If a doctor does not inform a patient that the FDA has not approved the use of a device or procedure, medical experts say, the patient cannot give meaningful consent because the potential problems that can result from the off-label use must be explained so that the patient can weigh the risks and benefits to determine whether to consent to the treatment.
Medical professionals point out that if a doctor wants to use a treatment that is not FDA approved because of a true belief that a certain patient would benefit from a specific treatment more than from others that are FDA approved, the doctor would not hesitate to explain the reasoning to the patient.The FDA Improvement Act reform bill introduced by Rep Hinchey would require doctors to inform patients when a product is used off-label and also provide more resources to the FDA to go after companies that promote off-label use of their products despite the fact that doing so is illegal.
In recent months, lawmakers have made it clear that investigation of the stenting for profit industry is a top priority and will include not only the device makers, but also the doctors and medical facilities performing the procedures.
Being Congress oversees the spending by public programs like Medicare and Medicaid, lawmakers would have to be blind not to notice the obscene rise in profits. According to the May 17, 2007 Wall Street Journal, "Americans spent at least $14 billion on coronary-stent procedures last year, including surgical and hospital fees."
Stenting doctors are very well paid. The median salary for invasive cardiologists who perform the procedures is roughly half-a-million dollars a year, says Darshak Sanghavi, a pediatric cardiologist and assistant professor of pediatrics at the University of Massachusetts Medical School, in Slate Magazine on May 8, 2007.
However, doctors and medical facilities may now be reevaluating the benefits of continued off-label stenting since law enforcement officials released information this month from an investigation by the FBI and the US Department of Health and Human Services of a cardiologist at a facility in Maryland that found 25 unnecessary stents implanted in patients in 2006 alone, with the majority billed to Medicare.
The bare-metal stenting procedure was originally marketed as a cheaper alternative to heart bypass surgery, but since the arrival of the DES, that claim is bogus. On February 25, 2007, the New York Times quoted the American College of Cardiology in reporting that the average cost of the DES procedure has risen to about $30,000, or almost equal to the price of open heart surgery for patients with multiple blockages.
The DES were promoted as being safer than bare-metal stents, but on March 8, 2007, the New England Journal of Medicine published an analysis of 4 studies that compared the 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 in the DES group at 93.3%, and 94.6% in the bare-metal group.
In December 2006, the FDA's Circulatory System Devices Advisory Committee held a hearing to review data on the outcome of DES stenting when they were implanted according to their label compared to when they were used off-label. Dr Ron Waksman, of the Washington Hospital Center, told the panel the rate of stent thrombosis almost doubled in patients with off-label use versus on-label use at 30 days and at 12 months.
He also said, "when we look at on-label and at off-label, the drug eluting stents are more thrombogenic than bare-metal stents."
With both on-label and off-label use, he informed the panel, over time, "late stent thrombosis is seen more in the DES versus the bare-metal stents."
Dr Waksman said that careful patient selection for DES is mandatory, and "off-label use should be reconsidered or restricted."
Diabetic patients with multi vessel disease should always be referred for bypass surgery, he added. DES should be contraindicated, he said, "for patients with poor compliance or allergic to Plavix or aspirin and need for upcoming surgery, and warning labeling should be considered for those when used off-label."
But experts point out that some studies have shown little benefit from taking the anti-clotting, blood-thinning drug Plavix to prevent stent-thrombosis. In October 2006, Dr Alaide Chieffo, made a presentation at a Transcatheter Cardiovascular Therapeutics meeting and reported a study of 3,021 DES patients that found 9 out of 16 patients who had developed late stent-thrombosis were being treated with Plavix at the time.
At the FDA meeting, Dr Peter Smith of Duke University discounted the claims that stenting is safer or as effective as bypass surgery and warned of the importance of weighing the risks and benefits to patients treated with the different procedures.
He stressed that since the introduction of DES, too many patients in need of bypass surgery are instead receiving off-label stenting procedures. "A current perspective," he said, "is that America's number one killer is predominantly treated with percutaneous methodology that has not been demonstrated to provide a survival advantage."
