Study design Prospective randomized open labeled multicenter study Hypotheses 1. In asymptomatic patients with ≥ 10% of myocardial ischemia: PCI (Percutaneous Coronary Intervention) with latest generation of drug eluting stents is superior to optimal medical therapy in terms of relative reduction in MACCE (Major Adverse Cardiovascular and Cerebrovascular events). 2. In symptomatic patients with ≥ 5% of myocardial ischemia: PCI with latest generation of drug eluting stents is superior to optimal medical therapy (OMT) in terms of improved life quality measured as an increase of SAQ (Self Assessment Questionnaire) score of 8 points after 6 months. Inclusion Criteria * CTO in native coronary artery * Myocardial ischemia in a territory supplied by CTO assessed by nuclear imaging. * Age ≥18 yrs. * Able to provide written Informed consent and willing to comply with the specified follow-up contacts * Target artery ≥ 2.5 mm Prior to randomization all patients undergo 3 months of OMT. Subsequently the population will be divided into: Cohort A: Asymptomatic (CCS \< 2 and SAQ QoL \> 60) patients with myocardial ischemia (≥ 10% of LV) in a territory supplied by CTO Cohort B: Symptomatic patients (CCS class ≥ 2 and/or SAQ QoL score ≤ 60 after treating non CTO lesions and after OMT) with Myocardial ischemia (5% of LV) in a territory supplied a CTO Cohort C: patients enrolled but not randomized in cohort A or B Exclusion criteria (for both cohort A and B) * NSTEMI or STEMI within 1 month * Coronary anatomy not suitable for CTO-procedure * Coronary artery disease involving the left main/three-vessel disease with indication for CABG following heart team conference * Life expectancy \< 2 years * Severe chronic pulmonary disease (FEV1 \< 30 % of predicted value) * Contraindication to dual anti-platelet therapy * Pregnancy * eGFR \< 30 mL/min/1.73 m2 * In multi-vessel disease: if it is deemed unsafe to treat the non-CTO lesion first. * Severe valvular heart disease Primary endpoint Cohort A: Composite endpoint of MACCE (all-cause mortality, stroke, any myocardial infarction, clinically driven revascularization\*), hospitalization for heart failure or incidence of malignant arrhythmias. \*CCS class ≥ 2 and/or QoL score \< 60. Same criteria used as for allocation to Cohort B Cohort B: SAQ Quality of Life Assessment after 6 months. Number of patients 1,560 (1200 in cohort A/360 in cohort B Follow up time Cohort A: 5 years Cohort B: 6 months