The Take Home: TCT
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Transcatheter Cardiovascular Therapeutics, held Sept. 16 to 19 in Boston, featured the latest clinical science in interventional cardiology, as well as forums on innovative technologies, regulatory matters and other topics.
Healio covered the meeting on-site and spoke to numerous experts for their insights on the most important developments from the meeting. Among those offering their assessments were Ori Ben-Yehuda, MD, from the Cardiovascular Research Foundation; Robert O. Bonow, MD, from Northwestern University Feinberg School of Medicine; Judy Hung, MD, from Massachusetts General Hospital; Roxana Mehran, MD, from Icahn School of Medicine at Mount Sinai; Sahil A. Parikh, MD, from Columbia University Irving Medical Center and Columbia University College of Physicians and Surgeons; and Michael Young, MD, from Geisel School of Medicine and Dartmouth-Hitchcock Medical Center.
Editor’s Note: All coverage from TCT can be found here .
PROTECTED TAVR
Young: Any complication for a patient is a terrible thing. We lose sleep over the thought of a patient suffering a stroke or dying. Arguably, a disabling stroke might be worse than death.
For the PROTECTED TAVR trial of 3,000 patients with aortic stenosis who underwent transfemoral transcatheter aortic valve replacement with or without a cerebral embolic protection device (Sentinel, Boston Scientific), the primary endpoint of stroke within 72 hours of TAVR or before discharge, whichever came first, in the intention-to-treat population occurred in 2.3% of the cerebral embolic protection group and 2.9% in the control group (difference, –0.6 percentage points; 95% CI, –1.7 to 0.5; P = .3). However, disabling stroke occurred in 0.5% of the cerebral embolic protection group and 1.3% of the control group (difference, –0.8 percentage points; 95% CI, –1.5 to –0.1; P = .02), according to the researchers. The number needed to treat with cerebral embolic protection to prevent one disabling stroke was 125.
What we have talked about programmatically is how to select the patients who would most benefit from a cerebral embolic protection device. It would be easier to answer the question if the subgroup analyses showed clearly that any patient subsets might benefit. What some programs are doing is in patients who are at higher risk for stroke — a prior stroke, significant calcium in the arch, very tortuous disease or other risk factors of their valve observed on echocardiography — taking a look very closely at the available data and trying to decide as a group where it makes sense to integrate cerebral embolic protection into practice. Cost considerations are important, too. Many hospitals operate on thin margins, so the decision to use the device will be very individualized.
It is great that we are studying this issue because while the majority of our patients who have TAVR do well, there are some who are prone to having a transient ischemic attack or stroke after the procedure, and we worry about that.
CLASP IID
Hung: This was a randomized clinical trial comparing the efficacy and safety of two transcatheter mitral valve repair devices: a newer one called Pascal (made by Edwards Lifesciences) and a second more established device, the MitraClip (made by Abbott). Specifically, this study aimed to show that the Pascal device was noninferior to the MitraClip device with respect to safety and efficacy in 180 patients with degenerative mitral regurgitation grade 3+ or 4+ who were considered to be at prohibitive surgical risk.
The safety endpoint was defined as percentage of major adverse events such as CV mortality, stroke and MI. The efficacy endpoint was defined as proportion of patients with mitral regurgitation less than or equal to 2+ at 6 months. In both cases, the devices were similar. The take-home message for this study is that the Pascal device was noninferior to the MitraClip in terms of both safety and efficacy endpoints.
This study provides another choice of device to perform transcatheter edge-to-edge repair in patients. Having additional device options offers more flexible and potentially better individualized therapeutic options for patients.
This was an analysis at 6 months, and it will be important to have follow-up at 5 years (as already intended in the trial) to assess long-term durability and safety of the devices.
PADN-CDFA
Mehran: This is just an early study that needs to have further evaluation. I think it’s fascinating, but I’m not so sure that at the moment it’s a pivotal trial that we should be thinking about going forward.
The PADN-CDFA sham-controlled randomized trial was conducted to evaluate the effects of pulmonary artery denervation in 128 patients with WHO group 1 pulmonary hypertension. Patients treated with pulmonary artery denervation experienced greater improvement in 6-minute walk distance compared with the sham group from baseline to 6 months, with a mean adjusted between-group difference of 33.8 m (95% CI, 16.7-50.9; P < .001).
The findings certainly will have to be repeated in a global sense before we would say this is the answer, but certainly it’s exciting to see something for these patients because they are among the most difficult patients to treat and often have poor outcomes.
We now have medications that are showing good outcomes for these patients too. We need to take that all into consideration. This trial is just an interesting observation, and we need more.
RADIANCE II
Bonow: The RADIANCE II trial has a significant signal of a transcatheter device that works. At 2 months, in 224 patients with uncontrolled hypertension with a history of treatment with zero to two antihypertensive medications, daytime ambulatory systolic BP declined 7.9 mm Hg in the group that underwent ultrasound renal denervation (ReCor Medical) and 1.8 mm Hg in the group that underwent a sham procedure (between-group difference in means, –6.3 mm Hg; 95% CI, –9.3 to –3.2; P < .0001).