"And this is particularly important," he advised, "for the treatment of multi vessel coronary disease where substantial quality of life and survival benefits have been conclusively demonstrated for bypass grafting."
Dr Smith informed the panel of some of the outcomes reported in peer-reviewed published trials, the first a study of 14,000 patients, which demonstrated a significant survival advantage for bypass grafting compared to stenting in three vessel heart disease, he said.
The ROBUST New York State audited database, he reported, of 23,000 patients with three vessel disease published in the New England Journal of Medicine also showed a significant survival advantage for bypass grafting compared to stenting at 3 years.
Dr Smith explained that bypass grafting is more effective because it provides complete revascularization. While stenting treats the isolated blockage, grafting bypasses about two-thirds of the vessel where current and future blockage can occur.
In addition, he noted, bypass risks increase little with increasing coronary disease severity while risks with stenting appear to increase with each additional stent.
He also told the panel, "surprisingly, when we looked at the bare-metal stent era data, we saw point estimate trends favoring bypass grafting even for low and intermediate severity disease, and an extension of the significant advantage that bypass grafting provides compared to intervention for high severity coronary disease."
Dr Smith said the introduction of the DES led to a tripling of the use of stenting for high severity coronary disease. "And for the first time," he noted, "less than half the patients were initially offered coronary bypass grafting."
"How can this happen," he pointed out, "with the absolute survival advantage that I've shown you from these observational data on 40,000 patients showing that at 1 year, there's a 2.3 percent advantage, absolute advantage in bypass grafting versus stenting; 4.3 percent at 3 years; 5.1 percent at 5 years."
That means 1 out of every 20 patients, he said, who were treated with stenting would have survived if they had had bypass grafting. When you translate into real world application, assuming that drug eluting stents are equivalent to bare-metal stents for the mortality outcome, he advised, approximately 1.5 million drug eluting stents are implanted worldwide, 850,000 in the US.
Using data from the DEScover trial about stents per patient in the incidence of three vessel disease, he said, we estimate that 160,000 are with DES worldwide and 92,000 in the US.
Dr Smith informed the panel that this translates into a rate of premature death at 1 year to 3,800 patients worldwide, with 2,000 in the US, and 16,000 patients deaths at 3 years, with 9,000 in the US.
"Annualized," he said, "this is 6,500 worldwide, 3,600 in the U.S."
At the end of his presentation Dr Smith addressed previous claims made to the panel by the industry that off-label extension of DES was meeting "an unserved need."
"We're not certain whose unserved need that is," he said, "but we're fairly certain that it's not the need of our patients."
Another major selling point used by the stent makers has been to claim that bypass surgery is riskier. However, a study presented at the American Heart Association's Annual Conference in April 2007, determined that the DES procedure and surgery have about the same risk for a major cardiac event based on an analysis of 799 DES patients and 799 bypass patients for outcomes in the first 30 days and during the following 3 years.
Lead author, Dr Wilson, a program director at St. Luke's Episcopal Hospital and Texas Heart Institute, said in Science Daily on April 21, 2007, "We found that the likelihood of any complication in the hospital was the same whether you had a drug-eluting stent or bypass."
"Five percent of drug-eluting stent patients," he said, "had some major complication in the hospital, mostly heart attack, as opposed to about 3.8 percent of the patients who had bypass." At 3 years, the study found, the death rate with bypass was 6.6% and 9% with drug-eluting stents.
The results of a study called COURAGE released in March 2007, may turn out to be the final nail in the coffin for Boston and J&J. The study involved over 2,000 patients who were treated for chronic, stable chest pain, and revealed that medication therapy alone reduced chest pain almost as well as when the drugs were combined with stenting.
Experts say the outcome is probably due to the fact that stenting only fixes one artery blockage at a time while drug treatment affects all arteries.
Many stable heart patients are conned into stenting because they believe that it will extend their lives and lower their risks for heart attack but according to the New York Times, the COURAGE study found that patients who received stents and drugs had the same life expectancy and same number of heart attacks as patients who received drugs only.
