DEFINE-PCI Hints at Fewer Cardiac Events After Tightly iFR-Optimized PCI

October 16, 2020

As much as intracoronary physiologic measures can help operators identify potential ischemia-producing targets for percutaneous coronary intervention (PCI), they may also verify whether the procedure — even when angiographic results look great — successfully cut the lesion's capacity for causing ischemia and thereby improved risk for future events.

That was a main message from the one-year analysis of the previously published, prospective DEFINE-PCI trial, reported this week at TCT Connect, the virtual edition of Transcatheter Cardiovascular Therapeutics (TCT) 2020.

In the trial's earlier primary report, all PCIs among its 500 patients were judged successful by standard angiography, yet many procedures left the stented target sites with a residual ability to cause ischemia, as measured by the post-PCI assessment of instantaneous wave-free ratio (iFR) index. The iFR index is a standard pressure-wire measure of flow reserve that is on par with fractional flow reserve (FFR).

A full 24% of patients in the trial had a residual iFR less than 0.90, the primary endpoint, after angiographically successful PCI. In more than 80% of those cases, the iFR deficit was attributed to potentially treatable focal lesions or stent edges encroaching on the lumen that were not apparent on angiography, said Manesh R. Patel, MD, Duke University Medical Center, Durham, North Carolina, when presenting the new analysis during TCT Connect.

At one year, in a prospectively planned analysis, patients with the most symptoms before PCI and who had almost no residual ischemia by iFR showed greater improvement in angina than the minority with post-PCI ischemia despite a "clear" angiogram.

Patel also presented a post-hoc analysis that identified a potential post-PCI iFR cut-point which, if achieved, might prolong the patient's event-free survival. Patients who showed a post-PCI iFR of 0.95 or higher, minutely close to full restoration of coronary patency, had about one third the risk of an endpoint consisting of cardiac death, spontaneous myocardial infarction (MI), or clinically driven target-vessel revascularization (TVR) over the next year compared with patients with lower residual iFR.

"Let's Check Our Work"

Typically, operators use physiologic readings like iFR or FFR before PCI to help identify the most appropriate target lesions when contrast angiography isn't discriminating enough, Allen Jeremias, MD, St. Francis Hospital, Roslyn, New York, not part of the trial, observed at a media presentation on DEFINE PCI during the TCT Connect sessions.

But, he said, "They are so confident in the angiogram to be able to see all the lesions that need to be treated, and then confirm that the result is adequate, that they frequently don't repeat physiology measurements afterwards to actually make sure the results were good."

One of the main lessons from the trial, Jeremias said, is that post-PCI physiologic readings seem important for achieving the best results overall. "Let's check our work, so we don't leave a quarter of patients behind with significant ischemia. We can see from the 1-year data that it obviously matters."

"If we can get to a good iFR, which we now know is 0.95 or greater, these patients have very, very good outcomes. But if we don't achieve that, of course, those patients might come back with recurrent symptoms."

The trial is "a great illustration of the importance of understanding the limitations of two-dimensional imaging" with PCI, Dee Dee Wang, MD, Henry Ford Health System, Detroit, Michigan, also not with DEFINE PCI, offered at the media briefing.

Assuming the kind of physiologically guided, physiologically optimized PCI procedures proposed by DEFINE PCI are validated in randomized trials, she said, "It will be very disruptive."

"The Headlines Are Really Good, but…"

Among all patients in the study with a baseline Seattle Angina Questionnaire angina frequency (SAQ-AF) score of 60 or lower, SAQ-AF scores went up at least 10 points in all patients with a post-PCI iFR of at least 0.95 vs 88.5% of patients with a post-PCI iFR that did not reach 0.95 (P = .01).

Patients with a post-PCI iFR of at least 0.95 showed a 1-year rate of the trial's composite primary endpoint of 1.8%, compared with 5.7% for patients with a post-PCI reading less than 0.95, for a hazard ratio (HR) of 3.38 (95% CI, 0.99 - 11.6, P = .04) for those with the smaller iFR reading.

The difference appeared driven by two components of the post-hoc endpoint, excluding TVR. The rates of cardiac death or spontaneous MI were 0% for the group with the higher iFR readings and 3.2% for those with post-PCI iFR less than 0.95 (P = .02).

After Patel's formal presentation of DEFINE PCI at TCT Connect, panelist Anthony H. Gershlick, MBBS, pointed out that there are possible "downsides" to a coronary stenting strategy that strives — with potential for both risk and reward — for a post-PCI iFR as dizzyingly high as 0.95.

"The headlines here are really good, but we need to know a lot more before we encourage people to go for broke in some of these vessels," said Gershlick, consultant cardiologist with University Hospitals of Leicester, United Kingdom.

"We're not advocating that people immediately change their entire practice and start going for an iFR value or physiologic value that's perfectly normal," Patel replied. "These are just early data in 500 patients."

Patel described the next step, a randomized trial in early stages called Distal Evaluation of Functional Performance With Intravascular Sensors to Assess the Narrowing Effect: Guided Physiologic Stenting (DEFINE GPS) that will test the iFR 0.95 threshold as a target for PCI for clinical outcomes in an estimated 3200 patients.

DEFINE PCI was funded by Philips' Volcano Corporation. Patel discloses receiving research support from Bayer AG and AstraZeneca; receiving fees for consulting or honoraria, or serving on a speakers bureau for Bayer AG and Janssen. Jeremias discloses receiving fees for consulting or honoraria, or serving on a speakers bureau for Abbott Vascular, Boston Scientific, Volcano Corporation, and ACIST. Wang discloses receiving research support from Boston Scientific and receiving fees for consulting or honoraria, or serving on a speakers bureau for Edwards Lifesciences, Boston Scientific, and Synchrony Labs. Gershlick has disclosed no relevant financial relationships.

Transcatheter Cardiovascular Therapeutics 2020. Late Breaking Clinical Science Session II. 1-Year Outcomes of Patients with Residual Physiologic Ischemia After Percutaneous Coronary Intervention: The DEFINE PCI Trial. Presented October 15, 2020.

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