A Heart Stent Gets a Reprieve From Doctors

A Heart Stent Gets a Reprieve From

A year after safety questions about drug-coated heart stents prompted doctors to change treatment for hundreds of thousands of cardiac patients, many physicians say the medical community overreacted and should now reverse course.

 

The alarm was caused by medical studies suggesting that drug-coated stents might be causing deadly blood clots. But with benefit of additional data and further analysis, many doctors say drug-coated stents may not be so risky after all, at least compared with various alternatives whose drawbacks may outweigh the risks of clotting.

Because the safety fears were widespread, however, even those rooting hardest for a rebound — the companies that make stents — are not expecting a quick resurgence for the drug-coated devices. Worldwide, stent sales have fallen by about $1 billion since last year, to $5 billion this year.

In the United States, stenting procedures, whether using drug-coated stents or older bare-metal versions, have declined by about 10 percent in the last year. And within that smaller pie the share of drug-coated stents has shrunk even more, to about 64 percent in recent months, down from about 88 percent in the spring of 2006.

“It takes a lot longer to regrow a forest than to cut it down,” said Dr. Donald S. Baim, the chief medical officer for Boston Scientific, the market leader in stents.

While fears about the safety of drug-coated stents are seen as a major factor in the decline of stenting, studies showing good results in patients relying solely on drugs have also contributed to the decline.

Stents are among the most extensively studied products in the history of the medical device industry. But the torrent of performance data reflects the largely uncoordinated and piecemeal way that medical research is gathered and publicized, and the medical uncertainty than can result.

Drug-coated stents are the newest and most popular form of the tiny mesh cylinders, which are used to keep coronary arteries propped open after plaque blockages have been cleared through the procedure known as angioplasty. The drug coatings reduce the risk of reclogging at the stent site, as frequently happens with the bare-metal versions. But the studies last year indicated the drug-coated versions could cause blood clots months or even years after they are implanted.

The medical reports of blood clots were amplified by sometimes alarmist media coverage, as when one cable news network described drug-coated stents as “tiny time bombs.” And federal regulators weighed in, issuing cautionary statements about the clotting risk.

Doctors responded by prescribing long-term use of a potent anticlotting medicine for drug-coated stent patients — a course that raised costs and the risks of various side effects. Many patients avoided the stents altogether in favor of alternative treatments, including bypass operations, with their own attendant risks.

Now, though, for drug-coated stents “there really is a turnaround in the texture and the direction of the data,” said Dr. Eric J. Topol, a cardiologist at the Scripps Clinic in La Jolla, Calif. Dr. Topol was among those chosen by the Food and Drug Administration to serve on an expert advisory panel on stent safety last December, which concluded that the clotting hazard was real.

While none of last year’s concerns have been proved unfounded, Dr. Topol said, the newer data indicate that a return to higher use of drug-coated stents is appropriate “if you are going to practice evidence-based medicine.”

Some experts still contend that the lesson of the last year is that all but the sickest patients should think twice about getting any form of stent. The first effort with coronary artery disease, they say, should be making changes in diet and exercise, and taking drugs like statins to reduce cholesterol and beta-blockers to control hypertension and heart rhythm.

A report presented last week at the annual meeting of the American Heart Association concluded that stents often are of little use for patients whose only symptoms are occasional chest pains. That group includes at least 30 percent of those who typically get stents and perhaps considerably more, according to the lead author of the study, Dr. William S. Weintraub, the chief of cardiology at the Christiana Health System’s Center for Outcomes Research in Newark, Del.

Still, for the sickest patients, there seems to be little disagreement that stents can help. And now, after re-examining last year’s original clinical trial data and looking at studies involving tens of thousands of real-world patients, the common view is that there is no safety disadvantage in using drug-coated stents in most patients after angioplasty.

“Safety is not the big issue any more,” said Dr. Jeffrey W. Moses, a cardiologist in New York at Columbia University’s Cardiovascular Research Foundation, the organization that — with strong financial support from industry — runs the largest annual meeting for interventionalists, as doctors who use stents are known.

The worrisome clotting data were first reported at a March 2006 cardiology meeting. But wider attention was paid only after two more studies with similar conclusions were reported six months later at another meeting in Europe. A short time later, Boston Scientific reported that its own data confirmed the clotting hazard.

