Tag: apaxiban

Apaxiban no Better than Aspirin for Preventing Recurrence in Cryptogenic Stroke and Atrial Cardiopathy

Trial comparing anticoagulant and antiplatelet therapy ends in a draw

Ischaemic and haemorrhagic stroke. Credit: Scientific Animations CC4.0

Administering apaxiban to patients with cryptogenic stroke and evidence of atrial cardiopathy to prevent recurrence was no more effective than giving aspirin, a large randomised trial has found. The trial, published in JAMA, did however find a possible slight advantage in safety of apaxiban over aspirin.

Cryptogenic stroke (CS) is cerebral ischaemia of obscure or unknown origin. One third of ischaemic strokes are cryptogenic. 

Atrial cardiopathy is defined as any complex of structural, architectural, contractile, or electrophysiologic changes affecting the atria with the potential to produce clinically relevant manifestations. Atrial cardiopathy is strongly associated with incident atrial fibrillation and plays a role in thromboembolism related to atrial fibrillation.

Atrial cardiopathy is associated with stroke in the absence of clinically apparent atrial fibrillation. But it was not known whether anticoagulation, which has proven benefit in atrial fibrillation, prevents stroke in patients with atrial cardiopathy and no atrial fibrillation. The Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) trial was therefore designed to determine whether anticoagulation is superior to antiplatelet therapy for preventing recurrent stroke in such patients.

From 2018 to 2023, the researchers conducted a multicentre, double-blind, phase 3 randomised clinical trial of 1015 participants with CS and evidence of atrial cardiopathy – defined as P-wave terminal force greater than 5000μV×ms in electrocardiogram lead V1, serum N-terminal pro-B-type natriuretic peptide level greater than 250pg/mL, or left atrial diameter index of 3cm/m2 or greater on echocardiogram. Participants had no evidence of atrial fibrillation at the time of randomisation.

The participants were randomised 1:1 to receive either apaxiban (5mg or 2.5 mg) twice daily or aspirin (81mg) once daily. The primary outcome measure of stroke occurrence was identical in both arms (40 patients, 4.4%).

There were zero intracranial haemorrhage events for apaxiban vs seven for aspirin, which is known to increase the risk of these. This supports a superior safety profile for apxiban over aspirin, but given the small number of events, the authors caution that this may be a chance finding.

Study limitations included a higher than expected dropout rate due to the COVID pandemic. Additionally, few patients met the atrial cardiopathy criterion of severe left atrial enlargement, but restricting the trial participants to this criterion would have rendered the trial infeasible.

Apaxiban Has Lowest Gastrointestinal Bleeding Risk of Common DOACs

Photo by Charlie-Helen Robinson on Pexels

A large-scale comparison of direct oral anticoagulants (DOACs), published in Annals of Internal Medicine, one of the two most common direct oral anticoagulants (DOACs), apixaban, has the lowest risk of gastrointestinal bleeding, with similar performance on stroke prevention and other side effects.

DOACs are used to prevent strokes for people with atrial fibrillation, a condition affecting over 33 million people worldwide. They have recently become gained popularity over warfarin, the previous standard treatment, as they do not require as much follow-up monitoring (which was particularly valuable during the COVID pandemic) and have less risk of side-effects.

For the new study, University College London researchers compared the efficacy and risk of side effects for the four most common DOACs. They reviewed data from more than 500 000 new DOAC users in the UK, France, Germany and the US, including 281 320 apixaban users, 61 008 dabigatran users, 12 722 edoxaban users, and 172 176 rivaroxaban users.

They found that all four drugs were comparable on outcomes for ischemic stroke, brain bleeds and all-cause mortality, while they did identify a difference in risk of gastrointestinal bleeding, which is one of the most common and concerning side effects of DOACs.

The study revealed that apixaban stood out as having lower risk of gastrointestinal bleeding, with 19-28% lower risks when compared directly to each of the other three DOACs.

The researchers found that their findings held true when looking at data only from those aged over 80, and those with chronic kidney disease, two groups that are often underrepresented in clinical trials.

Dr Wallis Lau (UCL School of Pharmacy), who jointly led the work along with her colleague Professor Ian Wong, said: “Direct oral anticoagulants have been prescribed with increasing frequency worldwide in recent years, but evidence comparing them directly has been limited. Our results indicate that apixaban may be preferable to other blood thinners because of the lower rate of gastrointestinal bleeding and similar rates of stroke, a finding that we hope will be supported by randomised controlled trials.

“As with all medications, potential risks and benefits can differ between people, so considering the full spectrum of outcomes and side effects will still be necessary for each individual patient.

Source: University College London