In the wake of a near-unanimous vote on June 13, 2012, by an advisory panel of the US Food and Drug Administration (FDA) recommending extending the use of the Sapien heart valve to patients with severe aortic stenosis at high risk for surgery, trial investigators said the move considerably expands the scope of transcatheter aortic valve replacement (TAVR) in the United States and marks another milestone for the entire field.

“This changes the [eligible] population from inoperable to either inoperable or high risk for operation, and that’s a fundamental difference,” Ted Feldman, MD, of Evanston Hospital (Evanston, IL), told TCTMD in a telephone interview. “And it’s another step along the path of the PARTNER trials, where PARTNER II is now moving from very high-risk to simply high-risk [patients]. Each step is important because this is all new territory.”

Jeffrey W. Moses, MD, of Columbia University Medical Center/Weill Cornell Medical Center (New York, NY), agreed. This “takes [TAVR] out of the [current] very narrow corridor of treatment in 2 respects,” he commented in a telephone interview with TCTMD. “First, the presently approved device is very large, and access is still a profound issue in this population. So [recommendation of] the transapical route [in addition to the transfemoral route] at least gives another choice to the physician and patient. Also, in inoperable patients the dilemma is that [in many individuals] TAVR becomes futile because comorbidities overwhelm the disease even if you fix the valve. This gives us a broader population in which, frankly, we’re more comfortable about the risk-benefit ratio.”

Dr. Moses stressed that the action of the Circulatory System Devices Panel is another step toward expanding the overall population of patients with severe aortic stenosis who who receive intervention. “This will open the door for consideration of surgery as well. I think it will allow for treatment of patients who were never treated before,” he added.

PARTNER Validated

“In the big picture, the fact that we have completed such a landmark trial as PARTNER I and that the utility of randomized data is being recognized [by the FDA] is really important,” Dr. Feldman observed. Dr. Moses added that “PARTNER was one of the most rigorously conducted trials I’ve ever been a party to.”

For that reason, Dr. Moses said he found it “a little unfair” that some panel members’ questions implied that the surgical arm was confounded by dropouts, thus preventing a valid interpretation.

“A lot of patients [randomized to surgery] changed their mind when they thought they drew the wrong card,” he explained.” Patients have rights, and they can drop out when they want. A lot of these patients won’t accept surgery.”

“My father was one of them” and was ready to accept the consequences of no treatment, Dr. Moses added. (Ultimately, his father qualified for the PARTNER trial and received TAVR, testifying in its favor before the panel.)

Although the panel said that overall the data, which came mostly from Cohort A of the PARTNER trial, gave “a reasonable assurance of safety and efficacy,” it discussed several potential caveats. These included increased risks of stroke (especially in transapical patients) and aortic regurgitation with TAVR as well as gender differences in response to the therapy (women tend to do better than men). Close monitoring of these issues is needed in post-approval studies, the panel said.

Acknowledging such concerns, Dr. Feldman said the bottom line is that the votes were “overwhelmingly favorable, and that’s in contrast to some prior panels where there was much more negative voting regarding safety issues. What I take from the voting is very strong support for therapy in the PARTNER A population.”

Dr. Feldman added that the language of a recent national coverage determination by the Centers for Medicare and Medicaid Services (CMS) ensures that if and when the FDA grants final approval for the new indication, it will automatically be reimbursed, provided the procedure meets certain requirements regarding patient assessment and care by a heart team as well as participation in a national registry.

“At last we’re catching up with the rest of the world in terms of indications [for TAVR],” Dr. Moses concluded, adding that he expects final FDA approval by the end of 2012.

Vote Breakdown

The FDA’s Circulatory System Devices Panel strongly favored the new indication for the Sapien valve system (Edwards Lifesciences, Irvine, CA), voting 12 to 0 that the therapy was effective, 10 to 2 that it was safe, and 11 to 0 (with 1 abstention) that the benefits outweigh the risks.

Although the FDA is not required to follow the recommendation of its advisory panels, it often does so.

The new indication specifically applies to patients with severe symptomatic native aortic valve stenosis who have been determined by a heart team, including a cardiac surgeon, to have at least a 15% mortality risk for valve replacement surgery. In this group, the Sapien valve can be delivered either transfemorally or, for patients whose vasculature is not amenable to this route, transapically.

Data supporting the expanded indication came primarily from Cohort A of the randomized PARTNER I trial, which found similar 1-year mortality rates for TAVR and surgery (24.2% and 26.8%; P = 0.44), meeting the criteria for noninferiority.

Panel members also discussed the need for more detailed informed consent, 5-year follow-up data to assess the long-term durability of the prosthetic valve, and future monitoring of the relationship between aortic regurgitation severity and mortality. They also noted the importance of adhering to trial criteria in selecting patients and performing the procedure.

Source:
US Food and Drug Administration. Proceedings from the Circulatory System Devices Panel Advisory Meeting; June 13, 2012; Gaithersburg, MD. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Medical
Devices/MedicalDevicesAdvisoryCommittee/CirculatorySystemDevicesPanel/UCM308355.pdf. Accessed June 18, 2012.

Realted Stories

• FDA Approves Sapien Transcatheter Valve for Inoperable Aortic Stenosis 
• PARTNER Cohort A Published: Surgical Candidates Obtain Similar 1-Year Survival with TAVI, Surgery 
• PARTNER: TAVR Remains as Effective as Surgery at 2 Years

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