Even as anxiety rose among the more than 1.5 million Americans who already had the stents, most new stent candidates continued to get the drug-coated devices.

But cardiologists, newly cautious, placed those patients on a regimen of anticlotting drugs for a year or more, instead of the few months that had previously been standard practice. The drugs’ protection came with the risk of unwanted bleeding and at the cost of about $1,400 in prescriptions annually. This new regimen continues to be the recommended course of treatment, as a precaution against even the slight risk of clotting. 

Meanwhile, tens of thousands of other American heart patients decided to avoid drug-coated stents altogether. Some of the sickest opted for bypass operations, with all the risks and discomfort that major surgery entails. Many more received bare-metal stents — older products that studies indicated were less prone to the clotting risk but that are often not as effective at keeping arteries open.

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And still other patients, typically those with less severe symptoms like intermittent chest pains and shortness of breath, decided to rely entirely on cholesterol and hypertension drugs for relief.

One major influence on those choices was the warning last December by the F.D.A.’s expert panel that most of the drug-coated stents were being put in patients who were sicker than those who had been studied in the clinical trials. Those real-world patients, the panel worried, might be even more vulnerable to the clotting than the test patients had been.

But newer evidence indicates that while sicker patients do have higher clotting risks, they may also reap the greatest benefits from the drug-coated stents’ ability to keep arteries open longer. There are even hints that the stents improve survival rates for such patients.

When drug-coated stents reached the American market in 2003, some researchers predicted they could present unique clotting risks. But many doctors expected that the devices would save lives compared with bare-metal stents. Because the drug coatings made it less likely that the stent site would become reclogged, they reasoned, there would be less need for repeat procedures.

So it was unnerving last year when researchers began reporting that the newer stents might actually be less medically safe in the long run. The formation of clots long after the stents had been put in place became known as “late stent thrombosis” to distinguish it from the slight but already known danger of clotting that can occur during any stenting procedure or shortly after.

But now many advocates of the stents say the safety calculus may even be swinging in favor of drug-coated stents. They cite reports like a recently published study tracking 7,500 patients who received stents between 2003 and 2005 in Ontario. That study concluded that the sicker patients with drug-coated stents are experiencing lower death rates than comparable patients who got bare-metal devices.

The biggest American study yet, which has not yet been published but was presented Monday at the American Heart Association meeting, checked on the health after two years of more than 17,000 patients who received stents in Massachusetts from April 2003 to September 2005.

There was a clear safety advantage for drug-coated stents: 9.4 percent of the drug-coated stent patients had died, compared with 11.9 percent of those that got bare-metal stents.

But the uncertainties are likely to continue with newer types of drug-coated stents on the horizon. The new models have thinner struts and different coatings, which some studies suggest are less likely to lead to late stent thrombosis.

One new model, the Endeavor, made by Medtronic, may get clearance from the F.D.A. as early as next month. And Abbott Laboratories’ Xience V, which Boston Scientific will also market under the Promus name, may arrive by next summer.

Those stents and numerous others are already used overseas. But there are no long-term clinical trials that demonstrate they are better at saving lives. And some experts predict it will remain impossible to conduct trials that settle all the safety questions before the industry moves on to even newer designs — and new uncertainties. 

Report: Ban Cloning or Prepare for Consequences

Report: Ban Cloning or Prepare for Consequences

Human cloning should be outlawed or else the world community needs to prepare to protect clones from potential abuse and discrimination, according to a new policy analysis by the United Nations University.

A legally-binding global ban on work to create a human clone , coupled with freedom for nations to permit strictly controlled therapeutic research, has the greatest political viability among options available to the international community, says the report, "Is Human Reproductive Cloning Inevitable: Future Options for UN Governance," released Nov. 12 by A.H. Zakri, director of UNU's Institute of Advanced Studies, based in Japan.

More than 50 nations have legislated bans on efforts to create human clones, said report co-author Brendan Tobin, although the United States is not yet one of them. However, negotiation of an international accord foundered at the UN in recent years due to disagreement over research cloning (also called therapeutic cloning).

Without an international prohibition, human reproductive cloning in certain countries could be judged legal by the International Court of Justice, said Tobin, of the Irish Center for Human Rights, National University of Ireland, Galway.

