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Among patients with stable coronary artery disease and fractional flow reserve (FFR)-confirmed stenoses -- defined as FFR of 0.80 or less -- stenting plus optimal medical therapy may be preferable to optimal medical therapy alone.

A comparison of the two treatment options -- FFR-guided percutaneous coronary intervention (PCI) versus optimal medical therapy -- revealed a significant difference in the need for urgent revascularization: 49 patients in the medical therapy arm versus seven in the stent group, according to a paper published online Tuesday by the New England Journal of Medicine.

There was no difference in death or MI, but a difference in the rate of urgent revascularization, 0.7% versus 9.5%, (HR 0.07; 95% CI 0.02 to 0.22, P<0.001) prompted a premature halt to the trial with just 888 patients enrolled and only 7 months of follow-up, Bernard De Bruyne, MD, of the Cardiovascular Center Aalst, Once-Lieve-Vrouw Clinic in Aalst, Belgium, and colleagues reported.

At that time, 447 patients were randomized to PCI. Most patients were in their early 60s and roughly three-fourths were men.

The trial was powered to detect a 30% relative risk reduction in the primary endpoint, a composite of urgent revascularization, MI, or death, which would have 816 patients in each group, followed for 24 months.

The findings, which emerged from the Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2 (FAME 2) study were simultaneously reported at the European Society of Cardiology meeting in Munich.

All patients had angiographically confirmed CAD and stenosis of 0.80 or less measured with coronary guidewire (Pressure Wire Certus or PressureWire Aeris, St. Jude Medical).

All patients received medical therapy consisting of aspirin, beta-blocker or beta-blocker combined with calcium channel blocker or nitrate, ACE inhibitor or angiotensin receptor blocker, statin, or statin plus ezetimibe.

De Bruyne and colleagues concluded that in patients with "stable coronary artery disease and at least one stenosis with an FFR of 0.80 or less, FFR-guided PCI with drug-eluting stents plus best medical therapy, as compared with best available medical therapy alone, decreased the rate of urgent revascularization."

But, they added, "the best available medical therapy alone resulted in an excellent outcome, regardless of the angiographic appearance of stenoses."

William E. Boden, MD, principal investigator of the COURAGE trial, which concluded that PCI was not superior to optimal medical therapy for treatment of stable coronary artery disease, found FAME 2 not quite so straightforward.

He noted that in "a nonblinded trial, as compared with a blinded trial -- even with concealed randomization -- there is concern that investigators may have had a lower threshold for recommending revascularization for a patient in the medical therapy group who had recurrent angina rather than attempting to continue managing the symptoms with aggressive medical measures."

Also, Boden noted, because ischemia was not confirmed with noninvasive tests, there was no objective confirmation of true damage to heart muscle, thus "it is possible that some patients had preserved myocardial perfusion, either through autoregulation of the arteriolar bed or enhanced collateral flow."

Robert Bonow, MD, professor of cardiology at Northwestern University's Feinberg School of Medicine in Chicago, told 乌鸦传媒, that he, too, had some reservations about the clinical implications of FAME 2.

"Why were these patients in the cath lab in the first place? It seems that there may have been a bias from the outset, and it doesn't appear that there was any noninvasive testing," he said.

Bonow agreed that FFR provided a useful technology, but he said that it is not commonly used today and he expected it would add additional cost.

The authors noted a number of limitations including the brief length of foll0w-up, which was "too short to see restenosis emerge as a complication of PCI. Additionally, "the best available medical therapy did not include interventions by nurse case managers that were aimed at lifestyle changes and risk-factor reduction, interventions that were included as part of the best available medical therapy in the COURAGE trial."

Boden said that an ongoing study -- the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) -- is likely to provide the best evidence about the relative merits of PCI and optimal medical therapy.

He noted that he is a principal investigator for ISCHEMIA, a trial that he said is "powered to evaluate the long-term superiority of revascularization plus the best available medical therapy as compared with the best available medical therapy alone with respect to cardiovascular death or myocardial infarction in patients with stable coronary disease and moderate-to-severe myocardial ischemia documented by means of noninvasive measures."

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