Precision testing strategy strongly benefits stable patients with suspected CAD
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CHICAGO — In stable symptomatic patients with suspected CAD, a precision testing strategy was linked to a 70% reduction in death, MI or catheterization without obstructive CAD at 1 year compared with the usual testing, researchers reported.
For the PRECISE trial, presented at the American Heart Association Scientific Sessions, Pamela S. Douglas, MD, MACC, FASE, FAHA, Ursula Geller Professor of Research in Cardiovascular Diseases at Duke University and past president of the American College of Cardiology, and colleagues randomly assigned 2,103 patients (mean age, 58 years; 50% women; 16% from historically underrepresented groups) who had nonacute chest pain or the equivalent, no history of obstructive CAD and no CAD test within the past year to undergo the precision testing strategy or the usual testing.
“New-onset chest pain is a common problem and requires performance of approximately 4 million tests annually in the United States alone,” Douglas said during a press conference. “All the practice guidelines agree on evaluation goals for such patients and propose similar strategies to accomplish them. These goals are to reduce unnecessary testing, to improve diagnostic yield, to reduce complications and costs and to optimize preventive treatment. However ... there is no randomized trial-level evidence to determine the best care pathway to accomplish all of these goals. Accordingly, the PRECISE hypothesis was that in stable, symptomatic patients with suspected CAD, a precision strategy, which is a care pathway based on guideline recommendations, will improve outcomes compared to usual testing.”
Patients assigned the precision testing strategy had their initial testing determined by the PROMISE Minimal Risk Score. Patients deemed to be low risk had their testing deferred. Patients determined to be not at low risk underwent coronary CTA with or without CT-derived fractional flow reserve (HeartFlow).
Patients assigned the usual testing had their testing strategy determined by their clinician. Regardless of risk level, patients underwent functional testing or were sent directly to the cath lab.
Because PRECISE was a pragmatic trial, after the initial test, subsequent testing was based on the determination of the clinician, and guideline-directed medical management was recommended for every patient, Douglas said.
The primary endpoint was death, MI or catheterization without obstructive CAD at 1 year. Catheterization without obstructive CAD was defined as catheterization despite the absence of a positive invasive FFR or instantaneous wave-free ratio or quantitative coronary angiography-measured stenosis of at least 50% in an epicardial vessel of at least 2 mm.
“We chose this composite as it defines a net clinical effectiveness for this low-risk population: efficacy in the cath endpoint and safety in the death and MI endpoints,” Douglas said during the press conference. “Catheterization without obstructive disease has been used as an endpoint in other trials, [where] it has been associated with greater quality of life, fewer complications and lower costs.”
The PROMISE Minimal Risk Score was developed using 4,631 patients from the PROMISE trial and is based on 10 clinical variables that predict minimal risk, Douglas said during the presentation, noting that it was validated in two other cohorts and the C statistic for all three cohorts combined was 0.76.
Among the cohort, 94% had at least one major CV risk factor, more than 80% had chest pain as their primary symptom, about one-quarter had typical angina and the average 10-year risk for atherosclerotic CVD was approximately 8%, according to the researchers.
In the precision strategy group, the initial test was coronary CTA without FFRCT in 48%, coronary CTA with FFRCT in 31%, SPECT/PET in 2%, stress echocardiography in 2%, treadmill ECG in 1%, stress cardiac MRI in less than 1%, direct to cath lab in less than 1% and no test in 16%, Douglas said during a presentation.
In the usual testing group, the initial test was SPECT/PET in 32%, stress echo in 30%, treadmill ECG in 11%, stress CV magnetic resonance (CMR) in 10%, direct to cath lab in 10%, coronary CTA in 1%, coronary CTA with FFRCT in less than 1% and no test in 7%, she said.
At 1 year, risk for the primary outcome was dramatically lower in the precision strategy group compared with the usual testing group (4.2% vs. 11.3%; HR = 0.35; 95% CI, 0.25-0.5; adjusted HR = 0.29; 95% CI, 0.2-0.41; P < .001; win ratio = 2.81; 95% CI, 1.36-6.41), Douglas said, noting the adjustments were for age, sex, CAD equivalent and intended first test.
The results were driven by catheterization without obstructive CAD (2.6% vs. 10.2%; aHR = 0.18; 95% CI, 0.12-1.3), Douglas said during the press conference, noting that nonfatal MI, all-cause death and death/nonfatal MI were similar in both groups.
Among those in the precision testing group who were designated for deferred testing, there were no cases of death or MI, she said.
The results were consistent across subgroups except that precision testing was favored to a greater degree in patients whose intended first test was invasive compared with patients whose intended first test was noninvasive (P for interaction < .001), Douglas said.
The precision testing group had fewer tests than the usual testing group (P < .01) but had a higher testing yield (18.3% positive vs. 13.3% positive), she said.