“Failure to outlaw reproductive cloning means it is just a matter of time until cloned individuals share the planet,” Tobin said.

“If failure to compromise continues, the world community must accept responsibility and ensure that any cloned individual receives full human rights protection. It will also need to embark on an extensive awareness building and sensitivity program to ensure that the wider society treats clones with respect and ensure they are protected against prejudice, abuse or discrimination.”

There have been no substantiated claims of cloned human embryos grown into fetal stages and beyond, but such an historic event is not far off, most experts agree.

Clones have been achieved with mice, cats, sheep, pigs, cows and dogs and U.S. researchers last summer accomplished the first cloning of a primate—a rhesus monkey embryo cloned from adult cells and then grown to generate stem cells.

Reproductive vs. therapeutic cloning

The report calls the prospect of human cloning “one of the most emotive and divisive issues to face UN negotiators and the international community in recent years.”

Efforts in 2005 to negotiate an international convention fell through over so-called research or therapeutic cloning.
Whereas reproductive cloning is meant to duplicate a person or animal, research cloning is meant to produce tissues that genetically match those of the person or animal whose cells are cloned.

Proponents of research cloning for regenerative medicine say it offers great hope of producing replacement tissue without the fear of immunological rejection, and that it offers a potential cure for millions of people suffering common diseases of the industrialized world—diabetes, stroke, spinal injury and neurodegenerative diseases such as Alzheimer’s or Parkinson’s.

Opponents view research cloning as the unethical production and destruction of living embryos to produce stem cells upon which such therapies are based. The clash of positions led to a compromise non-binding UN Declaration on Cloning.

Ethics

The report explores in depth the difficult ethical considerations behind the issue. Some cloning opponents claim reproduction should occur by chance and through natural selection. This argument may be based upon religious lines, or to natural selection and the importance of ensuring continued human diversity.

Others claim that cloning will turn human life into a commodity, leading to a spare parts market for harvesting human organs from cloned “brain-less bodies” for the rich as they seek to extend their lifespan.

“These are not issues which can be lightly dismissed," the authors wrote. "However, it is clear that any debate on human dignity needs to separate the various elements of the debate in order to consider whether opposition to cloning stems from concern for human dignity or respect for divine dignity.” 

The Birth of a Brain Cell: Scientists Witness Neurogenesis

The Birth of a Brain Cell: Scientists Witness Neurogenesis

New method allows researchers to pinpoint young nerve cells in the living human brain

	SQUARE MARKS THE SPOT:  New neurons visualized via NMR spectroscopy. The methodology may allow researchers to see how young neurons behave in neurological disorders.

For the first time, researchers have developed a way to view stem cells in the brains of living animals, including humans—a finding that allows scientists to follow the process neurogenesis (the birth of neurons). The discovery comes just months after scientists confirmed that such cells are generated in adult as well as developing brains.

"I was looking for a method that would enable us to study these cells through[out a] life span," says Mirjana Maletic-Savatic, an assistant professor of neurology at Stony Brook University in New York State, who specializes in neurological disorders such as cerebral palsy that premature and low-weight babies are at greater risk of developing. She says the new technique will enable her to track children at risk by monitoring the quantity and behavior of these so-called progenitor cells in their brains.

The key ingredient in this process is a substance unique to immature cells that is neither found in mature neurons nor in glia, the brain's nonneuronal support cells. Maletic-Savatic and her colleagues collected samples of each of the three cell types from rat brains (stem cells from embryonic animals, the others from adults) and cultured the varieties separately in the lab. They were able to determine the chemical makeup of each variety—and isolate the compound unique to stem cells—with nuclear magnetic resonance (NMR) spectroscopy. (NMR helps to determine a molecule's structure by measuring the magnetic properties of its subatomic particles.) Although the NMR could identify the biomarker, but not its makeup, Maletic-Savatic speculates it is a blend of fatty acids in a lipid (fat) or lipid protein. 

After pinpointing their marker, the team ran two tests to determine the method's sensitivity and accuracy: First, they injected a bevy of stem cells into a rat's cerebral cortex, an outer brain layer where neurogenesis does not normally occur. They then passed an electric current through the animals' brains; electric currents induce neurogenesis in the hippocampus, a forebrain structure that is one of two sites (the other being the subventricular zone) where new neurons are believed to arise.

