Think of fractional flow reserve (FFR) as a hex wrench. Or intravascular ultrasound (IVUS) as a screwdriver. Both imaging methods are highly useful in the right situation, according to physicians. Both methods can be highly effective, when used. However, there is some disagreement about where and when these tools should be applied.
Recently, a web survey offered physicians a perfect world setting to assess stenosis. Physicians could choose to look at provided angiographic surveys of intermediate stenoses or request further data from FFR, IVUS, quantitative coronary angiography or optical coherence tomography. Requests did not add time or costs; all physicians needed to do was to click a button. Nearly three-quarters of decisions made, however, were based solely on angiogram. Combined, physicians requested quantitative coronary angiography, IVUS and optical coherence tomography in only 7 percent of cases (Circ Cardiovasc Interv 2014;7:751-759).
The international report examined adherence to both European and American guidelines for assessing stenosis. The report noted that while physicians with more experience with a modality were more likely to use something other than angiography to assess lesions, rates were still low.
A sign post (of where we are)
“One of the major motivations at the time was to get a cross-sectional view of where people were at considering what has been several years of strong clinical trial results and fairly strong clinical guideline recommendations for the use of FFR for intermediate lesions,” says Nils Johnson, MD, of the Memorial Hermann Hospital in Houston. Johnson has led several studies on FFR and its value in understanding stenosis. While not part of the International Study on Interventional Strategy (ISIS) team, Johnson has paid close attention to these findings to explain what might be driving what he sees as underutilization in the U.S.
Going back to 2009, FAME (Fractional flow reserve versus Angiography for Multivessel Evaluation) and other studies established the utility of FFR for determining lesion severity and which, if any, stenoses needed stenting (Circulation 2014; 129: 1860-1870). In turn, these studies influenced the development of guidelines. “Obviously it’s no surprise whenever you try to change something, it’s not an instantaneous effect in the world,” Johnson says. “There’s always some time lag between when we decide we should be doing something differently and then when clinicians take that on as the majority. [ISIS] was a sense of where we are now.”
Analyses in the U.S. found that IVUS was more frequently used than FFR, although rates were still low. In 2010, FFR and IVUS use was around 6.1 percent and 20.3 percent, respectively (J Am Coll Cardiol 2012;60:2337-2339). These numbers hadn’t improved much in the subsequent two years in Medicare patients. FFR alone was used with 11 percent and 3.9 percent of PCIs and diagnostic catheterizations, respectively (J Am Coll Cardiol 2014;64:1655-1657).
The findings from ISIS and other studies underscore the conundrum: Why aren’t physicians making use of these tools? Johnson states that the answer is more complex than just one of guidelines or clinical trials, or even that of time, staffing or cost of procedure. “An important piece of ISIS’s [message] is that having this almost platonic survey where you say, ‘Don’t think about cost, don’t worry about what you have in your lab, let’s be in a test-taking environment’ … You can still see that even with all of those barriers removed there’s a real dominance of using angiography to decide treatment strategies for intermediate stenosis, even though evidence and the guidelines and everything else says that we should be using FFR in those cases.”
He also notes that physician characteristics, like experience and years of practice, weren’t enough to capture what is driving use—or lack of use—among physicians.
But why not?
Apparently, reasons physicians cite for not using IVUS or FFR haven’t changed much. “We did a survey in the mid ’90s,” says John McB. Hodgson, MD, professor of medicine at Case Western Reserve School of Medicine in Cleveland. “[Physicians said] it was cost. It was time. It was ‘I don’t understand what I’m looking at.’” Hodgson notes that in spite of efforts to improve education and a significant body of data behind the benefits of using IVUS, adoption has been slow.
“The culture in [the U.S.] is ‘We’re not going to do it.’ The culture in Japan is ‘Of course, we’ll do it.’ The culture in Korea is ‘Of course, we’ll do it.’ The culture in Europe is ‘Of course, we understand it. We’d love to do it but we can’t afford it,’” he says. Hodgson was involved in developing IVUS in the mid-1980s and has trained numerous physicians in the techniques.
While cost comes up as a stated reason for not using FFR or IVUS in the U.S., he doesn’t believe it’s a real barrier. “I’ve never had a lab where I worked say anything about ‘You can’t buy IVUS’ [or] ‘You can’t buy an FFR wire.’ Every study shows that you’ll save money doing that. You’ll put in less stents. You’ll treat people more effectively. No matter how you cut it, they’re going to do better.”
Culture and popular influence, he states, are the key. “When I teach a fellow, they understand the benefit. They’re likely to go out and want to use it.” But if they later join a practice that doesn’t use it, they may stop. “There’s this subtle peer pressure: ‘Why are you bothering with that?’ It’s a fascinating study in human relations. Unless you’re a really strong personality, you’re going to regress to the mean.”
Right tool for the right job
Part of that prevalent culture may be that some physicians are unconvinced FFR, or IVUS for that matter, is so broadly useful. Armin Arbab-Zadeh, MD, PhD, director of cardiac computed tomography at Johns Hopkins Hospital in Baltimore, suggests that low usage is due to the uncommon nature of the particular types of stenoses or patient profiles to which FFR is better suited.
