The STACCATO trial of TAVI (percutaneous aortic valve implantation) was halted due to problems, and the new data from the PARTNER A trial is less optimistic than previously hoped. More information from two articles published at the Heart.org (Heartwire.com) are re-posted below:
Dr Leif Thuesen (Aarhus University Hospital, Denmark), who presented the results of the STACCATO trial today at TCT 2011, said he is concerned about extending the indication of transapical TAVI to include patients who are candidates for surgery, especially given the increased risk of major stroke observed in this trial.
“There is no doubt there are patients who can’t be operated on, and they should be treated with TAVI,” Thuesen told heartwire. “But the patient who can be operated on—here, we should be very, very cautious. It’s the operable patients, the low-risk patients; they should not have the TAVI procedures, but that’s what is happening. We had one patient, for instance, who did not want the conventional operation, so he had the TAVI procedure in Canada. That’s how it is. Indications are slipping.”
The results of the study were presented during the late-breaking clinical-trials session, as well as during a morning press conference. After Thuesen’s presentation to the media, Dr Michael Mack (University of Texas, Dallas) pulled no punches in his criticism of the trial, saying the study was poorly designed and poorly executed. Mack said the trial was designed too optimistically and powered for event rates in the TAVI arm that were too low. Moreover, some of the events that stopped the trial, including one patient in the transapical-TAVI arm who died while on the waiting list for the procedure, skewed the results.
“I think there is some misinformation here, based on invalid trial design, that is likely to hurt the field,” Mack told heartwire.
The STACCATO trial
The STACCATO trial was designed three years ago and included elderly patients with valvular aortic stenosis who could be treated with surgery or transapical TAVI. Based on data from a surgery registry, they anticipated a surgical-event rate—defined as a composite of 30-day all-cause mortality, major stroke, and/or renal failure—of 13.5% and an estimated event rate in the TAVI arm of 2.5%. The study was stopped due to an increase in adverse events in the TAVI arm after the inclusion of 70 patients.
Regarding the primary end point in the transapical-TAVI arm, there was one non-treatment-related death, one left coronary artery blockage, two major strokes, and one patient who had renal failure requiring dialysis. In the surgical arm, there was one case of perioperative major stroke. Other adverse events in the TAVI arm included a transient ischemic attack followed later with a major stroke, two perioperative cases of severe paravalvular leakage, one perioperative aortic rupture, one left main occlusion during balloon valvuloplasty, and one case of major bleeding.
Thuesen emphasized that the study was initiated three years ago and that the transapical TAVI devices at that time were relatively “unsophisticated” and not available in the full range of sizes now on the market. Moreover, he noted that the study investigators were optimistic about the success of TAVI in this population, especially given their absence of clinical events before the study was started, and for that reason they assumed an event rate of 2.5%, which he admitted was “completely wrong.” He noted that the trial began after investigators had performed approximately 40 transapical TAVI procedures.
To heartwire, however, Mack said the event rates were too low and that investigators should have estimated an event rate closer to 13%, similar to the event rate assumed in the surgical arm. Dr Joseph Bavaria (University of Pennsylvania, Philadelphia), on the other hand, saw a silver lining in the data, especially for surgeons. He said that the study shows the great surgical results obtained in patients with an average Society of Thoracic Surgeons (STS) risk score of 3.4.
Discussing the results and the stopping of the trial, Thuesen said that operators are now much better at handling paravalvular leakage, and newer devices might provide a much better fit into the aorta. Moreover, multislice computed tomography (MSCT) is able to provide better preoperative assessments over echocardiography, which was used in STACCATO. Still, despite the limitations of the trial, Thuesen said that in the current phase of development, transapical TAVI is likely inferior to surgery.
Asked about patients who want TAVI despite eligibility for surgery, Thuesen told heartwire that “we should try to persuade them to have surgery, no doubt.” Mack, on the other hand, said that on the front lines surgeons are forced to tell patients that their surgical risks are too low for TAVI and that surgery is the recommended treatment. “The patients don’t want what I’m selling,” said Mack.
[I completely disagree – of course patients want what Dr. Mack is selling – a quick, easy fix.. Who is he kidding?? That’s why it’s important that we make sure the procedure is safe before expanding the indications for TAVI. – Cartagena Surgery].
New QoL data released today at TCT 2011 show that while high-risk, surgery-eligible patients treated via a transfemoral route in PARTNER A reported substantial QoL benefits compared with surgery in the early weeks postprocedure, this was not the case for patients treated via a transapical route.
