Doctors wary after cholesterol drug flop
Sun, 30 Mar 2008 21:53:39 GMT
By MARILYNN MARCHIONE, AP Medical Writer
CHICAGO - Leading doctors urged a return to older, tried-and-true treatments for high cholesterol after hearing full results Sunday of a failed trial of Vytorin.
Millions of Americans already take the drug or one of its components, Zetia. But doctors were stunned to learn that Vytorin failed to improve heart disease even though it worked as intended to reduce three key risk factors.
"People need to turn back to statins," said
Yale University cardiologist Dr. Harlan Krumholz, referring to Lipitor, Crestor and other widely used brands. "We know that statins are good drugs. We know that they reduce risks."
The study was closely watched because Zetia and Vytorin have racked up $5 billion in sales despite limited proof of benefit. Two Congressional panels launched probes into why it took drugmakers nearly two years after the study's completion to release results.
Results were presented at an American College of Cardiology conference in
Chicago Sunday and published on the Internet by the
New England Journal of Medicine.
Doctors have long focused on lowering LDL or
bad cholesterol as a way to prevent heart disease. Statins like
Merck & Co.'s Zocor, which recently came out in generic form, do this, as do niacin, fibrates and other medicines.
Vytorin, which came out in 2004, combines Zocor with
Schering-Plough Corp.'s Zetia, which went on sale in 2002 and attacks cholesterol in a different way.
The study tested whether Vytorin was better than Zocor alone at limiting plaque buildup in the arteries of 720 people with super high cholesterol because of a gene disorder.
The results show the drug had "no result — zilch. In no subgroup, in no segment, was there any added benefit" for reducing plaque, said Dr. John Kastelein, the Dutch scientist who led the study.
That happened even though Vytorin dramatically lowered LDL, fats in the blood called
triglycerides and a measure of artery inflammation — CRP.
Some doctors noted that hormone pills for menopausal women and torcetrapib, a promising cholesterol drug
Pfizer Inc. recently abandoned, also lowered cholesterol but were found in big studies to raise heart risks, not lower them.
Another ominous sign was the decision Friday by other researchers to expand enrollment in a more pivotal study of Vytorin to 18,000 people because early results suggest it will be harder than anticipated to see if it is any better than Zocor alone.
"It will be 2012 — ten years after the drug was introduced — before we know the answer," said Dr. Steven Nissen, a Cleveland Clinic cardiologist who has no role in the studies and has criticized the drugmakers over the one reported Sunday.
Dr. Robert Spiegel, chief medical officer for
Schering-Plough, said the study was done "with the highest integrity" and that doctors can believe the results "because of the time we took to make sure the data are right."
"We were disappointed that it was not a very balanced panel discussion" by the heart doctors who urged their peers to focus on more established treatments.
However, Kastelein said the data were far more consistent than anticipated and ample to show that the drug simply did not work.
"A lot of us thought that there would be some glimmer of benefit," said Dr. Roger Blumenthal, a
Johns Hopkins University cardiologist and spokesman for the
American Heart Association.
Many doctors have prescribed Vytorin without trying older, proven medications first, as guidelines advise. The key message from the study is "don't do that," Blumenthal said.
No one should ever stop any heart drug without talking with their doctors, heart specialists stressed.
However, doctors "should be thinking twice," said
Duke University cardiologist Dr. Robert Califf. He takes the drug himself because he cannot tolerate the high dose of statins he otherwise would need.
Dr. James Stein, director of preventive cardiology at the
University of Wisconsin-Madison, said many doctors prescribe Zetia and Vytorin because they seem to be safe ways to get cholesterol down quickly, without annoying side effects like flushing that some other medicines carry.
Stein, who has consulted for Schering-Plough, said that after six years on the market, it would have been good to see better results on a drug so many doctors believed would help, "but the reason we do research is so we don't have to rely on our 'beliefs' — we can rely on data."
The
New England Journal also published a report showing that Vytorin and Zetia's use soared in the United States amid a $200 million advertising blitz. In
Canada, where marketing drugs directly to consumers is not allowed, sales were four times lower.
Merck is based in
Whitehouse Station, N.J.; Schering-Plough, in Kenilworth, N.J.
In addition to the two Congressional committee probes, New York State
Attorney General Andrew Cuomo subpoenaed the companies in a similar probe in January.
"While these corporations profited, Americans were left in the dark," Cuomo said in a written statement Sunday. "The millions who take this drug, taxpayers who subsidize its use through the Medicaid and Medicare programs, and Merck and Schering-Plough's investors deserve to know why it took so long for the results to be made public. This new information underscores our concerns and advances our investigation, which we will pursue aggressively."
