BACKGROUND Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS Over a median of 3.2 years, 318 primary outcome events occurred in the invasivestrategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, −1.8 percentage points; 95% CI, −4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used.

Coronary computed tomography angiography (CTA) has emerged as a noninvasive method for direct visualization of coronary artery disease, with previous studies demonstrating high diagnostic performance of CTA compared with invasive coronary angiography. However, CTA assessment of coronary stenoses tends toward overestimation, and even among CTA-identified severe stenosis confirmed at the time of invasive coronary angiography, only a minority are found to be ischemia causing. Recent advances in computational fluid dynamics and image-based modeling now permit determination of rest and hyperemic coronary flow and pressure from CTA scans, without the need for additional imaging, modification of acquisition protocols, or administration of medications. These techniques have been used to noninvasively compute fractional flow reserve (FFR), which is the ratio of maximal coronary blood flow through a stenotic artery to the blood flow in the hypothetical case that the artery was normal, using CTA images. In the recently reported prospective multicenter DISCOVER-FLOW (Diagnosis of Ischemia-Causing Stenoses Obtained Via Noninvasive Fractional Flow Reserve) study and the DeFACTO (Determination of Fractional Flow Reserve by Anatomic Computed Tomographic Angiography) trial, FFR derived from CTA was demonstrated as superior to measures of CTA stenosis severity for determination of lesion-specific ischemia. Given the significant interest in this novel method for determining the physiological significance of coronary artery disease, we herein present a review on the scientific principles that underlie this technology.

In patients with chest pain, CCTA identifies increased risk for all-cause death. Importantly, a negative CCTA portends an extremely low risk for death.