This article is more than 5 years old. Information may no longer be current.
The Take Home: ESC
Click Here to Manage Email Alerts
In late August/early September, the annual European Society of Cardiology Congress was held in Barcelona, Spain, attracting more than 30,000 attendees. During the 5-day meeting, 4,597 abstracts were presented, including 27 Hot Line presentations and 15 clinical trial updates.
Cardiology Today’s Intervention staff were onsite and interviewed several experts on the data presented. Among them were Chief Medical Editor Deepak L. Bhatt, MD, MPH, of Harvard Medical School, Boston; Editorial Board member Anthony A. Bavry, MD, MPH, with the University of Florida College of Medicine; Cardiology Today Editorial Board members W. Douglas Weaver, MD, American College of Cardiology Past-President with Henry Ford Health System, Detroit; and Kim Allan Williams, MD, President-Elect of the American College of Cardiology with Rush University School of Medicine, Chicago; Heinz Drexel, MD, ESC spokesman with VIVIT Research Institute, Freiburg, Austria; Dipti Itchhaporia, MD, FACC, ACC Board of Governors Past Chair from Hoag Memorial Hospital Presbyterian, Newport Beach, Calif.; Sanjit Jolly, MD, MSc, with McMaster University, Hamilton, Ontario, Canada; and Bernard De Bruyne, MD, PhD, of the Cardiovascular Center Aalst, Onze Lieve Vrouw Ziekenhuis, Aalst, Belgium.
ATLANTIC
Bhatt: In the ATLANTIC trial, investigators examined patients with STEMI undergoing primary PCI who were randomly assigned to pretreatment with ticagrelor (Brilinta, AstraZeneca; n=906) — in the ambulance — or getting the drug in the cath lab (n=952). The overall co-primary endpoints of the study were surrogate endpoints, such as TIMI flow grade 3 and pre-PCI profusion, and there was no difference in those endpoints or in MACE. But in the secondary endpoint of 30-day definite stent thrombosis, a significant reduction was observed with ticagrelor pretreatment (0.2% vs. 1.2%; OR=0.19; P=.02). Purists will say that the trial was negative, but in my opinion the fact that pretreatment with ticagrelor reduces definite stent thrombosis and was not associated with increased bleeding is a positive. Added to which, from a cost perspective, there really is no difference between giving ticagrelor upstream or in the cath lab, assuming you’re going to be using ticagrelor. But of course if one isn’t going to use ticagrelor but rather clopidogrel, there are potential cost implications; but here if one has made the decision to use ticagrelor, it’s just a matter of when it’s given. So I think these are results that could have impact on practice, even in the United States. Of course, we’re not quite as set up as the Europeans are in delivering therapies in the ambulance. Nevertheless, what I’m going to extrapolate from these results is that it’s good to deliver ticagrelor as early as possible.
W. Douglas Weaver
Weaver: Although the ATLANTIC trial did not find a difference with the co-primary endpoints, the investigators did make one interesting observation: The rate of stent thrombosis was lower in patients who received ticagrelor early, in the pre-hospital setting, compared with those who received it in the cath lab. The study was not large enough to confirm whether this will have clinical importance, but we do know that stent thrombosis is a major problem that potentially leads to another MI or death, so this is an important observation. The investigators also showed that ticagrelor pretreatment is safe and doesn’t result in any extra bleeding or complications.
Image: Brian Ellis
I think the first take away from this study is that if you can give the drug sooner, you probably should. Second, I wouldn’t be surprised if they do a larger study to show that earlier administration of ticagrelor (before the cath lab) could make a big clinical difference.
CvLPRIT
Bhatt: In the CvLPRIT trial, researchers randomly assigned patients with STEMI undergoing PCI to either culprit lesion-only stenting (n=146) or to culprit lesion plus non-culprit lesion stenting during that index hospital stay (n=150). In addition, the majority of patients were treated during the index procedure itself and the remainder were treated in the index hospitalization. The study found that, overall, there was a significant reduction in 1-year MACE favoring complete revascularization (10% vs. 21.2%; HR=0.45; P=.009), supporting what a lot of us believe: When a patient comes in with STEMI, stent the culprit lesion, but stenting the non-culprit vessels is also helpful. There is still the question of what is the optimal timing. In other words, should it all be done during the index procedure or, as the trial investigators did, should it be left to the physician’s discretion? The ongoing, larger COMPLETE trial is being conducted by the McMaster University group and should help answer some of the remaining questions. Nevertheless, the two trials — PRAMI and CvLPRIT — taken in concert do support what many of us feel is optimal therapy for the STEMI patient.
FAME II
Anthony A. Bavry
Bavry: In this new analysis of the FAME II trial, investigators looked at the 2-year outcomes of fractional flow reserve-guided PCI with new-generation drug-eluting stents plus medical therapy (n=447) or medical therapy alone (n=441) in patients with stable CAD. What they found was that the primary composite endpoint — all-cause death, nonfatal MI or urgent revascularization — was significantly lower in patients in the FFR-guided PCI cohort (8.1% vs. 19.5%; HR=0.39; P<.001), which was driven primarily by the lower rate of urgent revascularization in the PCI group (4% vs. 16.3%; HR=0.23; P<.001).These results are good and even stronger than what was initially reported at 7 months. They performed a landmark analysis of death or MI from 8 days to 2 years and found a statistically significant reduction in the FFR-guided PCI group (4.6% vs. 8%; P=.04), which was surprising. It’s important to note that there was an early hazard — an increased risk for death or MI from day 0 to day 7 — from PCI, likely due to periprocedural MI.
In terms of the use of FFR, it appears to be increasing in the United States and abroad, but it is still less than what might be considered a “sweet spot.” There still might be a bias to stent a lesion rather than interrogate it, knowing that after interrogating it, you might have to leave it alone and medically treat the lesion, but that’s OK if it’s the right thing for the patient.
Deepak L. Bhatt, MD, MPH
Bhatt: What this new analysis of the FAME II trial shows is that when a landmark analysis is done after a week, there is a significant reduction afterward in death or MI favoring the FFR-guided PCI approach. This is, of course, a message that interventionalists want to hear and believe, and there are some intuitive aspects of it that reflect what I believe. However, in the context of a trial where the primary endpoint was positive, but death or MI overall was insignificantly reduced, you do need to interpret it with a little bit of caution. But it does seem to make sense — perform a procedure and there’s an early hazard, but if you survive that early hazard there’s a benefit, including on hard endpoints. So obviously the larger ongoing ISCHEMIA trial will take a much bigger look at whether patients with stable CAD will have reductions in death or MI with stenting, but FAME II does give us an early signal that it might indeed be the case.
FAMOUS NSTEMI
De Bruyne: The FAMOUS NSTEMI trial was a UK trial that included 350 patients with non-STEMI who were randomly assigned to either an FFR-guided invasive strategy (n=176) or an angiography-guided strategy (n=174). What they found, in a nutshell, is that clinical outcomes of both arms of the trial were very similar, but the use of resources was significantly less in the FFR-guided arm, with a higher rate of the primary endpoint — adoption of optimal medical therapy alone after randomization in the cath lab (22.7% vs. 13.2%; P=.022). It’s quite impressive that they measured FFR in all lesions, not just the culprit lesion, and that their success rate of measuring FFR was 100%. By itself, this is an achievement. The second thing is this is probably the first trial that really looked at the value of FFR in non-stable patients, in this case non-STEMI patients, which is key.
Bernard De Bruyne
However, there are a few things that are important and might be considered caveats. The first is that the trial was not powered for clinical outcomes, so we have to be very prudent when discussing the clinical outcomes in this trial. Second, these were non-STEMI patients, so these findings don’t necessarily apply to more acute patients like those with STEMI. Third, many of these patients with STEMI were catheterized only after the second or third day after the last angina or chest pain episode, so these were patients with clinically diagnosed STEMI, but probably very well “cooled off.” This being said, it’s an important trial because it’s the first investigating the value of FFR in acute patients and showed very interesting results, namely similar outcome for a smaller usage of resources.
Itchhaporia: The question most of us have is whether FFR is feasible and reliable in non-STEMI patients. We know that in STEMI, it is difficult to get the vasodilation and measure an accurate FFR. It was an interesting observation in FAMOUS NSTEMI that FFR was feasible and safe in patients with non-STEMI. In some ways it’s also provocative because if you do an FFR, you may also be able to avoid doing some other noninvasive study to risk stratify these patients. This may offset the cost of doing FFR, which is the other issue. If you do an FFR on every patient that comes in with a non-STEMI, how much would you save? There is also the possibility that if you do FFR and decide to defer the intervention, some patients will later have acute MI. Are you are still then saving money by not putting the stent in? So that is going to be a hard sell, especially when patients could become unstable. There is going to have to be really good data to justify that decision in a medical/legal environment. My sense is most interventionalists are not going to change their practice habits based on this study.
TASTE
Jolly: The registry-based TASTE randomized trial showed that at 1 year, there was no difference in mortality between thrombectomy (n=3,621) and no thrombectomy (n=3,623; thrombectomy, 5.3% vs. PCI only, 5.6%; HR=0.94; P=.57). I think people were expecting that there would be a difference at 1 year despite no difference at 30 days, and that the benefit of thrombectomy would increase over time. Unlike a drug therapy that’s ongoing, for example ticagrelor, thrombectomy is a one-time intervention. The major challenge with TASTE is that it had much fewer events than planned, and was really only powered for a 50% reduction in mortality. Going out to 1 year doesn’t fix that, necessarily. The earlier events are likely to be the most responsive to the intervention of thrombectomy. At late events, between 6 months and 1 year, people die for all sorts of reasons.
Sanjit Jolly
The trial certainly confirms that there is not an effect size of a 50% reduction in mortality with thrombectomy. What we don’t know is whether there are more modest reductions, like 20%. We hope that the TOTAL trial, a large, randomized study that recently completed recruitment of nearly 11,000 patients, will help answer that. I don’t think the 1-year results of TASTE are going to have any more impact on clinical practice than the initial 30-day results did. Clinicians have become less dogmatic about the use of thrombectomy and are now using it selectively in patients with large thrombus to optimize their angiographic results.
Kim Allan Williams, MD
Williams: The TASTE trial represents a new way of doing research that is completely different than what we’ve done in the past. The ability to glean data from a registry and have a randomized trial that is done, in a way, retrospectively and prospectively at the same time is fantastic and represents a big change in our capabilities.
This trial also helps inform us of something we probably shouldn’t be doing: routine thrombus aspiration. Going forward, we need to look at the issues of how thrombus aspiration is done and what the timing of it is, and find out whether there is a way to perform the procedure that is less traumatic to the vasculature. However, it may be that the most important thing to do, instead, is focus on making sure patients are receiving proper antiplatelet and anticoagulant therapy.
BIOSCIENCE
Itchhaporia: The noninferiority BIOSCIENCE trial looked at 12-month results of an ultrathin strut biodegradable sirolimus-eluting stent (Orsiro, Biotronik; n=1,063) vs. a durable polymer everolimus-eluting stent (Xience Prime/Xpedition, Abbott Vascular; n=1,056) in patients with chronic stable CAD or ACS. Researchers found no difference in the primary endpoint of target lesion failure or the rate of definite stent thrombosis. This study is provocative but certainly requires further study so that we can know if this is really the new-generation stent that we’d like it to be. The advantages are that this is the first time that an ultrathin biodegradable stent has been used. Previous biodegradable stents were much thicker.
For me, the issue with this study is that the follow-up period was only 12 months and the polymer doesn’t degrade until 12 to 24 months, so we need a longer study period to really know about efficacy. The other issue was that in this study, the biodegradable stent was smaller than the durable polymer stent, so we’re not really having an apples-to-apples comparison. However, this will require further study in STEMI patients as well as patients in general to see if this is our newer-generation stent.
RDN of Accessory Arteries
Drexel: This year we had the disappointing results of the SYMPLICITY HTN-3 trial that showed patients with resistant hypertension did not experience a significant BP reduction with renal denervation (RDN; Symplicity, Medtronic) compared with a sham procedure. Some of us thought this was the end for RDN. Now at ESC Congress, we have heard that better selection of patients and considering denervating accessory renal arteries may make a difference in outcomes. In the study, researchers enrolled patients with resistant hypertension (n=110) who had a mean baseline 24-hour ambulatory BP of 154 ± 10 /85 ± 9 mm Hg and mean office BP of 165 ± 15/85 ± 11 mm Hg. Patients with a complete renal denervation procedure had their office BPs decrease from around 171 mm Hg to 159 mm Hg, whereas patients with accessory renal arteries not completely ablated had BPs remaining similar to the levels documented at baseline (173 ± 25 to 170 ± 20 mm Hg). This makes sense because if you only destroy the nerves in one renal artery, the others would compensate for that and increase pressure by different mechanisms.
So, the statement of the moment should be that there is hope for RDN but no proof. One of the criticisms of SYMPLICITY HTN-3 was that the patient selection was not good. As we discussed here, this must be better and involve patients who are truly resistant. And second, you must look to do more with drugs than what was done in SYMPLICITY HTN-3. If the drugs work, that is enough and RDN should not be performed.