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Better Outcomes for Stents When Fractional Flow Reserve (FFR) is Used
Measuring Intracoronary Pressures Reduces Major Cardiac Events by 28% in FAME Study, Published in the New England Journal of Medicine

January 15, 2009 -- Published in today's New England Journal of Medicine, are the results of the FAME study (Fractional Flow Reserve vs. Angiography for Multivessel Evaluation). The study concludes that:

"Routine measurement of FFR in patients with multivessel coronary artery disease who are undergoing PCI with drug-eluting stents significantly reduces the rate of the composite end point of death, nonfatal myocardial infarction, and repeat revascularization at 1 year."

Conducted in 20 European and U.S. centers, FAME randomized over a thousand patients with multivessel coronary artery disease for treatment with angioplasty and drug-eluting stents into two groups. In the control group, standard angiography and previously performed stress or other tests were used to determine which lesions (blockages) needed stenting. This is the norm in most cath labs today: cardiologists look at a blockage, determine its size or severity and, if it is judged "significant", it is opened by a balloon and stented.

The second group relied on a measurement called Fractional Flow Reserve or FFR, in which a tiny wire with a sensor is threaded to the blockage, and the blood flow is measured on both ends of the narrowing to determine if the lesion is restricting blood flow to the heart, and causing ischemia -- a high risk factor for poor outcomes. In this group only lesions that measured 80% of normal blood flow or less were stented, no matter what the visually-oriented angiogram showed.

The result was that one-third fewer stents were used in the FFR group and the difference in outcomes at one year were significant: the FFR group showed a 28% lower incidence of major adverse cardiac events (repeat procedure to open the artery, heart attack or death) -- 18.3% vs. 13.2%. The implication in these results is that placing stents in lesions that are not responsible for ischemia is not only not necessary, but may cause worse outcomes.

Nico H.J. Pijls, MD, PhD
Nico H. J. Pijls, MD, PhD
Professor of Cardiology
Catharina Hospital
Eindhoven, The Netherlands

Co-principal investigator, Dr. Nico Pijls, told Angioplasty.Org that the study is about refining the procedure of stent placement (PCI) to make it more accurate, safer and cost-effective, while providing better patient outcomes, and he cautioned against misinterpreting the results as being "anti-stent". He stated:

"Patients should not be disquieted or scared and they should not lose their trust in interventional cardiology...stenting in itself is a very good procedure, but by this new technique, we can best define where we have to place the stent in the best possible way. So it's not a matter of stenting or not stenting. But it is a matter of placing the right stent in the right the end, 94% of all patients were stented, but they had less stents. They were stented in a more refined way."

Dr. Pijls explained the outcomes further. A non-ischemic lesion may have a 1% chance of causing a heart attack, whereas an ischemic lesion may carry a 5-10% risk. It is known that placement of a stent results in a 3% risk, so stents are good for reducing risk in severe lesions, but actually can increase the risk if used in areas where they are not necessary.

Another benefit seen in the FFR group was procedural cost. Since less stents were used per patient, the average cost of the procedure was $700 lower (this includes the specialized guide wire used to measure FFR). Less stents also meant approximately 10% less contrast dye. The procedural time was virtually the same for both groups.

Dr. Pijls initially presented the FAME results at last fall's TCT meeting in Washington. Today's publication in the peer-reviewed NEJM is titled "Fractional Flow Reserve versus Angiography for Guiding Percutaneous Coronary Intervention", and is accompanied by an editorial, authored by Dr. Steve Ellis of the Cleveland Clinic, which asked several questions about how stenting in the angiography only group was determined, the use of pharmacologic agents during the procedures and the rate of periprocedural MI. Dr. Pijls responded to those questions in his exclusive interview with Angioplasty.Org:

"The decision-making on what to stent was made in a classical traditional clinical way. We used the clinical data, the results of noninvasive testing, if they were available, the angiogram, and we only included a particular stenosis in the study if it was more than 50% and in a major coronary artery.... So our selection of patients was completely according to normal routine. That was the purpose of the study: that it reflect the normal routine.

"...the rate of peri-procedural myocardial infarction...was actually 3.4% in the angio group and 2.4% in the FFR group. So it was not higher than in the other studies. And in the FAME study, we had a lot of severe disease with an average of three vessels which were stenotic. We also had patients with very low ejection fractions, patients with acute coronary syndrome -- that was 30% of the population -- we had patients with previous PCI, so we had a population typical of the every day population we see in the cath lab. During the procedure, we used also used thiopyridines, or Plavix: a loading dose of 600mg was used in all patients and IIb/IIIa inhibitors were used in 31% of the patients, which is also the average."

Dr. Ellis' editorial concluded with a thought that "perhaps the research question addressed in the trial was itself something of a 'straw man,' since FFR does not have to be used on all or none of the stenoses that might be treated but rather can be used selectively". Dr. Pijls took issue with that observation, saying, "We have known already for years that we could use FFR in some lesions; the purpose of this study was just to show that it made sense to use it routinely."

Whether or not FFR will start being used routinely as a result of the FAME study is yet to be seen -- it is estimated that only 5% of procedures done in the U.S. use this technology. As for stents, some believe the results of the FAME study will mean less stents will be used. Dr. Pijls feels differently:

"I think that per patient, less stents would be used. But more patients will qualify for PCI – because you have a treatment, and let’s say that you can decrease the risk of the treatment by 30% -- so the threshold to apply that treatment will become lower. What I believe is that you can do it better, by less stents per patient. And because you do it better, there are more patients, either from medical therapy who were previously treated only medically, or patients who need surgery at the moment -- all those patients can also be helped by PCI. So I think that in the end, the number of stents used will be the same, but they will be redistributed."

The FAME study was supported by Radi Systems, a privately-held Swedish company which manufactures an FFR wire. Radi was acquired only three weeks ago by St. Jude Medical. Volcano Corporation also manufactures an FFR wire, along with a number of other intravascular devices, such as IVUS, OCT, etc. It may be that these various intravascular imaging, measuring and treatment devices will have a role in changing and refining the practice of interventional cardiology in the future.


Reported by Burt Cohen, January 15, 2009