Proposed new cholesterol guidelines could lead to millions
of patients receiving unnecessarily aggressive treatment,
argue a group of experts in the June 3 issue of the
British Medical Journal.
The proposed guidelines put forward
by the influential American National Cholesterol Education
Program propose that LDL cholesterol should be lowered
to less than 1.81 mmol/l in people at high-risk of cardiovascular
disease. That's aggressive treatment by any standard,
but it's especially radical when so much of today's
population can be considered high risk. Another recent
BMJ study calculated that if 2003 European cholesterol
guideline criteria were applied to Norway, one of the
world's healthiest countries, 85% of adult men and 20%
of adult women would be classified as high risk.
DATA
DEARTH
One of the biggest problems, according to the authors,
is that reducing LDL cholesterol to the levels now advocated
in many guidelines will require truly vast prescribing
of statins at doses far greater than those in common
use today. The researchers say we're not ready to unleash
high-dose statins on the public at this point because
there is too little research on outcomes, especially
in women and older patients.
They point to last year's Incremental
Decrease in Endpoints through Aggressive Lipid-lowering
(IDEAL) trial, published in the Journal of the American
Medical Association, which compared the usual 20mg
dose of simvastatin with 80mg atorvastatin. The more
potent statin brought no significant added improvement
in mortality, but the trial showed a surprisingly high
number of adverse events, including myopathy, rhabdomyolysis,
myalgia, diarrhea, nausea and abdominal pain in both
patient groups, but especially those on a high dose.
Debate about the interpretation
of the IDEAL results is currently raging in the letters
pages of JAMA. Indeed, these letters and those
responding to the BMJ piece speak volumes about
physicians' frustrations with the conflicting results
of several recent large-scale statin trials. "The IDEAL
study is one of four recent large clinical trials that
have examined whether high-dose statins improve outcomes
compared with conventional doses," note Michigan physicians
Paul S Chan, Brahmajee K Nallamothu and Rodney A Hayward
in their letter in the June 7 issue of JAMA.
"The first two trials (PROVE-IT and A to Z) enrolled
patients with acute coronary syndromes (ACS), whereas
the latter two trials (TNT and IDEAL) enrolled patients
with stable coronary artery disease. The results from
these trials appear to conflict: PROVE-IT and TNT found
statistically significant differences, whereas A-to-Z
and IDEAL did not."
The New England Journal of Medicine
published the TNT (Treating to New Targets) study last
year. It found that, in the average patient, not even
the biggest 80mg pill was sufficient to get LDL cholesterol
below 1.81 mmol/l as the new guidelines recommend. The
statin did not reduce overall mortality as the reduction
in cardiovascular deaths was offset by a slight increase
in deaths from other causes. However, atorvastatin did
apparently reduce the incidence of non-fatal cardiovascular
events.
Proponents of widespread statin
use suggest the frequently poor quality of today's western
diet, the prevalence of obesity, and the failure of
public health campaigns to modify most people's behaviour
leave little option if we are to reduce deaths from
cardiovascular disease.
"It's true that obesity is common,"
concedes Dr Morley Sutter, a physician and professor
emeritus of pharmacology at the University of British
Columbia and one of the authors of the BMJ paper.
"But relating it to heart disease is not that easy,
as it's not a straightforward relationship."
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