FFR Guidance for PCI Misses High-Risk Lesions by OCT in Trial

Even coronary lesions that fractional flow reserve (FFR) readings have indicated are of low risk for causing ischemia could be of high risk if optical coherence tomography (OCT) intravascular imaging indicates they are vulnerable to rupture, suggests a prospective study of patients with diabetes referred for angiography.

Of coronary plaques in a cohort that were low-risk by FFR, about one fourth were characterized as having thin-cap fibroatheroma (TCFA) at OCT imaging. That is, they registered as having a high lipid content that is thought to make the lesion vulnerable to rupture, potentially triggering an ischemic event.

Moreover, in the study, the risk for clinical events such as death, hospitalization, and myocardial infarction (MI) associated with the target lesion was fourfold higher at 18 months in patients with vs those without the target lesions containing TCFA.

The findings, therefore, suggest that adding OCT imaging to FFR may sharpen risk assessment of potential target lesions, at least for patients with diabetes, in whom coronary disease tends to follow a more aggressive progression than occurs with patients who do not have diabetes. The findings also support a role for OCT in identifying coronary plaques that could potentially be threatening in the future.

The trial, called COMBINE (OCT-FFR), showed "for the first time" that a high percentage of patients with diabetes and coronary lesions that were considered nonischemic by FFR actually had high-risk lesions, as indicated by TCFA on OCT imaging, said Elvin Kedhi, MD, PhD, when presenting the research on October 14 during TCT Connect, the 2020-style virtual edition of the annual Transcatheter Cardiovascular Therapeutics (TCT) sessions.

The combined use of FFR and OCT imaging in some patients "can improve the accuracy" of identifying higher-risk lesions "and therefore should be embraced" in clinical practice, said Kedhi, of Hôpital Erasme, Université libre de Bruxelles, Belgium.

A novel insight from the study, he said, is that there appears to be a disconnect between the current functional impact of a coronary lesion, as assessed by FFR, and the lesion's later propensity for causing clinical events. "Ischemia and future adverse events represent, to a large extent, two separate concepts."

It's been shown that FFR guidance of coronary stenting, now common in cath labs, can reduce ischemia and symptoms for patients, but "until now, OCT was mostly seen only as a modality that you can use to improve your stent result," Kedhi explained to theheart.org | Medscape Cardiology.

The current study shows, at least in patients with diabetes, that "OCT can also be used for qualitative plaque analysis and to detect vulnerable plaque, which is a strong predictor of future adverse events," he said.

"I believe that the combination of these two modalities is very useful, and they work definitively in a synergetic way."

Currently, Kedhi said, OCT imaging may "best be used in patients with high risk of fast atherosclerosis progression," such as those with diabetes, and for nonculprit lesions in patients with ACS, "as well as patients with diffuse or calcified lesions."

Panelists at a media briefing on COMPARE (OCT-FFR) mulled a question implicit in the study's results: what actions could clinicians take based on a determination that a low-risk lesion by FFR may be a high-risk vulnerable plaque by OCT?

Pathologist Renu Virmani, MD, CVPath Institute, Gaithersburg, Maryland, said she would first try to prevent those potential future events "with high-dose statins or an aggressive therapy that would be medical."

Stenting of the TCFA lesions wouldn't currently be appropriate, she said. "As yet, I think there isn't enough data to say go invasively. I would go noninvasively."

Many interventionalists take the view that their patients are well managed after they receive appropriate contemporary care, after "they've quieted things down by a variety of treatments, both PCI and medical therapy," said panelist Ajay J. Kirtane, MD, New York–Presbyterian Hospital and Columbia University Irving Medical Center, New York City.

But studies like COMPARE (OCT-FFR) "suggest that even those patients who are 'quiet' for the time being are not actually quiet," he said. There may be more treatment options for those patients in the future, but for now, he agrees that medical therapy is currently the best approach.

The trial, conducted at 14 centers, included 390 patients with stable angina or acute coronary syndromes (ACS) with nonculprit coronary lesions considered of low risk for causing ischemia by showing an FFR higher than 0.80. There were also 112 such patients with high-risk lesions marked by an FFR of 0.80 or lower. All assessed target lesions were of angiographically intermediate severity, that is, they were 40% to 80% in luminal diameter by core-laboratory readings; they could not be culprit lesions in the patients with ACS.

Those with high-risk lesions by FFR went on to revascularization, and the patients with the low-risk lesions underwent OCT imaging. Of the latter, 98 were fidentified as having TCFA target lesions, and 292 had non-TCFA lesions.

Of those with TCFA lesions, 13.3% showed the primary endpoint, major adverse cardiac events (MACE) associated with the target lesion over 18 months. The corresponding rate was only 3.1% for those without TCFA lesions by OCT. MACE consisted of cardiac death, MI, clinically driven revascularization, or hospitalization due to unstable or worsening angina.

The adjusted hazard ratio (HR) for the primary endpoint, TCFA vs no TCFA, was 4.7 (95% CI, 2.0 – 11; P = .0004).

The study missed its main secondary endpoint, which compared MACE in the patients with target lesions that were low-risk by FFR but featured TCFA by OCT vs those with lesions that were high-risk by FFR and were revascularized (HR, 1.25; 95% CI, 0.28 – 5.6; P = .77). Kedhi said the study was underpowered for the secondary endpoint.

Speaking as a panelist after Kedhi presented the COMPARE (OCT-FFR) results, Virmani seemed charmed that OCT imaging in the study identified high-risk lesions among those considered low-risk by FFR, which wouldn't otherwise be treated. "FFR-negative lesions you're not supposed to touch," she said. "I think it really validates the fact that vulnerable plaque is a reality."

COMBINE (OCT-FFR) was funded by St. Jude Medical, now part of Abbott Vascular. Kedhi discloses consulting and receiving institutional grants from Abbot Vascular and Medtronic. Virmani had no disclosures. Kirtane discloses grant support from or research contracts with Medtronic, Abbott Vascular, Boston Scientific, CSI, Siemens, Philips, and ReCor Medical.

Transcatheter Cardiovascular Therapeutics (TCT) 2020: Late-Breaking Clinical Trial Session 1. COMBINE (OCT–FFR): A Prospective Natural History Study Using OCT Imaging in Patients with Diabetes, presented on October 14, 2020.

Follow Steve Stiles on Twitter: @SteveStiles2. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.

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