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Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis

BMJ 2003; 326 doi: (Published 26 June 2003) Cite this as: BMJ 2003;326:1423

Rapid Response:

Mixing up evidence of statins with believes in cholesterol

The article of Law et al1 heaped up all evidence on the cholesterol
lowering properties of statin therapy for cardiovascular risk management.
Strangely, the reductions of hard disease events, as observed in major
trials and compiled in a meta-analysis,2 figure only in footnote.

Cohort studies studying correlations of cholesterol with mortality
are not randomised clinical trials (RCT) of statins. A cohort involves
people, whose cholesterol level is one of many risk factors predicting
heart disease, some known, some unknown, to which these people are exposed
for life. A RCT observes the unconfounded effects of statins, a drug with
manifold and uncertain activities, in randomised populations. The history
of female hormone replacement therapy in the prevention of vascular
disease must not be forgotten: a wealth of observational evidence of
benefit, but only experimental evidence of harm. Equating short term
effects of complex drugs with poorly understood effects such as statins
with lifelong correlations of LDL with CHD mortality shows a naive belief
in simplistic linear models 3 .

And why would we wish to calculate the health effects of a belief, if
we have hard data? In table 3, Law et al show convincingly, once more,
that the observed risk reduction in coronary heart disease is nearly
constant and somewhat over 30 percent for all time periods of three years
and more. Reductions in stroke incidence are supported by the same hard
evidence4 5. There is little evidence that event reduction by statin use
differ either by type of drug, duration taken (after 2 years of use) or
dose. Only in the 4S trial reductions over 40 percent have been observed
in myocardial infarction survivors with increased cholesterol and very
high risks. Evidence of benefits even higher than this do not exist. Why
would we want to exaggerate the great benefits of statins?

Indeed, if this issue of the BMJ is worth keeping, it is as an
historical example of the dangers of extrapolation. Extrapolate LDL
cholesterol into nothingness, and eradicate 99.9 percent of coronary heart
disease. Extrapolate one century of world records of the 100 metres
sprint into the far future, and in thousand years we will run 100 meters
in less than 1 second.


1. Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low
density lipoprotein cholesterol, ischaemic heart disease, and stroke:
systematic review and meta-analysis. Bmj 2003;326(7404):1423.

2. LaRosa JC, He J, Vupputuri S. Effect of statins on risk of coronary
disease: a meta-analysis of randomized controlled trials. Jama

3. Libby P, Aikawa M. Mechanisms of plaque stabilization with statins. Am
J Cardiol 2003;91(4A):4B-8B.

4. Corvol JC, Bouzamondo A, Sirol M, Hulot JS, Sanchez P, Lechat P.
Differential effects of lipid-lowering therapies on stroke prevention: a
meta-analysis of randomized trials. Arch Intern Med 2003;163(6):669-76.

5. Hebert PR, Gaziano JM, Chan KS, Hennekens CH. Cholesterol lowering with
statin drugs, risk of stroke, and total mortality. An overview of
randomized trials. Jama 1997;278(4):313-21.

Competing interests:  
None declared

Competing interests: No competing interests

15 July 2003
Oscar H Franco
Scientific Researcher
Luc Bonneux
Erasmus University, Department of Public Health. P.O. Box 1738, 3000 DR Rotterdam, The Netherlands