BACKGROUND: In-stent restenosis (ISR) is commonly encountered even in the era of contemporary percutaneous coronary intervention (PCI). There is a paucity of data on the comparative outcomes of PCI for ISR lesions versus de novo lesions. METHODS AND RESULTS: An electronic search was conducted for MEDLINE, Cochrane, and Embase through August 2022 for studies comparing the clinical outcomes after PCI for ISR versus de novo lesions. The primary outcome was major adverse cardiac events. Data were pooled using a random-effects model. The final analysis included 12 studies, with a total of 708 391 patients, of whom 71 353 (10.3%) underwent PCI for ISR. The weighted follow-up duration was 29.1 months. Compared with de novo lesions, PCI for ISR was associated with a higher incidence of major adverse cardiac events (odds ratio [OR], 1.31 [95% CI, 1.18–1.46]). There was no difference on a subgroup analysis of chronic total occlusion lesions versus none (Pinteraction =0.69). PCI for ISR was associated with a higher incidence of all-cause mortality (OR, 1.03 [95% CI, 1.02–1.04]), myocardial infarction (OR, 1.20 [95% CI, 1.11–1.29]), target vessel revascularization (OR, 1.42 [95% CI, 1.29–1.55]), and stent thrombosis (OR, 1.44 [95% CI, 1.11–1.87]), but no difference in cardiovascular mortality (OR, 1.04 [95% CI, 0.90–1.20]). CONCLUSIONS: PCI for ISR is associated with higher incidence of adverse cardiac events compared with PCI for de novo lesions. Future efforts should be directed toward prevention of ISR and exploring novel treatment strategies for ISR lesions. © 2023 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
