The detection of high-risk plaque on coronary CT angiography may have only limited prognostic value among patients with stable ischemic heart disease, researchers determined from a substudy of the PROMISE trial.
High-risk coronary atherosclerotic plaques — those with signs of positive remodeling, low CT attenuation, or napkin-ring phenomena — in people with stable chest pain were associated with more major adverse cardiovascular events (MACE) over a median 25 months of follow-up (6.4% versus 2.4% for peers without such plaques, HR 2.73, 95% CI 1.89-3.93).
That was true even after adjusting for atherosclerotic cardiovascular disease risk (ASCVD) risk score and significant stenosis (adjusted HR 1.72, 95% CI 1.13-2.62), Maros Ferencik, MD, PhD, MCR, of Oregon Health and Science University in Portland, and colleagues reported online in JAMA Cardiology.
Yet adding high-risk plaque to a risk stratification model that including ASCVD risk score and stenosis assessment did not result in a better C-index (0.69 to 0.71, P=0.12), despite better continuous net reclassification (0.34, 95% CI 0.02-0.51). Notably, only 6.4% of patients with high-risk plaque developed MACE, while 67.2% of those who suffered an event had no high-risk plaque detected at baseline.
Such a low positive predictive value associated with high-risk plaque likely precludes any clinical utility for now, Raymond Gibbons, MD, of the Mayo Clinic in Rochester, Minnesota, suggested in an invited commentary.
“Given the absence of important historical variables, electrocardiographic variables and other coronary CT angiography variables, I do not believe that the current study demonstrates that assessing high-risk plaques by coronary CT angiography is truly incremental to established risk assessment,” he wrote.
He questioned whether the reclassification was really meaningful. “[The researchers] assess the ability of a new test to move patients across these thresholds, prompting clinical actions that will hopefully improve outcomes. In the case of high-risk plaques, the potential outcomes might include more aggressive risk factor modification or invasive coronary angiography.”
“However, given the low incidence of MACE in this substudy (3.0% overall and 1.2% for hard cardiac events), it is very difficult to project that either one of these steps will improve outcomes,” he emphasized.
The prespecified nested observational cohort study by Ferencik’s group included stable, symptomatic outpatients who required noninvasive cardiovascular testing and got coronary CT angiography (n=4,415). The overall PROMISE trial randomized patients with stable chest pain to coronary CT angiography or functional testing. In the main findings, coronary CT angiography did not lead to better outcomes but increased the number of procedures done.
Significant stenosis was defined as 70% or greater stenosis in any vessel or at least 50% in the left main coronary artery. It turned out that patients with significant stenosis had similar MACE rates whether or not they had high-risk plaque.
High-risk plaque seemed to be most telling of future risk for those with nonobstructive coronary artery disease, women, and younger patients.
“Sex-based differences in plaque size and composition have been more pronounced in younger women and more attenuated in women older than 65 years. We speculate that when high-risk plaques are present in younger women, they portend a higher risk of future MACE,” according to Ferencik and colleagues.
Their PROMISE substudy led Gibbons to highlight the need to increase value and reduce waste in biomedical research.
“Novel risk markers should be rigorously evaluated before they are used routinely in clinical practice. The detection of high-risk plaques by coronary CT angiography is an appropriate subject for future research exploring the pathophysiology of plaque biology and its intersection with acute coronary syndromes,” he wrote. “However, in my opinion, the evidence is not yet strong enough for us to use it in the clinical care of patients with stable ischemic heart disease.”
The PROMISE trial was funded by National Heart, Lung, and Blood Institute grants.
Ferencik reported a grant from the American Heart Association.
Gibbons disclosed personal fees from Peer View Institute and Astellas Pharmaceuticals.
Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner