Incident COronary EveNts Identified by Computed Tomography

Acute myocardial infarctions resulting from unstable plaque in patients with coronary artery
disease (CAD) account for a significant portion of cardiovascular morbidity and mortality.
Although prediction models that incorporate traditional risk factors have been developed in
order to risk stratify patients at highest risk for development of subsequent cardiovascular
events, such models lack precision and are often found to over or under-estimate risk.
Moreover, current clinical practice has focused on stenosis severity as a predictor of future
plaque erosion and/or rupture, in spite of the fact that evidence from intravascular
ultrasound (IVUS) studies, such as the PROSPECT trial, demonstrate that ACS events are more
likely to occur in less than severely stenotic lesions. Furthermore, there is incomplete
understanding of the influence of gender on atherosclerotic plaque composition and downstream
coronary events, given the chronologic and prognostic differences between men and women in
atherosclerotic cardiovascular disease.

Several studies have attempted elucidating characteristics of vulnerable plaque using
invasive imaging modalities such as IVUS. However, such studies have several limitations,
most significantly is the fact that plaque characterization was performed after an acute
coronary event, which limits the ability to isolate baseline plaque characteristics from
changes following the acute event. Noninvasive evaluation of atherosclerotic coronary disease
using coronary computed tomographic angiography (CCTA) has been established as an accurate
and readily available imaging modality in clinical practice. In addition to the evaluation of
diameter stenosis, CCTA is capable of evaluation plaque composition as well as arterial
remodeling, in a similar fashion to IVUS. The agreement between plaque characterization using
IVUS and CCTA has been demonstrated in several large-scale trials. Nevertheless, there are
several key aspects that have yet to be addressed, including the utility of plaque
characterization by CCTA for determination of future cardiovascular events, and gender-based
differences in atherosclerotic plaque composition in patients with stable and unstable
coronary artery disease.

The ICONIC trial was designed as a nested case-control study based on the previously
published CONFIRM registry, evaluating demographic, clinical as well as baseline
CCTA-determined plaque composition in 238 patients with subsequent ACS events and 238 matched
patients without ACS events. As previously described, ICONIC utilizes CCTA to comprehensively
assess plaque morphology and characteristics, in addition to arterial wall changes in order
to determine characteristics implicated in future adverse events, beyond what has been
traditionally described using invasive imaging modalities. The primary goal is to investigate
differences in atherosclerotic plaque composition in patients with ACS, compared to patients
with stable coronary disease. The secondary goal is to determine gender-specific differences
in plaque composition in both stable and unstable coronary artery disease.

Cases:

Inclusion criteria:

- Age ≥18 years.

- Adjudicated STEMI / NSTEMI / UA / Unclassified MI (except for type 4a, 4b, or 5 MI)

- Baseline CCTA.

Exclusion criteria:

- Myocardial infarction not meeting the definition of ACS with missing cardiac
biomarkers.

- Prior history of CAD (revascularization or MI).

- Prior revascularization (PCI or CABG).

- ACS in a previously revascularized segment.

- Type 4a, 4b, or 5 MI.

Controls

Inclusion criteria:

- Age ≥18 years.

- Propensity score matched.

Exclusion criteria:

- Prior history of CAD (revascularization or MI).

- Death as an outcome.