaban were, however, associated with increased risks of deaths from any cause in all patients when compared with warfarin, which may reflect closer monitoring of patients taking warfarin or may be related to other underlying conditions, suggest the researchers.
Overall, apixaban had the lowest numbers needed to treat over six months to avoid one extra major bleed (182 patients with AF and 138 without), compared with warfarin. In contrast, rivaroxaban had the lowest numbers needed to harm to observe one extra death (202 with AF and 61 without).
The researchers point out that this is an observational study, so no firm conclusions can be drawn about cause and effect, and they outline some limitations, such as possible misclassification due to patients not taking their medication.
Nevertheless, they say their study shows that “the risk of major bleeding is lower in apixaban users regardless of the reason for prescribing, appearing to show apixaban to be the safest drug.”
“Our results give an initial, reassuring, indication of the risk patterns for all patients taking anticoagulants, in particular with respect to those prescribed apixaban,” they conclude.
Importantly, the researchers stressed: “All patients on these medicines will be under regular follow up by their GP. If patients have concerns and want to discuss different treatment options, then they can do that at their next review appointment. It is very important that people do not change their medication before seeing their GP.
— Ends —
Our academics can now be interviewed for broadcast via our Media Hub, which offers a Globelynx fixed camera and ISDN line facilities at University Park campus. For further information please contact a member of the Communications team on +44 (0)115 951 5798, email mediahub@nottingham.ac.uk or see the Globelynx website for how to register for this service.
For up to the minute media alerts, follow us on Twitter
Notes to editors:
The University of Nottingham is a research-intensive university with a proud heritage, consistently ranked among the world's top 100. Studying at the University of Nottingham is a life-changing experience and we pride ourselves on unlocking the potential of our 44,000 students - Nottingham was named University of the Year for Graduate Employment in the 2017 Times and Sunday Times Good University Guide, was awarded gold in the TEF 2017 and features in the top 20 of all three major UK rankings. We have a pioneering spirit, expressed in the vision of our founder Sir Jesse Boot, which has seen us lead the way in establishing campuses in China and Malaysia - part of a globally connected network of education, research and industrial engagement. We are ranked eighth for research power in the UK according to REF 2014. We have six beacons of research excellence helping to transform lives and change the world; we are also a major employer and industry partner - locally and globally.
Impact: The Nottingham Campaign, its biggest-ever fundraising campaign, is delivering the University’s vision to change lives, tackle global issues and shape the future. More news…