Long-term outcome after percutaneous coronary intervention (PCI) depends on vessel diameter; however, there is insufficient evidence on particular drug-eluting stent (DES) types in this setting. The aim of the study was to assess long-term performance of PCI depending on stented vessel size and DES generations. This observational study from a prospective Registry of PCI with DES assessed safety (stent thrombosis) and efficacy (major adverse cardiac and cerebrovascular event (MACCE)) of the implantation of first- (DES1) or second-generation DESs (DES2) in small and large vessels. Of 699 patients included in the analysis, 337 (48%) patients underwent PCI in small vessels. PCI in small vessels, especially the left anterior descending artery (LAD) (hazard ratio (HR) 2.6, 95% confidence interval (CI) 1.5–4.5), was associated with a higher rate of MACCEs than that in large vessels (20% vs. 14%, p
= 0.025) with no difference in the rate of stent thrombosis (ST). No significant difference in safety and efficacy was found between DES1 and DES2 in small vessels. For large vessels, a higher incidence of MACCEs (21% vs. 9.2%, p
= 0.002) driven by a higher rate of re-PCI (15% vs. 6%, p
= 0.006) and a higher rate of cumulative stent thrombosis (3.5% vs. 0.5%, p
= 0.04) was shown for DES1 than DES2. In multivariate analysis, DES1 was a significant risk factor for MACCEs in large, but not in small vessels. The risk of PCI in small vessels, especially LAD, remains high independent of the type of DES. In contrast, DES2 as a modifiable variable during PCI of a large lesion might improve long-term prognosis.
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