TAVR Travelers: Medical Tourism Gaining Ground

We’ve all heard stories of ailing celebrities or business scions seeking unconventional and expensive medical treatments outside of the United States. It seems extreme, even exotic, but these days a select group of ordinary people is doing just that to obtain something not very exotic at all: a transcatheter aortic valve replacement (TAVR).

TAVR was approved by European regulatory authorities in 2007, but in the United States, the procedure remains unapproved despite good evidence that it is a feasible alternative to surgery for the many patients with symptomatic, severe aortic stenosis whose age or illness makes them poor surgical candidates.

This summer, the Circulatory System Devices panel of the US Food and Drug Administration (FDA) voted to recommend approval of the Sapien transcatheter heart valve (Edwards Lifesciences, Irvine, CA). The panel, which met July 20, 2011, voted 9 to 0 (with 1 abstention) in favor of approval, indicating that the benefits of the valve outweighed the risks.

Still, the device remains unavailable outside of research trials here for the time being, with clinical sites that were involved in the prospective, randomized PARTNER (Placement of AoRtic TraNscathetER) trial likely to be among the first to offer it after FDA approval. Roll-out is expected across the country in the months following approval as other centers become ready to provide the technology.

A Successful PARTNERship

Favorable results from Cohort B of PARTNER, published in the New England Journal of Medicine, formed the basis for the premarket approval application submitted to the FDA by Edwards Lifesciences (Irvine, CA).

The trial, with a primary endpoint of 1-year mortality, included 2 cohorts (A and B) of more than 1,000 patients with symptomatic, severe aortic stenosis. In cohort A, patients who were surgical candidates were randomized to TAVR with the Edwards Sapien valve or surgery, while in cohort B, patients at high surgical risk received either TAVR or medical management (including valvuloplasty).

Overall, there was a relative risk reduction in all-cause mortality of 46% with TAVR compared with medical therapy. The trial also found a cardiovascular mortality risk reduction of 61% compared with patients receiving optimal medical care. Combined risk of death or repeat hospitalization also was lower in TAVR-treated patients, although the risk of stroke and vascular complications was higher.

Patients Caught Up in Regulatory Limbo

While the FDA panel’s affirmation of the device is largely viewed as a victory for TAVR in the United States, some patients and their physicians have sought out treatment in other countries because they cannot or will not wait for approval here.

“These are generally people who could benefit clinically and anatomically from TAVR but don’t qualify for the trial,” said Ted Feldman, MD, of Evanston Hospital (Evanston, IL), in a telephone interview with TCTMD. (TCTMD attempted to contact numerous physicians for this story, but many were reluctant to discuss the issue.) “They generally have an STS (Society of Thoracic Surgeons) score of less than 10 and they are reasonable candidates for the therapy by many standards but not by the standards of the PARTNER trial.” Many such patients would be considered eligible in Europe, however.

“In my experience, there are patients who are turned down by several surgeons and who don’t qualify [at PARTNER sites] because they don’t meet the trial benchmarks of severity of comorbid illness, and they’re stuck,” he said. “It seems to me that this is a population that we could be serving that we are not.”

Available, Yes. Affordable, . . . ?

But Dr. Feldman added that although some of his patients have inquired about going abroad for TAVR and have done their own research into potential centers that might accept them, few have actually done so.

First and foremost, TAVR is expensive. And second, there is the issue of being in a foreign country and needing to travel long distances to return home after having the procedure.

Even so, some companies have sprung up to help patients who are serious about going abroad for TAVR and have the necessary funds. HeartBridge, located in Zurich, Switzerland, is one such company. Under contract with the German Heart Centre (Munich, Germany), HeartBridge arranges air travel, lodging, and ground transportation for patients and a companion from home to the hospital in Munich. According to the HeartBridge Web site, the cost is approximately (US) $200,000 to $225,000 depending on a patient’s physical condition and the degree of clinical accommodations required.

“It’s an interesting phenomenon that we are seeing because you have to remember that this is still a major procedure,” Barry T. Katzen, MD, of the Baptist Cardiac and Vascular Institute (Miami, FL), told TCTMD in a telephone interview. “When it goes well, it’s very dramatic, but it’s still high risk. If you have complications, you are in a foreign country and you better have a pretty open bank book.”

Dr. Katzen said he has had some patients go offshore because although he has referred them to a PARTNER site, they did not want to be in a clinical trial with all the attendant rules and regulations regarding follow-up.

Although it may seem like an extreme choice, clinicians like Dr. Katzen think their patients are entitled to know that an alternative such as this is out there, if they can afford it.

