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GAITHERSBURG, Md. -- An FDA advisory panel has voted 9-0, with one abstention, to recommend approval for Edwards Lifesciences' Sapien transcatheter heart valve -- a novel device intended as an alternative for patients with severe aortic stenosis who are too frail for open-heart surgery.
The FDA's Circulatory System Devices panel voted on Wednesday in favor Edwards Lifesciences' Sapien transcatheter heart valve for transfemoral delivery in patients with severe aortic stenosis who are too sick for open aortic valve replacement but who are well enough to be expected to derive a benefit from a valve replacement procedure.
While the panel was concerned with the stroke risk observed in the company's clinical trials, it ultimately felt the benefits of the device -- 20% more patients were alive one year after receiving the Sapien device compared with standard therapy -- outweighed the risks.
The Sapien valve is the first of its kind that doesn't require major surgery. It's threaded through the femoral artery via a small incision in the groin. The whole procedure takes one to three hours, whereas open-heart surgery takes between three and five hours.
"This is an innovative technology that is going to meet unmet needs for a population that is clearly going to be helped," said panelist Ralph Brindis, MD, a cardiologist at Oakland Kaiser Medical Center in Oakland, Calif.
The panel analyzed results from the company's two-part PARTNER trial, which tested the transcatheter technology in patients too frail to undergo surgery as well as in patients who were candidates for surgical repair. The study found high-risk patients who underwent transcatheter aortic valve implantation/replacement (TAVI, sometimes called TAVR) with the novel heart valve had better overall survival than those who underwent standard treatment for severe aortic stenosis.
The primary endpoint was a comparison of survival through the full duration of the study, and patients with the Sapien device had better survival rates at one year than those in the control group -- 69% compared with 50% (P<0.0001).
Panelists were concerned about the limited data beyond two years after implantation and suggested if the FDA approves the device, that patients continue to be followed as part of a post-approval study.
The panel voted 9-1 that the device is effective. They weren't as sure about safety and voted 7-3 that the Sapien is safe, citing concerns over the higher incidence of stroke observed in the trial: After 30 days, 13 patients in the TAVI group had a stroke, compared with just three in the standard. After one year, 25 patients in the TAVI group had a stroke, compared with eight in the control group.
In total, 14% of patients in the TAVI group suffered some type of neurological event, compared with 4.5% of patients in the control group. The early half of the neurological events occurred more than 30 days after the procedure, indicating a continued risk of neurological events with the Sapien.
The panel debated what the risk of stroke means for the very elderly patients who would get the valve if it is approved.
"When I see patients who are in their mid-80s or older and have debilitating disease, they don't want to have a sternotomy, but what they don't want to have more than that is a stroke," said panelist Jeffrey Borer, MD, a cardiologist. "I think stroke is a very major issue and I think it's worse than death for this population."
However, he pointed out that several nurses who testified earlier in the day told the panel stories of their very elderly patients with poor quality of life who got an extra couple of vibrant years after receiving the Sapien device in clinical trials. Borer said that sort of quality of life improvement is impressive.
"I think the primary concern in this population is quality of life," Borer said. "I think the preponderance of data is that quality of life is improved."
Panelists agreed that the stroke risk needs to be noticeably marked on the device's label and clearly explained to patients.
"We have to let the patient know, 'Yes, you can get this therapy, but there is a higher risk for stroke,'" said panelist Valluvan Jeevanandam, MD, a cardiac and thoracic surgeon at the University of Chicago.
About half of all patients who received the Sapien device had an adverse vascular event associated with the procedure, such as iliac artery injury and femoral artery injury, but the panel wasn't overly concerned about the vascular injury rates, and said it hopes that medical societies, the device maker, hospitals, and others appropriately train physicians to perform the procedure.
The panel also heard from several medical groups, including the Society for Cardiovascular Angiography & Interventions and the Society of Thoracic Surgeons, who spoke in favor of approval and said that the successful TAVI procedures are likely to occur in high-volume medical centers with multidisciplinary medical teams.