All large statin trials excluded patients with New York Heart
Association class III and IV heart failure such that long term safety of
statins in patients with heart failure has not been established.
HMG CoA-reductase inhibitors or statins
are an effective class of drugs for lowering LDL cholesterol. These drugs have
been associated with some beneﬁcial impact on cardiovascular morbidity and
mortality. As such, statins have become some of the most widely prescribed
drugs in the United States with many millions of patients taking them on a
regular basis. According to the most recent NCEP (National Cholesterol
Education Program) guidelines, the indications for the use of statins have been
broadened such that patients with even low normal LDL cholesterol levels are
now being treated in hopes of favorably altering the incidence of stroke and
myocardial infarction. Statins are frequently used in the
elderly and have gained very broad acceptance in the medical community.
Statins have been noted to have signiﬁcant anti-inﬂammatory and
plaque-stabilizing effects which has added to their broader usage.
is well established that the mevalonate pathway is involved not only in the
biosynthesis of cholesterol but also in the biosynthesis of the essential
co-factor required for energy production, coenzyme Q 10 (CoQ10,
ubiquinone). As such, HMG CoA reductase inhibitors block the cellular
production of both cholesterol and of coenzyme Q10 [23,59].
This drug-nutrient interaction has been reviewed [7,8].
Coenzyme Q10 is
the coenzyme for mitochondrial enzyme complexes involved in oxidative phosphorylation
in the production of ATP [38,46,47]. This bioenergetic effect of CoQ10 is
believed to be of fundamental importance in its clinical application,
particularly as relates to cells with exceedingly high metabolic demands such
as cardiac myocytes. The second fundamental property of CoQ 10
its antioxidant (free radical scavenging) functions [5,67]. CoQ10
the only known naturally occurring lipid soluble antioxidant for which the body
has enzyme systems capable of regenerating the active reduced ubiquinol form
. CoQ10 is carried in the blood with low density
lipoprotein and serves to diminish the oxidation of LDL cholesterol in settings
of oxidative stress . CoQ10 is
known to be closely linked to vitamin E and serves to regenerate the reduced
(active) alpha-tocopherol form of vitamin E  as well as the reduced form of
ascorbate . Other more recently discovered aspects of CoQ 10
include its involvement in extramitochondrial electron transfer, e.g. plasma
membrane oxidoreductase activity , involvement in cytosolic glycolysis
, and potential activity in both Golgi apparatus and lysosomes [22,53]. CoQ10 also
plays a role in improvement in membrane ﬂuidity . The multiple biochemical
functions of CoQ10 have been reviewed by Crane .
Coenzyme Q10 is
clearly necessary for cellular ATP production and is of particular importance
in heart muscle function given this tissue’s extreme energy requirements. A deﬁciency
of CoQ 10 in the blood and the heart muscle has been
documented in congestive heart failure [19,28]. An Australian group of
cardiovascular surgeons has recently documented impairment in myocardial
function secondary to age-related CoQ10 deﬁciency
in patients undergoing coronary artery bypass surgery (CABG). That impairment
was completely eliminated with incubation of the atrial myocardium with CoQ10 .
Later these researchers performed a trial of preoperative supplemental CoQ10 therapy
and found improved outcomes in coronary artery bypass surgery . The
clinical experience with supplemental CoQ 10 in
cardiovascular disease, including congestive heart failure, ischemic heart
disease, hypertensive heart disease and heart surgery has been reviewed
In the US we are
presently in the midst of a congestive heart failure (CHF) epidemic, with a
signiﬁcant increase in the incidence of CHF over the past decade. The annual
number of deaths directly from CHF increased from 10,000 in 1968 to 42,000 in
1993. The rate of hospitalizations for heart failure increased more than three
times between 1970 and 1994. In the largest health system study of its kind,
researchers at the Henry Ford Heart and Vascular Institute in Detroit found
that the annual number of heart failure cases more than doubled from 1989 to
1997. Over that nine-year period, 26,442 cases were identiﬁed in the Henry Ford
Health System in Detroit. Strikingly, the annual prevalence rose from 9 to 20
cases per 1000 health system patients . These results were compiled in the
Resource Utilization Among Congestive Heart Failure (REACH) study .
