The
findings were considered to be so important that The New
England Journal of Medicine made the study freely available
on its Web site one month earlier than the April 8 publication
date. Two cholesterol-lowering statin drugs—Lipitor (atorvastatin)
and Pravachol (pravastatin)—were compared in a clinical
trial that involved 4,162 people who had been hospitalized
for a sudden attack of chest pain due to heart disease.
Lipitor proved to be more effective at reducing the rate
of deaths from heart disease, heart-related problems and
the need for procedures, such as bypass surgery and angioplasty.
Once the news caught media attention, the reporting made
the benefit appear larger than it is.
Some
of the participants, all of whom had heart disease and
low levels of LDL, the so-called bad cholesterol, benefited
from even further reductions in their LDL with Lipitor.
The finding is widely expected to lead to a lowering of
what constitutes the ideal level of LDL. Currently, people
are told to keep their LDL below 100 mg.
The
participants had been randomly assigned to take either
a higher than normal dose of Lipitor (80 mg) or the standard
40 mg dose of Pravachol each day. Because of the high
stakes, drug companies rarely pit their drug against a
competitor in a clinical trial. Bristol-Myers Squibb,
maker of Pravachol, lost big time by sponsoring this trial.
It was designed to prove that Pravachol, which had been
losing market share, is just as good as the more costly
high dose Lipitor.
At
the time this trial was planned, Pravachol's highest dose
was 40 mg. The study is known by the catchy name of Prove
It,
or Pravastatin or
Atorvastatin Evaluation
and Infection Therapy.
Here
are the differences in outcomes in the Prove It trial:
After two years, the people on Pravachol had a combined
rate of heart attack, bypass surgery, angioplasty, stroke
and death of 26.3% compared with 22.4% for people on Lipitor.
The death rate from heart disease was 1.1% for the Lipitor
group compared to 1.4% for the Pravachol group. The rate
of death from any cause was 2.2% for people on Lipitor
and 3.2% for people on Pravachol.
These
1- 3% differences in favor of Lipitor have cardiologists
across the country quite excited and ready to raise the
statin dose and lower the threshold for safe LDL levels.
The Prove It results would be exciting if we
had the full picture on high-dose Lipitor. As is often
the case, the serious adverse effects experienced by the
study participants taking Lipitor were not reported.
Christopher
P. Cannon, MD, who led the Prove It trial, was asked about
this information gap. “We do plan a separate full publication
of all the safety data soon…the journal only allows a
certain amount of space for only one paper,” he responded
by e-mail. “There were more liver function test abnormalities
with Lipitor at 80 mg, but these were all transient and
were resolved when the dose was stopped or reduced.” Still,
adverse reactions caused nearly one out of every three
participants to stop the drug. 3% more people in the Lipitor
group stopped taking the drug. Besides liver failure,
muscle pain is a known consequence of high-dose statin
therapy.
Dr.
Cannon said that his study found Lipitor to be better
than Pravachol for both men and women, though women represented
only 22% of the participants (911). The above-quoted statistics
apply to all participants, and the researcher did not
break things down to show how large the benefits are to
women, or whether they have a higher rate of serious adverse
reactions.
90%
of participants were white and the rest were not specified.
This leaves an information gap for everyone else. Earlier
studies have shown that Asians, for example, are at a
higher risk for severe muscle damage if they take any
statin at daily doses of 80 mg. For unknown reasons, the
drug tends to remain in the body longer in Asians, which
raises their odds of this and other adverse effects. Dr.
Cannon and colleagues suggest that their findings point
to the need for 62 mg as the new LDL threshold for people
with “established coronary heart disease.”
Judging
from the media reports of Prove It trial, many cardiologists
seem poised to extend its results to people without heart
disease. None of the physicians quoted in the media warned
that this would amount to a dangerous experiment. In all
the previous clinical trials that involved people without
heart disease, statin drugs were administered in doses
no higher than 40 mg. Only one prevention trial involved
people taking Lipitor. None lasted more than seven years.
Interestingly,
the new results have revived an old controversy about
whether the benefits of statins are due to their cholesterol
lowering, anti-inflammatory or some other effects. “Unfortunately,
we do not know the precise mechanism of action responsible
for atorvastatin's [Lipitor's] superiority,” wrote Eric
J. Topol, MD, of the Cleveland Clinic in an accompanying
editorial. Dr. Topol believes that “only a fraction of
the patients who should be treated with a statin are actually
receiving such therapy.” He sees cost as the biggest stumbling
block. Lipitor, at the recommended starting dose of 10
mg, is about $900 per year. At the 80-mg dose used in
the Prove It trial, Lipitor costs about $1,400 per year.
What
you can do
Here
are several non-drug ways to reduce your odds of having
a heart attack.
-
Cut trans fatty acids from your diet because they have
long been known to be damaging to the heart. Trans fatty
acids are formed during the hydrogenation of either vegetable
or fish oils. They are used extensively in processed foods
to ensure a longer shelf life. Certain foods like donuts,
potato chips and other snack foods are particularly high
in trans fatty acids. Look for the words “partially hydrogenated
oil” or “shortening” on the ingredients list.
-
Take niacin supplements. The Coronary Drug Project followed
3,908 men taking a placebo or niacin therapy for nine
years. The niacin group had a lower rate of non-fatal
heart attacks and an 11% lower rate of all-cause mortality
than the men in the placebo group. A recent survey of
the various types of niacin on the market found that immediate-release
niacin is the least expensive and safest version
to purchase (and the no-flush niacin products
are useless, see HealthFacts January 2004).
-
Add heart healthy foods with omega-3 fatty acids and folic
acid to your diet. Omega-3 fats can be found in fish,
omega-3-enriched eggs, walnuts and flax seeds. Folic acid
is in green vegetables, beans, wheat germ and certain
fruits and vegetables.
--
Maryann
Napoli, April 2004
