Over the past decades, percutaneous coronary intervention (PCI) has become the most common modality for myocardial revascularisation, and it is increasingly used in patients with advanced coronary artery disease. Antithrombotic therapy, including antiplatelet and anticoagulant drugs, plays a key role and should be part of the optimal revascularisation strategy in the early phase as well as in the long-term prevention of ischaemic events. An antithrombotic therapy regimen of increased intensity and/or duration may mitigate part of the ischaemic burden associated with complex PCI. However, patients undergoing complex PCI are often at increased bleeding risk, challenging, therefore, the decision-making process. In this setting, the optimal antithrombotic treatment is still a matter of debate and has become a field of intensive research. In this state-of-the-art review, we analyse the evidence related to the different approaches regarding the periprocedural and long-term antithrombotic management of patients undergoing complex PCI. Since a "one-size-fits-all" approach cannot be justified in this clinical setting, our aim is to tailor the antithrombotic strategy to each patient's profile and PCI complexity. We discuss the type and duration of antithrombotic regimens that can be selected for patients undergoing complex PCI, with a focus on prolonged dual antiplatelet therapy, P2Y12 receptor inhibitor monotherapy, and dual pathway inhibition. We also address antithrombotic management in specific scenarios (left main disease, coronary bifurcations, chronic total occlusion) and in patients undergoing complex PCI who require oral anticoagulant therapy.