Statins were ﬁrst
released in 1987 and are considered the most effective medications for managing
elevated concentrations of low-density lipoprotein cholesterol. Although it is
believed that they are generally well tolerated by most patients they can
produce a variety of muscle-related complaints or
of which rabdomyolysis is the most serious one. The
issue was recently discussed in an article by Thompson et al.  where the
following are indicated as the possible mechanisms of statin-induced muscle
reduction of the cholesterol content of skeletal muscle
reduction of the levels of ubiquinone
reduction in farnesyl pyrophosphate, an intermediary for
the production of ubiquinone, which is required for the activation of small
GTP-binding regulatory proteins.
In the present
article we will examine the existing literature on animal studies and human
trials evaluating the effect of statins on coenzyme Q blood and/or tissue
levels. Statin-induced depletion of CoQ10 must
be considered in the above mentioned epidemic of heart failure. The coenzyme Q 10 lowering
effect of statin medications has clinical relevance and must be considered by
all physicians when prescribing this class of medication.
through 2001 there have been 15 published animal studies
involving six different animal species – six rat studies, three hampster
studies, three dog studies, one rabbit study, one guinea pig study and one
study looking at squirrel monkeys, mini pigs and hampsters – evaluating the
effect of statins on coenzyme Q blood and/or tissue levels. Nine of these 15
studies looked speciﬁcally at the adverse consequences of this statin-induced
CoQ depletion: decreased ATP production, increased injury after
ischemia/reperfusion, increased mortality in cardiomyopathy, and skeletal
muscle injury and dysfunction. Some of the animals use coenzyme Q9 as their
native ubiquinone which is a shorter chain homologue of coenzyme Q10
in those cases the term coenzyme Q or CoQ is used.
animal data was published in 1990 by Willis et al. and
documented statistically signiﬁcant decreases in CoQ concentration in blood,
heart and liver in 45 adult male Holtzman rats when treated with lovastatin.
This statin-induced blood and tissue CoQ deﬁciency could be completely
prevented by supplementing the lovastatin treated animals with coenzyme Q10 .
In 1992, Low et al. found similar decreases in ubiquinone in liver and heart in
rats treated with lovastatin (mevinolin), conﬁrming observations by Willis et
Fukami et al. studied simvastatin treated rabbits and
speciﬁcally looked at those animals with elevations in creatinine kinase,
lactate dehydrogenase, and skeletal muscle necrosis . The simvastatin
treated rabbits were noted to have signiﬁcantly reduced liver and cardiac
muscle CoQ content as compared to the control group. Interestingly, skeletal
muscle ubiquinone content in this study was not affected. Also in 1993,
Belichard et al. studied lovastatin in cardiomyopathic hamsters and found a 33%
decrease in ubiquinone content in heart muscle as compared to control .
Cholesterol lowering in cardiomyopathic hamsters with fenoﬁbrate did not lower
coenzyme Q10 levels. Statins are the only class of
lipid-lowering drugs that are known to block the synthesis of mevalonate.
Diebold et al. documented a depletion in CoQ10 content
in heart muscle in guinea pigs when treated with lovastatin in older age (2
years of age) animals, and further observed no signiﬁcant depletion in CoQ10 content
in heart muscle in the guinea pigs in the younger age group (2 to 4 months of age)
. The authors evaluated mitochondrial function as measured by the potential
to phosphorylate ADP to ATP, and again documented a decrease by up to 45% in
cardiac mitochondria in the 2-year-old animals treated with lovastatin, and no
signiﬁcant decrease in phosphorylation in the younger age group animals. This
sensitivity for older animals to show clinically relevant heart muscle CoQ10 depletion
is of concern in humans as older patients are treated with statin medications
and are observed to be more fragile and more susceptible to side effects. Also
in 1994, Loop et al. documented again that lovastatin decreased CoQ content in
rat liver that could be completely prevented with supplemental coenzyme Q .
Satoh et al. evaluated ischemic reperfusion in dog hearts
and documented that simvastatin signiﬁcantly decreased myocardial CoQ10 levels
and worsened ischemia reperfusion injury . Water soluble pravastatin was
also studied in this dog model and did not appear to cause worsening of mitochondrial
respiration in the dog heart muscle, nor did the pravastatin reduce myocardial
CoQ10 levels. It is believed that the lipid soluble
simvastatin may be more detrimental in this model due to better membrane
penetration of this fat soluble drug.
Morand et al. studied hamsters, squirrel monkeys, and
mini pigs, and documented CoQ 10 depletion
in heart and liver with simvastatin treatment . The investigators saw no
decrease in CoQ10 in heart and liver using the experimental
cholesterol lowering drug 2,3-oxidosqualene:lanosterol cyclase, which blocks
the synthesis of cholesterol below the mevalonate level and thus does not
impair the biosynthesis of coenzyme Q10.