In fact, said Dr David Cohen (Saint Luke’s Mid America Heart Institute, Kansas City, MO), who presented the results, “for patients eligible only for the transapical approach, there was no benefit of transcatheter aortic-valve replacement over surgical aortic-valve replacement at any time point, and in fact, QoL tended to be better with surgical replacement both at one and six months.”
Life after TAVI
For a number of secondary end points, TAVI and surgery were associated with differences in procedure-related complications and valve performance at 12 months, but the impact of these differences on patient QoL was previously unknown, Cohen said.
For the current analysis, Cohen et al measured QoL in PARTNER A using the Kansas City Cardiomyopathy Questionnaire (KCCQ), the SF-12, and the EQ-5D, with questionnaires administered at one, six, and 12 months.
For the overall comparison, researchers saw differences between TAVI and surgery at three months, but these had disappeared by six and 12 months. What was clear, however, was that there was significant interaction between the treatment effect and the type of TAVI procedure.
Cohen and colleagues therefore conducted further analyses of QoL according to whether patients had undergone a transfemoral or transapical procedure.
“For the transfemoral group, the message is one that clinicians won’t find surprising,” Cohen said—these largely reflect the QoL findings from PARTNER B. The less invasive nature of the transfemoral [TAVI] procedure results in pretty important differences in QoL at one month, although by six and 12 months the patients have really come together.”
At one month, however, the improvement in QoL was meaningful—in line with about a one to 1.5 level improvement in NYHA class, Cohen said.
“But on the flip side, the transapical group was really somewhat of a surprise and showed certainly no benefit in terms of QoL of transapical over surgery at any time point, not a hint of a benefit. And for several different measures, [transapical TAVI] was actually doing worse. The trends were all toward worse QoL at one month with the transapical approach.”
At one month, scores were numerically lower for transapical TAVI compared with surgery across the various QoL scales used. At six months, this difference was actually “of borderline statistical significance” at p=0.04 for the primary end point (KCCQ overall summary). By 12 months, all differences disappeared.
The hardest cuts
His hypothesis, although it’s yet to be proven in this setting, is that healing from the medial sternotomy is actually easier and less painful than healing from the smaller, cosmetically “better” lateral thoracotomy used for transapical TAVI.
“A lot of what really hurts and impairs breathing and other sorts of things in these patients after cardiac surgery is motion of the wound. So if the wound is fixed, if the sternum is wired back together so it really can’t move, patients heal quite well, and it doesn’t cause a tremendous amount of pain once the first couple days are past. Whereas the smaller incision, the lateral thoracotomy, is always moving every time you take a breath. There is no way to wire that back together. I think it’s a more painful incision for patients to recover from.”
Cohen expects his presentation to meet with much debate, since it’s the first real suggestion that TAVI is not better than surgery, at least via the transapical route.
And Cohen agreed that centers in Europe, which have a longer history with these devices and procedures, may have found ways of improving patient recovery, involving better technique or using local anesthesia or nerve blocks, after transapical TAVI.
Already, however, while some registry data in Europe have pointed to much better results with a TA approach than those reported today, other European data have hinted that alternatives to the transfemoral route, such as the subclavian approach, may yield outcomes closer to those of the transfemoral route. So far, the Medtronic CoreValve is the only established TAVI device (approved in Europe) that can be implanted via a subclavian route. The CoreValve is still in the early stage of its pivotal clinical trial in the US.
Cohen acknowledged that done well, the transapical procedure is “slick, smooth, and quick,” but “we can’t assume just because the incision is small that the procedure is going to be easier to recover from.”
Mack, however, was less concerned, pointing out that the surgery group in PARTNER A did better than expected. “I think we cannot ignore [these results] and say there are not some concerns here . . . but I’m not as concerned about it as the data may [suggest].”
Still, the results should raise some eyebrows, experts speaking to the media seemed to agree. Dr Samir Kapadia (Cleveland Clinic, OH), speaking at the press conference, said, “This is a little bit shocking. This is a learning [moment]—it’s clear we have to improve the transapical procedure.”
|Cohen disclosed receiving grant support/research contracts from Abbott Vascular, Boston Scientific, Medtronic, AstraZeneca, and Edwards Lifesciences and consulting/honoraria/speaker’s bureau fees from Daiichi-Sankyo/Eli Lilly, and Medtronic.|
Both of these studies were presented at the 2011 TCT (Transcatheter Cardiovascular Therapeutics) conference in San Francisco – going on November 7th through 11th.