HMG-CoA reductase inhibitors are essentially the statin drugs: atorvastatin (Lipitor™), cerivastatin (Baycol™,
withdrawn 8/01), fluvastatin (Lescol™), lovastatin (Mevacor™), pravastatin (Pravachol™), simvastatin (Zocor™),
pitavastatin and rosuvastatin (Crestor™), which were introduced to lower total cholesterol (TC) levels, and especially
LDL-cholesterol (LDL) levels, ostensibly to prevent coronary heart disease (CVD).
The book consists of 8 chapters by nominally highly qualified authors in the form of review articles of the sort
normally found in medical journals. These are devoted to the pharmacology and supposed benefits of statin drugs.
The writing is in expert medical language and is consistent, well-written, well-edited and very well-referenced, in
quantity if not in quality. The index is inadequate.
All chapters attempt to justify the wide use of the statin drugs to lower TC and LDL by citing references in support
of the claims that high levels have been correlated with cardiovascular disease (pp1,19,35,81,84,99,121,126). Such
claims are unfounded (Ravnskov U, The Cholesterol Myths, Washington, DC, New Trends, 2000).
The supposed benefits of the statins, beyond a large, but meaningless lowering of TC and LDL, are usually given
as lowered relative risks (RR) of mostly non-fatal heart attacks without the slightest indication of the magnitude of the
more meaningful reduction of absolute risk (pp101,103,106,115,122,124,137). This misrepresentation has been
noted (Ravnskov, 2000; Gigerenzer G, Calculated Risks: How to Know When Numbers Deceive You, New York,
NY, Simon & Schuster, 2002). So the usual tout of pravastatin in the WOSCOPS trial of a 22% drop in all-cause
mortality was noted without the information that this was only an 0.9% drop absolute in the 5-year trial period
(p106). The higher all-cause death rates in 2 of the big trials were ignored, as was the higher breast cancer rate (RR
= 1500%) in the CARE trial (Ravnskov, 2000).
Besides cancer, the other side effects of statins listed were incomplete, and should have included myalgia,
myopathy, polyneuropathy, liver and kidney damage, congestive heart failure and amnesia. Side-effects were said to
affect 2% of patients (p115-6) and 2-6% (p123). In fact, a recent review noted side-effects in 20% of patients above
the placebo rate, and no change whatever in the all-cause death rate for atorvastatin (Newman CB, Palmer G,
Silbershatz H, Szarek M. Safety of Atorvastatin Derived from Analysis of 44 Completed Trials in 9,416 Patients.
Am J Cardiol 2003;92:670-6).
Statins decrease the body's production of the essential coenzyme Q-10 and dolichol, among other things. This
was not mentioned as a problem in any chapter. While this was shown in one biochemical diagram (p65), it was not
in another (p82). Low Q-10 levels are strongly associated with congestive heart failure.
"Statins are contra-indicated during pregnancy and breastfeeding. The reason for this is that cholesterol is an
essential component for fetal development, including the synthesis of steroids and cell membranes" (p116). The
authors seem unable to comprehend that cell membranes, steroids and coenzyme Q-10 are needed by all humans.
The rare familial hypercholesterolemia, in which TC > 400 mg/dL, was represented as more deadly than it really
is (p99,111), (Ravnskov, 2000).
There was some recognition that statins operate to lower non-fatal heart attack rates by mechanisms other than
cholesterol lowering, but not that their desirable effect on thromboxane A2 is less than men can obtain with buffered
aspirin (p71), or that the desirable effect of raising nitric oxide (NO) levels is less than one can obtain with the
supplement L-arginine with no side-effects. There was no understanding that these effects of statins are independent
of initial or final TC or LDL levels (Nielsen JV. Serun lipid lowering and risk reduction? Where is the connection?
Br Med J Rapid Response, 19 Nov 01, to Kmietowicz Z. Statins are the new aspirin, Oxford researchers say. Br
Med J 2001;323:1145), and thus there is no way to determine who should be treated, or what the dose should be.
An entire chapter is devoted to the cost-benefits of statin use (p138ff). Since the use of statins for primary
prevention of CVD has been shown to increase all-cause mortality by 1% over a 10-year period (Jackson PR, et al.
Statins for primary prevention: at what coronary risk is safety assured? Br J Pharmacology 2001;52:439-446), and statins
have very little effect in secondary prevention, it would seem that there is no cost-benefit (Kauffman JM, "Do
Hypolipidemic Drugs Lower Medical Expenses?" Pharmacotherapy 2001;22(12),1583-1586).
This book may be of use for a pharmacologist looking for an overview, however narrow in outlook, with literature citations.
---Joel M. Kauffman, 6 Oct 03