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On the Net:
New England Journal: http://www.nejm.org
Cardiology conference: http://www.acc.org
Small hospitals push to do heart work
Sat, 29 Mar 2008 18:13:16 GMT
By MARILYNN MARCHIONE and LINDA A. JOHNSON, Associated Press Writers
CHICAGO - Is it safe to have your arteries unclogged at a hospital that lacks heart surgeons who can operate if something goes wrong?
Many states ban this except in emergencies like heart attacks. But more small hospitals are trying it in non-urgent cases, and the largest study ever done of this, released on Saturday, suggests it may not be as risky as has been feared.
If confirmed by other ongoing studies, it could change policies in many states. That would mean money for community hospitals struggling to stay profitable and options for patients who must travel to big cities for care.
"What we don't want is a huge proliferation of hospitals" doing this without strict quality safeguards, or in places that already have many heart centers, said Dr. Ralph Brindis, a heart specialist at the California-based Kaiser Permanente health plan.
He heads a 300,000-patient national database maintained by the
American College of Cardiology used in the study. Results were reported at a joint meeting of several cardiology groups in
Chicago.
Blocked arteries deprive the heart of blood and can lead to a heart attack. A popular treatment is angioplasty. Doctors push a tiny balloon into an artery, inflate it to flatten the clog, and often place a stent to prop the vessel open.
Medical guidelines allow most hospitals to do these for heart attacks. However, most angioplasties are for chest pain and non-urgent situations, and the rules say hospitals should not offer these unless they have doctors who can do bypass surgery if problems arise.
Small hospitals, which can earn $15,000 or more on each angioplasty, have pressed for a new look at the guidelines. They say stents that came on the market in recent years have made angioplasty safer, by limiting how many times the balloon is inflated and the risk of puncturing an artery.
The patient registry is not definitive science, but suggests that at small hospitals doing this now, with strict quality controls, safety is pretty good.
Researchers compared results from January 2004 through March 2006 on 9,029 patients who had angioplasty at 61 centers without on-site cardiac surgery to 299,132 patients at 404 centers with heart surgeons. Only about half of the hospitals without surgical backup did more than three dozen angioplasties a year.
Yet complications and success rates were similar, said study leader Dr. Michael Kutcher of
Wake Forest University in
Winston-Salem, N.C.
Roughly four of every 1,000 patients needed emergency bypass surgery — far less than in the past. Nearly 2 percent died at hospitals without backup surgery versus just over 1 percent at larger hospitals, but there was no significant difference once researchers factored in age, severity of illness and other differences among patients.
Results did not differ for urgent or non-urgent angioplasties, though a greater portion of those at small hospitals were emergencies.
The findings should lead to a new look at the guidelines, Brindis said.
"We know from European centers that it can be done safely and effectively. Over half of all angioplasties in
Europe and in many countries are done without on-site surgical backup," he said.
"It could have a huge impact in this country," said Dr. W. Douglas Weaver, a
Detroit heart specialist and president-elect of the
American College of Cardiology.
Dr. Harlan Krumholz, a quality-of-care researcher at
Yale University School of Medicine, said: "I think we are at a place where it can be done safely. But there is no reason to do it unless there is not a major center nearby. That is the catch — we should not have these everywhere."
The issue has been most contentious in
New Jersey. The nation's most densely populated state has 18 hospitals with heart surgery programs — one within a half-hour of virtually every resident — and they don't want more competition.
New Jersey's participation in a nine-state study comparing how patients fare at hospitals with and without heart surgeons led to a lawsuit against the state. Some big hospitals claimed patient safety was jeopardized, but a court allowed the state to remain in the study. The results aren't expected for at least two years.
James and Marie Clark of Roselle Park, N.J., took part in the study. Marie, 76, had nonemergency angioplasty and a stent last September; her 75-year-old husband got the same treatment last week, both at
Raritan Bay Medical Center, a 388-bed community hospital in northeastern New Jersey.
Both said they had no qualms about going to a hospital without backup heart surgeons because their longtime cardiologist did the procedures.
"I didn't have any fear," said James Clark, a retired electrician. "I just didn't give it a thought."
Doctors will wait for more definitive studies to say the practice is safe, said Brindis, the Kaiser Permanente doctor.
"What they're concerned about is, is it the best possible practice? If all things were equal would it be best for your aunt to have angioplasty in a hospital with surgical backup?"
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Medical writer Marilynn Marchione reported from
Chicago; Business writer Linda A. Johnson reported from Trenton, N.J.
