Evolving cardiovascular uses of direct-acting oral anticoagulants: a paradigm shift on the horizon?

Direct-acting oral anticoagulants (DOACs), by virtue of pharmacological properties perceived as innovative, are changing the therapeutic scenario of patients requiring short- and long-term anticoagulation. The evidence gathered so far (from pre-approval pivotal trials to real-world post-marketing observational data) consistently confirms that DOACs are overall comparable to vitamin-K antagonists (VKAs) in terms of safety, efficacy, effectiveness and unequivocally documents a clinically relevant reduced risk of intracranial bleeding in the settings of non-valvular atrial fibrillation (AF) and venous thromboembolism. The following issues are attracting considerable clinical interest: (a) identifying specific subpopulations of patients with AF most likely to benefit from one of these agents (the so-called tailored therapy), and (b) expanding therapeutic indications in emerging diseases characterized by arterial and venous thromboembolic risk. In these scenarios, the risk–benefit profile of DOACs, as compared to VKAs or heparins, is still incompletely characterized. In cardiology, the challenging task of selecting a suitable or even the most appropriate DOAC for patients with AF and a particular phenotype prompted experts to provide suggestions based on careful review of subgroups of patients from pivotal RCTs. However, in the past few months, variegated multicenter trials have been published (RE-CIRCUIT, PIONEER-AF-PCI, GEMINI-ACS-1), with potential influence on clinical practice. Therefore, this review aims to update the latest evidence on the evolving therapeutic uses of DOACs in the cardiovascular area, addressing potential impact for clinicians.