Non-major bleeding was substantially less in patients on apixaban compared with those on warfarin in the Apixaban for Reduction in Stroke and other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. 

A total of 18,140 patients with atrial fibrillation (AF) who had received at least one dose of apixaban or warfarin were evaluated. Non-major bleeding was a composite of clinically relevant bleeding (i.e. that was not major but led to hospital admission, medical or surgical treatment, or a change in antithrombotic therapy) and minor bleeding.

Major bleeding is defined as bleeding accompanied by a decrease in the haemoglobin level of at least 2 g/dL or requiring a transfusion of at least two units of packed red blood cells, occurring at a critical site, or resulting in death.

Non-major bleeding was three times more common than major bleeding, 2,204 cases (12.1%) vs 692 (3.8%). Non-major bleeding was less frequent with apixaban than warfarin 6.4 vs 9.4 per 100 patient-years; HR 0.69 (95% CI: 0.63-0.75).

The most frequent sites of non-major bleeding were haematuria (16.4%), epistaxis (14.8%), gastrointestinal (13.3%), haematoma (11.5%) and bruising (10.1%), accounting for 69% of non-major bleeds. Medical or surgical intervention was similar among those with non-major bleeding on warfarin versus apixaban (24.7% vs 24.5%).

Clinically relevant, but not major, bleeds were independently associated with an increased risk of overall death HR 1.70 (95% CI: 1.32-2.18) and subsequent major bleeding HR 2.18 (95% CI: 1.56-3.04).

These results suggest that less severe forms of bleeding in patients with AF treated with anticoagulation therapy can be important and might not be quite as minor as we had previously thought.

The study authors conclude: ‘These findings reinforce the safer profile of apixaban versus warfarin for patients with AF, and highlight the importance of any severity of bleeding in patients with AF treated with anticoagulant therapy, suggesting that non-major bleeding, including minor bleeding, might not be minor.’

Dr Peter Savill

Bahit MC, Lopes RD, Wojdyla DM et al. Non-major bleeding with apixaban versus warfarin in patients with atrial fibrillation. Heart 2017;103:623-28