September 22, 2010 (Washington, DC) — It worked, and it worked darn well. That's the simplest way to summarize the cohort B results from the long-awaited randomized controlled PARTNER trial comparing a novel percutaneous valve implanted via the femoral artery with standard therapy in people with severe aortic disease unable to undergo surgery .
Survival was markedly higher and the risk of a composite end point of dying or needing repeat hospitalization was reduced when patients in the study were treated with the Sapien transcatheter valve (Edwards Lifesciences), as opposed to best medical care, including balloon valvuloplasty. Risk of stroke and of vascular complications was higher in the transcatheter aortic-valve implantation (TAVI) group.
The trial findings, pertaining only to the arm of the study that enrolled nonsurgical candidates, were published online September 22, 2010 in the New England Journal of Medicine, one day before their release here at TCT 2010.
"On the basis of a rate of death from any cause at one year that was 20 percentage points lower with TAVI than with standard therapy, balloon-expandable TAVI should be the new standard of care for patients with aortic stenosis who are not suitable candidates for surgery," the authors, led by Drs Martin Leon and Craig Smith (Columbia University, New York, NY), conclude. "These results cannot be extrapolated to other patients with aortic stenosis."
As the promise of transcatheter valves has gradually eclipsed the excitement of the now-mainstream drug-eluting stents among interventional cardiologists, the one-year data from PARTNER have become some of the most eagerly anticipated findings in recent memory. Noninterventionalists have also been watching developments closely, hoping to end up with a new option for roughly 300 000 patients in the US alone who suffer from severe aortic stenosis, one-third of whom are never considered or eligible for surgery.
The Promise of PARTNER
PARTNER cohort B enrolled 358 patients at one of 21 centers in the US, Canada, and Germany and randomized them to either transcatheter valve implantation or standard care. Within the first 30 days, strokes and major vascular complications were higher in the TAVI group, a difference that reached statistical significance for vascular complications. At one year, however, the rate of all-cause death was 30.7% in the TAVI group, compared with 50.7% in the standard-therapy group. The co-primary composite end point of death or repeat hospitalization was also dramatically lower in the TAVI group. For those who survived 12 months, rates of NYHA class 3 or 4 heart failure were higher among patients in the standard-therapy group.
TAVI vs Standard Therapy at One Year: Primary End Points
|End point||TAVI (%)||Standard (%)||HR (95% CI)||p|
|1-y all-cause death||30.7||50.7||0.55 (0.40-0.74)||<0.001|
|1-y all-cause death or repeat hospitalization||42.5||71.6||0.46 (0.35-0.59)||<0.001|
TAVI vs Standard Therapy Secondary End Points
|End point||TAVI (%)||Standard (%)||p|
|30-d major stroke||5.0||1.1||0.06|
|30-d vascular complications||16.2||1.1||<0.001|
|1-y cardiac death||19.6||41.9||<0.001|
|1-y major bleeding||22.3||11.2||0.007|
|Survivors: Cardiac symptoms at 1 y||25.2||58.0||<0.001|
The striking findings for the primary end point of all-cause death were underlined by the PARTNER authors. In the first year, they note, "only five patients needed to be treated to prevent one death, and only three patients needed to be treated to prevent either a death or repeat hospitalization. They also draw attention to the comparable 30-day survival in both groups, which was notable given that the procedure was relatively new to operators, who typically learned on early-generation systems that have since been refined--in particular, the development of lower-profile devices. They also speculate that the newer, smaller devices and delivery systems, in combination with cerebral-protection devices, will help reduce the rate of strokes seen in PARTNER.
Still to come are answers from the cohort A randomization in PARTNER, which is comparing TAVI with surgical valve replacement in high-risk patients. This arm of the study is permitting both TAVI, as studied in cohort B, as well as transapical delivery--where the valve is delivered via a small incision in the apex of the heart--in the TAVI arm.
Speaking about the findings with heartwire , Smith, co–primary investigator for the trial, called the findings "quite striking."
"They show a clear benefit for the device at an acceptable price," he said. That price--the strokes and vascular injuries--were "not unexpected," based on previous studies, he added.
He also stressed the need for some circumspection, given the fact that cohort B looked only at very sick patients--those ineligible for surgery. "We have to wait for results for cohort A to know just how well this stands up against surgery." Those results may be out as early as spring 2011, he predicted.
Of "concern," he continued, is how to control off-label use of transcatheter valves and whether excitement over the cohort-B findings could lead to a downward slide of the definition of "surgery ineligible."
In Europe, however, where the devices are already available, there has been "some downward drift," but not as much as some might have predicted, Smith points out. "Europe is not known for its regulatory fervor or for practitioners to stick to guidelines, so that suggests that physicians recognize this device is not for low-risk patients."
On the other hand, some interventionalists are already predicting that surgeons may respond by being more aggressive in the type of patient they label as nonsurgical, a theory that cardiac surgeon Dr John Conte (Johns Hopkins University, Baltimore, MD) takes exception to. Speaking with heartwire , he points out that most surgeons would turn only a few patients away from surgery per year and that it is the referring cardiologist or internist--the gatekeepers--who steer patients away from surgery, typically because they are too old or too frail or have other comorbidities.
Conte, who says he's an investigator for the planned CoreValve transcatheter valve trial, makes a point that many have made in the past--and that surgeons have a new reason to be concerned about--that the decision for how to best manage a patient should be made by a team and not by a single physician with a "parochial" interest in one specific line of therapy.
That said, he admits, the cohort B findings are "wonderful results."
"We have here a 20% improvement in survival. Has a beta blocker every been shown to do that? No."
Still, he said, the higher stroke rate in the TAVI subjects is concerning and represents a key area for improvement. "We have to get better at delivering these things so that patients don't have strokes."
Heartwire from Medscape © 2010 Medscape, LLC
Cite this: Transcatheter Valves Slash Deaths, Hospitalizations vs Standard Care: PARTNER - Medscape - Sep 22, 2010.