Cost-effectiveness Favors Anatomic Over Functional Testing for Stable Chest Pain

For the initial evaluation of low-risk patients with stable chest pain, anatomic testing—coronary CT angiography (CTA) with or without noninvasive fractional flow reserve (FFR)—is cost-effective compared with functional testing, a new analysis based on PROMISE trial data indicates.

Over the course of a patient’s life, using CTA alone instead of functional testing would be cost-effective with an incremental cost-effectiveness ratio (ICER) of $2,743 per quality-adjusted life-year (QALY). Coronary CTA supplemented with noninvasive FFR (FFRCT) dominated functional testing, with greater effectiveness and less cost.

Researchers led by Júlia Karády, MD (Massachusetts General Hospital, Boston), report in JAMA Network Open that the findings “suggest that anatomic strategies may present a more favorable initial diagnostic option in the evaluation of low-risk stable chest pain compared with functional testing.”

To TCTMD, senior author Udo Hoffmann, MD (Massachusetts General Hospital), said “this is probably the most fundamentally sound cost-effectiveness analysis in this area” because the microsimulation model that was used could be validated using 2-year data from the PROMISE trial. The findings support a CTA-first strategy, he added.

“If you have a low-to-intermediate-risk chest pain patient in front of you and you want to exclude the possibility of obstructive CAD, you do a coronary CTA—you don’t need to do an FFR, you just do a coronary CTA,” Hoffmann said. “And in most patients you will exclude obstructive CAD, but you will find some atherosclerosis and it will help . . . to optimize your medical therapy.”

That will also help motivate patients, he added, because prior studies have demonstrated “that if you can show people the disease they have, they’re much more motivated to, for example, be compliant with their statin therapy.”

European guidelines have already given a class I indication to coronary CTA—alongside noninvasive functional imaging—as an initial test option for diagnosing CAD in symptomatic patients for whom clinical assessment alone cannot exclude obstructive CAD. It’s unclear if and when US guideline writers will follow suit, but the results of this analysis “support a change of the guidelines and a higher valuation of CT as an anatomic approach,” Hoffmann said.

CTA Cost-effective Across Wide Range of Scenarios

In their paper, the investigators note that $15 billion is dedicated each year in the United States to noninvasive diagnostic testing for suspected CAD, with most spent on functional assessments of myocardial ischemia, like SPECT and stress echocardiography. Coronary CTA is used in less than 5% of evaluations.

Randomized studies comparing functional and anatomic testing for stable chest pain have provided mixed results. PROMISE showed no difference between strategies in terms of incident MACE at 2 years, whereas SCOT-HEART demonstrated a 41% reduction in nonfatal MI at 5 years in patients randomized to coronary CTA versus standard care. Some commentators, however, found the latter finding hard to believe.

In the current analysis, Karády et al delved into the long-term health and economic consequences of choosing one type of initial test for stable chest pain over another. They created a Markov microsimulation model based on data from the 10,003 participants in the PROMISE trial.

That model accurately estimated the type of initial evaluation, testing results, referral to invasive coronary angiography, revascularization and MACE rates, as well as costs at 60 days and 2 years, compared with observations in the PROMISE trial.

Because of its greater sensitivity in detecting CAD, anatomic evaluation was associated with increased rates of invasive coronary angiography and revascularization at 60 days, 2 years, and 5 years compared with functional testing, but it was also more effective. The 60-day revascularization-to-invasive angiography ratio, for example, was higher with CTA plus FFRCT (59.5%) and CTA alone (53.7%) than with functional testing (40.7%).

QALY gains through 5 years showed that CTA with or without FFR was associated with about 1.5 months of longer life in perfect health compared with functional testing over that span.

Over a lifetime, choosing an anatomic testing strategy as the initial approach was projected to add roughly 6 months of life in perfect health compared with functional testing in a cost-effective manner, even in a situation of declining adherence to statin therapy over time. Assuming a willingness-to-pay threshold of $100,000 per QALY, CTA-based testing was cost-effective in more than 65% of modeled scenarios.

The results “suggest that anatomic approaches are cost-effective compared with functional testing across a wide range of assumptions in clinical care and patient characteristics, mostly because of a higher sensitivity to detect nonobstructive and obstructive CAD and the ability to tailor statin therapy accordingly,” the researchers write.

‘What Are We Waiting For?’

Commenting for TCTMD, Erin Michos, MD (Johns Hopkins University School of Medicine, Baltimore, MD), who wrote an accompanying editorial with Philip Greenland, MD (Northwestern University Feinberg School of Medicine, Chicago, IL), said “the advantage of doing an anatomical test first is that you don’t miss the nonobstructive disease,” which would not be picked up by functional testing.

In PROMISE, Michos noted, about two-thirds of CV deaths and MIs occurred in patients who had normal stress tests at baseline; most, however, had nonobstructive disease on CTA. “If we rely entirely on stress tests, we’re going to miss opportunities to implement comprehensive preventive measures,” she said, agreeing with Hoffmann that patients are more likely to stick with treatment if they can see the disease.

It’s possible, Michos argued, that a CTA-first approach can be even more cost-effective than demonstrated in this study if more patients are started on medical therapy rather than taken to the cath lab for a costly procedure when CAD is detected. The COURAGE and ISCHEMIA trials, she said, suggest that even when there’s obstructive disease, if there’s no high-risk anatomy then patients don’t necessarily need to undergo an invasive procedure. “A lot of stable chest pain, including [that caused by] obstructive disease, can be managed up front with good medical therapy.”

Moreover, the SCOT-HEART results show that a CTA-based evaluation can have an impact on patient outcomes. “I do believe that if you see disease, particularly nonobstructive disease, and treat it, you can actually reduce meaningful outcomes,” Michos said.

Both Hoffmann and Michos indicated that US adoption of anatomic testing as the initial evaluation in patients with stable chest pain may be getting held back by financial incentives to perform functional testing. And not all payers cover CTA, Michos pointed out. Hoffmann added that a shortage of skilled CTA readers is stifling uptake as well.

What it’s going to take to increase use of CTA in the evaluation of chest pain, Michos said, is buy-in from the cardiovascular community, as the evidence to support it is there. “What are we waiting for? Why has CTA not been uniformly adopted as first-line for the evaluation of stable chest pain in a patient at intermediate-risk probability? We know that an anatomical approach can reduce outcomes and it may be cost-effective, too, so I think that we have enough mounting evidence that there should be a paradigm shift in how we’re approaching [this].”