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Background: In an effort to contain procedural costs while limiting the risk of in-stent restenosis, hybrid percutaneous revascularization (ie, stenting with at least one sirolimus-eluting stent [SES] and at least one bare metal stent [BMS] in the same patient) is felt to be a cost-effective alternative to exclusive SES use., Objective: To describe the outcome of hybrid percutaneous revascularization for the treatment of patients with multiple coronary artery lesions., Methods and Results: Fifty-six patients (42 men; mean age [+/- SEM] 64+/-2) underwent hybrid stenting (average of 1.2 SES/patient and 1.3 BMS/patient). SES were used to treat lesions at higher restenotic potential, including longer lesions, smaller target vessels and bifurcation lesions (mean stent length [+/- SEM] was 21.1+/-1.2 mm for SES and 16.0+/-0.6 mm for BMS; stent diameter mean [+/- SEM] was 2.9+/-0.0 mm for SES and 3.1+/-0.1 mm for BMS; bifurcation lesions were 43% for SES and 7% for BMS; all P<0.01). At nine months of clinical follow-up, no death or myocardial infarction was reported. Twenty-one patients underwent clinically driven repeat coronary angiography at a mean (+/- SEM) of 8+/-1 of months (range two to 12 months) follow-up. Target lesion revascularization procedures were recorded in six patients (11%) for nine lesions (6%). Of these lesions, seven were categorized after blinded analysis as due to in-BMS restenosis and two to in-SES restenosis (P=0.01); three patients (5.4%) underwent reangioplasty for de novo lesions. There was one case of acute in-SES thrombosis. SES showed significantly less neointimal hyperplasia (late lumen loss was 0.4+/-0.1 mm for SES and 1.3+/-0.1 mm for BMS; loss index was 0.15+/-0.05 for SES and 0.48+/-0.05 for BMS; all P<0.001)., Conclusions: The use of SES resulted in less neointimal hyperplasia even when used to treat lesions at higher risk for restenosis based on angiographic characteristics. BMS implantation significantly limits this beneficial effect, compromising the outcome of hybrid percutaneous coronary revascularization.