After performing each procedure, the team used NMR spectroscopy to capture images of the living rats' brains. There was, however, too much visual interference on the scans to find their biomarker. The researchers called upon Stony Brook electrical engineering professor Petar Djurić to help them come up with an algorithm to cut through the clutter and glean a clear picture of their target compound.

With the analytical method helping to decode their scans, they could clearly see increased biomarker levels in the cortex after a neural stem cell injection. Similarly, after the animals were given electric shocks, levels of the compound clearly went up in the hippocampus.

The team next turned its attention to humans, enlisting 11 healthy volunteers, ranging in age from eight to 35, who each spent 45 minutes in an NMR scanner. Hippocampal scans turned up more of the marker than the cortical images. In addition, the older subjects showed lower levels of the biomarker than younger ones (a finding consistent with earlier studies). "This is the first technique that allows detection of these cells in the living human brain," says Maletic-Savatic.

Fred Gage, a genetics professor at the Salk Institute for Biological Studies in La Jolla, Calif., and co-author a 1998 report in Nature Medicine that announced the discovery of neurogenesis in the adult human brain, praises the new approach. "It seems that they are measuring proliferation rather then maturation based on their results," he says. "It will be important for them to knock down neurogenesis in a mouse and show that [this] signal disappears to confirm the causal link with neurogenesis."

If the new work is replicated and confirmed, it may allow for faster diagnosis and tracking of myriad psychiatric and neurological conditions. Among them: chronic depression. Study co-author Grigori Enikolopov, an associate professor of molecular biology at Cold Spring Harbor Laboratory in Long Island, N.Y., showed last year that antidepressants lead to new nervous system cells, raising questions about the role these cells play in the causation of the ailment.

"Although we are only just beginning to test applications, it is clear that this biomarker may have promise in identifying cell proliferation in the brain, which can be a sign of cancer," Enikolopov says. "In other patients, it could show us how neurogenesis is related to the course of diseases such as depression, bipolar disorder, Alzheimer's, Parkinson's, MS, and post-traumatic stress disorder." 

NASA pressed to avert catastrophic Deep Impact

NASA pressed to avert catastrophic Deep Impact

NASA penny-pinching risks exposing humankind to a planetary catastrophe if a big enough asteroid evades detection and slams into Earth, US lawmakers warned Thursday.

But the US space agency said the chances of a new "Near-Earth Object" (NEO) like the one that wiped out the dinosaurs were too remote to divert scarce resources.

Scott Pace, head of program analysis and evaluation at NASA, said the agency could not do more to detect NEOs "given the constrained resources and the strategic objectives NASA already has been tasked with."

Pace and other NASA officials were grilled at a congressional hearing on the existing NEO program, which seized the public imagination in the late 1990s through the movies "Armageddon" and "Deep Impact."

Lawmakers decried the threatened closure of a giant radio telescope in Puerto Rico run with NASA's assistance that is the world's foremost facility for tracking space objects.

"We're talking about minimal expense compared to the cost of having to absorb this type of damage," Republican Congressman Dana Rohrabacher said. "After all, it may be the entire planet that is destroyed!"

Puerto Rico delegate Luis Fortuno fretted over the economic impact on his impoverished US territory, but also warned of the broader consequences for the entire planet.

"We must take action now to enhance our awareness to prevent a catastrophe," he told the hearing.

The National Science Foundation has earmarked the Arecibo Observatory, which featured in science-fiction movie "Contact" and the James Bond installment "Goldeneye," for closure after 2011 if new private-sector money is not found.

NASA officials said they would get by with new monitoring systems, including a network of four telescopes being built in Hawaii by the US Air Force.

Critics say NASA has imposed big cuts on many research programs in a bid to meet President George W. Bush's goal of returning astronauts to the Moon by 2020 and use it as a stepping stone for manned missions to Mars and beyond.

The hearing of the House of Representatives space and aeronautics subcommittee highlighted one small asteroid named Apophis, about 250 meters (273 yards) wide, which some scientists say could swing by Earth on Friday, April 13, 2029.

NASA says there is a one in 45,000 chance that Apophis could pass through a "gravitational keyhole" and return to hit the planet in 2036.

