The Take Home: TCT

Issue: January/February 2016

The Transcatheter Cardiovascular Therapeutics Scientific Symposium was held from Oct. 11 to Oct. 15, 2015, in San Francisco.

At the symposium and afterward, Cardiology Today’s Intervention spoke with experts who provided insight on some of the most notable presentations. They include Ori Ben-Yehuda, MD, with New York-Presbyterian Hospital/Columbia University Medical Center and the Cardiovascular Research Foundation;Stephen G. Ellis, MD, with Cleveland Clinic; Aloke V. Finn, MD, with Emory University School of Medicine; Sanjit S. Jolly, MD, MSc, with McMaster University and Population Health Research Institute; John R. Laird, Jr., MD, with the University of California Davis Medical Center; Daniel I. Simon, MD, with University Hospitals Case Medical Center and Case Western Reserve University School of Medicine; and Editorial Board member Gregg W. Stone, MD, with New York-Presbyterian Hospital/Columbia University Medical Center and the Cardiovascular Research Foundation.

Stone: ABSORB III was the first large randomized trial comparing the Absorb bioresorbable scaffold (Abbott Vascular) with the Xience cobalt chromium everolimus-eluting stent (Abbott Vascular). It showed in 2,008 randomized patients who had simple and moderately complex lesions, stable CAD and stabilized ACS, that within 1 year, the results were noninferior according to the prespecified noninferiority criteria. There were no significant differences between Absorb and Xience in these patients in terms of either the primary endpoint of target lesion failure (difference, 1.7 percentage points; 95% CI, 0.5 to 3.9) or most of the secondary endpoints, including scaffold thrombosis (P = .13).

In those with reference vessel diameter by quantitative coronary angiography of < 2.25 mm, which is roughly equivalent to a visually estimated reference vessel diameter of < 2.5 mm, the thicker-strut Absorb seemed to be associated with a higher risk for TLF and scaffold thrombosis. It suggests that particular caution is required when implanting the device in such very small vessels, and that if an operator does choose a very small vessel, they should routinely post-dilate the Absorb with a noncompliant balloon at high pressure.

The trial was designed to show noninferiority but not superiority at 1 year. It did not show superiority, and nobody thought that it would be superior to Xience within 1 year. The objective of the device is that it will be better over time, at 3 years, 5 years, etc. That’s going to require many years to determine whether or not that is true.

Ellis: The ABSORB III 1-year results were really intended to assess any safety penalty that might occur using this device in comparison with contemporary second-generation DES. We know the device is larger. The strut thickness is about 150 microns as opposed to about 80 for most stents. So we expected a thrombotic penalty of some sort because of that. The issue was how much. That has to play out in terms of the potential gain — which has yet to be proven — an improvement on the 2% to 2.5% annual event rate associated with stents over the long haul.

None of us who were involved with the study were surprised that there was a slight numeric disadvantage. The study results were well within the statistical criteria for noninferiority.

It’s important to understand that when we started the study, our understanding of the optimal implantation technique wasn’t fully developed. In fact, we had some misconceptions. Initially, we were telling people not to post-dilate and not to cross the scaffold with an imaging device for fear of dislodging it. We were also concerned about overstretching the device and breaking it. Fairly soon after we started, we realized that post-dilation was important, and we stressed that at some of the later investigator meetings. But I think the 65% post-dilation rate is suboptimal. When Martin B. Leon, MD, spoke from the podium, he said he did not think that the operators did that good of a job with implantation of the device. He may well be right.

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LEADERS FREE

Stone: The LEADERS FREE study was the first true test of a metallic DES with no polymer. The concept of having a polymer-free metallic DES is that once the polymer is completely gone, a BMS is left behind, and you would be able to get along with a shorter dual antiplatelet therapy. And hopefully in the long term, you would avoid late polymer reactions.

The BioFreedom stent (Biosensors International) was tested in a large trial of more than 2,500 patients compared with a standard metallic DES in patients at high risk for bleeding, in whom 1 month of DAPT was indicated. The study showed that it was as safe as the BMS (HR for primary safety endpoint of stent thrombosis, CV death or MI = 0.71; 95% CI, 0.56-0.91), but it was more effective, and it reduced TLR (HR = 0.5; 95% CI, 0.37-0.69), like you would expect from a DES. Whether it is as good as a true polymer-based DES that controls the dose and elution rate of the drug is not known. And the stent thrombosis rates were still relatively high. We don’t know if this is the optimal device, but it certainly performed safer and more effective than a BMS in this setting.

This has opened up future investigation of polymer-free metallic DES. It also opens up the whole field of very short, even 1 month, DAPT with a DES. That’s very exciting and has a lot of relevance to patients at high risk for bleeding if they are maintained on DAPT.

TUXEDO-INDIA

Finn: TUXEDO-India was an important trial to examine whether or not the mechanism-of-action of different stents — one employing paclitaxel and one employing everolimus — made a difference in outcomes in 1,830 patients with diabetes and CAD. The answer was, it did not. In fact, the everolimus-eluting stent was superior to the paclitaxel-eluting stent (RR = 1.89; 95% CI, 1.2-2.99), similar to results we have seen in patients without diabetes.

This confirms a lot of already-existing data. In the U.S, we don’t have the paclitaxel-eluting stent any longer. So it’s consistent with the company decision to not do this system anymore.

