Angina or myocardial ischemia with nonobstructive coronary artery disease (ANOCA/INOCA) is associated with an elevated risk of adverse outcomes. This study aimed to evaluate the prognosis of patients with ANOCA/INOCA who received tailored therapy according to their endotype, as defined by invasive coronary function testing (CFT).

This prospective, multicenter observational study included ANOCA/INOCA patients who underwent an invasive CFT. The primary outcome was a composite of total episodes of myocardial infarction, emergency department visits for chest pain, or hospital admissions for angina or heart failure that occurred during a long-term follow-up. Negative binomial regression was used to assess the association between endotypes and total events, with risk estimates expressed as incidence rate ratios (IRR).

From January 2020 to November 2023, a total of 308 patients were enrolled. Patients were stratified into 4 endotypes: microvascular dysfunction (n=141), epicardial spasm (n=66), microvascular spasm (n=26), or negative-CFT (n=75). At a median follow-up of 1.8 years, the incidence rates of the composite outcome per 100 patient-years were 35.3, 12.9, 31.0, and 10.2 in microvascular dysfunction, epicardial spasm, microvascular spasm, and negative-CFT endotypes, respectively (P <.001). After multivariable adjustment, microvascular dysfunction emerged as the only independent predictor of the composite outcome (IRR, 3.24; 95%CI, 1.12-9.05; P=.029).

Despite tailored medical therapy, ANOCA/INOCA endotype classification revealed significant prognostic differences, with microvascular dysfunction being the endotype associated with the highest burden of recurrent events.