Outcomes in Patients With Angina but Without Obstructive CAD

Study Questions:

What are the determinants of long-term prognosis in patients with angina without obstructive coronary artery disease (CAD)?


The authors performed a systematic review and meta-analysis for studies published in English between 1980 and January 2017, assessing the composite primary outcome of all-cause death and nonfatal myocardial infarction (MI) using random-effects models to estimate pooled incidences. Secondary outcomes were the single occurrence of all-cause death, nonfatal MI, and cardiovascular hospitalization defined as chronic heart failure, cardiac arrhythmias, acute coronary sydromes, or any other manifestation of ischemic heart disease. Search terms included “syndrome X” and “microvascular angina.” Planned subgroup analyses were according to: (i) definition of “normal” coronary arteries (less than obstructive coronary artery disease [CAD], i.e., <50% coronary stenosis vs. absence of any angiographically appreciable atherosclerosis); (ii) presence or absence of documentation of myocardial ischemia including documented coronary dysfunction) as a prerequisite inclusion criterion in the various studies; (iii) the clinical presentation: typical angina, vasospastic angina, and “undefined” angina type, including patients with atypical angina or angina equivalents, and (iv) the diagnostic modality to assess CAD, either invasive coronary arteriography (ICA) or coronary computed tomography angiography (CCTA). Exclusion criteria: studies including acute coronary syndrome, and stress and other cardiomyopathies.


A total of 54 studies had outcomes in 35,039 patients (mean age 56 years, male/female ratio 0.51, 99,770 person-years) with angina and no obstructive CAD. After a median follow-up of 5 years (interquartile range, 3-7 years), the pooled incidence of the primary outcome was 0.98/100 person-years [95% confidence interval (CI), 0.77–1.19%], with considerable heterogeneity among studies (I2 = 91%, p < 0.001). The primary outcome was associated with prevalent dyslipidemia (p = 0.016), diabetes (p = 0.035), and hypertension (p = 0.016). Studies enrolling patients with less than obstructive CAD showed a higher incidence of the primary outcome (1.32/100 person-years, 95% CI, 1.02–1.62) compared with studies including only patients with “entirely normal” coronary arteries (0.52/100 person-years, 95% CI, 0.34–0.79, respectively; p < 0.01). The incidence of the primary outcome did not differ significantly between studies enrolling only patients with documented myocardial ischemia and those studies enrolling patients regardless of presence of ischemia. However, ischemia documented by noninvasive imaging techniques was associated with a higher incidence of events (p = 0.02). Overall, these patients, however, suffered from a high incidence of recurrent hospitalization.


Angina without obstructive CAD has a heterogeneous prognosis. A main determinant of major adverse events is the presence of “some” coronary atherosclerosis, with unequivocal myocardial ischemia being associated with worse clinical outcomes. Patients’ quality of life is also worsened by the high incidence of hospitalization, angina recurrence, and repeated coronary angiography.


Among patients with angina, the absence of “significant CAD,” defined as <50% diameter stenosis in any major epicardial vessel, is reported in 20–30% of those undergoing coronary angiography regardless of the previous documentation of ischemia. Drawing conclusions from single reports and systematic reviews of angina without obstructive CAD suffer from heterogenous inclusion criteria. It is reassuring that with the exception of those with nonsignificant atherosclerosis and evidence of ischemia, the other cohorts have a 5-year risk equivalent to the low-risk primary cardiovascular disease risk category. Cardiovascular risk factors should be treated in the setting of less than significant coronary atherosclerosis, whether obtained by ICA or CCTA.

Clinical Topics: Acute Coronary Syndromes, Arrhythmias and Clinical EP, Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Stable Ischemic Heart Disease, Atherosclerotic Disease (CAD/PAD), Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Interventions and ACS, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Computed Tomography, Nuclear Imaging, Hypertension, Chronic Angina

Keywords: Acute Coronary Syndrome, Angina Pectoris, Variant, Arrhythmias, Cardiac, Atherosclerosis, Coronary Angiography, Coronary Artery Disease, Coronary Stenosis, Diabetes Mellitus, Diagnostic Imaging, Dyslipidemias, Heart Failure, Hypertension, Metabolic Syndrome X, Microvascular Angina, Myocardial Infarction, Myocardial Ischemia, Primary Prevention, Quality of Life, Risk Factors, Tomography, X-Ray Computed

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