Nakahara et al. evaluated simvastatin (a lipophilic
inhibitor of HMG CoA-reductase) or pravastatin (a hydrophilic inhibitor) .
In group I, rabbits were treated with simvastatin at 50 mg/kg per day for four
weeks. There was a 22% to 36% reduction in ubiquinone content in skeletal
muscle and the observation of skeletal muscle necrosis and elevated CK levels.
Group II rabbits were treated with pravastatin at 100 mg/kg per day for four
weeks, which did not cause skeletal muscle injury and reduced CoQ10
skeletal muscle by 18% to 52%. In group III, treated with high dose pravastatin
at 200 mg/kg per day for three weeks followed by 300 mg/kg per day for another
three weeks, there was a greater reduction in CoQ10 skeletal
muscle content from 49% to 72% depletion and evidence of skeletal muscle
necrosis and CK elevation. In 1998, Sugiyama observed that pravastatin caused a
signiﬁcant decrease in the activity of mitochondrial complex I in diaphragm
skeletal muscle in rats age 35–55 weeks . The authors concluded that careful
clinical examination of respiratory muscle function is necessary in patients
treated with pravastatin, particularly in the elderly.
Ichihara et al. studied the effect of statins on ischemia
reperfusion in dogs and observed that pretreatment of the dogs with the
lipophilic HMG CoA-reductase inhibitors simvastatin, atorvastatin, ﬂuvastatin,
and cerivastatin all worsened recovery of myocardial contraction after ischemia
reperfusion, but the water soluble pravastatin had no detrimental effect on myocardial
contraction in this model . In 2000, Satoh et al. further observed a
detrimental effect from atorvastatin, ﬂuvastatin, and cerivastatin in dog
ischemia reperfusion, conﬁrming that lipophilic HMG CoA-reductase inhibitors
enhance myocardial stunning in association with ATP reduction after ischemia
and reperfusion .
In 2000, Caliskan et
al. studied rats treated with simvastatin and found signiﬁcant reductions in
plasma cholesterol and ATP concentrations, indicating an impairment in bioenergetics
related to CoQ depletion . In 2000, Marz et al. studied hamsters with
inherited cardiomyopathy and concluded that lovastatin but not pravastatin at a
dose of 10 mg/kg body weight signiﬁcantly increased the mortality of
cardiomyopathic hamsters, as a result of inhibition of myocardial ubiquinone
. Finally, in 2001 study by Pisarenko et al. in rats treated with
simvastatin at 24 mg/kg for 30 days showed a signiﬁcant decrease in ATP and
creatinine phosphate in myocardium, again indicating that statin-induced CoQ 10 depletion
has a detrimental impact on energy production in the heart muscle .
of animal studies
to date uniformly document varying degrees of
coenzyme Q depletion in blood and in tissue with statin therapy, and that the
coenzyme Q deﬁciency is associated with adverse effects in cardiomyopathic
hamster models, in the ischemia reperfusion injury in dog models, as well as in
liver and cardiac coenzyme Q content in rabbits causing skeletal muscle damage.
A decrease in cardiac CoQ content and in ATP production has been documented in
two years old (elderly) guinea pigs. Signiﬁcant CoQ depletion was documented in
the heart and liver in hamsters, squirrel monkeys, and mini pigs. It is also
noteworthy that the lipid soluble statins appear to show more animal toxicity,
particularly in the ischemia reperfusion dog models. One can surmise from these
animal studies that statins have the potential to produce clinically meaningful
coenzyme Q depletion in several animal species and that the depletion is dose
related. In all animal studies where supplemental coenzyme Q was given to the
animals prior to the institution of statins, the coenzyme Q blood and tissue
depletion was completely prevented.
to date there have been 15 published studies in humans
evaluating the effects of statins on CoQ10.
Nine of those were controlled trials and eight of those nine studies demonstrated
signiﬁcant CoQ10 depletions secondary to statin therapy.
on the interaction between statins and coenzyme
Q 10 were ﬁrst published in 1990 by Folkers et al.,
that observed ﬁve patients with pre-existing cardiomyopathy that exhibited a
signiﬁcant decline in blood CoQ10 level
and clinical deterioration after having been started on lovastatin . That
decrease in CoQ10 blood level and decline in clinical status was
reversed through an increase in supplemental CoQ10.
Watts et al. studied 20 hyperlipidemic patients treated
with a low cholesterol diet and simvastatin and compared them to 20
hyperlipidemic patients treated with diet alone and 20 normal controls .
