Last week The Annals of Internal Medicine roiled the medical world by publishing a study suggesting that the drug-coated stents produced by companies like Boston Scientific and J&J may not be quite as miraculous as first advertised.Following a two-year study, researchers at the Cedars-Sinai Medical Center in Los Angeles are now suggesting that the “putative superiority” of drug-coated stents "is founded on questionable premises. Or as The Wall Street Journal put it, the clinical trials of drug-coated stents (mostly funded by manufacturers), may “have exaggerated their real-life advantage.

Stents, you may remember, are those tiny metal scaffolds that cardiologists use to prop arteries open after they have been cleared of fatty deposits. Since they were approved in the early 1990s, manufacturers have made a fortune peddling the devices which, they say, can prevent a future heart attack while avoiding riskier and more invasive bypass surgery Today, stents are used in 85% of all coronary interventions in the United States.

Before turning to the new Cedars Sinai study, it should be said that THCB has long harbored doubts as to whether these cunning devices represented the best solution for quite so many patients. Back in 2003, THCB quoted a Stanford study which suggested that, over the long term, patients with multi-vessel disease would achieve better outcomes, at a lower cost, if they opted for the bypass.In 2005 THCB questioned the cost-effectiveness of the new, improved “drug-coated” stents that are designed to prevent the growth of scar tissue inside the artery. Granted, the drug coating has a real advantage: without it, scar tissue can cause the artery to narrow again. And while there is no proof that the coated stent improves survival (the scaring rarely leads to deaths from heart attack), scarring can affect a patient’s quality of life by causing chest pain. And ultimately, he or she may need to have the area opened up again.

Thus, drug-coated stents have become wildly popular, thanks in part to what The Annals of Internal Medicine describes as “aggressive marketing” and the unbridled expectations of patients Wall Street likes them too. At $2300 a pop (vs. a mere $700 for the uncoated, bare-metal variety), the newer stents are far more profitable. Despite the hoopla, nine months ago THCB was once again forced to ask “Are Stents A Waste of Money?” after reading about a study of 826 patients, published in Lancet, which suggested that the drug-coated stents made by J&J and Boston Scientific aren’t cost-effective for all patients and should be restricted to those at highest risk for heart attack.

A second 2005 study, published in The New England Journal of Medicine, added to the uncertainty about the widespread use of stents by reporting that patients suffering minor heart attacks do equally well with drug therapy. "In a study colliding with established practice, recovery from small heart attacks went just as well when doctors gave cardiac drugs time to work as when they favored quick, vessel-clearing procedures,” the NEJM reported. "The surprising Dutch finding raises questions over how to handle the estimated 1.5 million Americans annually who have small heart attacks – the most common kind. Most previous studies support the aggressive, surgical approach. ‘I think both strategies are more or less equivalent. I think it is more a matter of patient preference, doctor preference, logistics and, in the long run, it could be a matter of cost,’ said the Dutch study’s lead researcher, Dr. Robbert J. de Winter of the University Amsterdam."

Against that background, it should come as no surprise that the newest study published in the Annals last week is making hospitals think twice about using coated stents.

For
according to the Cedar-Sinai researchers, the benefits just don’t
justify the price–especially when drug-coated stents are compared to
the newest, thinnest bare-metal stent available. But that’s not what
the products’ backers used as a point of comparison. Instead, when
companies like Boston Scientific ran clinical trials to show the
superiority of their coated stent, they compared it to “thick-strut
stents” which, the Cedars Sinai researchers point out, increase the risk of scarring:

Had
the trials used the best available benchmark—thin-strut stents . . .
instead of a suboptimal [thick-strut] bare metal stent—they may have
determined a more reliable estimate of the true benefits of a
drug-coated stent in reducing scarring. Thus, the impressive
[performance of the coated stent] observed in the pivotal trials may,
in fact, be exaggerated because of the "inferior performance" of the
control bare metal stent compared with the "superior performance" of
the [drug-coated] stent.

