Effect of State-of-the-Art Treatment on Symptoms, Absolute Coronary Artery Flow, and Resistance Among Patients With Ischemia and Non-Obstructive Coronary Arteries (STAR-INOCA Study): Study Design and Rationale.

A significant proportion of patients referred to the cardiac catheterization laboratory for ischemia and/or angina do not have obstructive coronary arteries. This condition (INOCA and/or ANOCA, respectively) is frequently associated with coronary microvascular dysfunction (CMD). CMD causes myocardial ischemia, persistent symptoms, impaired quality of life, and increased healthcare utilization. Despite its clinical relevance, evidence-based therapeutic strategies remain limited, as prior studies regarding the treatment have been small and heterogeneous. Recently, an expert consensus proposed a standardized, stepwise management strategy for ANOCA/INOCA, built on the limited evidence currently available. However, the clinical effectiveness of this therapeutic algorithm has never been evaluated, either from a subjective perspective through patient-reported symptom burden or from an objective standpoint using invasive hemodynamic measurements. This prospective, single-center study aims to evaluate whether the state-of-the-art treatment recommended by the EAPCI Expert Consensus Document improves invasive measures of coronary microcirculation and symptoms in patients with ANOCA/INOCA. A total of 40 patients with angina, and objective evidence of ischemia on non-invasive testing, and CMD confirmed by continuous intracoronary thermodilution (coronary flow reserve ≤2.5) will be enrolled. Patients will receive sequential pharmacological therapy in 3 stages: (1) statins, beta-blockers, and ACE inhibitors; (2) conditional addition of a calcium channel blocker in case of persistent angina or pathological exercise treadmill test; and (3) conditional addition of ranolazine in case of persistent angina or pathological exercise treadmill test. At baseline and after each treatment stage, symptoms and quality of life will be assessed using the Seattle Angina Questionnaire (SAQ-19) and the EuroQol-5D (EQ-5D-5L). Invasive reassessment will be performed once patients report complete symptom resolution or once the complete therapeutic algorithm has been completed. This study will provide the first prospective evaluation of a sequential, guideline-based pharmacological strategy in CMD using both objective physiological measures and patient-centered outcomes. Findings may inform future guideline recommendations, improve clinical management of ANOCA/INOCA, and advance personalized treatment approaches in this understudied population.