Patients treated with simvastatin had signiﬁcantly lower plasma coenzyme Q10 levels
and a lower coenzyme Q10 to cholesterol ratio than either patients on
diet alone or normal controls. The depletion of plasma CoQ10 was
signiﬁcantly associated with the dose of simvastatin. It was concluded that
simvastatin may lower plasma CoQ10 concentration
and that that reduction may be proportionally greater than the reduction in
cholesterol. The authors felt that that adverse effect of simvastatin on the
biosynthesis of coenzyme Q10 may be clinically important and requires
further study. Also in 1993, Ghirlanda et al. studied 30 hypercholesterolemic
patients and 10 healthy volunteers in a double-blind controlled trial,
comparing placebo with either pravastatin or simvastatin for a three-month
treatment period . These HMG CoA-reductase inhibitors showed signiﬁcant
reduction in both total cholesterol and plasma CoQ10 levels,
not only in hypercholesterolemic patients but also in the normal healthy
Bargossi et al. performed a randomized controlled trial
evaluating 34 hypercholesterolemic patients treated with either 20 mg of
simvastatin for six months or 20 mg of simvastatin plus 100 mg of supplemental
CoQ10 . The study demonstrated that simvastatin
lowered both LDL cholesterol and plasma and platelet CoQ10 levels.
The depletion of CoQ10 in both plasma and platelets was prevented in the
group without affecting the cholesterol
lowering effect of simvastatin.
Laaksonen et al. documented a signiﬁcant decrease in
serum CoQ 10 levels in hypercholesterolemic patients
treated for four weeks with simvastatin, with no reduction in skeletal muscle
CoQ10 . In 1996, Laaksonen et al. evaluated
skeletal muscle biopsy specimens in 19 hypercholesterolemic patients treated
with simvastatin at 20 mg per day and found no depletion of skeletal muscle CoQ10 concentration
as compared to control subjects .
De Pinieux et al. evaluated 80 hypercholesterolemic
patients – 40 patients treated with statins, 20 patients treated with ﬁbrates,
and 20 untreated controls . Further, they evaluated 20 non-hyperlipidemic health
controlled patients. Serum CoQ10 levels
were signiﬁcantly lower in statin treated patients and were not depleted in ﬁbrate
treated patients or in untreated controls. Lactate to pyruvate ratios were
signiﬁcantly higher in statin treated patients, indicating mitochondrial
dysfunction in patients treated with statins, which was not observed in
untreated hypercholesterolemic patients or in healthy controls.
Palomaki et al. studied 27 hypercholesterolemic men in a
double-blind placebo controlled crossover trial with six weeks of lovastatin at
60 mg per day . Lovastatin therapy was associated with a signiﬁcant decline
in serum ubiquinol content as measured per LDL phosphorus, and there was an
increased oxidizability of LDL in the lovastatin treated patients. [one of 4
reasons why statins don’t prolong life.
Oxidation of LDL is the starting point for plaque buildup--jk.]
Mortensen et al. studied 45 hypercholesterolemic patients
in a randomized double-blind trial with either lovastatin or pravastatin for 18
weeks . A dose-related signiﬁcant decline in total serum CoQ10 was
found in the pravastatin group from 1.27 ± 0.34
to 1.02 ± 0.31 mmol/L, p<0.01. In the lovastatin
group, there was a more
pronounced decrease in serum CoQ 10 level
from 1.18 ± 0.36 to 0.84 ± 0.17
mmol/L p<0.001. The authors concluded that although HMG
CoA-reductase inhibitors are safe and effective within a limited time horizon,
continued vigilance of a possible adverse consequence from coenzyme Q10 lowering
seems important during long-term therapy.
Palomaki et al. evaluated 19 men with
hypercholesterolemia and coronary artery disease treated with lovastatin with
or without CoQ10 supplementation . In statin treated
patients supplemented with ubiquinone the lag time in copper mediated
oxidation of LDL increased by 5% (p= 0.02).
Upon AMVN (2,2-azobis (2,4-dimethylvaleronitrile)) oxidation the faster
depletion of LDL ubiquinol and shortened lag time in conjugated diene formation
during lovastatin therapy was signiﬁcantly ameliorated with CoQ10 supplementation.
