PROSPECTIVE OBSERVATIONAL MULTICENTER STUDY ON THE MANAGEMENT OF INTERMEDIATE CORONARY STENOSES: The Functional or morphological Lesion Assessment for the eValuation of coronary Occlusions for Revascularization (FLAVOR) Study Prof. Imad Sheiban, Division of Cardiology San Giovanni Battista, Turin, Italy Under the auspices of the Società Italiana di Cardiologia Invasiva (SICI-GISE) BACJGROUND There is ongoing debate on the most appropriate treatment of patients symptomatic for angina pectoris or those with significant silent myocardial ischemia and concomitant coronary artery disease with the presence of coronary stenoses which do not appear clearly critical (also known as ambiguous or intermediate lesions). This is due to the major progresses of maximal medical therapy, and, on the other hand, to the favorable risk-benefit profile of percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Indeed, the most appropriate approach for an intermediate coronary stenosis is still unclear, even if several methods are currently used to improve imaging or functional assessment of the target lesion, such as quantitative coronary angiography (QCA), intravascular ultrasound (IVUS), intravascular continuous Doppler analysis, fractional flow reserve (FFR), and, most recently, optical coherence tomography (OCT). Despite several relevant randomized clinical trials on the topic, such as the recent and pivotal Fractional Flow Reserve versus Angiography for Guiding PCI in Patients with Multivessel Coronary Artery Disease (FAME) Study, there is a paucity of large and up to date observational studies, able to include all patients with intermediate coronary lesions, irrespective of subsequent management or concomitant adverse baseline features. AIMS The aim of the Functional or morphological Lesion Assessment to eValuate coronary Occlusions for Revascularization (FLAVOR) Study is to appraise the mid-term (1 year) e long-term (2 years) outlook of patients with coronary angiographic evidence of at least one intermediate stenosis, which, during the same procedure or within 4 weeks thereof, are appraised by means of QCA, IVUS, Doppler, FFR, or OCT, or undergo directly PCI on the intermediate lesion(s). In addition, functional class, quality of life and direct costs will be appraised up to 2 years of follow-up in a subset of patients. DESIGN The FLAVOR Study will be a prospective observational multicenter physician- originated registry study. PARTICIPATING CENTERS AND TIMING It is expected that at least 20 Italian tertiary care centers will partecipate. Patients will be enrolled during an 18-month interval, and will then followed for up to 24 months. PATIENTS Patients will be enrolled during coronary angiography, based on the coronary angiographic evidence of at least one intermediate stenosis, which, during the same procedure or within 4 weeks thereof, are appraised by means of QCA, IVUS, Doppler, FFR, or OCT, or undergo directly PCI on the intermediate lesion(s). Main exclusion criteria will be age<18 years, lack of negative pregnancy test within 7 days prior to treatment for women of child bearing potential, and unwillingness or inability to provide written informed consent for study participation. FOLLOW-UP Patients will be followed according to routine clinical practice, without any additional test except those routinely warranted on the basis of clinical findings, up to 2 years after study enrolment. END-POINTS AND EVENT ADJUDICATION The primary end-point of the study will be the occurrence of major adverse cardiac events (MACE), defined as death, myocardial infarction, or repeat revascularization at 12 months. Secondary end-points will be individual components of MACE at 1, 6, 12, and 24 months, the Canadian Cardiac Society (CCS) functional class, quality of life according to the EuroQoL tool, and direct costs associated with treatment. All fatal events will be externally adjudicated by an independent clinical event committee. All other unclear or debated events/outcome estimates will undergo external monitoring and adjudication. SAMPLE SIZE COMPUTATION AND STATISTICAL ANALYSIS Hypothesizing a global MACE rate of 20% at 1 year, and in order to achieve event rate estimates with a 95% confidence interval<6% (+3; -3%) for the overall patient population, it will be necessary to include at least 800 subjects. Statistical analysis will be based on univariate, bivariate (chi-squared, Fisher, Gossett t, Mann-Whitney U, ANOVA, Kruskal-Wallis, Kaplan-Meier, and log-rank tests), and multivariable analyses (linear and logistic regression, Cox proportional hazard analysis). Spefically, pre-specified analyses will be focused on the degree of stenosis after functional or morphological assessment, the location of the intermediate stenosis, the type of management, and presence of diabetes. Supported by: