ACC/i2 2014: Cardiologists Carefully Consider TAVR, Renal Denervation

WASHINGTON, DC—Much of the data presented at this year’s annual American College of Cardiology (ACC)/i2 Scientific Session, held March 29-31, 2014, focused on 2 hot topics—transcatheter aortic valve replacement (TAVR) and renal denervation. In addition, attendees had access to a multitude of presentations on many other relevant issues and questions affecting their daily practice.

New Trials Shed Light on CoreValve

One of the first late-breaking trials to be presented was an analysis of 795 patients with severe aortic stenosis at increased surgical risk randomized to TAVR with the CoreValve self-expanding nitinol bioprosthesis (Medtronic, Minneapolis, MN) or surgery at 45 US centers. CoreValve demonstrated superiority over surgery with regard to the primary endpoint of 1-year mortality. TAVR also lowered MACCE at 30 days and 1 year compared with surgery, and there was no difference in stroke rate between the 2 groups. The CoreValve device was, however, associated with a higher rate of permanent pacemaker implantation.

In an interview with TCTMD, Cindy L. Grines, MD, of Detroit Medical Center (Detroit, MI), said the trial showed results “very different than the other valve studies that have been done,” adding that the Sapien valve (Edwards Lifesciences, Irvine, CA) showed an increased risk of stroke. “I think it’s exciting because this is really just the first generation,” she continued. “With years of experience, both with operators as well as new developments and this valve and others, [TAVR is] going to become safer and [more] effective and could potentially completely eliminate surgical AVR.”

Similarly, the CHOICE trial randomized 241 high-risk patients to TAVR with the balloon-expandable Sapien XT valve or the self-expandable CoreValve at 5 major hospitals in Germany. Device success, a technical composite endpoint, was higher for the balloon-expandable compared with the self-expandable valve, driven by a less frequent occurrence of more-than-mild aortic regurgitation and less frequent need for more than 1 valve. Cardiovascular mortality at 30 days was similar between the groups, as were the combined safety endpoint and the rate of MACCE.

“They designed this trial such that the primary endpoint was paravalvular leak, which is kind of unfair because we do know that with acute implantation the CoreValve has more paravalvular leak. Well, lo and behold, that’s what they found,” Dr. Grines commented. “With CoreValve we don’t really know whether mild-to-moderate degrees of paravalvular leak are even important, and then over time, since it’s a self-expanding valve, the degrees of paravalvular leak tend to get better.”

Since physicians still face plenty of unanswered questions when selecting 1 device over another, Dr. Grines suggested that although more comparator trials are needed, “right now if you are at a CoreValve site, you should stick with that technology.”

Additionally, researchers from Korea looked more specifically at the permanent pacemaker implantation rate in 117 patients who underwent TAVR with CoreValve. They found that variables related to implantation depth and stretching of the non-coronary cusp are independent predictors of the need for a pacemaker.

Conflicting Results with Renal Denervation

Since January, when Medtronic announced that the SYMPLICITY HTN-3 trial failed to meet its primary endpoint, the interventional community has anxiously awaited the full results of the study. Deepak L. Bhatt, MD, MPH, of Brigham and Women’s Hospital (Boston, MA), presented data on 535 patients with severe resistant hypertension randomized to renal denervation with the Symplicity Catheter System (Medtronic, Mountain View, CA) or a sham procedure at 88 US centers. All patients were prescribed a minimum of 3 antihypertensive medications, including 1 diuretic. While there were no safety issues associated with the procedure, office and ambulatory blood pressure as well as heart rate at 6 months were similar between the groups, demonstrating a lack of efficacy.

Dr. Grines expressed disappointment in the results. “I was struck by the fact that one of the reasons it was negative was that there was such an incredible placebo effect,” she said. “So I think there is a lot to be said about the ability of a patient to do biofeedback. If they think that they have had a procedure done, then they become more calm and [relaxed], and can lower their own blood pressure.”

However, she said, “this isn't the end of renal denervation.... There are other technologies that offer deeper penetration and could potentially perform [the procedure] more accurately.”

Looking at results of the Global SYMPLICITY Registry, a different picture emerges, Dr. Grines observed. The study included 1,000 patients with uncontrolled hypertension who were treated with the Symplicity system at 231 international sites in 37 countries. At 6 months, renal denervation proved safe, and rates of major adverse events were comparable among the overall population, patients in the overall population who met the inclusion criteria for SYMPLICITY HTN-3, and the treatment arm of the SYMPLICITY HTN-3 trial. Additionally, treated patients experienced significant reductions in office BP at 3 and 6 months.

The results suggest that the technology might have the largest benefit in patients with the highest blood pressure elevations, Dr. Grines explained. “But there is also a lot of thought of applying it to patients with hyperadrenergic tone, patients who have congestive heart failure, [and] other applications,” she said.

HEATing Things Up

The HEAT Primary PCI trial generated quite the stir among panelists regarding ethics and consent. In total, 1,829 STEMI patients undergoing primary PCI were randomized without consent to receive either unfractionated heparin or bivalirudin prior to the procedure. Bivalirudin was associated with higher rates of MACE and stent thrombosis compared with heparin, while bleeding was similar between the groups.

What overshadowed the clinical results, though, were concerns about the informed consent process used in the study, which the authors termed “delayed” consent, obtained from patients after treatment and during recovery.