"It's a very unlikely situation and one we can drive to zero, probably," said Donald Yeomans, who manages the NEO program at NASA's Jet Propulsion Laboratory.

NASA now only tracks NEOs larger than one kilometer (0.62 miles) in diameter, which come near Earth only once every few hundred thousand years.

Objects of that size can cause global disaster through their immediate surface impact and by triggering rapid climate change.

"Extinction-class" objects measuring at least 10 kilometers, such as the object that crashed into Mexico's Yucatan peninsula about 65 million years ago, would be rarer still.

Lawmakers complained that NASA had failed to come up with a budget in line with a 2005 act of Congress that mandated an expanded search for NEOs that are at least 140 meters in diameter.

The agency's annual NEO budget of 4.1 million dollars was attacked as being too meager to cover this goal.

There are about 20,000 smaller objects with the potential to hit home, according to NASA, and Republican Representative Tom Feeney said "they could still inflict large regional impacts if they struck the Earth."

Options to divert space rocks on a collision course with Earth include slamming nuclear missiles into them, although scientists believes that in most cases involving smaller debris, conventional rockets would do the job.

Yeomans said also that while the European and Japanese space agencies are stepping up their own NEO programs, more than 98 percent of the work is now done by NASA.

 
Artist's rendition released by NASA shows an asteroid belt in orbit around a star. ...

Are Cigarettes More of a Drag on Teens than Marijuana?

Are Cigarettes More of a Drag on Teens than Marijuana?

New study shows that adolescents who toke up function better than those who also use tobacco

	SMOKING HABITS:  New study shows that teenagers who only use marijuana fare better than those who smoke both pot and cigarettes.

Reefer madness? Apparently not, according to a new Swiss survey of students that concludes teenagers who smoke pot function better than those who also use tobacco. In addition, researchers at the University of Lausanne report in the Archives of Pediatrics & Adolescent Medicine, teens who only use marijuana are apparently more socially driven and have no more psychosocial problems than those who neither smoke nor toke.

The scientists surveyed 5,263 Swiss students (2,439 females) aged 16 to 20 years, including 455 who said they smoked weed only; 1,703 who reported being tobacco and marijuana users; and 3,105 who said they did not imbibe at all. 

"The gateway theory hypothesizes that the use of legal drugs (tobacco and alcohol) is the previous step to cannabis consumption," the authors wrote. "However, recent research also indicates that cannabis use may precede or be simultaneous to tobacco use and that, in fact, its use may reinforce cigarette smoking or lead to nicotine addiction independently of smoking status."

Among their findings: Compared with students who reported using both drugs, those who smoked pot only were more likely to be male (71.6 percent versus 59.7 percent); get good grades (77.5 to 66.6 percent); play sports (85.5 to 66.7 percent); and live with both parents (78.2 to 68.3 percent).

Cannabis-only smokers were also less likely than their cigarette-and-joint smoking brethren to have used other illegal drugs or to have been soused or have used pot more than twice in the previous 30 days, according to the study.

In contrast to those who shunned both substances, the pot-only crowd was more likely to be male (71.6 to 47.7 percent); have a good relationship with friends (87 versus 83.2 percent); and play sports (85.5 versus 76.6 percent). They were less likely than the abstainers, however, to get along well with their parents (74.1 percent compared with 82.4).

The researchers stressed that whereas students who smoked and toked seemed more prone to psychosocial problems, the marijuana-only users should not be dismissed.

"Even though they do not seem to have great personal, family or academic problems," they wrote, "the situation of those adolescents who use cannabis but who declare not using tobacco should not be trivialized."

Groups working toward the decriminalization of marijuana especially for medical purposes praised the findings.

"Studies like this show associations, not cause and effect," says Bruce Mirken of the Washington, D.C.–based Marijuana Policy Project, a lobby that believes marijuana should be legalized but also regulated and taxed much like cigarettes and alcohol. "But the drug czar's office regularly uses associations between marijuana use and problems like poor grades to frighten parents into thinking that cause and effect is proven. So will [it] now say that smoking marijuana makes teens have better peer relationships and be more likely to participate in sports?"

"No one wants to encourage teens to smoke marijuana," he adds, "but this study strongly suggests that the most serious problems for teens and parents isn't occasional marijuana use, but heavy use of multiple substances, which is likely a sign of kids who are seriously troubled and need help."