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Doubt cast on targeting ‘bad’ cholesterol to curb heart disease risk
Setting targets for ‘bad’ (low-density lipoprotein: LDL)
cholesterol levels to ward off heart disease and death in
those at risk might seem intuitive, but a systematic review of
decades of research have failed to show any consistent benefit
for this approach, reveals an analysis by researchers at the
University of New Mexico, Albuquerque, Bahiana School of
Medicine, Salvador, Brazil, and the University of Grenoble,
of the available data. If anything, it is failing to identify many
of those at high risk while most likely including those at low
risk who don’t need treatment, say the researchers, who call
into question the validity of this strategy.
Cholesterol-lowering drugs are now prescribed to millions of
people around the world in line with clinical guidelines. Those
with poor cardiovascular health, those with LDL cholesterol
levels of 190 mg/dl (4.92 mmol/l) or higher, adults with diabetes,
and those whose estimated risk is 7.5% or more over the next
10 years, based on various contributory factors, such as age and
family history, are all considered to be at moderate to high risk
of future cardiovascular disease. But although lowering LDL
cholesterol is an established part of preventive treatment, and
backed up by a substantial body of evidence, the approach has
never been properly validated, say the researchers.
They therefore systematically reviewed all published
clinical trials comparing treatment with one of three types of
cholesterol-lowering drugs (statins, ezetimibe, PCSK9) with
usual care or dummy drugs (placebo) for a period of at least
a year in at-risk patients.
Each of the 35 included trials was categorised according to
whether it met the LDL cholesterol reduction target outlined
in the 2018 American Heart Association/American College
of Cardiology guidelines. The researchers then calculated the
number of people who would need to be treated in order to
prevent one ‘event’, such as a heart attack/stroke, or death,
and the reduction in absolute risk in each study that reported
significantly positive results.
Their analysis showed that over three-quarters of all
the trials reported no positive impact on risk of death and
nearly half reported no positive impact on risk of future
cardiovascular disease. And the amount of LDL cholesterol
reduction achieved didn’t correspond to the size of the
resulting benefits, with even very small changes in LDL
cholesterol sometimes associated with larger reductions in
risk of death or cardiovascular events, and vice versa.
Thirteen of the clinical trials met the LDL cholesterol-
reduction target, but only one reported a positive impact on
risk of death; five reported a reduction in the risk of events.
Among the 22 trials that didn’t meet the LDL-lowering target,
four reported a positive impact on risk of death while 14
reported a reduction in the risk of cardiovascular events. This
level of inconsistency was evident for all three types of drugs.
The researchers acknowledge that some of the 35 trials
weren’t designed, or of the size needed, to assess the clinical
outcomes included in this analysis. Nevertheless, they point
out that while setting targets for lowering LDL cholesterol
based on risk ‘should prevent cardiovascular events in
patients at highest risk while avoiding unnecessary treatment
in low-risk individuals. Unfortunately, the risk-guided model
performs poorly in achieving these goals.’
Because LDL cholesterol is considered essential for the
development of cardiovascular disease, ‘it seems intuitive
and logical to target (it),’ say the researchers. But they add:
‘Considering that dozens of (randomised controlled trials)
of LDL cholesterol reduction have failed to demonstrate a
consistent benefit, we should question the validity of this
theory.’
They conclude: ‘In most fields of science the existence
of contradictory evidence usually leads to a paradigm shift
or modification of the theory in question, but in this case
the contradictory evidence has been largely ignored, simply
because it doesn’t fit the prevailing paradigm.’
Source:
Medical Brief 2020