For Now, a ‘Grassroots’ Movement

“It’s really not that different than if I were to send a patient to a specialty center here in the United States, which happens on occasion,” Dr. Katzen said. “Many of the [foreign] doctors that I’ve talked to are very sensitive to the needs of a patient traveling from a distance. One of the issues obviously is the ability to speak English, especially among nurses and other staff who take care of the patient.” But by far the biggest issue, he said, is that the patient needs to be convinced themselves that the risk-benefit ratio is in their favor.

Dr. Katzen believes these so-called ‘TAVR travelers’ are part of a much larger movement in the United States related to restrictions on access to advanced technologies. “There are more and more patients who are going offshore not just for TAVR but for other cardiovascular devices as well, such as MitraClip and aneurysm therapy,” he said. “Most of it has been based on local doctor-patient relationships, where the doctor here is able to refer to someone they know in another country. I would call it more of a grassroots movement at this point as opposed to a consumer-driven movement.”

In addition, numerous physicians contacted by TCTMD described receiving letters from medical facilities outside the United States that offer TAVR to US patients who can afford to travel abroad for such procedures.

Dr. Katzen added that while some may say that European interventionalists are using Americans’ dilemma as a money-making opportunity, he does not believe that is the case.

“I think these centers [that are taking American patients] are responding to demand more than creating demand,” he said.

But Michael J. Mack, MD, of Baylor Health Care System (Dallas, TX) and president of the STS, cautioned in a telephone interview with TCTMD that he does not believe there is a “tsunami of patients leaving the United States” for TAVR. However, he did acknowledge that in the early stages of the PARTNER trial, when access to the valve was limited, some patients were sent to Canada and Germany for the procedure if they had the means to pay for it. Dr. Mack was a co-author of the PARTNER cohort B paper and a member of the trial’s steering committee. In fact, 2.2% of patients randomized to the control group in the PARTNER B trial underwent TAVR at a nonparticipating site outside the United States. According to the paper, the 1-year rate of death in that group was 0%.

But when patients opt to leave the country for a procedure they feel entitled to even though it is not available, Dr. Mack said both patients and physicians may be acting prematurely.

“It’s a very fine line between determining safety and effectiveness of a new device and introducing it in an expeditious manner,” he said. “Every stakeholder obviously has a different view. But even on their best day, the FDA is going to be criticized by clinicians or patients or industry for either not doing enough or doing something too quickly. They are constantly trying to strike the right balance between allowing devices that are safe into the US population and yet not withholding lifesaving therapy from a population that has no alternative.”

However, Dr. Katzen said a valid criticism of the FDA relates to how its decisions affect the ability of researchers and manufacturers to simultaneously gather data and make changes based on this feedback.

Important details gathered by the PARTNER sites could be useful in evolving inclusion criteria to include patients who otherwise were thought to be ineligible for the technology, for example. But until the FDA approves the device, that cannot happen, and even then, PARTNER sites and expanded sites eligible to provide TAVR will offer it only to the narrow population already studied.

“This is part of the challenge of how you study new technology, because [the FDA] is interested obviously in protecting patients so when you have a totally new technology, it tends to be tested and approved first in those at highest risk even though that is not the largest cohort,” Dr. Katzen said.

He compared the situation surrounding the narrow indication for TAVR to the early days of carotid stenting. “Prior to CREST, all the studies were directed at high-risk patients, which is probably about 10% of the carotid revascularization population,” he said. “Now things are finally changing, but it has taken a long time.”

No One Tracking Patients 

One issue central to this phenomenon that everyone who spoke with TCMTD agreed on is that no central registry appears to be keeping track of patients who travel outside the country for TAVR. That means there are no hard numbers to indicate just how many patients are travelling for the procedure and, more importantly, no data on how these patients fare. Such details might help other patients and their clinicians decide if this option is a reasonable one.

A representative for Edwards LifeSciences acknowledged that the company does not keep records of this sort of activity either.

The few records that do exist seem to come from small centers, such as one in Cali, Colombia, that has worked with physicians in Miami to bring patients there for treatment with the CoreValve system (Medtronic, Minneapolis, MN).

Dr. Katzen, who is currently working on developing a TAVR program outside the United States on behalf of his institution, said such record-keeping is important moving forward, even after TAVR is approved here.

“I think the situation is only going to get worse, not better [after approval],” he said. “You are going to have more and more patients who want this technology and they are going to find a way to get it.”

 

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Sources:
1. US Food and Drug Administration. Proceedings from the Circulatory System Devices Panel Advisory Meeting; July 20, 2011; Gaithersburg, MD.

2. Leon MB, Smith CR, Mack M, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med 2010; 363:1597–1607.

 

 

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