PARIS – A meta-analysis covering 4,529 patients presented at EuroPCR closed the door on a five-year argument over what diagnostic tool will be the gold standard in the catheterization lab for helping physicians decide whether or not to stent a coronary lesion.
The results of the combined results from DEFINE-FLAIR and IFR-SWEDEHEART were already known to cardiologists, having been published in March in the New England Journal of Medicine and concurrently presented at the meeting of the American College of Cardiology.
New at EuroPCR was the roll-out of the system for performing the assessment by Amsterdam-based Royal Philips NV, which holds exclusive rights thanks to its acquisition of Volcano Corp.
The argument over the superiority of the competing techniques for determining the severity of a coronary lesion broke out during a scientific session at EuroPCR 2012 and in a rare moment in the annals of cardiology congresses quickly turned into a maddening exchange of mudslinging between the inventor of fractional flow reserve, Nico Pijls, and the London-based Imperial College researcher, Justine Davies, who presented an alternative method. (See Medical Device Daily, May 17, 2012.)
This year the tables were turned as the compilation of clinical data demonstrated an equivalence between the techniques, and statistically significant advantages for Davies' instantaneous wave-free ratio (IFR) for patient outcomes.
The current gold standard for measuring the physiology of a culprit lesion is Pijls' fractional flow reserve (FFR) acquired by St. Paul-based St. Jude Medical that at EuroPCR was for the first time integrated under the branding of Abbott Vascular Inc. based in Santa Clara, Calif.
The DEFINE FLAIR clinical trial led by Davies randomized 2,492 patients between IFR-guided or FFR-guided coronary revascularization with a one-year primary endpoint for major adverse cardiac events (MACE). The study found IFR was noninferior to FFR guidance, that the rate of adverse procedural signs and symptoms was lower, and the procedural time was shorter.
The SWEDEHEART trial led by Matthias Götberg from Skåne University Hospital in Lund, Sweden, enrolled 2,037 patients with stable angina or an acute coronary syndrome who were randomly assigned to undergo revascularization guided by either iFR or FFR. The study also found IFR-guided revascularization was noninferior to FFR for MACE at 12 months.
Pooling the study groups for a patient-level analysis the meta-analysis focused on the deferred patients, those who did not receive a stent based on the guidance to determine whether outcomes were similar and to assess any difference between those patients who have a stable coronary disease (SCD) and those with acute coronary syndrome (ACS).
One-year MACE rates were not found to be significantly different for deferred patients presenting with either ACS or SCD when iFR guidance was used, but that MACE was higher for ACS patients when FFR guided the clinical decision.
"What it means is that there is a clear differentiator in terms of outcomes, that for the first time ever there is a statistically significant disadvantage for doing FFR over IFR," Davies told Medical Device Daily.
"That MACE is higher with FFR than with iFR in itself will change the metrics. Now rather than attacking IFR, clinicians will be in a position to defend IFR," he said.
"What is different today is not just that ACS patients do worse when the decision is guided by FFR, but that there is an alternative with iFR and these patients do better. This is the real change," he added.
Both techniques employ a pressure wire to measure hemodynamics of suspected lesions.
Despite 20 years of studies showing that FFR guidance can improve decisions about stenting in real time the technique has lagged far behind an expected adoption by clinicians. The technique requires added procedure time, and also requires racing the patient's heart with an injection of adenosine.
In contrast, IFR can measure the physiology of the artery when the patient is at rest, and it taps into the computational power that was not available to Pijls when he developed his method in 1996.
The joint engineering of Philips and Volcano have tapped into the digitally compatible calculations of IFR to introduce the IFR Roadmap technology, shown for the first time at EuroPCR but not yet approved with a CE mark, and Syncvision IFR co-registration. The Roadmap option is not a stand-alone and requires a Philips system where Syncvision IFR is designed to be compatible with any existing catheter lab suite.
"What we have done is move physiology in front of the treating physician to show where in the vessel there are big pressure drops and tell them that if they treat that area, this is the likely improvement you will get," said Davies.
"We have moved into a new realm, from single lesion assessment with FFR to full vessel assessment with IFR," he said, adding, "It works very well, and it is available here today."
He explained that as the physician slowly pulls back the pressure wire inserted in the artery, dots appear on the screen anatomically coregistered to the site of a measurement.
"Where there are lots of dots stacked together, the physician sees there is a high energy loss there and that this is the place to put a stent. If the dots are diffuse, we know that stents don't work very well in these cases and perhaps they will be better off with an optimal medical therapy or bypass surgery," said Davies.
Three new clinical studies are planned for IFR, and Davies said that a full economic analysis will be presented at Transcatheter Cardiovascular Therapeutics (TCT) in late October 2017.
"We know there are fewer stents and revascularization for procedures performed in the IFR arm of the two studies," he said. "We know that the procedural time is shorter. And we know that in FLAIR there were fewer unplanned revascularizations. These three things are going to drive the cost-effectiveness models. You can see it just looking at the crude numbers. But we need a proper health economic study to support it."
Behind the economic argument comes reimbursement, which Davies called "the biggest barrier of all, without any doubt. At the moment people are encouraged to implant stents whenever possible. It is a change of mindset to say this tool can help make the right decisions for the best treatment. In some cases it means to defer from placing a stent, in other cases it may be to place the stent.
"If we incentivize physicians to guide therapy with these tools, they will follow it. This can be done with a carrot or a stick. In the United States, the Appropriate Use criteria is a stick. It says if you do not do this you will not be reimbursement. The other, more clever thing that can be done is to reimburse physicians for making physiological assessments. That is what will drive adoption."