A Medicare advisory panel has concluded that while ventricular assist devices can play a key role in managing end-stage heart failure, there are still considerable holes in the evidence base, particularly for patients who have less advanced disease.

CMS convened the Medicare Evidence Development and Coverage Advisory Committee at its Baltimore headquarters on Nov. 14 to gather independent feedback from panelists on the available evidence for ventricular assist devices (VADs), in an effort geared toward possibly revising its national coverage policies.

The Medicare agency does not currently have a national coverage determination open on the products, though “we do anticipate opening [an] NCD,” said Jyme Schafer, director of the Division of Medical and Surgical Services for CMS’ Coverage and Analysis Group, at the hearing.

It was left ambiguous, however, the extent to which a new NCD would constrict or otherwise adjust Medicare coverage compared to what the agency currently provides for three different VAD indications: short-term support following open-heart surgery (postcardiotomy); bridge-to-transplant (while patients await heart transplantation); and destination therapy (when patients are not candidates for heart transplantation).

To inform their assessment, panelists relied largely on data from the national INTERMACS registry, a joint effort of the National Heart, Lung and Blood Institute, CMS and FDA. Launched in 2006, INTERMACS collects data on patients with commercially available ventricular assist devices, mostly consisting of Thoratec’s devices, such as its HeartMate II left ventricular assist system. All destination therapy-implanting hospitals are part of INTERMACS, and the registry comprises 85% of the nation’s VAD implants.

As of Oct. 22, some 8,000 patients have been enrolled in the registry at 144 hospital sites. The survival rate for VAD patients in the registry is roughly 80% at one year and 70% at two years, researchers reported during the MedCAC panel.

However, panelists expressed concern throughout the day over the fact that more than 50% of INTERMACS’ subjects are in the most symptomatic and advanced stages of heart failure – classified in New York Heart Association class IV and INTERMACS level one or two. The experts were also critical of the fact that functional capacity data and patient-reported outcomes such as quality of life, compared to the mortality results, are lacking in the registry.

“We are in desperate need of a mandate from the medical profession and from the regulatory profession about making requirements to collect certain kinds of information on every patient” – INTERMACS investigator James Kirklin

“I’m kind of torn. I think we’ve got good evidence that survival benefit exists in some classes of patients who get this therapy,” said panelist Robert Kormos, professor of surgery at the University of Pittsburgh Medical Center.

But, “I struggle with the quality-of-life information as to how we get to that. I really don’t know how much more cardiac output produces a better quality of life. Does it really get rid of a heart failure state, or is it that once somebody is tagged with a heart failure state, they are always going to have exercise limitations because of things such as frailty and de-conditioning and attitude differences?” Kormos, who is also an INTERMACS co-principal investigator, asked.

“I am less convinced we have enough evidence to understand how quality of life and functioning changes based on risk scores,” echoed Art Sedrakyan, vice chair of the panel and associate professor of public health at the Weill Cornell Medical School in New York. “Aside from INTERMACS classes one and two and maybe three, I wasn’t sure if I can differentiate these risk factors from bridge to transplant vs. destination therapy. I think the profiles seem too similar for both conditions.”

“It seems like there have been a lot of missed opportunities by not making the registry data as broad as possible,” concluded panelist Robert Steinbrook, adjunct professor of internal medicine at the Yale School of Medicine.

INTERMACS includes a quality-of-life questionnaire with questions pertaining to mobility, pain and anxiety, but whether it is administered to patients depends on any given hospital’s operating procedures and the health of the patient, researchers explained. For some of the questions, there are currently less than 100 responses recorded in the registry.

In addition, functional capacity measurements such as a six-minute walk test and oxygen consumption levels have been conducted for some INTERMACS patients, but not many.

To get that data, “It may require a push from CMS or FDA,” Yale’s Steinbrook said.

“We have a paucity of data,” admitted INTERMACS investigator James Kirklin, professor of surgery at the University of Alabama at Birmingham, during a presentation on the registry data. “We are in desperate need of a mandate from the medical profession and from the regulatory profession about making requirements to collect certain kinds of information on every patient.”

