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Background Overlapping first generation sirolimusand paclitaxel-eluting stents are associated with persistent inflammation, fibrin deposition and delayed endothelialisation in preclinical models, and adverse angiographic and clinical outcomes— including death and myocardial infarction (MI)—in clinical studies. Objectives To establish as to whether there are any safety concerns with newer generation drug-eluting stents (DES). Design Propensity score adjustment of baseline anatomical and clinical characteristics were used to compare clinical outcomes (Kaplan-Meier estimates) between patients implanted with overlapping DES (Resolute zotarolimus-eluting stent (R-ZES) or R-ZES/ other DES) against no overlapping DES. Additionally, angiographic outcomes for overlapping R-ZES and everolimus-eluting stents were evaluated in the randomised RESOLUTE All-Comers Trial. Setting Patient level data from five controlled studies of the RESOLUTE Global Clinical Program evaluating the R-ZES were pooled. Enrolment criteria were generally unrestrictive. Patients 5130 patients. Main outcome measures 2-year clinical outcomes and 13-month angiographic outcomes. Results 644 of 5130 patients (12.6%) in the RESOLUTE Global Clinical Program underwent overlapping DES implantation. Implantation of overlapping DES was associated with an increased frequency of MI and more complex/calcified lesion types at baseline. Adjusted in-hospital, 30-day and 2-year clinical outcomes indicated comparable cardiac death (2-year overlap vs non-overlap: 3.0% vs 2.1%, p=0.36), major adverse cardiac events (13.3% vs 10.7%, p=0.19), target-vessel MI (3.9% vs 3.4%, p=0.40), clinically driven target vessel revascularisation (7.7% vs 6.5%, p=0.32), and definite/probable stent thrombosis (1.4% vs 0.9%, p=0.28). 13-month adjusted angiographic outcomes were comparable between overlapping and non-overlapping DES. Conclusions Overlapping newer generation DES are safe and effective, with comparable angiographic and clinical outcomes—including repeat revascularisation—to non-overlapping DES. [ABSTRACT FROM AUTHOR]