Road mapping ATLAS ACS 2: are we there yet?

The interface between recurrent thrombotic arterial events and the potential bleeding hazards of antithrombotic treatment after an acute coronary syndrome (ACS) occupies a central position in the practice of contemporary cardiovascular medicine. Although substantial progress has occurred in modelling the likelihood of recurrent events in this setting, it is somewhat ironic that the very characteristics, i.e. advanced age, female sex, low body weight, and chronic kidney disease, that presage negative ischaemic outcomes commonly co-exist in models predicting the risk of bleeding from antiplatelet/anticoagulant therapy.Nonetheless, tenacious pursuit of novel therapies directed towards platelet-mediated vascular events has resulted in the recent approval of two novel antiplatelet agents, prasugrel and ticagrelor. Whereas each has proven superior when compared with clopidogrel in percutaneous coronary intervention (PCI) and/or acute coronary syndrome (ACS) patients receiving background aspirin therapy, both therapies extracted a price in the form of excess major bleeding.1,2 Somewhat remarkably, ticagrelor also increased fatal intracranial bleeding, yet had a beneficial overall impact on cardiovascular death: this favourable efficacy/safety profile facilitated recent regulatory approval.In parallel with these advances in inhibiting platelet function has been the search for novel anticoagulants that are alternatives to warfarin either by directly inhibiting thrombin or, most recently, through the inhibition of factor Xa (FXa). Dabigatran was the first thrombin inhibitor approved as an alternative to warfarin, initially as prophylaxis for deep venous thrombosis, and most recently for patients with non-valvular atrial fibrillation. The latter development was based on a reduction in the risk of systemic embolism or stroke produced by dabigatran as compared with warfarin.3 While the risk of haemorrhagic stroke was also lower, there was more gastrointestinal bleeding with the use of dabigatran and a trend towards more myocardial infarction. Its future role in other thrombotic disease settings such as the ACS population …