The study reported the rate of heart attack, stroke or death in patients who received stents was 20%, compared to 19.5% in patients who used drugs alone. At the end of 4.6 years, there were 211 deaths, or 19% among patients in the group who received stenting compared with to only 202 deaths, or 18.5% in the medication group.
"Our findings parallel those reported in recent trials," said William Boden, chief of cardiology at Buffalo General and Millard Fillmore Hospitals.
"In the aggregate," he told United Press International on March 26, 2007, "these studies ... show that percutaneous coronary intervention -- angioplasty plus stenting -- has no effect in reducing major cardiovascular events."
"There are hundreds of thousands of Americans who are currently getting stents placed who do not need it as initial therapy," said Dr Raymond Gibbons, professor of medicine at the Mayo Medical School and president of the American Heart Association, to UPI.
In response to the study, on the March 28, 2007, WSJ Health Blog, Dr Andy Demajio wrote, "It has been distressing to see how interventional cardiologists have been happily stenting their patients to fatten their wallets."
"This immoral practice should come to a stop," he wrote. "My hope is that the COURAGE data may help payers take action against these doctors."
It appears that doctors and hospital administrators are thinking twice about off-label DES stenting. On May 17, the Wall Street Journal reported that April marked the 10th consecutive month of share decline for DES, quoting the Millennium Research Group, a firm that surveys about 140 US hospitals, that put the percentage of stentings with a coated stent at 69.7%, down from almost 90% last in June 2006.
Until April doctors had largely replaced the more-expensive DES with older, bare-metal stents, the Journal said. "The new data," it notes, "indicate that doctors and patients may be skipping stentings completely in favor of drug treatment."
It sure looks that way according to Boston's first quarter SEC filing, that reported worldwide sales of its DES had dropped to $468 million in the first quarter of 2007, down from $633 million during the first quarter of 2006.
The SEC filing also shows that J&J has plenty of other problems. For instance, the company is currently facing over 75 class action lawsuits and 1,100 individual lawsuits related to potentially defective defibrillators and pacemakers manufactured by Guidant, a company Boston acquired in April 2006.
J&J future isn't looking too rosy either. Sales of the Cypher stent are down by more than 25%, according to the firm's first quarter SEC filing and in addition to DES, J&J is currently under federal investigation over the marketing practices for several other products including the antipsychotic Risperdal, the anti-seizure medication Topamax, the heart-failure drug Natrecor, and paying kickbacks to doctors for using the firm's orthopedic devices.
In March 2007, J&J received new subpoenas from US attorneys in Philadelphia, Boston and San Francisco pertaining to the investigations of the 3 drugs seeking information about corporate supervision and oversight of the subsidiaries that market the drugs including Janssen, Ortho-McNeil and Scios.
In addition, according to SEC filings, as of December 31, 2006, 100 lawsuits were pending against J&J related to the Charite artificial spinal disc, basically alleging that the company knew the disc was defective and boosted profits by marketing the device for off-label uses.
On May 10, 2007, the Wall Street Journal reported the filing of a lawsuit against J&J by two former salesmen with documents showing how the company "sought to boost sales of its blockbuster anti-anemia drug Procrit by offering contracts that fattened doctors' profits and urging its salespeople to push higher-than-approved doses."
This bit of news came shortly after federal lawmakers ordered J&J to cease all direct-to-consumer advertising and physician incentives for Procrit until the FDA could determine whether steps needed to be taken to protect the public following investigations that revealed the rampant off-label sale of the anemia drug was causing serious injuries and death among kidney and cancer patients.
READ MORE LEGAL NEWS
Legal experts are predicting that Boston and J&J will be swamped with lawsuits over the off-label marketing of DES, but say the defendants listed in the complaints will likely include the names of doctors and medical facilities that helped the device makers turn the stenting industry into a billion dollar baby.
Also see: Feds Investigate Profits From Off-Label Heart Stent Procedures - Part I