“At the end of the day, INTERMACS reflects the actual practice of care for patients with VAD therapy,” he explained. “So, to the extent that the standard of care is to get this additional information, then we would be able to provide very useful information. But we are hampered right now.”

Looking Ahead To REVIVE-IT, ROADMAP

In the meantime, two separate clinical trials – REVIVE-IT and ROADMAP – may provide better answers going forward, panelists agreed.

Funded by the National Institutes of Health and HeartWare LVAD system maker HeartWare, REVIVE-IT will enroll patients with class III heart failure who are not eligible for a heart transplant – a less advanced population compared to the end-stage heart failure patients included in current guidelines and FDA labeling for left ventricular assist devices (LVADs). Subjects will be randomized to treatment with the HeartWare LVAD system, including the firm’s miniature HVAD pump, or to standard medical therapy.

The study fits into HeartWare’s long-term strategy to expand its market base to a broader set of less-acute patients. The company’s LVAD system has yet to be approved for marketing in the U.S. for any patients, but it gained a positive FDA panel vote in April for its PMA seeking a bridge-to-transplant indication for end-stage heart failure patients. (See Also see "FDA Panel Supports HeartWare VAD, Despite Trial Shortcomings" - Medtech Insight, 30 April, 2012..)

HeartWare is primed to enter the bridge-to-transplant market to compete with Thoratec’s HeartMate II, which dominates the space. (See Also see "Thoratec Downplays Threats From Competing HeartWare Pump" - Medtech Insight, 6 August, 2012..)

Separately, Thoratec is sponsoring ROADMAP, which is enrolling patients to compare HeartMate II to medical therapy in subjects with less acute heart failure than those who typically get the device. But the patients in ROADMAP (class IIIB/IV heart failure patients who are not dependent on intravenous inotropic support) are relatively sicker compared to those targeted enrolled in REVIVE-IT.

“How do we appropriately identify a less sick patient? On the ground we’ll have the REVIVE-IT study to help us out,” said panel member and cardiologist Ralph Brindis, a senior advisor for cardiovascular disease at the Oakland Kaiser Permanente Medical Center. “Basically we’re looking at finding the sweet spot for destination therapy. The challenge is that it’s going to be changing as technology changes and as experience changes.”

INTERMACS’ Kirklin also said that the trials could be a positive influence on the data gathering process for registry hospitals. “The reality is that if we can get centers to agree and embrace the idea that the standard is to collect this information, then it will be put into INTERMACS and we can monitor it.”

During the hearing, CMS was silent on the extent to which REVIVE-IT or ROADMAP’s results would impact future national coverage policy development. “We should meet again in another couple years to see where we’re at,” Schafer said.

DT, BTT: Just Semantics?

Panelists broached another topic during the hearing: Whether separate indications for destination therapy (DT) and bridge to transplant (BTT) even make sense from a clinical standpoint. In practice, most VAD patients don’t fit into such neat boxes, many argued.

“We can identify who’s a transplant candidate, but after that I’m not so sure,” said the University of Pittsburgh’s Kormos. “Maybe they’re DT; maybe they’re not. But that’s where perhaps a heart failure indication has more relevance than this sort of intellectualized subset of classes that was really developed by industry to help them qualify their devices. It has nothing to do with the reality of how we work.”

Panelist Kevin Donovan, director of the Center for Clinical Bioethics at the Georgetown University Medical Center, called the distinction a “false dichotomy.”

“I’m not sure BTT and DT serve the best interests of the patient. Maybe they shouldn’t exist,” he said.

Panel members also stressed the importance of adhering to CMS’ VAD coverage criteria for facilities, including, but not limited to, the requirement that facilities must have at least one member of the VAD team with experience implanting at least 10 VADs or artificial hearts over the course of the previous 36 months.

“It’s more of an issue now because we heard there are more VADs going to non-transplant centers where they may not have a team and [the device] may not be in the culture,” said panel chair Rita Redberg, professor of medicine at the University of California, San Francisco. “What the team consists of would be very important to outcomes.”

Medicare Panel Laments Holes In Ventricular Assist Device Evidence Base

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