iFR Cheaper Than FFR Over Trajectory of 1 Year: DEFINE-FLAIR Analysis

This shouldn’t be seen as a contest between technologies but rather encourage physiologic assessment as a whole, Manesh Patel stressed.

iFR Cheaper Than FFR Over Trajectory of 1 Year: DEFINE-FLAIR Analysis

ORLANDO, FL—Using instantaneous wave-free ratio (iFR) to guide decisions on whether or not to revascularize intermediate lesions is, by 1 year, cheaper than using fractional flow reserve (FFR). Based on numbers from the DEFINE-FLAIR trial, researchers estimate the difference to be around $900.

But Manesh R. Patel, MD (Duke University Medical Center, Durham, NC), who presented the findings today at the American College of Cardiology (ACC) 2018 Scientific Session, told TCTMD that iFR coming out ahead isn’t what matters most.

Instead, he said, “the most powerful thing is we need people to do more coronary physiology in the cath labs around the country and around the world, because we do believe—and we have pretty good data—that physiologic assessment in the cath lab [to direct] revascularization improves outcomes.”

Going into DEFINE-FLAIR, a noninferiority trial, researchers hoped to “demonstrate that these two strategies, at bare minimum, are pretty similar [or to] find out if they’re different,” Patel said, adding, “Once we’ve demonstrated similar outcomes, then it’s about increasing utilization of these technologies.”

FFR involves using adenosine—which carries the risk of side effects and costs money, critics say—as well as measuring the pressure gradient across a lesion during hyperemia. By contrast, iFR is calculated during diastole and does not require use of hyperemic agents.

At last year’s meeting, DEFINE-FLAIR joined another study, iFR-SWEDEHEART, in reporting that use of iFR was associated with a noninferior risk of MACE at 1 year compared with FFR measurement. By having similar designs—with the same endpoints and approaches to adjudication—the two trials in combination provide a strong message on behalf of physiological assessment, according to Patel.

Bina Ahmed, MD (Dartmouth-Hitchcock Medical Center, Lebanon, NH), speaking with TCTMD, said, “what’s not surprising is that FFR costs more [since] doing the test costs more based on the cost of adenosine.”

What’s harder to know is cost-effectiveness over time, she commented, noting that the trial is slated for 5-year follow-up. At 1 year, “if you look at the cost breakdown, a lot of the advantage iFR receives is through lower costs related to CABG, lower costs related to PCI and angioplasty. . . I have a feeling that over time, those differences [related to less repeat revascularization with iFR] will even out.”

That said, the news that iFR isn’t any more expensive, and in fact is “a little less expensive,” compared with FFR may provide clinicians who are comfortable with the older approach with “yet another reason to transition to iFR,” Ahmed suggested.

There is no doubt that [iFR offers] streamlined workflow, lower cost, and the same outcomes. Morton Kern

William F. Fearon, MD (Stanford University Medical Center, Stanford, CA), who served as co-principal investigator for the FFR trials FAME and FAME 2, and now as PI of FAME 3, said the financial advantage here for iFR is interesting but not earth-shattering. “It’s incremental, but I’m not sure in the grand scheme of things it’s that big of a difference, cost-wise,” he commented to TCTMD.

The big driver of the 1-year difference, Fearon said, is that “FFR-guided PCI identified more significant lesions, so more PCI was performed upfront, and whether that ultimately leads to long-term catch-up phenomenon in the iFR group will be seen.”

Per-Patient Costs

At ACC 2018, the DEFINE-FLAIR investigators sought to better understand the economic implications of the two technologies. They estimated costs from a US healthcare payer perspective.

Both use pressure wires, so there was no difference there. But during the index procedure, expenses related to laboratory and staff time, medications (including adenosine), and the tools needed for PCI all were, on average, lower in the iFR group.

Index Procedure: Mean Cost per Person in 2017 USD




Pressure Wire



Laboratory and Staff Time






Other Angiography Costs






Guide Wire






Other PCI Costs




Then, over the course of 1 year, costs related to planned CABG, ambulatory care, and admissions for PCI/CABG, nonfatal MI, or nonfatal stroke all favored iFR. The mean total cost was $7,442.23 for iFR and $8,243.39 for FFR.

The final difference after adjustment was $896 and “in general the health outcomes [and quality-adjusted life-years] were fairly similar between the two groups,” Patel told ACC attendees.

Asked by TCTMD whether such an amount would be big enough to sway practice, Patel replied that it’s hard to tell how individual physicians and others will weigh the cost disparity. But in a world where value in healthcare gets ever more attention, he explained, “every health system is going to say, ‘What can we do [to ensure] we deliver better care at lower cost?”

Morton Kern, MD (University of California, Irvine), during the discussion that followed Patel’s presentation, cautioned that these data stem from an “extension” of a noninferiority trial involving a patient population at moderate-to-low risk and therefore merit careful interpretation. “But there is no doubt that [iFR offers] streamlined workflow, lower cost, and the same outcomes,” he commented. While the “track record” is longer for FFR, the new findings show “very positive, favorable economic results,” Kern added.

The question, which he posed to Patel, is whether this analysis will change practice. “I hope so,” Patel replied. But when it comes to physiologic assessment, it’s not a contest between iFR and FFR, he stressed. "We should stop arguing about which one to use and use more of it, first and foremost.”

Fearon agreed, noting, “What we should be focusing on is improving and optimizing our approach to PCI. And certainly, incorporating physiology is one of the key components that is underutilized.” Encouraging its use is more important than “fighting over which index one uses,” he said. “That shouldn’t be the focus.”

One element that goes unaddressed by the current per-patient analysis, though, is what upfront costs are borne at the hospital level and whether iFR’s status as a proprietary technology affects the math.

Via email, Justin Davies, MBBS, PhD (Imperial College, London, England), DEFINE-FLAIR’s lead investigator, told TCTMD that commercial questions fall outside of his purview. But based on the most appropriate use criteria, all cath labs ought to have the technology to perform physiologic assessment, he noted, and some already have multiple systems. “Saving close to $1,000 per case means that even if they need to invest in a new system [to do iFR] its costs would be covered rapidly, and I’m sure ongoing savings would be realized in a short time frame,” Davies said.

Caitlin E. Cox is News Editor of TCTMD and Associate Director, Editorial Content at the Cardiovascular Research Foundation. She produces the…

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  • Patel MR. Comparative cost effectiveness of the instantaneous wave-free ratio versus fractional flow reserve in coronary revascularization decision-making. Presented at: ACC 2018. March 10, 2018. Orlando, FL.

  • DEFINE-FLAIR was funded by Philips Volcano.
  • Patel reports receiving research grants from AstraZeneca, Bayer, Jansen, the National Heart, Lung, and Blood Institute, Procyrion, and Phillips-Volcano as well as serving on the advisory board of or consultant to AstraZeneca, Bayer, Jansen, Medscape, and DukeHeart On The Go.
  • Davies reports receiving consultant fees/honoraria from Medtronic and Volcano Corp, having other financial relationships with Volcano Corp, and receiving research grants from Medtronic and Volcano Corp. Ahmed reports no relevant conflicts of interest.
  • Fearon reports receiving consultant fees/honoraria from Heartflow and research/research grants from ACIST, CathWorks, Edwards Lifesciences, Medtronic, and St. Jude Medical.