Shelley Wood

May 15, 2012

May 15, 2012 (Paris, France) — Patients with stable coronary artery disease (CAD) in whom fractional flow reserve (FFR) identifies at least one "hemodynamically significant" stenosis face more than a 10-times-higher risk of urgent revascularization if they are initially treated with optimal medical therapy (OMT) rather than PCI. That difference in urgent revascularizations was what led to the premature halting of FAME II last fall.

The new findings should help physicians single out which stable CAD patients will, in fact, do better with PCI than OMT and vice versa, Dr Bernard De Bruyne (OLV Clinic, Aalst, Belgium) told the press prior to his late-breaking clinical-trials session presentation here at EuroPCR 2012.

De Bruyne emphasized that the data set is preliminary: the primary end point of the study was a composite of death, MI, and urgent revascularization, and those results have not yet been calculated.

He also stressed that the FAME II results are not "anti-COURAGE," referring to the blockbuster trial of 2007 showing no benefit to PCI over OMT in patients with stable CAD.

"This should be considered as a complement to, an extension of COURAGE."

A Rise to FAME

Before its halt, FAME II had randomized 1219 patients found on FFR to have hemodynamically relevant disease (and were scheduled for one-, two-, or three-vessel stenting), and another 166 patients were included in a separate registry, FFR having failed to detect important stenosis. Of these, De Bruyne's presentation today included a total of 822 patients who had at least one stenosis associated with an FFR <0.80 and were randomized 1:1 to either OMT or OMT plus PCI and 131 from the registry cohort who received OMT alone. After one year, the rate of urgent revascularization among OMT-treated patients with no hemodynamically significant disease was nearly identical to the low rate of urgent revascularizations among patients found to have hemodynamically relevant disease and who were randomized to PCI, at approximately 0.6%. But by contrast, patients who had hemodynamically significant disease on FFR who were randomized to OMT had urgent revascularization rates of 6% at follow-up, a statistically significant difference compared with rates in PCI-treated patients (HR 11.2, log-rank p<0.0001).

Rates of any revascularization showed an even more striking difference between the randomized groups, at 12.1% vs 1.7% (HR 7.63, log-rank p<0.0001).

"In this preliminary data set of the FAME II trial, in patients with stable CAD and at least one hemodynamically significant stenosis (FFR<0.80) in at least one major epicardial artery, OMT alone was associated with a significantly larger number of urgent revascularizations than FFR-guided PCI plus OMT," De Bruyne said. By contrast, "in patients with stable CAD without invasively documented ischemia-inducing lesions (FFR>0.80) OMT alone was associated with a very favorable clinical outcome."

Setting FAME II and COURAGE Apart

Anticipating the response this will elicit from interventionalists who have long maintained that PCI still has a role to play in stable CAD patients, De Bruyne cautioned that the randomized patients in FAME II were "very different" from the COURAGE cohort. For one, they were selected on the basis of FFR-proven hemodynamically significant lesions, rather than simply a "strong suspicion of ischemia" based on noninvasive data. Second, PCI was performed according to FFR-guidance, rather than a blanket approach of "quick-and dirty" PCI or balloon inflation. Third, all patients were treated with drug-eluting stents (DES) in FAME II (less than 3% of PCI-treated patients in COURAGE received DES).

Lastly, De Bruyne reminded reporters, "We are actually almost 20 years later than the [time] when COURAGE was conceived."

As for its everyday role in cath labs, FFR use during PCI "varies dramatically" from country to country, De Bruyne told heartwire --as low as 5% to 8% worldwide, he estimated. But PCI patients are not actually the appropriate denominator, he explained, since FFR is increasingly being used during the diagnostic angiography to determine which patients should not proceed to stenting at all.

"If [the angiogram] is perfectly normal, no need for FFR," he explained. "If you have a patient with typical symptoms and one critical lesion on the angiogram, corresponding to the ECG, again, no need for FFR. But for all the others--and there are very often one or two lesions for which you don't know what to do--then for these lesions FFR might be helpful, and it might change the approach to the patient with CAD or suspected CAD, which means these patients might actually take a shortcut to the lab, bypassing all of the noninvasive stuff."

Following De Bruyne's presentation today, Dr David Holmes (Mayo Clinic, Rochester, MN) called the study a "terribly important" and "groundbreaking" trial.

"This extends observations that we have already made and reminds us we should be treating ischemia, not lesions," Holmes said.

He did have questions about the degree of OMT in the study, which, if suboptimal, could partly explain the results.

But providing some numbers, De Bruyne noted that over 86% of patients received beta blockers, 90% received ACE inhibitors, and 93% received statins. "So I have no concerns about [suboptimal OMT]," De Bruyne said.

Dr Ron Waksman (Washington Hospital, DC) raised another concern about the study, pointing out that neither patients nor physicians were blinded to treatment randomization. "The thing we tend to forget is that we are not only dealing with repeat revascularizations, we are also dealing with relieving symptoms. If you want your angina to go away tomorrow, rather than in three months with OMT, you will ask for a stent," Waksman said.

In response, De Bruyne said he agreed with Waksman's point, "but this is exactly why we made the distinction between urgent and nonurgent revascularization." Urgent-revascularization events were stringently reviewed by a clinical event committee, he explained, and typically involved a patient presenting to the emergency room with severe symptoms, being hospitalized, and receiving PCI within that same hospitalization.

De Bruyne disclosed receiving research contract and consulting payments from St Jude Medical, which sponsored FAME II.

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