In Part I of this article, the definitions, prevalence, and clinical presentation of chronic total occlusions (CTOs) were reviewed, the histopathology of CTOs was examined, efforts to replicate human CTOs with experimental models were appraised, and the clinical relevance and rationale for CTO revascularization were evaluated. 1 In Part II, we summarize the technical approach to and outcomes after percutaneous coronary intervention (PCI) of occluded coronary arteries, describe the novel devices and drugs approved and undergoing investigation for CTO recanalization, and conclude with practical perspectives on managing the patient with 1 or more chronic coronary occlusions.

R emarkable progress in the percutaneous management of coronary artery disease has been achieved over the last decade. The scaffolding properties of coronary stents have resulted in percutaneous coronary intervention (PCI) becoming a predictable procedure, with reduced rates of acute closure and late restenosis compared with balloon angioplasty alone. 1,2 More recently, the site-specific delivery of antiproliferative agents from drug-eluting stents has been demonstrated to markedly attenuate vascular responses leading to neointimal hyperplasia, further reducing the occurrence of clinical and angiographic restenosis to Ͻ10% in most patients. 3,4 PCI in patients with acute coronary syndromes and acute myocardial infarction (AMI) has also been proven to save lives, reduce rates of myocardial infarction (MI), and enhance quality of life compared with alternative treatment modalities. [5][6][7] With these advances in perspective, it is often stated that successful recanalization of chronic total occlusions (CTOs) of native coronary arteries represents the "last frontier" of PCI. This statement is made in deference to the fact that CTOs represent the most technically challenging lesion subset that interventional cardiologists face, with procedural success rates considerably lower than those achieved in nonoccluded coronary vessels or acutely occluded arteries. Moreover, no consensus exists with regard to the definition of CTO, the factors related to procedural failure and/or complications, and the optimal technical approach. Indeed, until recently, the clinical benefits of PCI in CTOs had not been demonstrated.An international panel of 47 physicians from 9 countries was therefore convened in New York City for 2 days in January 2004, the purpose of which was to reach consensus on the current state of the art of CTO angioplasty (see Appendix in the online-only Data Supplement for a complete participant list). This goal was approached through a series of didactic lectures, roundtable discussions, breakout focus groups, and the performance of 14 live case demonstrations of CTO angioplasty by many of the world's most skilled operators in this subspecialty. The present report represents a synthesis of the findings from this meeting and also incorporates a literature review from the field of CTO intervention. Topics covered in Part I of this review include definitions, prevalence, and clinical presentation of CTOs; the anatomy and histopathology of coronary occlusions; experimental CTO models; and the clinical relevance and rationale for CTO revascularization. Part II will review the technical approach to and clinical outcomes after percutaneous intervention of CTOs and describe the novel devices and drugs approved and undergoing investigation for CTO recanalization.

Background New-generation drug-eluting stents (DES) have been mostly investigated by means of head-to-head non-inferiority trials, which typically showed comparable efficacy and greater safety as compared with early-generation DES. Evidence related to new-generation DES versus bare-metal stents (BMS) is more limited, and there remain uncertainties on their comparative safety profile. Methods We performed an individual patient data (IPD) meta-analysis of randomized trials comparing new-generation DES with BMS among patients undergoing percutaneous coronary intervention. The protocol of the study was registered in PROSPERO (CRD42017060520). The primary outcome was the composite of cardiac death or myocardial infarction. Data were pooled in a one-stage random effects metaanalysis and examined at maximum follow-up and with 1-year landmark. Risk estimates are reported as hazard ratio (HR) with 95% confidence intervals (95%CI). Findings We obtained IPD data from 20 randomized trials including a total of 26,616 patients, with 3•2±1•8 years mean follow-up. The primary outcome occurred in fewer patients in the DES group than in the BMS group (HR 0•84, 95%CI 0•78 to 0•90, P<0•001) owing to lower risk of myocardial infarction (HR 0•79, 95%CI 0•71 to 0•88, P<0•001) and weaker evidence for a possible cardiac mortality benefit (HR 0•89, 95%CI 0•78 to 1•01, P=0•075). All-cause death was unaffected (HR with DES, 0•96, 95%CI 0•88 to 1•05, P=0•358), but DES reduced the risk of definite stent thrombosis (HR 0•63, 95%CI 0•50 to 0•80, P<0•001) and targetvessel revascularization (HR 0•55, 95%CI 0•50 to 0•60, P<0•001). There was evidence for a time-dependent treatment effect, with DES being associated with lower risks of the primary outcome during the first year followed by a null effect in the subsequent years. Interpretation New-generation DES instead of BMS were associated with sustained reduction of cardiac death or myocardial infarction owing to lower event rates within the first year without offsetting effects thereafter.

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Late-acquired ISA was observed in 5.1% of patients after DES implantation and is related to regional vessel positive remodelling. The relationship between late-acquired ISA and long-term adverse outcomes (e.g. stent thrombosis) requires further analysis.

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