RIVER-PCI

Stone: RIVER-PCI was a negative study of ranolazine (Ranexa, Gilead Sciences) in 2,561 patients with incomplete revascularization after PCI, a situation associated with reduced quality of life and a high readmission rate for recurrent ischemia and need for revascularization. The anti-anginal agent ranolazine did not improve outcomes in that setting (HR for primary endpoint of time to first occurrence of ischemia-driven revascularization or ischemia-driven hospitalization without revascularization = 0.95; 95% CI, 0.82-1.1), so we need new approaches for patients with incomplete revascularization. Most importantly, not getting incomplete revascularization.

The idea behind ranolazine as a possible solution was that ischemia is what drives recurrent angina, repeat procedures and the need for rehospitalization, and ranolazine is a very effective anti-ischemic agent. But in this setting, for whatever reason, it was not effective. There are hypotheses in The Lancet manuscript on the trial. It may have to do with the drug. It may have to do with the types of lesions.

DRAGON

Simon: In this study of 2,042 real-world patients undergoing PCI, transradial and transfemoral access were not different in freedom from MACCE at 12 months (P for noninferiority < .001), but transradial access was associated with fewer complications from bleeding at 7 days (P < .001).

What’s interesting is there are two diverging paths here. One is that interventions are getting more and more complex. We are doing cases now, such as chronic total occlusion and multivessel disease, that we did not tackle in the past. There are advantages of femoral access in these cases. One of the things that I’d hate to see is our trainees and fellows lose the techniques that you need to do these cases.

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Certainly, femoral access will still be required for some procedures and I think there is a question of what’s the appropriate mix, but it certainly seems that you can make a very strong case for radial access in ACS because that’s where I think the data are most robust.

TOTAL

Jolly: I presented the 1-year results of the TOTAL trial. There were a lot of people who were very excited about thrombus aspiration with PCI after the TAPAS trial, and it had gone into clinical practice. People believed in it; it was almost like a religion. In the TOTAL trial, we randomized more than 10,000 patients and at 30 days didn’t find a reduction in mortality or other ischemic events. Interestingly, we also found a significant increase in stroke.

At 1 year, we asked whether if surrogate outcomes like ST resolution and angiographic distal embolization were reduced, would we begin to see the curves separate over time? And that wasn’t the case. We did not see a difference in the primary outcome of ischemic events (HR = 1; 95% CI, 0.87-1.15), and we still saw this signal of stroke (HR = 1.66; 95% CI, 1.1-2.51).

The important message for clinicians is that we need to be careful of small trials, especially small trials that change practice when we actually don’t know the truth. TOTAL is important because it was a large trial that was looking to verify the results of a smaller trial, and allowed clinicians to question their practice. As a clinician, I have changed my practice. No longer do I feel that it’s religion to do routine thrombus aspiration. We should use it much more selectively or in bailout fashion. I’m very happy to have this new information.

IN.PACT SFA

Laird: I presented 2-year data from IN.PACT SFA, which was a randomized comparison of drug-coated balloons compared with balloon angioplasty in 331 patients with femoropopliteal disease. The study showed sustained and durable benefit of a DCB over standard balloon angioplasty in the superficial femoral artery and proximal popliteal artery. Primary patency at 2 years was significantly better with the DCB: 78.9% vs. 50.1% (P < .001). Target lesion revascularization was significantly lower after treatment with DCB compared with a standard balloon (9.1% vs. 28.3%; P < .001). We were able to get better results when treating SFA disease, potentially without the need for stents or other permanent implants in this artery, which could improve our patients’ longer-term outcomes, relieving their symptoms and improving their quality of life. In some circumstances, it could potentially prevent loss of limb.

The clinical implication is that for those patients with peripheral artery disease, which is growing in prevalence with the aging of our population, we now have a potentially better technique to treat their PAD. I think this will ultimately result in a paradigm shift in how we treat PAD, particularly in the femoropopliteal segment, which is the most common location for patients to get occlusive lesions.

PARTNER II S3

Ben-Yehuda: For the 1-year follow up of the PARTNER II S3 (SAPIEN 3) trial, the cohorts presented included inoperable and high-risk patients. In the inoperable group, which had an estimated mortality of 50% with surgery, there was a 1-year mortality rate of 14.4% with transcatheter aortic valve replacement (Edwards Lifesciences), for a survival rate of 85.6%. In both groups combined, there was a 1-year survival rate of approximately 88%, and in the high-risk group, it was approximately 89%. The rate of significant strokes was approximately 4.5%.

While not a cure in all patients, it is a marked advance from where we were a few years ago. It shows that TAVR is becoming a mainstream therapy for patients. We are seeing TAVR becoming a safer therapy, more applicable to a greater number of patients, and we are seeing an iterative improvement in results as the devices, the selection of patients and operator competency has improved over the years. We still have a lot of research to do and a lot more to learn, but these results are fantastic and will improve patients’ quality of life and longevity.

Disclosures: Ben-Yehuda reports speaking and consulting for Merck/Schering-Plough. Ellis reports consulting for Abbott Vascular, Boston Scientific and Medtronic. Finn reports sponsored research agreements with Boston Scientific and Medtronic. Jolly reports receiving grant support from Medtronic and personal fees from AstraZeneca and St. Jude Medical. Laird reports consulting for Abbott Vascular, Bard Peripheral Vascular, Boston Scientific and Medtronic, and receiving research grants from Medtronic and W.L. Gore. Simon reports serving on advisory boards for HeartFlow and Medtronic. Stone reports consulting for Reva Medical.