The Take Home: ESC Congress 2012

Issue: November/December 2012

In August, nearly 28,000 participants from 140 countries congregated in Munich for the European Society of Cardiology Congress, making it once again the largest meeting in cardiology.

Cardiology Today Intervention was on-site and spoke with several experts during the meeting, who each provided their take on some of the most talked about trials presented. Among them were Cardiology Today Intervention Chief Medical Editor Deepak L. Bhatt, MD, MPH, with Harvard Medical School; Associate Medical Editor Roxana Mehran, MD, with Mount Sinai Medical Center, New York; Editorial Board members Anthony A. Bavry, MD, MPH, with the University of Florida, Gainesville, and Kenneth Rosenfield, MD, with Massachusetts General Hospital, Boston; SCAI spokesman Ajay Kirtane, MD, SM, with Columbia University/New York-Presbyterian Hospital, New York; and European Society of Cardiology spokesman Helmut Schühlen, MD, with Vivantes Auguste-Viktoria-Klinikum, Berlin.

FAME II

Anthony A. Bavry

Bavry: In FAME II, investigators performed fractional flow reserve on indeterminate lesions and randomly assigned those with an FFR <0.8 to either PCI plus optimal medical therapy (OMT) or OMT alone. Patients who had an FFR >0.8 were included in a registry. The trial was terminated early when it was discovered that there was a lower rate of the primary outcome, which was death, MI or urgent revascularization in the PCI group. Of the composite outcome, urgent revascularization was primarily driving the difference. Among patients requiring urgent revascularizations, 21.4% was due to an MI, so they were not insignificant events that triggered the repeat procedure. The trial did not affect the hardest endpoints such as death and MI; however, the study was terminated early at 7 months of follow-up. Had the trial been allowed to continue longer, we might have seen a difference in hard outcomes.

We also learned that patients who had a high FFR did well and had a low event rate over the follow-up period. This compliments our practice, where we routinely defer patients who have an FFR >0.8.

Bhatt: A press release had already been issued on this trial earlier in the year and the top-line results were already known, but now the authors have drilled down further into the findings and it really does show a significant benefit for FFR-guided PCI vs. medical therapy in patients with stable CAD. So it is a landmark study that proves the value of appropriately guided PCI in stable patients. Some might try to compare and contrast this to the findings of COURAGE, which didn’t show any clear benefit on hard endpoints with a strategy of initial PCI vs. medical therapy in stable CVD; however, this was a different population, different trial and different endpoint that was reduced — the need for urgent revascularization. Hard endpoints weren’t significantly reduced, but the trial was stopped prematurely by the Data Safety Monitoring Board because they saw a large benefit in the reduction of urgent revascularization. So the question of whether revascularization in stable patients reduces death or MI is an open question, and potentially the large, NIH-funded ISCHEMIA trial might answer this question, though that trial will take several years to complete.

Ajay Kirtane

Kirtane: FAME II is a very important contemporary trial conducted in patients with stable ischemic heart disease. Although preliminary data were presented at EuroPCR and in a company-issued press release before that, seeing the results in their complete form was even more striking for me. The fact that the study was profoundly positive in that PCI was able to safely reduce unplanned hospitalizations leading to urgent revascularization (a second procedure) within a 6-month time frame is very encouraging. The time to event curves in the manuscript indicate an even more pronounced and continued benefit to 1 year favoring FFR-guided PCI over medical therapy alone. These data demonstrate that the benefit of ischemia-guided PCI in patients with stable CAD extends beyond symptom relief to an additional quality-of-life benefit for patients: namely, preventing future unplanned hospitalizations leading to urgent revascularization for suspected ACS.

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TRILOGY ACS

Deepak L. Bhatt

Bhatt: TRILOGY ACS was a randomized clinical trial of prasugrel (Effient, Eli Lilly/Daiichi Sankyo) vs. clopidogrel (Plavix, Sanofi-Aventis) in patients who were initially medically managed for ACS. In this overall population of more than 7,000 patients, there was no significant benefit of prasugrel vs. clopidogrel, perhaps a little surprising given the results of TRITON-TIMI 38 that did show prasugrel was superior to clopidogrel, albeit in the setting of PCI and ACS.

Aside from the study’s main finding, recurrent events were also examined and were significantly reduced with prasugrel. There were also other insights that will come from this trial, not so much right now, but at future meetings.

PROTECT

Bhatt: This trial examined two first-generation drug-eluting stents, pitted them against each other, and overall, no significant differences were observed, although the rates of target vessel revascularization were lower with the sirolimus-eluting stent (Cypher, Cordis) vs. the first-generation zotarolimus-eluting stent (Endeavor, Medtronic). Neither stent is used much anymore in the United States, so this is perhaps not directly a relevant trial to clinical practice, but it is still interesting that there are differences emerging between these two stent types. It just goes to show that not all DES are created equal.

Furthermore, there were differences in definite stent thrombosis favoring the zotarolimus-eluting stent, although the difference in the combination of definite and probable stent thrombosis, the prespecified primary endpoint, was not statistically significant. So a few different messages from this trial: overall both stents looked pretty good, but again first-generation DES have largely been eclipsed in the United States and worldwide.

Another important message is that long-term follow-up is critical in evaluating differences between DES because this was a 3-year study and it took 3 years for differences to clearly emerge.

Bavry: Since we are not currently using the stents tested in this trial, the results don’t apply to the patients I’m implanting stents in presently, but the trial does have merit to the millions of patients worldwide who already have these coronary stents implanted. Although there was no difference in stent thrombosis between these two stents, there was still a low, persistent risk of thrombotic events, which is something I have always been concerned about with my patients. I tend to leave them on long-term dual antiplatelet therapy (ie, longer than the minimum of 12 months) if they have a first-generation DES. With our newer-generation stents, like the everolimus-eluting stent (Xience, Abbott), I’m more comfortable terminating therapy at 12 months; these devices appear to be safer in regard to the risk of very late stent thromboses.

This trial also highlights that interventional cardiology is a moving field right now. PROTECT was a large, well-designed and conceived trial, but by the time it was reported, we already moved into other devices. So this is a rapid pace field that is at times hard to keep up with.

Helmut Schühlen

Schühlen: The original hypothesis for this trial was that more neointimal proliferation might create a bit more restenosis, but due to the full tissue coverage of all stent struts, less stent thrombosis. As stent thrombosis typically leads to abrupt vessel occlusion, clinical consequences may be more critical like MI or even death. The trial did show lower stent thrombosis rates in some subgroup analyses, but we have to acknowledge that the primary endpoint of this trial was negative. The trial hypothesis is further challenged if you take a closer look at other trials with newer-generation stents. There we see minimal neointimal proliferation and lower restenosis rates with newer-generation stents, but also very low stent thrombosis rates. So, despite their ability to suppress neointimal proliferation more effectively, some of these newer-generation stents yielded significantly lower stent thrombosis rates. We might need to acknowledge that suppressing neointimal proliferation is not necessarily suppressing endothelial coverage. The latter is crucial to prevent stent thrombosis.

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DeFACTO

Kenneth Rosenfield

Rosenfield: The DeFACTO study found that FFR by CT provided a more accurate determination of which lesions require invasive evaluation compared with standard coronary angiography. This brings up all kinds of interesting possibilities in terms of earlier and more accurate diagnosis made by a noninvasive means as opposed to having to perform a catheterization and a catheterization-based FFR. We know from the FAME II trial that FFR is a very accurate means of determining the functional significance of a lesion and whether it needs to be treated. In fact, the FAME II trial showed pretty clearly that patients with normal FFRs don’t need to be treated and patients with abnormal FFRs have a higher event rate if they’re not treated. So, if there is a way to obtain an FFR with a less invasive approach then this could lead to a paradigm shift in the way we approach the assessment of the severity and functional significance of a coronary lesion. This is exciting from a patient standpoint. Having this information accrued noninvasively is a big step forward. Obviously, there remains some work to be done in terms of proving the diagnostic accuracy of CT-based FFR, but these preliminary data are certainly intriguing.

However, it looks like there is a way to go in terms of proving the diagnostic accuracy of CT-based FFR. For example, questions remain as to whether it works in all comers and whether it is the same across the board with all comers as intravascular FFR, and how large the vessel needs to be in order to accurately evaluate the FFR through CT-guided algorithms. Despite these lingering questions, the DeFACTO trial certainly presents some exciting preliminary data.

IABP-SHOCK II

Bavry: This was an interesting trial because most physicians would have assumed that a patient with acute MI complicated by cardiogenic shock would be benefited by a balloon pump. It’s one of those areas of medicine that seems intuitive and some might have argued that a study wasn’t necessary to answer this question, but the IABP-SHOCK II investigators are to be congratulated for conducting this study. They found that a balloon pump did not improve outcomes, which was to my surprise. As a result of this large trial, the current guidelines recommendations will likely need to be modified.

ALKK-PCI REGISTRY

Roxana Mehran

Mehran: Analysis of data from the German ALKK-PCI registry suggested that women were less likely to receive a drug-eluting stent if they had stable CAD, non-STEMI, STEMI, were aged between 70 to 80 years and older than 80 years of age. One cannot move away from the probable underlying reason of this discrepancy that is not captured in case-report forms, which is the perception of increased rate of bleeding in older women and the impact of prolonged dual antiplatelet therapy in this population. From these data, it is beyond the age of 70 years where the differential in DES usage is seen in female patients, as is the risk for bleeding. Therefore, I do believe that this factor is playing a role in this study. It is important to note that in the United States, the National Cardiovascular Data Registry only looks at in-hospital events. I think the fear has to do with the prolonged/chronic use of DAPT in patients, especially in the elderly — male or female. That is where there is less enthusiasm for DES.

Disclosure: Bavry, Kirtane and Rosenfield report no relevant financial disclosures; Bhatt receives research grants from Medtronic, is on the steering committee for the OPTIMIZE trial and was on the steering committee for the TRILOGY ACS trial; Mehran receives research grants to the institution from and is a consultant for several pharmaceutical and device manufacturers; Schühlen received honoraria for speaking on behalf of Cordis and Medtronic more than a year ago.