Re: New Questions on Treating Cholesterol

On Fri, 18 Jan 2008 06:07:09 -0800, Rita <Rita@xxxxxxxxxxx> wrote:

On Thu, 17 Jan 2008 23:44:14 -0800, El Castor <No_One@xxxxxxxx> wrote:

On Thu, 17 Jan 2008 17:26:49 -0800, Rita <Rita@xxxxxxxxxxx> wrote:

New York Times
January 17, 2008
New Questions on Treating Cholesterol
By ALEX BERENSON

For decades, the theory that lowering cholesterol is always beneficial
has been a core principle of cardiology. It has been accepted by
doctors and used by drug makers to win quick approval for new
medicines to reduce cholesterol.

But now some prominent cardiologists say the results of two recent
clinical trials have raised serious questions about that theory ? and
the value of two widely used cholesterol-lowering medicines, Zetia and
its sister drug, Vytorin.

Duh. Zetia is unique and is not a statin and Vytorin is just Zetia
combined with a statin. The statin alone works fine. It is Zetia that
is the problem.

Other new cholesterol-fighting drugs,
including one that Merck hopes to begin selling this year, may also
require closer scrutiny, they say.

?The idea that you?re just going to lower LDL and people are going to
get better, that?s too simplistic, much too simplistic,? said Dr. Eric
J. Topol, a cardiologist and director of the Scripps Translational
Science Institute in La Jolla, Calif. LDL, or low-density lipoprotein,
is the so-called bad cholesterol, in contrast to high-density
lipoprotein, or HDL.

The beneficial effects of statins have been amply demonstrated, but I
strongly recommend that every drug company hating lefty in this group
throw their statins in the trash and go holistic. If I got down on one
knee and begged, would that help? This entire post is disgusting
hyperbole.

For patients and drug companies, the stakes are enormous. Led by best
sellers like Lipitor from Pfizer, cholesterol-lowering medicines,
taken by tens of millions of patients daily, are the largest drug
category worldwide, with annual sales of $40 billion.

Despite widespread use of the drugs, though, heart disease remains the
biggest killer in the United States and other industrialized nations,
and many people still have cholesterol levels far higher than doctors
recommend.

As a result, drug companies are investing billions of dollars in
experimental new cholesterol-lowering medicines that may eventually be
used alongside the existing drugs. If the new questions result in
slower approvals, it would be yet another handicap for the drug
industry.

Because the link between excessive LDL cholesterol and cardiovascular
disease has been so widely accepted, the Food and Drug Administration
generally has not required drug companies to prove that cholesterol
medicines actually reduce heart attacks before approval.

They have not had to conduct so-called outcome or events trials
beforehand, which are expensive studies that involve thousands of
patients and track whether episodes like heart attacks are reduced.

So far, proof that a drug lowers LDL cholesterol has generally been
enough to lead to approval. Only then does the drug?s maker begin an
events trial. And until the results of that trial are available, a
process that can take several years, doctors and patients must accept
the medicine?s benefits largely on faith.

?You?ve got a huge chasm between F.D.A. licensure and a clinical
events trial,? said Dr. Allen J. Taylor, the chief of cardiology at
Walter Reed Army Medical Center.

Nonetheless, the multistep process has worked well for several
cholesterol drugs ? including Lipitor and Zocor, which are in a class
of drugs known as statins. In those cases, the postapproval trials
confirmed that the drugs reduce heart attacks and strokes, adding to
confidence about the link between cholesterol and heart disease.

Doctors generally believe that the amount by which cholesterol is
lowered, not the method of lowering it, is what matters.

That continues to be the assumption of Dr. Scott M. Grundy, a
professor of medicine at the University of Texas Southwestern Medical
Center who was the chairman of a panel in 2001 that set national
guidelines for cholesterol treatment.

?LDL lowering, however it occurs, delays development of coronary
atherosclerosis and reduces risk for heart attack,? Dr. Grundy said
this week. In atherosclerosis, plaque builds up in the arteries,
eventually leading to blood clots and other problems that cause heart
attacks and strokes.

In the last 13 months, however, the failures of two important clinical
trials have thrown that hypothesis into question.

First, Pfizer stopped development of its experimental cholesterol drug
torcetrapib in December 2006, when a trial involving 15,000 patients
showed that the medicine caused heart attacks and strokes. That trial
? somewhat unusual in that it was conducted before Pfizer sought
F.D.A. approval ? also showed that torcetrapib lowered LDL cholesterol
while raising HDL, or good cholesterol.

