WASHINGTON -- Shortly after the Food and Drug Administration in 2001 approved the heart failure drug Natrecor for hospitalized patients, two sales representatives from the manufacturer visited Dr. David L. Brown to promote the use of it elsewhere.
Natrecor is now flooding into outpatient clinics nationwide, being taken for longer periods than what was tested prior to FDA approval. Instead of a stopgap treatment for severe congestive heart failure given in a hospital setting, the use for which the drug was tested, some outpatient clinics intravenously administer Natrecor twice weekly for up to 12 weeks.
Critics say no study has been conducted to confirm whether protracted use is safe or effective.
While individual doctors can prescribe drugs in ways not explicitly approved by the FDA, manufacturers are prohibited from promoting such uses. Prosecutors aided by company whistle-blowers have collected multimillion-dollar settlements from other drug makers because of illegal promotion.
The Natrecor trend has alarmed state Medicare managers. Four years ago, total sales of the drug were just under $12 million, but reimbursements for outpatient use alone soared to $37.6 million in the first nine months of 2004, according to a report issued late last month by the Government Accountability Office. ''The major contributing factor" to the increase was regular use of Natrecor, especially in outpatient clinics, according to the Medicare managers.
The trend worries cardiologists, too, because even limited use of the drug is linked to higher mortality rates and kidney problems. And it has incensed critics of Scios, a division of
Dr. Steve Nissen, a Cleveland Clinic cardiologist, notes that Scios distributes a 48-page guide for doctors that includes Medicare reimbursement codes for outpatient use of Natrecor.
''My moral compass went off when I saw this," Nissen said. ''It felt like the company was promoting the use of a drug to profit physicians, rather than to benefit patients."
Another opponent of the overuse of Natrecor, Dr. Jonathan Sackner-Bernstein, regularly prescribed it until a spring 2002 journal article suggested that a slight increase in the amount given increased health risks.
''I read that paper and I said, 'This is not good,' " said Sackner-Bernstein, a cardiologist at North Shore University Hospital in New York.
After digging through data, he co-authored journal articles published this spring that link the drug to kidney problems and higher death rates. The analysis suggests the chance of dying 30 days after Natrecor use is sharply increased. That means that as many as 10,000 to 20,000 more heart patients taking the drug die each year than those on other medications, Sackner-Bernstein said.
''The fact that the Medicare stamp of approval is on this drug is laughable," he said.
Scios and Johnson & Johnson, which in 2003 acquired the Fremont, Calif., biotech company, said they have not encouraged unapproved use of Natrecor. Mark Wolfe, a Johnson & Johnson spokesman, said in a written statement that ''Scios does not promote Natrecor for regular, scheduled outpatient infusions."
But the drug's label does not specify where it should be dispensed. That vagueness has spawned a crop of outpatient clinics that charge about $500 per treatment and can treat patients dozens of times. Natrecor is expected to generate $600 million in sales this year and become a billion-dollar drug in 2006. It is unclear what percentage of that growth is attributable to outpatient clinics. Medicare figures are not up to date and do not include payments from private insurers.
Ray Lipicky, who was director of the FDA's division of cardio-renal drugs when Natrecor was approved, said the agency never intended it to be used in outpatient clinics. ''If we were smart enough," Lipicky said, the label would have read, ''Now, don't you dare use it in any way other than what we have described here."
A panel of prominent cardiologists and heart failure doctors who met at the urging of Scios in June advised the company to conduct a study that would track mortality rates and kidney function in people using Natrecor. The doctors also urged Scios to make it clear to doctors that the drug is for patients whose symptoms are so severe they have go to a hospital.
Darlene P. Horton, Scios senior vice president of clinical research and medical affairs, said a label revision is unlikely. ''That is certainly not the plan," she said.
About 5 million Americans suffer from heart failure. In its acute stage, heart failure is the number one reason for the hospitalization of patients older than 65.
In many instances, Medicare picks up the bill for outpatient treatments. Funding decisions are made at the state level.
For example, in the fourth quarter of last year, New Mexico's allowable outpatient claims for Natrecor totaled $114,307 with 15 treatments per patient. During that same time, Texas allowed $263,017 for patients averaging 20 treatments each in physicians' offices and $4.1 million in allowable claims for hospital outpatient Natrecor use. Those patients averaged 23.1 Natrecor treatments each, according to TrailBlazer Health Enterprises, a Medicare contractor.
Dr. Larry Altschul, who opened the nation's first Natrecor outpatient clinic eight years ago at South Bay Cardiovascular Associates in West Islip, N.Y., has a different opinion. He said he performs 40 to 100 Natrecor weekly treatments, and most of his patients are weaned off the drug after 12 weeks.
Altschul said Natrecor helps insurers save money and patients enjoy a better quality of life.
''We're all being painted as bad guys, but we're not," he said. ''This is a great thing that we're doing."
Diedtra Henderson can be reached at firstname.lastname@example.org.