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Left main coronary artery (LMCA) disease is a pathological condition of great clinical relevance due to its significant impact on both morbidity and mortality of patients with ischemic heart disease. Due to its bidimensional nature, angiography does not enable an accurate evaluation of the extension, distribution and morphology of LMCA disease. Intravascular ultrasound (IVUS) is the invasive imaging modality of choice for the evaluation of LMCA disease, due to its ability to accurately characterize atherosclerotic disease in all the segments of LMCA bifurcation (including LMCA ostium). IVUS is therefore useful in each step of LMCA procedures: (i) to assess stenosis severity and to evaluate the need for revascularization; (ii) to select the appropriate treatment strategy of LMCA bifurcation (e.g. single vs two stents); (iii) to guide all steps of percutaneous coronary intervention (PCI) (e.g. lesion preparation, decision of the landing zone, stent sizing, proximal optimization, side branch rewiring, kissing balloon); (iv) to optimize stent result (e.g. expansion, apposition, geographical miss, major dissections). Although data obtained from randomized clinical trials are limited, several meta-analyses and registry studies suggest the superiority of IVUS-guided LMCA PCI as compared with LMCA PCI guided by angiography alone in terms of mortality, non-fatal myocardial infarction, stent thrombosis, restenosis, and target lesion revascularization.

The recognition that obstructive disease of the epicardial coronary arteries, causing ischaemic heart disease, can be treated with a percutaneous coronary intervention (PCI) has been a major discovery in cardiology in the last 40 years contributing, in particular, to the reduction of mortality associated to acute myocardial infarction (AMI). However, even in the era of drug-eluting stent (DES) implantation, a sizable proportion of patients who undergo PCI may develop late or very late post-implantation complications, that occur in the form of restenosis, neoatherosclerosis, and/or in-stent thrombosis. Such complications are clinically relevant since they can cause AMI and negatively impact on the outcome. The underlying pathophysiological mechanisms are complex but related to inhibition of neointimal proliferation by DES that, on the hand, reduces the rate of in-stent restenosis, but, on the other hand, causes dysfunctional vessel healing, persistent inflammation, platelet activation, and adverse immunological responses. Multiple approaches have been developed or are under evaluation to target DES-related complications including pharmacotherapy, procedure-related imaging methods, novel stent designs, and drug-delivery methods. The aim of this review is to provide an update on the latest preclinical, translational, and clinical pharmacotherapeutic developments in this setting that target novel cellular mechanisms and pathways that might contribute to neoatherosclerosis. Due to the importance of secondary prevention in the reduction of DES-associated complications, this review also provides a short overview of pharmacological agents that are established or currently being investigated in this regard., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)