In addition, she said, the precision testing group had fewer catheterizations than the usual testing group and was one-third as likely to have catheterization without obstructive disease and about half as likely to have a catheterization that did not proceed to revascularization. However, she said, revascularization was more common in the precision testing group.
The precision testing group had greater use of lipid-lowering medications and antiplatelet medications (P < .001 for both), according to the researchers.
There was “a similar and substantial reduction in angina in both arms” (P = .24), Douglas said during the press conference.
“PRECISE demonstrates the net clinical effectiveness of the precision strategy,” she said. “PRECISE addressed critical knowledge gaps in the evaluation of symptomatic low- to intermediate-risk patients with suspected CAD by defining and then testing a specific care pathway that is concordant with guideline recommendations. Outcomes were improved using deferred testing for quantitatively determined minimal-risk patients and CT with selective FFR-CT in all others.”
Douglas said she could not predict whether guidelines would be updated based on the trial, but noted that “this is the first time we have randomized trial evidence supporting CT with selective FFR-CT. It has been observational until this point. This is the first-ever time in this space that we have done a prospective validation of a risk score to do less: Can we save money and reduce the burden for our patients?”
In a discussion at the press conference, Julia Indik, MD, PhD, professor of medicine, Flinn Foundation and American Heart Association Endowed Chair in Electrophysiology and Heart Disease Research and director of the cardiovascular disease fellowship program at the University of Arizona College of Medicine in Tucson, said although the algorithm in the 2021 AHA/American College of Cardiology/Multisociety Guideline for the Evaluation and Diagnosis of Chest Pain is supported by evidence, “you have to ask, with all of those tests that are being recommended in this algorithm, every test you do runs the risk of a false positive ... and then we subject the patient to needless other tests, risky tests. Unnecessary tests could be avoided with [the precision] strategy.”
Perspective
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This is an interesting study that unfortunately seems to imply that finding no obstructive CAD is a finding to avoid, perhaps because this is a “benign condition.” In fact, multiple reports document that no obstructive CAD in patients with clinically stable symptoms (usually chest pain) is associated with adverse outcomes (mostly frequent hospital visits for recurrent chest pain or HF) that consume considerable health care resources and portend poor quality of life.
Furthermore, the British Heart Foundation-sponsored randomized CorMicA trial found that among patients with no obstructive CAD, stratified medical therapy based on invasive coronary functional testing significantly improved angina and quality of life compared with usual care. This beneficial treatment effect was observed by 6 months and was sustained over the initial year of follow-up. Thus, such an opportunity is lost when coronary functional testing is avoided in patients with chest pain but no obstructive CAD.
Perspective
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Matthew I. Tomey, MD, FACC, FSCAI
It is important to stipulate that this was a study of stable patients with symptomatic suspected CAD and not ACS. Chest pain is a common complaint brought by patients to their physician or cardiologist. The approach we take to evaluation of this complaint has substantial implications for patient symptoms, patient safety, patient outcomes and resource utilization. In this context, PRECISE is a trial of great importance.
PRECISE was a well-designed, carefully-executed and highly-pragmatic trial in which physicians retained authority to direct care with or without the information provided by a “precision strategy” integrating the PROMISE Minimal Risk Score and, for elevated-risk patients, cardiac CT, with or without FFR-CT.
The study was well-powered to detect a difference in an interesting primary composite endpoint combining death, nonfatal MI and catheterization without obstructive CAD.
Outcomes differed starkly with a precision strategy vs. usual care, with a significant 71% reduction in the primary composite endpoint. This difference appeared to be explained by a marked reduction in catheterization without obstructive CAD (2.6% vs. 10.2%; adjusted HR = 0.18).
One might say that the precision strategy led to more “actionable” catheterizations — there was, in fact, more revascularization in the precision strategy arm. This finding is all the more interesting when juxtaposed with the absence of evidence for reduction in death, nonfatal MI or frequent angina.
It was encouraging to see that the precision strategy led to greater utilization of medical therapies including lipid-lowering medication and antiplatelet therapy.
In summary, use of a precision strategy incorporating the PROMISE Minimal Risk Score and CT imaging in evaluation of symptomatic suspected CAD appears to substantially decrease the likelihood of bringing patients to the catheterization laboratory only to find no obstructive CAD.
A hypothesis-generating finding of relevance is that the precision strategy also led to greater utilization of medications that may modulate the natural history of atherosclerosis. This finding, if true, serves to bolster an argument for integration of anatomic investigations (such as CT) capable of identifying atherosclerotic plaque independent of the presence of discernible ischemia on other noninvasive tests common in usual care. The available 12-month follow-up of PRECISE might preclude recognition of longer-term benefits of such anti-atherosclerotic medical therapy.
Mount Sinai Morningside
Assistant Professor of Medicine (Cardiology)
Icahn School of Medicine at Mount Sinai
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Douglas PS, et al. LBS.06: Drugs and Strategies in ACS and Revascularization. Presented at: American Heart Association Scientific Sessions; Nov. 5-7, 2022; Chicago (hybrid meeting).
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