In a recent debate, Arbab-Zadeh argued against using FFR in all patients. In his position statement, he suggested that some may have misinterpreted FAME’s findings (Circulation 2014; 129: 1871-1878). “We shouldn’t believe that FFR guidance is necessary to identify patients who are a greater risk vs. not a greater risk of hard endpoints,” Arbab-Zadeh says about the data. In most cases, he notes the culprit of a patient’s symptoms is a known quantity.
“The value of FFR is if you have a patient who has several coronary artery stenoses and the patient is symptomatic,” he argues. “You think he or she might benefit from PCI for symptomatic relief and you’re not sure whether a particular lesion is related to the symptoms or not. In that case, FFR can help you [determine that] this is a lesion that might be causing symptoms and this one is not.”
He admits that when FFR is used, the number of PCIs may go down and when PCIs decrease, so does cost to the healthcare system.
FFR is most useful, Johnson says, when it is used to answer the right questions. “I often think about it by the question that needs to be answered,” Johnson says, adding that FFR’s real strength is determining whether a lesion should be treated. “The first question we often have is, do we need to treat this lesion at all with revascularization, be that PCI or CABG. … I see it almost as different things in your toolbox for different problems: Sometimes you need the screwdriver and sometimes you need the hammer. It depends a little bit on the problem you’re going after.”
Benefit is there
Hodgson recommends that physicians on the fence go back to the studies and see costs and outcomes. “For IVUS, it’s less restenosis, lower death rate, less stent thrombosis, more optimal expansion of the stents.” According to the ADAPT-DES study (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents), IVUS-guided PCI patients had half the rate of stent thrombosis at one year. MI rates were also significantly lower (Catheter Cardiovasc Interv 2014;83:509-518). He also notes that physicians have better understanding of complications and stent failure issues as well as an easier time planning complicated procedures.
The findings on FFR from FAME and others are not dissimilar. Composite rates of MI, repeat revascularization or death at one year were 35 percent lower among patients who had FFR-guided treatment. Major adverse events rates were 30 percent lower in these patients. “[When using] FFR, you’re only going to treat lesions that really need it,” Hodgson says. “We know from many studies now that when you stent lesions that don’t need it, they do worse.”
When looking at patient outcomes against cost of procedure, Johnson considers FFR a savings in the long run based on FAME economic analyses. “FFR was a dominant strategy over angiography, dominant in the sense that patients did better and it cost less money, which is kind of a rare thing in medicine,” he says of FAME 1. FAME 2 trial data found that when PCI was performed using FFR data, quality adjusted life-years were well within cost-effectiveness range, at $36,000 for year one.
While FAME 2 showed that medical therapy costs less in initial cumulative costs, over time those costs increased significantly compared to FFR-guided PCI, indicating a potential cost benefit for FFR-guided PCI down the road (Circulation 2013;128:1335-1340).
With data pointing toward improved outcomes and lower costs, Hodgson asks, “Can you really justify withholding a treatment that’s been shown to reduce mortality by 30 percent from your patients?”
IVUS adopter sounds off on MOZART
MOZART (Minimizing cOntrast utiliZationWith IVUS Guidance in coRonary angioplasTy) attempted to reduce contrast use in PCI with intravascular ultrasound (IVUS) and contrast reduction techniques. The protocol succeeded, using more than a third less contrast, but taking 14 minutes longer than angiography (J Am Coll Cardiol Intv 2014;7:1287-1293).
Contrast use was reduced between the two groups by 44.5 ml and contrast nephropathy was more than halved by the technique (7.3 percent vs. 19 percent, respectively). While IVUS may not be possible for all patients, these findings are promising.
Using IVUS in this study was about focusing on a group of patients who would benefit most from the reduction of contrast to improve their outcomes. “It’s kind of a select group of patients who are vulnerable to contrast nephropathy, so we don’t use [IVUS] on everyone,” says Kreton Mavromatis, MD, director of the Atlanta Veterans Affairs Medical Center. Mavromatis is also an assistant professor of medicine in the cardiology department at Emory University School of Medicine in Atlanta. He provided an accompanying editorial with publication of the trial’s results. “You can never eliminate angiography, but you can come close and reduce it a lot.”
While cost was not part of the analysis by MOZART’s authors, Mavromatis observes that less contrast may lead to lower costs. As some of the biggest perceived barriers for using IVUS are cost and time, he says, these findings might influence others to look at the technique.
Fearon, FAME and FFR
A few words on FFR and IVUS from William F. Fearon, MD, lead researcher of FAME (Fractional flow reserve versus Angiography for Multivessel Evaluation) and associate professor at Stanford University in California.
On the benefits of FFR: “FFR is the gold standard for diagnosing myocardial ischemia. It has better spatial resolution than noninvasive stress imaging studies. It has a wealth of clinical outcome data supporting it. Other techniques (e.g. IVUS) do not provide information about the ischemic potential of a lesion, but just anatomic information, which can be misleading.”
On the benefits of IVUS: “There are data suggesting IVUS helps optimize stent deployment.”
Who benefits most from FFR? “Patients with moderate to severe coronary lesions with equivocal/negative or unavailable noninvasive testing, multivessel CAD [coronary artery disease] patients in particular or nonculprit vessels in ACS [acute coronary syndrome].”