But it’s not just that manufacturers
over-estimated the benefits; they underestimated the new risk that the
coated stent introduces. For after reviewing outcomes research, Cedars Sinai’s clinicians found that
the drug-coated stents increase the danger that a blood clot will form
inside the stent– months, or even years after the procedure. Such
clots can be life-threatening. One study suggests that they lead to
death about half the time. Why do the coated stents encourage clotting?
Because the drug which discourages scarring also inhibits healing
around the stent, The Wall Street Journal explains: 

“leaving
an area akin to an open wound that attracts blood clots. Doctors
generally prescribe anti-clotting drugs to stent recipients, and
manufacturers recommend that those with drug-coated stents take them
for three to six months. But some doctors say the anti-clotting drugs
— which cause rashes and bleeding and cost about $100 a month — could
be needed indefinitely.”

Given the risks, the cost, and the limited benefits of the $2300 stent, the  Cedars Sinai researchers concluded:
"it makes little clinical, economic, or common sense to forsake a
therapy that works well for most patients (bare metal stent) in favor
of a costly new therapy (drug-eluting stent) that has no effect on
important clinical outcomes but increases the risk for stent thrombosis
[clotting], a life-threatening complication."

Practicing
what they preach, physicians at Cedars Sinai doubled their use of
bare-metal stents (from 7% of all stents to 14%) in the first four
months of this year. And they are not alone.

According to the Journal,
doctors at the Cleveland Clinic, the University Chicago and Brigham and
Women’s Hospital in Boston all report a “small but significant decline”
in their use of coated stents. Not all physicians agree—and this most
recent study is far from the last word on drug-coated stents. No doubt
the controversy will continue. But the accumulated weight of evidence
does suggest that the costly coated stents may have been used too often
in recent years. (It is worth noting that just last fall, Dr. Eric Topol, chairman of the cardiology department at the Cleveland Clinic, warned Consumer Reports that
excessive enthusiasm could be leading to overuse). "Unfortunately, the
extensive use of such stents is far ahead of the data that can be cited
to support them."

What’s
certain is that the stent story illustrates a major problem in our
money-driven health care system. When a product is very profitable, it
is promoted to the skies—and, in such cases manufacturers tend to put
the very best face on their clinical research. A head-turning study
published last month in the Journal of the American Medical Association comparing
clinical trials funded by for-profit entities to clinical trials funded
by nonprofit entities underlines the point: it seems that  that
the industry-funded trials were far more likely to report positive
findings.

 

Of
104 trials funded solely by nonprofits, just 49 percent reported
evidence favoring the newer treatment while 51 percent favored the
existing standard of care or showed no difference between the two. By
contrast, of the 127 trials funded solely by industry, more than
two-thirds favored the new treatment.What’s striking is that the
average rate of success in the nonprofit trials corresponds very
closely to the average rate of success in phase III randomized clinical
trials of new medical products. Even when researchers’ belief that the
new therapy is better than existing therapies is based on good
preliminary evidence, the results of phase III randomized clinical
trials prove them wrong about half of the time.

 

Most
patients (and even many physicians) tend to assume that, when it comes
to medical technologies, "newer" means "better.” This is why, when
asked to participate in a randomized clinical trial, some patients
refuse, fearing that they will “miss out” on receiving what they assume
is the newer, better product. Yet the odds that the bleeding-edge
therapy will be better are only about 50/50. As Americans we tend to
believe in what’s new—as if medical science progressed  in a straight linear fashion, one breakthrough after another, from Madame Curie to me.  As a result, we pay  more—and more—and more—as drug makers and device-makers flood the market with “new, improved” products.

In Money-Driven Medicine: The Real Reason Health Care Costs So Much,
I quote Kaiser Permanente CEO George Halverson who points out that few
modern researchers are willing to risk betting their own money on their
newest products or procedures. In some cases, he reports, when health
care plans have been asked to cover a new, as yet unproven treatment,
they have said: ‘Try it. If it works, we’ll pick up the bill. If it
fails, then it’s your cost, not ours.’”

Researchers
virtually never take the bet because they “know that most research
fails,” say Halvorson. “So having their personal incomes tied to the
actual success of their unproven care isn’t at all attractive. There is
some irony in the fact that the same researchers who enthusiastically
extend hope to individual patients are, almost without exception, far
too practical about the actual value of their experimental care to risk
their own income.”

The tale of the drug-coated stent serves as a reminder: all
that can be said with certainty about the newest therapies is that we
know less about them. In some cases, time proves the merit of
miraculous breakthroughs, but for every success there are many
failures. And in some cases, it can be years before the risks of a much
ballyhooed product become apparent.