“This generated a lot of controversy,” Dr. Grines said. “Also, the results were very different than what we’ve seen in any other trial.... It raises some questions about acute administration of bivalirudin, that’s for sure, particularly in this kind of population. They might have been sicker patients as their overall mortality was 11%, and they had some cardiogenic shock patients. So perhaps in really sick patients we shouldn’t use it. Secondly, perhaps we should use longer infusions of bivalirudin until you can get some antiplatelet agents on board.”

What’s NEXT for Biodegradable Polymers?

NEXT continued to demonstrate the noninferiority of a novel biolimus A9-eluting, biodegradable-polymer stent compared with a current-generation EES at 2 years with regard to death/MI and TLR. Researchers randomized 3,235 patients with mostly stable CAD undergoing PCI with DES at 98 Japanese centers to receive either the Nobori BES (Terumo, Tokyo, Japan) or the Xience V/Promus EES (Boston Scientific, Abbott Vascular) in an all-comer study design.

The results could “be due to a number of reasons,” according to Dr. Grines. “First, they continued to give…  dual antiplatelet therapy to about 70% of [patients]. But also the comparator group was Xience, and Xience has a uniquely low rate of stent thrombosis. In this current generation of drug-eluting stents, it may be very difficult for any stent to beat current technology.”

Potential for Stem-Cell Therapy

The MSC-HF trial demonstrated the potential for stem-cell therapy to successfully treat severe ischemic heart failure. Fifty-nine patients were randomized to intramyocardial injection of mesenchymal stromal cells or placebo. The stem cells were isolated, culture expanded, and injected into an ischemically viable region of the myocardium using the NOGA XP cardiac navigation system (Cordis, Miami, FL). After 6 months, the primary endpoint of left ventricular end systolic volume was reduced in the treatment arm, and these patients also saw improvements in ejection fraction, stroke volume, and end systolic myocardial mass.

“I think it was a great study,” Dr. Grines said. “We’ve talked a lot about stem cells for acute myocardial infarction and it’s certainly a lot easier to give stem cells in that setting. When you’re talking about chronic heart failure though, you no longer have the ongoing inflammation where the infusion of stem cells is going to hone right to the area of injury. So what you have to do is administer the stem cells through an invasive approach.”

The small size of the trial was a problem, she said, adding, “We have to now expand into larger trials to be sure.”

ZES Bests BMS with Tailored Dual Therapy

In an unusual trial design, researchers behind the ZEUS trial enrolled 1,606 patients at either high bleeding risk, high thrombotic risk, or low restenosis risk at 20 European sites. Patients were randomized to implantation with either the Endeavor ZES (Medtronic Vascular, Santa Rosa, CA) or a BMS. Dual antiplatelet therapy was assigned according to the patient clinical risk profile, irrespective of stent type used. One-year MACE was lower with ZES compared with BMS, driven by reductions in TVR, MI, and definite/probable stent thrombosis.

ZEUS was “a necessary trial to conduct but I have several problems with it,” Dr. Grines commented. “First, it’s a very heterogeneous trial... so right off the bat, I don’t know how they could even design [such] a trial and how they could do sample size calculations for that.” Also, she continued, “I’m not sure why they chose the Endeavor stent. If you look at the network meta-analysis, it actually isn’t that great. It doesn’t reduce restenosis that well and it actually has one of the higher risks of clotting in the first 30 days or so.”

Since 20% of the stents used in the United States are still BMS, she reported, the results are “an eye opener.”  Regarding the dual antiplatelet therapy designations, Dr. Grines said future studies should take a hint from ZEUS. “We’re still using sort of old philosophies about the days where we had first-generation drug-eluting stents,” she said. “We should probably treat the patient rather than the stent.”

Other studies from ACC/i2 2014 of interest to the interventional community included:

  • EUROMAX: Extended bivalirudin dose given during PCI may hold the key to treating acute stent thrombosis that occurs shortly after primary PCI in STEMI patients
  • PCI-CAMPOS: PCI performed at hospitals without onsite surgical backup is safe compared with hospitals with onsite surgeons and in some cases may even be safer
  • TAV-in-BAV: TAVR could be an effective option for high-risk patients with diseased bicuspid aortic valves
  • High-sensitivity troponin: Using high-sensitivity troponin testing might eliminate unnecessary hospital admissions for patients who present to the ER with chest pain
  • Melody post-approval study: In patients with RVOT conduit dysfunction, transcatheter pulmonary valve replacement demonstrates high procedural success, excellent short-term function, and low reintervention rates at 1 year
  • GIPS III: The commonly prescribed diabetes medication metformin failed to preserve LV function or provide any other cardioprotective benefits in nondiabetic patients undergoing PCI after STEMI
  • POISE-2: Giving aspirin pre-noncardiac surgery failed to decrease mortality or nonfatal MI and increased bleeding risk
  • CTCOMPARE: Providing higher sensitivity and positive predictive value, coronary CT angiography  also provides rapid discharge at less expense than exercise treadmill testing and should be considered the first-line diagnostic methodology for assessing low-intermediate chest pain in the emergency room

 

 


 

Source:Presentations at: American College of Cardiology 63rd Annual Scientific Session; March 29-31, 2014; Washington, DC.

 

 

 

 

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Disclosures
  • Dr. Grines reports no relevant conflicts of interest.

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