Clinical case A 39-year-old smoker woman underwent a percutaneous coronary intervention with two Zotarolimus-eluting stents implantation due to right coronary artery occlusion in the context of ST-elevation myocardial infarction (MI). She was medicated with dual antiplatelet therapy and high-intensity statin and stopped smoking. Nine months later, due to angina symptoms, cardiac catheterization with intravascular ultrasound showed severe restenosis, treated with a drug-coated balloon (DCB). Two months later, she was admitted due to non-ST elevation MI and the cardiac catheterization presented thrombotic occlusion of previously implanted stents, treated with balloon dilatation. After two months, she remained with angina and a dobutamine stress echocardiogram showed inferior wall ischemia. The angiographic revision revealed proximal in-stent restenosis, treated with DCB. About a year later, a fifth coronary angiography was performed due to recurrence of angina. Diffuse in-stent restenosis by neo-atherosclerosis was identified by optical coherence tomography. The lesion was treated with a cutting balloon and Everolimus-eluting stent implantation. The cholesterol-lowering treatment was optimized and the patient remained stable for some months. However, she is currently reporting recurrence of angina. Clinical management and guidance await Heart Team discussion. Learning points