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[DewDiligence]

New Studies Hint at Overuse of Stents

[Just a coincidence that this WSJ cover story coincides with JNJ’s quarterly CC today?]

http://online.wsj.com/article/SB116952187425084569.html

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By RON WINSLOW
January 23, 2007

Few innovations have transformed medicine more rapidly than the popular heart device known as a stent. In just over a decade, cardiologists have implanted the tiny metal scaffolds more than 20 million times to prop open diseased arteries.

Now a series of studies suggests aggressive drug treatment would serve many patients just as well as stents, if not better, while saving billions of dollars in health costs. Just last month, a paper in the Journal of the American College of Cardiology reported that drugs were as effective as stents in improving blood flow through the coronary arteries in patients who were stable after a heart attack.

Recent studies also suggest that for patients with especially serious heart disease, stents may fail to match up to the more-invasive procedure they were supposed to replace: bypass surgery.

Stents are big business. Cardiologists who implant them have built lucrative practices and largely supplanted heart surgeons as the generals in the fight against heart disease. The devices have proved vital profit-makers for Johnson & Johnson and Boston Scientific Corp., which dominate the $6 billion global market.

The new findings aren't definitive, but they are emerging as cardiologists temper their enthusiasm for advanced versions of stents that are drug-coated to prevent reclogging of blood vessels. In rare instances, drug-coated stents may trigger fatal blood clots long after they are implanted in patients, recent studies have shown.

"The clotting risks ended up changing the equation a little bit, and are forcing a broader re-examination" of America's passion for stents, says Steven Nissen, chairman of cardiovascular medicine at the Cleveland Clinic.

There is wide agreement that stents save lives when used to treat patients in the midst of a heart attack or to prevent an impending attack in people who suffer from acute chest pain. Stents are especially effective -- more so than medications alone -- at providing fast, lasting relief from chest pain, or angina, which is a telltale symptom of heart disease.

Weak Evidence

But critics say a significant portion -- perhaps 25% or more -- of the million or so Americans treated with stents each year have generally mild or stable symptoms that don't require urgent treatment. Others have no symptoms at all. A large body of evidence shows that drugs to lower cholesterol, control blood pressure and thin the blood can prevent heart attacks and death in such people. The evidence in favor of stents is weaker.

In a 2,166-patient study, stents provided no benefit over drug therapy in patients whose arteries remained blocked at least three days after suffering a heart attack, researchers reported at a meeting of the American Heart Association in November.

At a big meeting of the American College of Cardiology in March, doctors will unveil results of a seven-year randomized study comparing aggressive drug treatment against stents plus drugs in 2,700 patients with stable heart disease. If stents fail to win that face-off, "it will be a major challenge to current practice," says Christopher Cannon, a cardiologist at Brigham and Women's Hospital, Boston, who isn't involved with the study.

Heart surgeons, long among the most prestigious and well-compensated doctors in medicine, have seen their business erode dramatically with the rising popularity of stents, especially since the drug-coated devices were introduced in 2003. The number of patients discharged from hospitals each year after bypass surgery has fallen nearly 20% since 2002 to just over 230,000, according to health-data company Solucient LLC, Evanston, Ill. In bypass surgery, surgeons connect replacement vessels to the heart to circumvent those that are clogged.

Birinder S. Madan found out last month he had heart disease in three arteries, including a 95% blockage in the most critical vessel. Doctors at a Long Island hospital recommended triple-bypass surgery. But the 65-year-old chief executive of a Brooklyn, N.Y., commercial food-equipment company worried he'd have to take a couple months off work after the operation, which involves cracking open the chest.

For another opinion, he went to Samin Sharma, director of interventional cardiology at Mount Sinai Medical Center, New York, who assured Mr. Madan that drug-coated stents could handle his problem. "One hospital is saying I need a triple bypass. On the other hand, I have a shortcut," Mr. Madan says. "And Dr. Sharma was so confident."

Clotting worries with the stents caused Mr. Madan to hesitate, but a New Year's Eve phone call from Dr. Sharma persuaded him. Early this month, during two procedures a week apart, Dr. Sharma implanted five stents in Mr. Madan's coronary vessels. Mr. Madan plans to be back at work this week. "The majority of patients are going to stents for this," Dr. Sharma says.

