Off-Label Stenting For Profit

Evelyn Pringle March 2007

On March 1, 2007, US House of Representatives, Henry Waxman (D-CA), the chairman of the House Oversight and Government Reform Committee, asked two medical device makers to turn over documents as part of an investigation into the safety and off-label marketing of drug-eluting stents.

Stents are small wire-mesh tubes inserted in arteries to keep them open after they are unclogged with balloon angioplasty. There are two kinds of stents, bare metal and drug-eluting. Stenting became popular because it was thought to be a safe alternative to heart bypass surgery.

DES were promoted as being more effective than bare-mental stents in keeping arteries open and quickly reduced the use of bare-metal stents when they came on the market. The use of DES has a current rate of up to 80% of all stenting in some countries.

The Taxus, marketed by Boston Scientific, and the Cypher, by Johnson & Johnson, are the only two DES approved for use in the US, but Medtronic and Abbott Labs sell their versions in other countries and are expected to enter the US market in the next couple of years.

Off-label stenting occurs when doctors use a DES to treat conditions other than those approved by the FDA. According to the FDA in December 2006, over 60% of the devices are being implanted off-label in sicker patients with more complex heart problems than the patients the devices were tested on.

Doctors can legally use an FDA approved device for uses that are not approved, but it is illegal for a device maker to influence doctors to implant the device for an off-label use.

Stenting is big business. In 2006, combined sales for Boston Scientific and Johnson & Johnson, totaled close to $3 billion. A bare-mental stent costs roughly $700, compared to about $2300 for a DES.

Some experts are questioning the over-use of both types of stents. According to the American Heart Association, bypass surgery is recommended for patients with complications or major blockage in two or more arteries.

Experts say, stent makers can no longer claim that stenting is cheaper than surgery. On February 25, 2007, the New York Times reported that the cost of stenting has risen with the introduction of newer devices and that surgery and stenting are now comparable in price for patients with multiple blockages, on average about $30,000, according to the American College of Cardiology.

John O Goodman, a leading consultant to cardiovascular doctors, told the Times that the average income of a stent specialist has risen to $550,000 from an inflation-adjusted $392,000 in 1990. Mr Goodman says he expects bypass surgeries to begin rising this year.

In a blatant case of stenting for profit, on March 7, 2007, the Daily Times in Salisbury Maryland, reported that at least 25 patients received unnecessary stent procedures performed by Dr John McLean, at Peninsula Regional Medical Center in 2006, and said the hospital is seeking to determine whether any more patients are at risk.

According to the Times, the hospital’s initial probe found that many of patients did not meet the minimum 70% blockage guideline used to determine whether a stent is needed.

The hospital said, “it would rectify the situation by paying back full medical fees to patients and their health insurance providers for the procedure.”

Paying back the cost of the device and procedure will do nothing to calm the worry of patients who must now live out their lives wondering whether they will develop a blood clot each day.

DES came on the market in 2003, and as happens so often these days, the new devices were heavily promoted and have been implanted in million of patients. Now studies show the DES works no better than the far cheaper bare-metal stents, and in fact they are more dangerous, according to some studies.

An analysis in the March 8, 2007, New England Journal of Medicine, of data on 4,958 patients in 14 randomized trials comparing DES to bare-metal stents, with a follow-up interval of 12 and 59 months, found DES, “does not have a significant effect on overall long-term survival and survival free of myocardial infarction, as compared with bare-metal stents.”

“The risk of stent thrombosis,” the authors state, “is at least as great as that seen with bare-metal stents.”

Another NEJM pooled analysis of 4 randomized trials and 1,748 patients compared DES and bare-metal stents with 4 years of follow-up, and found no significant differences in the rates of death, myocardial infarction, or stent thrombosis with the survival rate at 4 years in the DES group at 93.3%, and 94.6% in the bare-metal group.

A March 2006 presentation of the Basel Stent Kosten Effektivitäts Trial, Late Thrombotic Events (BASKET-LATE) suggested that between 7 and 18 months after implant, the rates of nonfatal myocardial infarction, death from cardiac causes, and angiographically documented stent thrombosis were higher with DES than with bare-metal.

In another study in the NEJM, Dr Bo Lagerqvist, MD, PhD, of the Swedish Coronary Angiography and Angioplasty Registry, and colleagues, reviewed data from 6,033 patients who were treated with either Cypher or Taxus, and 13,738 patients who were implanted with bare-metal stents.

At six months, the study showed DES had lower event rates. But after six months, "patients with drug-eluting stents had a significantly higher event rate, with 12.7 more events per 1,000 patients per year.”

"At three years post procedure, mortality was about 18% higher for drug-eluting stent patients," and from six months to three years, the adjusted relative risk for death was 1.32.

Another study from a registry of almost 20,000 patients who were treated in Sweden in 2003 and 2004, found that, after one year, there were 5 stent thrombosis in Cypher patients verses none in the bare-metal group, and that there were nine cases of stent thrombosis reported in patients with Taxus, verses 2 in patients implanted with bare-metal stents.

Finally, another recent study proved that angioplasty, the procedure in which stents are used, did not help patients when used to open an artery days after a heart attack occurred. That could mean 50,000 such procedures were done unnecessarily every year, according to Forbes.com on December 13, 2006.

Specialists are now realizing the potential problems that may be developing. Although the risk of blood clots is less than 1% per patient per year, experts note, that risk could still add up to thousands of extra heart attacks.

On February 25, 2007, Dr Kirk Garratt, the director of research on heart therapies at Lenox Hill Hospital in New York, one of the nation’s leading stenting centers, acknowledged in the New York Times: “We as cardiologists have probably pressed forward on stent technology a little faster than we should have.”

Dr William Maisel, of Beth Israel Deaconess Medical Center and Harvard Medical School, chaired the FDA stent advisory committee hearings in December 2006, and told Forbes.com on February 13, 2007, "I think it's unfortunate we are here four years after device approval and many of these questions are unanswered."

"I think it represents a failure of the system,” he said, “I think manufacturers and the FDA should have had the foresight that these products would go out to millions of people."

In January 2007, the Society for Cardiovascular Angiography and Interventions, representing 3,700 cardiologists worldwide, emphasized the importance of cautious patient selection and regular use of the blood-thinning drug Plavix to prevent blood clots.

However, Plavix comes with its own risks. For instance, excessive bleeding can occur if a patient is in an accident, and it must be stopped if surgery or dental work is needed. There is also the matter of cost, with Plavix averaging $1,400 a year. Experts say they are concerned that some patients may not be able to afford the drug, and some may not remember to take the medications each day.