With RADIANCE II, we need to delve into the medical therapies for the patients, as medical therapy also works at reducing BP. If achieving BP control means adding one more drug for someone who is already taking one or two drugs, and you can get the same reduction in BP as with renal denervation, then transcatheter treatment may not be needed. Ajay J. Kirtane, MD, SM, appropriately discussed the essentials of lifestyle and drug therapy, and the renal denervation would be considered only when you have a patient who is not responding to drug therapy. There are a lot of drugs, and in most patients, they work.
The issue is whether the patients take their medications. For patients who are not adherent, we now have data on a procedure that may provide long-lasting effects. However, this could be problematic if some patients and clinicians want to move in that direction early. It is worth emphasizing that drug therapy has other advantages that you do not get from device therapy. For example, there are effects on the myocardium and on the systemic vasculature that can be cardioprotective, and can protect the kidneys, too. The long-term results of renal denervation trials will be interesting to see. If we can follow the results of optimal drug therapy of patients on the sham side, we can determine if drug therapy has benefits beyond just lowering BP.
There is some uncertainty as to where device therapy should fit in. Once these procedures are approved for treating hypertension, there is concern of inappropriate early use. We will have to see what the indications will be in terms of how many drugs are tried, and for how long, whether side effects from drugs are a reason to proceed with device therapy, etc. The medication history of the patients in this trial is going to be very important to examine.
BEST
Ben-Yehuda: The gold standard remains randomized clinical trials. We need to make them more inclusive to apply to a bigger population. Randomized trials, of which BEST is one, are important because they eliminate selection bias. With that in mind, the results are reassuring that the differences are not great between CABG and PCI in this population.
In the extended follow-up (median, 11.8 years) of 880 patients from the BEST trial comparing CABG with PCI with an everolimus-eluting stent (Xience, Abbott), the primary endpoint of death, MI or target vessel revascularization occurred in 34.5% of the PCI group and 30.3% of the CABG group (HR = 1.18; 95% CI, 0.88-1.56; P = .26). In the main results, reported at 4.8 years, the primary endpoint had occurred more often in the PCI group than in the CABG group.
At the end of the day, coronary disease is a complex disease. We have to be careful in this regard and should tailor the therapy to individual patients, when we have options, and use shared decision-making, which of course includes the patient. At lot of the decision-making is based on anatomy. Is the artery ideal for grafting? Are the lesions proximal or distal? Is there a good target to put the graft in? How many lesions are there? The SYNTAX score and the other scores we have do not capture everything, so I do think there is a role for clinical judgment and a good interpretation of the angiogram. We try to do that on a daily basis.
FLASH registry
Parikh: We have seen interim data cuts from this registry of patients with pulmonary embolism before. The final data resemble closely what was seen in the prior data cuts, and convey that this thrombectomy technique is very safe. The safety numbers have been consistent with our experience and are perhaps better than what we would have expected. The on-table hemodynamic changes that were described are also consistent with my experience. That is important to cardiologists, especially, who live and die by pressure gradients and cardiac output indices of right ventricular function.
In the final data from a registry of 800 patients with PE who underwent mechanical thrombectomy with a system (FlowTriever System, Inari Medical) that extracts PE thrombus by aspiration or mechanical modes without need for thrombolytics, the primary major adverse event endpoint — device-related death at 48 hours, major bleeding at 48 hours and intraprocedural device- or procedure-related events — occurred in 1.8% of patients. There were no deaths, 11 major bleeds and three intraprocedural device- or procedure-related events. The rates of all-cause mortality were 0.3% at 48 hours, 0.8% at 30 days and 5% at 6 months.
What remains up in the air is what are the long-term benefits. We think that resolving pulmonary arterial obstruction is important for long-term outcomes, but we don’t have any proof of that. The numbers in the study are relatively low, but are consistent with our expectation for this patient population. We all agree that this is a large, robust, core lab-controlled dataset that gives us confidence. It shows very good safety and acute efficacy. The question remains as to what the long-term benefits are. We think we are doing the right thing, and you can make the argument that if it is safe, it is worth a shot, because the consequences of not succeeding are very significant to this patient population. It remains an open question as to in whom should we do this vs. conventional medical therapy, what is the long-term benefit and whether there is a long-term risk. The risk question is relatively well answered. The benefit question remains open.
The guidelines are not going to change until the randomized controlled trials come back, and there are two important ones. The first is HI-PEITHO, which is examining the more fundamental question of whether something like catheter-directed thrombolysis (Ekos Endovascular System, Ekos Corp.) is better than medical therapy in the form of anticoagulation. The second is PEERLESS, which is designed to compare broadly defined catheter-directed thrombolysis against mechanical thrombectomy with the FlowTriever. It is looking at endpoints that are mixed between cost-effectiveness outcomes, patient-centered outcomes and clinical outcomes. There will be interesting findings from both of those studies, which will be good news for this field, which has been bereft of any good randomized data until now, but they are not yet ripe or ready for publication. It is going to take those studies to move guidelines. I am hopeful that those results will move us toward invasive therapy for this complicated patient population.
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