Paris – One-year outcomes were significantly worse in patients with acute coronary syndrome whose revascularization was deferred based upon the results of fractional flow reserve than with instantaneous wave-free ratio, in the largest-ever study of patients whose revascularization decision was guided by physiologic measurements obtained via a pressure guidewire.

“The hypothesis that some authors have put forth – that in an ACS the hyperemic response of the myocardium is blunted by the ACS, and that this will affect the FFR hyperemic index – is now strengthened,” Javier Escaned, MD, said in presenting the study results at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

The study was a pooled, patient-level meta-analysis of the 4,529 participants with angiographically determined intermediate-risk stenoses in the previously reported randomized DEFINE FLAIR (N Engl J Med. 2017 May 11;376[19]:1824-34) and iFR SWEDEHEART (N Engl J Med. 2017 May 11;376[19]:1813-23) studies. The primary endpoint was the composite of death, nonfatal MI, or unplanned coronary revascularization within 12 months. And while the analysis brought unwelcome news for proponents of FFR with regard to the subset of patients with ACS, such patients comprised only 17% of the total study population.

Dr. Escaned opted for a glass-half-full approach. Stepping back to look at the big picture, he noted that in the entire population of 2,130 patients with deferred myocardial revascularization, 1-year event rates were low and virtually identical in the two study arms: 4.12% with iFR and 4.05% with FFR.

“I think that overall these results are very reassuring. The big finding is that we have dramatically improved the safety of deferral of revascularization using pressure guidewires. If you look at the MACE [major adverse cardiovascular event] rate in the deferred ACS group, it was about 6%, which is much less than the event rate at 1 year with deferral in patients with stable coronary disease in the pivotal DEFER trial [Circulation. 2001 Jun 19;103(24):2928-34], which was our former standard,” observed Dr. Escaned, an interventional cardiologist at San Carlos Hospital in Madrid and a DEFER coinvestigator.

He attributed these greatly improved outcomes of physiologically guided revascularization during the past 15 years to vastly improved stent technology and more effective optimal medical management.

Among the key findings of the combined analysis of DEFINE FLAIR and iFR SWEDEHEART:

• More patients were deferred from PCI when iFR was used for decision-making: 50%, compared with 45% in the FFR arm. Yet 1-year outcomes were as good in the deferred iFR group as in the FFR group overall, and better than with FFR in the deferred ACS patients.

• Event rates were significantly higher in deferred ACS patients overall than in deferred patients with stable coronary disease: 5.9% versus 3.6%. But the deferral tool made a difference: When iFR was utilized, the 1-year event rate was 5.4% in deferred ACS patients, not significantly different from the 3.8% rate in deferred patients with stable coronary disease. In contrast, the event rate in ACS patients with FFR-based deferral was 6.4%, significantly higher than the 3.4% rate in FFR-deferred patients with stable coronary disease.

Dr. Escaned noted that this finding is consistent with the cautionary results of several recent studies, including one, albeit tenfold smaller, in which ACS patients in whom revascularization was deferred based on FFR had a 25% rate of major adverse cardiovascular events at 3.4 years, compared with a 12% rate in patients with stable coronary disease (J Am Coll Cardiol. 2016 Sep 13;68[11]:1181-91).

Discussant Peter Jüni, MD, professor of medicine at the University of Toronto, said “the main results of your study show in a completely waterproof fashion that there is no signal of harm with the experimental strategy” of deferred revascularization based on physiologic measurements, at least in patients with stable ischemic coronary disease.

The results, however, also raise the question of whether physiology-based revascularization decision-making in ACS patients is the best strategy.

“Considering that the event rate in the deferred ACS group was nearly twice as high compared with stable patients, my question to you is: Should we ignore any functional testing in ACS patients and just say, ‘Let’s move forward with revascularization because this clinical presentation is a very good clinical characteristic for risk stratification?’ ”

Dr. Escaned rejected that option. He noted that both the European and U.S. guidelines now state that it’s inappropriate to base a revascularization decision solely on a coronary vessel’s angiographic appearance, because that has been shown to result in unnecessary treatment, which causes harm. Adoption of pressure guidewires to assist in revascularization decision making, whether by FFR or iFR, is still limited in interventional cardiology. The priority in the field now should be to encourage more widespread use of this technology, regardless of which method is selected, he argued.

“The biggest room in the world is the room for improvement,” the cardiologist mused.

“I think one of the real problems that’s impeding adoption of physiologic testing is that many physicians are still afraid of leaving a stenosis without treatment,” he continued. “It’s strange: If you perform angioplasty and it wasn’t indicated and there is a complication, physicians seem to have some type of peace of mind that they did their best and they were trying to help the patient. That’s why it’s so important to establish that deferring revascularization – not treating when it is not needed – is safe.”

The DEFINE FLAIR and iFR SWEDEHEART studies were funded by unrestricted grants from Philips Volcano. Dr. Escaned reported serving as a consultant to Abbott, AstraZeneca, Biosensors, Boston Scientific, Medtronic, OrbusNeich, and Philips Healthcare.

bjancin@frontlinemedcom.com

FFR stumbles in revascularization deferral decisions for ACS