Some doctors aren't so sure they should. Recent evidence supports bypass surgery as the preferred option for many patients with disease in all three of the heart's main vessels, or with other complicating factors such as diabetes.

Duke University researchers published results of an 18,000-patient study in the Annals of Thoracic Surgery last year showing a significant survival advantage for bypass surgery over stents in patients followed for up to 18 years. A similar five-year, 6,000-patient study at the Cleveland Clinic in 2004 came to the same conclusion.

Tough Questions

Both studies had important statistical limitations, and most of the patients were treated with bare-metal, as opposed to drug-coated, stents. In Europe, a study comparing drug-coated stents with bypass surgery in patients with disease in several vessels found stents were comparable. Nevertheless, some heart experts say the trend raises tough questions about the rush to treat complicated patients with the devices. "Maybe we've abandoned bypass surgery too quickly," says the Cleveland Clinic's Dr. Nissen, who is a cardiologist, not a heart surgeon.

Stent companies and interventional cardiologists, as those who perform stent procedures are known, strongly defend current use of the technology. Donald S. Baim, chief medical and scientific officer at Boston Scientific, Natick, Mass., readily acknowledges that for the average heart patient, stents don't reduce risk of death or heart attack -- nor, he says, does bypass surgery.

"The main driver is lifestyle and symptom relief and the ability to conduct normal activities without having angina," says Dr. Baim, who recently joined the company after a 26-year career as a cardiologist and professor at Harvard Medical School. "If you're happy having angina 10 times a day, you don't need a procedure. But 99.9% of patients want to be able to walk their dog or play tennis and not have angina."

Kirk Garratt, an interventional cardiologist at Lenox Hill Hospital, New York, says even in patients with stable disease, it can be risky to leave untouched an obstruction reducing the supply of oxygen-rich blood to the heart's muscle. He thinks stents are often warranted in such cases. "Symptoms don't tell the whole story," Dr. Garratt says. "The relationship between insufficient blood flow and the probability of a patient's dying within two years is robust."

In a statement, Johnson & Johnson said its drug-coated stent "is an important and meaningful option for the treatment of coronary artery disease and suitable for many patients with the disease."

Like other medical breakthroughs, stents have captured the public imagination. Many patients feel they're getting second-class treatment if they don't have one, says Neil Shadoff, an interventional cardiologist in Albuquerque, N.M. He says he routinely advises patients who suffer from only occasional twinges of chest pain while golfing or climbing stairs that medication is a good option. Often, he meets resistance.

"These patients are convinced they're going to have a heart attack and die," Dr. Shadoff says. "If you have a procedure that can be done to fix the problem, they look at that as being very positive. They approach the idea of medication as not being aggressive enough."

A common scenario, says Dr. Nissen, is a patient without symptoms whose treadmill test during a routine physical reveals potential trouble. That leads to an angiogram, where a doctor sees some narrowing and puts a stent in. "What is the scientific evidence that we've done anything positive for that patient?" Dr. Nissen asks.

The stent's roots go back to 1977, when legendary cardiologist Andreas Gruentzig, using a device fashioned in his own kitchen, performed the first coronary balloon angioplasty procedure in Zurich. The patient's chest pain was immediately cured. The event heralded the age of interventional cardiology, offering the promise that patients could get diseased arteries fixed without open-heart surgery.

Angioplasty involves threading a balloon-tipped catheter from an artery in a patient's groin to a blockage in the arteries that supply the heart. The balloon is then inflated to clear the obstruction and restore blood flow to the heart's muscle.

But angioplasty was far from perfect. One problem: vessels stretched open by the balloon were prone to snapping shut within days of a procedure, potentially causing a heart attack.

Enter the stent. It is a wire-mesh scaffold, delivered to the blockage via an angioplasty catheter. The stent provided a structure to prevent the vessel from snapping closed. When Johnson & Johnson introduced the first coronary stent in the U.S. in 1994, it quickly became the hottest device in medicine.

