Medical Device Daily Washington Editor

GAITHERSBURG, Maryland — Much of the thinking that goes into circulatory system disease is that if you can clean debris out of the blood or keep it from circulating into vulnerable areas of the human anatomy, you can prevent a good share of the more frequent deadly events that occur each year. In the case of stroke, this is part of the rationale behind closure devices for the foramen ovale – a hole between the left and right atria in the heart – when it is large enough to be described as "patent."

In the case of congestive heart failure (CHF), this line of thinking also is behind the use of blood filtration devices that remove the molecules of sodium that fosters fluid retention. Fluid retention, well known as a symptom of CHF, also exacerbates congestive heart failure, and the fact that diuretics tend to lose their efficacy after repeated treatment has created problems for physicians, many of whom have resorted to the use of ultrafiltration (UF) devices to draw out the sodium, allowing patients to discharge excess fluid.

The extra ingredient in all this in public policy terms is the huge cost of heart failure to society, which may be part of what prodded FDA into holding an advisory committee hearing on the subject this past Wednesday. However, the fact that UF is not indicated for CHF – and is thus an off-label use – was the primary driver for the meeting of FDA's gastroenterology and urology devices advisory committee.

Ann Ferriter, leader of the cardiothoracic and peripheral vascular devices branch at the Center for Devices and Radiological Health, told the panel that medical device reports (MDRs) connected with the use of UF have been trending upward sharply in recent years, exceeding 9,000 last year from about 5,000 in 2005. On the other hand, her numbers indicated that use of UF in heart failure accounted for less than 10% of such reports, although there were reports indicating patients with both conditions.

Kevin McBryde, a medical officer at FDA with a background in pediatric nephrology, reminded the panel that "clearly heart failure represents a huge portion" of Medicare expenditures. However, McBryde remarked that co-morbidities are an issue. He cited a "huge overlap of medical care for patients with heart failure and chronic kidney disease."

A presentation at last year's scientific sessions of the American Heart Association (Dallas), confirmed McBryde's comments. Robert Page, PharmD, an associate professor of clinical pharmacy at the University of Colorado School of Pharmacy and Medicine (Denver), is said to have reported that in 2005, Medicare beneficiaries with heart failure accounted for 37% of all Medicare spending and nearly 50% of all inpatient costs. Page also stated that the numbers suggested that the average cost of a severe heart failure patient ran toward $24,000 a year, roughly eight times the overall average of $3,000 per beneficiary.

One of the clinical trials that was repeatedly referred to during the day's proceedings was the UNLOAD (Ultrafiltration Versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated Heart Failure) trial, which randomized 200 patients to ultrafiltration or medical therapy. In the published analysis appearing in the January 2007 edition of Circulation, the journal of the American College of Cardiology, the 90-day analysis indicated that only 18% of patients on UF had been re-hospitalized vs. 32% of those on diuretic drugs. Patients in the UF arm also had fewer re-hospitalizations, fewer unplanned visits to their doctors, and zero deaths vs. 11 in the drug group, again at 90 days.

The first question FDA put to the panel dealt with the fact that some UF devices are approved for treatment of volume overload without regard for the disease causing the overload, asking whether this state of affairs is appropriate. Panelist Jeffrey Borer, MD, chief of the division of cardiovascular medicine at the SUNY Downstate Medical Center (New York), said it was not. "How you take away the fluid may have a tremendous impact" on the course of disease, at least in the case of heart failure. "I don't think one size fits all."

One panelist observed that there is no strict definition of the term "volume overload," adding that the drugs used to treat overload are not approved for the condition, but for similar conditions such as edema. After further discussion, panel chairman Clyde Yancey, MD, medical director of the Baylor Heart and Vascular Institute (Dallas) summarized that "the panel believes the etiology of volume overload" suggests something about treatment, including that "there is some sense that the time course required to remove the volume" of fluid differs between disease states.

Perhaps of greater interest to industry was the question of the role of UF in the treatment of heart failure. Panelists generally did not favor the use of UF as a front-line treatment, with one panelist remarking that it should be "limited to those who have failed to respond to conventional therapies."

Yancey summarized that "in the absence of a robust data set, the panel feels it should be therapy that comes after diuretic." Although the panel shot down UF as a first-line therapy, Yancey said that as a second-line approach after the first administration of diuretics, "I think it is promising."

As for the omnipresent question of clinical trial construction, one panelist argued that extant registry data and Medicare data would flesh out at least the safety aspect of the treatment in a way that would reflect real-world use more fully than a trial conducted by first-rate physicians in world-class medical centers.

The panel concluded that a randomized, controlled trial was not necessary, but did recommend that follow-up go to a year. The panel also declined to recommend death as a primary endpoint – a nod to the profundity of the illness – but suggested death as a secondary endpoint for any trials.