Dabigatran is the first of a series of new direct acting oral anticoagulants that was clinically introduced for the prevention of ischaemic stroke in patients with atrial fibrillation (AF). In the randomized evaluation of long-term anticoagulation therapy (RE-LY) study, dabigatran was shown to be superior or non-inferior to warfarin in preventing ischaemic stroke, depending on the dose administered (150 or 110 mg twice daily, respectively).1 This phase III trial opened the door to the clinical introduction of this direct thrombin inhibitor, resulting in a swift clinical uptake around the globe. This was rapidly followed by the introduction of a number of direct factor Xa antagonists, after similar large warfarin-controlled trials showed non-inferiority (or superiority) of rivaroxaban, apixaban and finally edoxaban for preventing ischaemic stroke in patients with AF. The RE-LY study was accompanied by a number of substudies on safety aspects, including genetic and other determinants of dabigatran blood concentrations in relation to clinical outcomes.

In the Heart publication, another analysis of RE-LY is presented, showing that the use of dabigatran is associated with a reduction in plasma apoB levels, suggesting an unexpected pleiotropic side effect with potential clinical consequences.2 The authors observed a ±7% reduction in apoB, an effect that was not dose-dependent, but is clinically relevant when compared with the effects of statins (estimated by the authors as about 25% of the effect obtained with high-dose statin treatment). Importantly, the effect was still evident in subjects that were on actual statin treatment. ApoB is an important cofactor in atherogenesis …