September 24, 2010 (Washington, DC) — Dr Martin Leon (Columbia University, New York, NY), co–principal investigator for the trial everyone here is talking about, took the stage to present the full-color, larger-than-life, high-definition results for PARTNER cohort B on the 150-foot-wide screen unveiled Thursday at the TCT 2010 meeting.
|Dr Martin Leon|
As reported by heartwire , the full black-and-white results were published early online Wednesday evening in the New England Journal of Medicine. This did not deter meeting attendees from packing into what became a standing-room-only theater to hear Leon's presentation and see for themselves the 46% relative risk reduction in mortality (a 20% absolute difference) and 61% relative risk reduction in cardiovascular mortality.
"This is truly a landmark trial," Dr Stephan Windecker (Bern University Hospital, Switzerland) commented to heartwire . "There are not many interventions in medicine that have such a therapeutic benefit."
"Obviously the results are phenomenal," cardiac surgeon and PARTNER investigator Dr Matthew Williams (New York Presbyterian Hospital, NY) told heartwire . "These are really beyond what everyone expected they would be."
In Every Complication, an Opportunity
|Dr Stephan Windecker|
Leon's talk covered all of the primary clinical outcomes published in the journal, as well as details for a number of secondary end points, many published in a supplemental appendix to the journal. These included results for the six-minute-walk test, which were significantly increased at both 30 days and one year in the transcatheter aortic-valve implantation (TAVI) group, as compared with the standard-therapy group, and bar graphs for NYHA class in survivors, showing increasing numbers of TAVI patients moving into NYHA class 1 and 2, a pattern not seen in the standard-care group. Echo findings showed mean aortic-valve gradients decreasing by 30 days in the TAVI group and remaining relatively static out to one year, while the control group showed a dip, then continued growth over the follow-up period.
But everyone discussing the trial focused on the 20% absolute risk reduction in mortality and the increased rates of stroke, major bleeding, and vascular complications in this group.
A discussion panel hashing over the results was almost universally effusive, and most viewed the adverse events as an opportunity.
|Dr Ian Meredith|
Dr Antonio Colombo (Columbus Hospital, Milan, Italy) noted that the striking risk reduction seen among TAVI-treated patients was achieved despite the fact that PARTNER used older, bulkier technology. "With the newer devices, you can imagine that two years from now, if this study were to be repeated, the difference [between groups] would be staggering. This study opens the door to a future that is difficult to imagine."
Dr Ian Meredith (Monash Medical Center, Melbourne, Australia), likewise, called PARTNER a "remarkable trial."
"To see these results . . . so early in the field, is really encouraging and very positive," he enthused. The complications that were higher in the TAVI group are "all things that can actually be improved as the technique is refined with smaller devices and embolic protection," he said. "One hopes that mortality [could be] improved upon further."
Getting Complications Down
|Dr Ganesh Manoharan|
Indeed, several European interventionalists who already have access to the newer Edwards Sapien XT device and spoke with heartwire agreed.
"Edwards has invested a lot to improve the delivery system and the valve in the past two years, and the technique that was used for the trial was with the old-generation device, [so] getting results like these is amazing," Dr Ganesh Manoharan (Royal Victoria Hospital, Belfast, Northern Ireland) commented. "I have no doubt that with a smaller device, the vascular complication and stroke rates almost surely will come down."
And Dr Giulio Guagliumi (Ospedali Riuniti di Bergamo, Italy) said of his hospital, "We are using the newer ones, and I think we've already demonstrated this. It's very different compared with the first-generation [devices], much more friendly."
Even just the increased sensitivity to these complications will mean they are less likely to occur going forward, he added.
"Once you become more aware, you place much more attention [on preventing complications] in terms of scrutinizing the patient and in terms of patient selection and approach."
Strokes and Leaks Warrant Further Study
A number of observations in PARTNER still need to be further explored. According to Leon, the higher stroke rate--a 5% higher stroke rate in TAVI patients over the first 30-days--did not comprise simply periprocedural strokes. PARTNER coauthor Dr Michael Mack (Medical City Dallas Hospital, TX) will be presenting details on the stroke findings later in the meeting, Leon noted.
Others, mostly surgeons, point to the 12% rate of paravalvular leaks seen at one year in the TAVI-treated patients--something almost never seen when patients are treated surgically. "We are looking at that very carefully," Leon told heartwire , noting, "We have not seen any ventricular remodeling or any other deleterious clinical consequence from the paravalvular leaks, but that needs to be followed closely in the future."
The Legacy of the "Heart Team"
A more open-ended question is whether the "heart-team" approach used in PARTNER will translate into clinical practice, assuming that the transcatheter valve is eventually approved for use in the US. At PARTNER sites, two independent surgeons needed to agree that a patient was not eligible for surgery for that patient to be enrolled: a full 66% of patients were screened but never included in the trial as a result.
According to Leon, the spirit of collaboration and mutual respect among PARTNER investigators was something he's never experienced before, culminating in a 20-hour "retreat," where all study authors wrote the manuscript together, in person.
"Typically, as you know, at most sites there is an embedded antagonism between the interventionalist and the surgeon that grew out of the early days of angioplasty," Leon said. "Certainly at our site, and I think the vast majority of PARTNER sites, that's now evaporated, and there is a collegial relationship that has emerged. I think it's going to be good for cardiovascular medicine. I think it's going to change the way we train young people and how we take care of patients."
Whether that will continue out five years after the device is approved remains to be seen, Leon said, but he pointed out that Edwards plans to train sites, not individuals, in the use of its product.
In Europe, according to DrHélène Eltchaninoff (University of Rouen, France), the notion of the heart team has truly taken hold. Not, perhaps, with two surgeons at the gate, but at least with one surgeon, one interventionalist, and one general practitioner reviewing patients on a case-by-case basis.
"We are supposed to take the decision within the team, combining these different doctors, and it's really important to do that, in order to avoid expansion of indications that are not appropriate today," she said.
Just Because We Can?
The mean age of patients enrolled in PARTNER was 83, with 20% of patients over the age of 90. Mean STS score was 11 to 12, mean EuroSCORE ranged from 26 in the TAVI group to 30 in the standard-care group, and 19% of TAVI patients and 11% of the control group had extensively calcified ("porcelain") aortas. All of which leads to the mother of all philosophical questions sweeping into PARTNER's wake, which is not just whether elderly frail patients can be fixed, but whether they should.
|Dr Craig Smith|
"That's a very legitimate point," co–principal investigator Dr Craig Smith (Columbia University) admitted, "and one that I personally have qualms about. And maybe all of us did. . . . We were very careful to make sure that the patients who were enrolled in this trial had a reasonable chance of living at least one year. They knew their own first name, they may not have remembered what they had for breakfast that morning, but we purposely avoided those who were crippled and disabled and demented, so we could restore reasonable function as well as add months of life."
Mack characterized the initial phase of the trial as moving "Lourdes to the US, multiplied times 20: 'Bring me your old, your frail, your sick, your crippled, and we'll cure them.' That's kind of what the attitude was. And it's become clear to us that we can't cure everyone and that TAVI is not for everyone."
Heartwire from Medscape © 2010 Medscape, LLC
Cite this: Digesting PARTNER: Physicians React With Superlatives to TAVI Results - Medscape - Sep 27, 2010.