A Flaw

It soon emerged, however, that stents had a flaw of their own: the tendency to promote formation of scar tissue that often reclogged the artery, triggering a recurrence of chest pain. The problem was called restenosis, and in 15% to 25% of cases, it required a repeat procedure, usually within six months of the first one.

Paul Cormier, a 73-year-old retired Newton, Mass., policeman, has had 11 stents implanted on three occasions over the past decade after suffering problems with scar tissue. Mr. Cormier previously had triple-bypass surgery in 1992 following a heart attack. Despite the need for multiple stents, Mr. Cormier says the procedures, along with plenty of pills, seem to have stabilized his disease.

"As long as I'm dealing with good doctors, I put my trust in them," says Mr. Cormier, who both swims and meditates at least once a week as part of his still-active life.

Nonetheless, the restenosis problem prompted many patients to stick with bypass surgery. Cardiologists believed if they could solve it, the triumph of stents would be complete.

Intense Interest

That explains the intense interest in drug-coated stents, which carry medication to prevent the growth of the scar tissue. In one early study of 120 patients who received Johnson & Johnson's Cypher drug-coated stent, none developed restenosis. By June 2003, when the new J&J device was approved, patients were lining up on waiting lists to get it. By year's end it had captured an estimated 80% of the stent market. Industry sources put the U.S. stent market at about one million patients a year, though estimates based on hospital discharge data by Solucient are lower.

Boston Scientific's Taxus drug-coated stent hit the U.S. market in March 2004, triggering a marketing war that fueled interest in the technology.

Some doctors say other factors, including financial and aesthetic considerations, also fanned enthusiasm for the device. A doctor's fee for implanting a stent is typically around $1,000, much more than what doctors get for sending patients home with a few prescriptions after a routine office visit.

"It's a medicine-for-dollars scenario," says Kevin Graham, director of preventive cardiology at the Minneapolis Heart Institute. "The doctor who practices disciplined medicine makes significantly less money than the doctor who is trying to find some justification for stenting a patient. That's the system. People get paid for doing things."

A stent is implanted through the same catheterization procedure used to determine whether a patient needs the device. With little risk of restenosis, it becomes easier -- some say more tempting -- for doctors to implant a stent even if the angiogram, or picture of the vessel, is ambiguous. "Once you're there, you've got tubes up there, you've got the team ready, you might as well do it," says John Osborne, a preventive cardiologist at Cardiac Specialty Associates of North Texas.

Some cardiologists speak half-jokingly of an "oculo-stenotic reflex" -- the impulse among doctors to treat any stenosis, or obstruction, as soon as they see it [LOL]. On an angiogram, a wide-open vessel treated with a stent looks elegant compared with the hourglass-like narrowing that marks the spot where plaque obstructs blood flow.

Stent proponents reject such notions, saying the interests of patients drive use of the device. Most cardiologists "are seeking to provide relief of symptoms," says J.P. Reilly, assistant director of cardiac catheterization at Ochsner Health System, New Orleans. "I don't believe people were hell bent on putting in stents."

Dr. Osborne agrees that stents are "good for symptoms," but says their apparent inability to provide significant protection against heart attacks suggests a crucial insight: Atherosclerosis is a systemic disease, not a single obstruction in a blood vessel. "Stents don't treat the disease, they treat the narrowing," he says. "We're kidding ourselves if we think that just by pushing the plaque around that we're treating the disease."

Dr. Nissen says his research suggests that in patients with established disease, plaques are present in at least 80% of an artery. Even if a stent successfully prevents a specific plaque from causing a heart attack, it only covers perhaps 1% of the disease, he says. "You can't alter the outcomes of the other 99%."

By contrast, drugs, while less effective in quickly relieving chest pain, provide a systemic treatment for the disease. Treatment guidelines now call for most patients with established heart disease to take aspirin as well as drugs to lower cholesterol and blood pressure, whether or not they've had a stent. Yet only about 25% of such patients are consistently taking the recommended regimen.

"Systemic therapies are ultimately going to be more important than a mechanical fix," says Paul Ridker, director of the Center for Cardiovascular Disease Prevention at Brigham and Women's Hospital.
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