Background and objectives. The absence of obstructive coronary artery disease (CAD) in patients with angina is common, but its prognosis is debated. We investigated outcomes of such patients to identify predictors of cardiovascular events.

Methods. We selected 1014 patients with angina, evidence of myocardial ischemia at the electrocardiogram (ECG) exercise test or imaging stress tests, and non-obstructive CAD (absence of lumen diameter reduction >= 50%) at coronary angiography between 1999 and 2015. Note that, 1905 age- and risk factors-matched asymptomatic subjects served as "real-world" comparators. The primary endpoint was the occurrence of all-cause death or myocardial infarction.

Results. At 6-years median follow-up (Interquartile range, 3-9 years), the primary endpoint occurred in 53 patients (5.5%, 0.92/100 person-years). Besides similar event rates compared with asymptomatic subjects (Hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.62-1.15, p = 0.28), the index population showed a very heterogeneous prognosis. Patients with non-obstructive CAD (HR 1.85, 95% CI 1.02-3.37, p = 0.04, compared with "normal" coronary arteries) and with ischemia at imaging tests (HR 2.11, 95% CI 1.07-4.14, p = 0.03, compared with ischemia detected only at the ECG exercise test) were at higher risk and those with both these components showing even >10-fold event rates as compared with the absence of both. Three hundred and twenty-five patients (34%) continued to experience angina, 69 (7.2%) underwent repeat coronary angiography, and 14 (1.5%) had consequent coronary revascularization for atherosclerosis progression.

Conclusion. Apart from the impaired quality of life, angina without obstructive CAD has an overall benign but very heterogeneous prognosis. Non-obstructive CAD and myocardial ischemia at imaging tests both confer a higher risk.