Torcetrapib?s failure, Dr. Taylor said, shows that lowering
cholesterol alone does not prove a drug will benefit patients.

Then, on Monday, Merck and Schering-Plough announced that Vytorin,
which combines Zetia with Zocor, had failed to reduce the growth of
fatty arterial plaque in a trial of 720 patients. In fact, patients
taking Vytorin actually had more plaque growth than those who took
Zocor alone.

Despite those drawbacks, that trial, called Enhance, also showed that
patients on Vytorin had lower LDL levels than those on Zocor alone.
For the second time in just over a year, a clinical trial found that
LDL reduction did not translate into measurable medical benefits.

The Enhance trial was not an events trial and was not intended to
study whether Zetia or Vytorin were effective at reducing heart
attacks. But the growth of fatty plaque is closely correlated with
heart attacks and strokes.

Without data from events trials for Zetia and Vytorin, no one can be
certain if the drugs help or hurt patients. But Merck and Schering did
not begin an events trial for the drugs until 2006, nearly four years
after the F.D.A. approved Zetia. That trial will not be completed
until 2011.

Dr. Robert M. Califf, the vice chancellor for clinical research at
Duke University, and a co-lead investigator on the Zetia trial still
under way, said companies should have started the trials more quickly.
?Outcome trials ought to start when you know you?re going to get on
the market,? he said.

On Tuesday, the American Heart Association called for the Zetia
outcome trial to be completed as quickly as possible.

Merck has asked the F.D.A. to approve its drug Cordaptive, which
raises HDL cholesterol and lowers LDL, without waiting for the results
of an events trial. Merck has begun an events trial for Cordaptive,
but data will not be available until 2013.

Merck has submitted the application for Cordaptive and has said it
expects an answer from the F.D.A. before July. Doctors, patients and
the drug industry will be waiting to see whether regulators are still
willing to accept the theory that lower cholesterol is always a good
thing.

May or may not be only hyperbole. I think there will be fewer true
believers however about a drug that has not gone through the time
consuming "outcome trials." And that is to the good as every drug
needs to be vetted in this manner.

Research on statins began in the 50's, and was taken over by an
American drug company in 1978. After wading through layers of
bureaucracy and test upon test they brought lovastatin to the market
nine years later. Since then there have been many more studies and
statin drugs have prevented literally millions of heart attacks and
strokes. So you get all upset and wave your arms in the air when Zetia
(a non-statin) is shown to be worthless -- not significantly harmful,
just not beneficial. How about the millions who have been helped by
other drugs? How many more years would you have people wait and die to
satisfy your hatred of drug companies and thirst for absolute proof?
How many extra years in excess of nine should we have waited for
lovastatin?

if statins cause you grief then please don't take them. As a member of
the other 95%, I will continue to enjoy the benefits.

.

Relevant Pages

  • Re: Cholesterol Drug Has No Benefit in Trial
    ... Many cholesterol drugs do that, ... A clinical trial of Zetia, a cholesterol-lowering drug prescribed to about 1 ... trial has ever shown that it can reduce heart attacks and strokes - or even ...
    (soc.retirement)
  • Re: Cholesterol Drug Has No Benefit in Trial
    ... Many cholesterol drugs do that, ... A clinical trial of Zetia, a cholesterol-lowering drug prescribed to about 1 ... some few people have livers that react badly to statins. ...
    (soc.retirement)
  • Re: Cholesterol Drug Zetia Doesnt Benefit Health
    ... Zetia, a cholesterol-lowering drug prescribed to about a million ... shows the drug confers no medical benefit to users. ... almost doubled in patients taking Zetia (ezetimibe) along with another ... No one is disputing that Zetia can lower levels of LDL "bad" cholesterol ...
    (sci.med.cardiology)
  • Cholesterol Drug Zetia Doesnt Benefit Health
    ... Zetia, a cholesterol-lowering drug prescribed to about a million ... shows the drug confers no medical benefit to users. ... Zocor alone, the study found. ... No one is disputing that Zetia can lower levels of LDL "bad" cholesterol ...
    (sci.med.cardiology)
  • Cholesterol as a Danger Has Skeptics
    ... Cholesterol as a Danger Has Skeptics ... its sister drug, Vytorin. ... For patients and drug companies, ... patients and track whether episodes like heart attacks are reduced. ...
    (sci.med.cardiology)