- Restenosis is associated with acute myocardial infarction (MI) either at presentation or related to complications of target lesion revascularization (TLR). The cumulative late effect of TLR after drug-eluting or bare metal stent placement on cardiac death or MI is uncertain. Of the 1,057 patients with one native coronary lesion randomized to a sirolimus-eluting stent or bare metal stent in the Sirolimus-Eluting Stent in De Novo Native Coronary Lesions (SIRIUS) trial, the 983 who survived free of MI for the first 30 days were evaluated for the primary outcome of cardiac death or MI for 5 years. Patients with events occurring at or after TLR were assigned to TLR group. Cox proportional hazards regression analysis with TLR as a time-dependent variable and adjustment for baseline clinical and demographic covariates was used to assess the independent effect of TLR on the primary outcome. TLR occurred in 160 patients (16.3%) and was an independent predictor of the primary end point (hazard ratio 2.8, 95% confidence interval 1.7 to 4.5). This association was significant for sirolimus-eluting stents and bare metal stents. TLR was also associated with an increased risk of subsequent stent thrombosis and nontarget vessel revascularization. Intracoronary brachytherapy in the TLR group was associated with an increased risk of cardiac death or MI. In conclusion, restenosis requiring TLR was associated with an increased risk of cardiac death or MI occurring at TLR and during the subsequent 5 years.