The Take Home: EuroPCR

 

Morton J. Kern, MD

The FAME II data presented at EuroPCR found that with fractional flow reserve-guided PCI, patients were seven times less likely to be hospitalized and 11 times less likely to be hospitalized and need urgent revascularization compared with optimal medical therapy alone. There were a couple of reasons the study was stopped: The safety committee thought it was unethical to continue with so many patients being hospitalized for developing acute unstable coronary syndromes, and they were not prepared to wait for death or MI to be an endpoint to stop trial enrollment. The trial will continue and patients will be followed over the course of the next several years so that perhaps some death and MI endpoints will be achieved.

 

Morton J. Kern

I believe the data support the treatment of ischemia through revascularization as compared with medical therapy alone. This is different from the COURAGE trial, which examined patients without demonstrated ischemia, and of course, PCI in that group is of no benefit. This is what the FAME I trial showed, that if you randomly assign patients to ischemia-directed PCI or all-comer angiographic-guided PCI, the ischemia-guided PCI does better with fewer deaths and MI at 2 years.

It is also important to note how challenging FAME II was to complete. The reason for this was that it’s difficult for US physicians to have participated in this trial because they don’t believe in managing medically patients who have significantly abnormal FFR across stenoses, so it took a great deal of willpower to leave those patients on maximum medical therapy to see how they did. Some did OK, but many did not. There were a lot of return visits from that group.

Overall, FAME II was a well-done trial that was a very positive step forward in our understanding of how to treat coronary disease: The study design was good, it had substantial numbers and the outcomes will be soon to follow. I know many were disappointed in that they wanted more harder endpoints, like deaths or MI, but I don’t think that is a reasonable expectation.

ADVISE

Results from the ADVISE Registry were also presented, which further evaluated instantaneous wave-free ratio (iFR; Volcano Corp.), the adenosine-free index of lesion assessment. The data demonstrated that iFR had pretty good correlation to FFR. When compared with FFR for the same lesion distribution, iFR functionality showed 94% relative diagnostic accuracy.

The results of this trial counter those found in the VERIFY Registry, which were presented in March at the American College of Cardiology Scientific Sessions. The VERIFY Registry was a comparison of the data obtained from a group in England and Holland that used what was described in the methods portion of ADVISE, but they could not duplicate the results. Part of the reason was that the methods were slightly different, so there is still work to be done to validate iFR. If iFR turns out to be good, that would be good for everyone because it would be easier to use than FFR. If it turns out that it’s not quite as good, we will look for other indices that may be equal to or better than FFR, along with easier and simpler to use. However, FFR is quite straightforward and well-developed at this time.

Disclosure: Dr. Kern was a member of the clinical events committee for the FAME II trial; he is also a consultant for St. Jude Medical and Volcano Corp.

Alexandre Abizaid, MD

COMFORTABLE AMI

COMFORTABLE AMI, one of the late-breaking trials presented at EuroPCR, was a very important trial because acute MI is an anatomical, clinical situation in which bare-metal stents still play an important role; despite the evidence that drug-eluting stents are superior because of less target lesion revascularization, 50% of the patients worldwide will still receive a BMS.

 

Alexandre Abizaid

The BioMatrix stent (Biosensors International) was one of the first platforms tested that uses a bioabsorbable polymer; the stent releases biolimus, which goes away in roughly the first 40 days, and the polymer in 6 to 9 months. They designed the COMFORTABLE AMI study to test this device in more than 1,000 patients with STEMI. Patients were randomly assigned the BioMatrix stent vs. BMS, and, in terms of major cardiac events (a composite of cardiac death, target vessel re-infarction and ischemia-driven target lesion revascularization), there was a clear advantage for the BioMatrix stent, with an overall RR reduction of 51%.

In some indications, the use of DES are still questionable. With newer-generation platforms, I am more convinced that if you change the polymer technology to be fully bioabsorbable or polymer-free, you are going to have safer devices.

Bioabsorbable Stents

In terms of DES and BMS vs. fully bioabsorbable stents, the new data are supporting the fully bioabsorbable platform. One of the most promising is Elixir Medical’s DESolve bioresorbable coronary scaffold, which combines a PLLA-based scaffold coated with a matrix of bioresorbable polylactide-based polymer along with the drug myolimus. In fact, first-in-man results from the DESolve trial, which evaluated the device, were presented at this meeting and demonstrated excellent safety and effectiveness. Although there are other contenders in this market, including the Absorb (Abbott) and ReZolve (REVA Medical) bioabsorbable stents, the DESolve stent with its interesting properties is a little different than what we see from other companies.

TAVR Maturation

Another very promising technology discussed at this meeting was the Acurate aortic valve replacement system (Symetis). I presented the first-in-man cases in which we implanted the device using the transfemoral approach; there is a great deal of experience, along with CE mark approval, for the transapical approach. The Acurate device is an interesting hybrid design because it is a nitinol self-expanding stent but has a self-centering mechanism in which you first release three stabilization arches to center it. This is important because we deal with different anatomies — sometimes very diseased, complex aortas — so this centering device helps to better position the valve, centralize and make it stable, so when you deploy, dislodgement is less likely to happen and you have a more predictable result. It also has a small skirt with the same pericardium that you suture the valve with and that skirt is an important feature that may help to avoid paravalvular leak and insufficiency. We are now entering the era of a new generation of valves that will perhaps make the procedure safer and more predictable.

So my take-home message on TAVR from EuroPCR is that it is getting to a more mature phase. At this meeting we saw different devices coming up, and we are getting close to expanding the indication. We started with inoperable patients, but now with more data coming, we are moving toward less sick patients.

Embolic Protection

Other important data from the meeting involved the introduction of interesting solutions for embolic protection. For instance, the Claret CE Pro (Claret Medical) device is the one that is currently most advanced. In the first-in-man study presented here, the device was placed via the right radial or brachial artery prior to TAVR in 40 patients and removed after the procedure. Technical success rate with delivery of the proximal and distal filter was 60% for the first-generation device and 87% for the second-generation device. There were no procedural transient ischemic attacks or minor or major strokes reported, and at 30 days, one minor stroke and two major strokes occurred.

Now that the device has been shown to be feasible, they are moving ahead and designing bigger studies, including pre- and post-MRI.

Disclosure: Dr. Abizaid’s hospital has received research grants for each study he participates in, including those evaluating the Absorb, Elixir and ReZolve stents, as well as the Acurate and Claret CE Pro devices.