Miyake et al. studied 97 non-insulin-dependent diabetic
patients treated with simvastatin and observed a signiﬁcant decrease in serum
CoQ10 concentrations along with the decrease in serum
cholesterol . Oral CoQ10 supplementation in diabetic patients receiving
simvastatin signiﬁcantly increased serum coenzyme Q10 level
without affecting the cholesterol levels. Furthermore, the supplemental
coenzyme Q10 signiﬁcantly decreased cardiothoracic ratios
from 51.4 ± 5.1 to 49.2 ± 4.7%
(p< 0.03). The authors concluded that serum
coenzyme Q10 levels in diabetic patients are decreased by
statin therapy and may be associated with subclinical diabetic cardiomyopathy,
reversible by coenzyme Q 10 supplementation.
De Lorgeril et al. studied in a double-blind fashion 32
patients treated with 20 mg of simvastatin compared to 32 patients treated with
200 mg of fenoﬁbrate . Serum CoQ10 levels
were signiﬁcantly reduced after treatment with simvastatin but not with fenoﬁbrate.
No signiﬁcant change in left ventricular ejection fraction could be determined
after 12 weeks of therapy. They observed a loss of myocardial reserve with a ﬂattening
of the ejection fraction response to exercise, which could be explained by the
statin-induced diastolic dysfunction in those patients. Unfortunately, only systolic
measurements of ejection fraction were obtained in this study.
Bleske et al. failed to show a depletion in whole blood
CoQ10 in 12 young, healthy volunteers with normal
cholesterol levels treated with either pravastatin or atorvastatin for four
weeks . Also in 2001, Wong et al. documented that the beneﬁcial anti-inﬂammatory
effect of simvastatin on human monocytes was completely reversible with
supplemental mevalonate but not with CoQ10,
indicating that supplemental CoQ10 would
not interfere with this important statin-mediated anti-inﬂammatory effect .
The most recent statin/CoQ study was a randomized controlled trial by Jula et
al., published in JAMA . Simvastatin at 20 mg per day caused a reduction in
serum short term trial.
In human trials evaluating coenzyme Q10 in statin therapy there appears to be frequent
and signiﬁcant depletion in blood CoQ10 levels, particularly when statins are taken at higher doses and
most notably in the elderly. In one study involving patients with preexisting
CHF, the depletion in blood coenzyme Q 10 levels was associated with a drop in ejection fraction and
clinical deterioration. Supplemental CoQ10 has been found to prevent the depletion of CoQ10 in blood and in one study also to prevent the
depletion measured in platelet CoQ10
The serum depletion of CoQ10
associated with an elevation in lactate to
pyruvate ratio, suggesting an impairment in mitochondrial bioenergetics,
secondary to statin-induced CoQ10
Furthermore, two trials demonstrated enhanced
oxidizability of LDL cholesterol related to the lowering of serum CoQ10 by statins. Supplemental CoQ10 has been shown to increase the CoQ10 content in low
density lipoproteins and to decrease signiﬁcantly
LDL cholesterol oxidizability. One trial
demonstrated no signiﬁcant CoQ10 depletion in 12 young normolipidemic volunteers treated with
statins and one trial found no skeletal muscle depletion of CoQ10 in statin treated hypercholesterolemic
patients. In diabetic patients, the CoQ10 depletion with statin therapy appears to be associated with
subclinical cardiomyopathy, with signiﬁcant improvement in cardiothoracic
ratios upon CoQ10 supplementation.
From these studies, one
can conclude that supplemental CoQ10 prevents
the statin induced CoQ10 deﬁciency state without altering the
cholesterol-lowering ability of these drugs and appears to have beneﬁt both in
terms of decreasing the oxidizability of low density lipoprotein cholesterol,
as well as preventing or reversing observed detrimental clinical changes. [PhARMA
doesn’t disseminate this side effect of statins; their mantra is safe and
Safety and drug interactions
Q10 is sold in the United States and abroad as an
over-the-counter nutrient and is widely recognized as completely safe with no
reported toxicity in over a thousand published human and animal trials. The
most recent animal safety study was published in 1999 by Williams et al. .
Potential CoQ10 toxicity was assessed in rats administered CoQ10
oral gavage for 1 year at 100, 300, 600, and 1200 mg per kg body weight per
day. No adverse changes in mortality, clinical signs, body weight, food
consumption, or clinical pathology results occurred.
clinical trials the highest doses used were 1200 mg/day
in 23 patients with Parkinson disease  and up to 3,000 mg/day in case study
in patients with familial cerebellar ataxia with primary muscle CoQ10
 with no adverse effects noted. To date, there have been at least 34
placebo controlled trials using CoQ10 in
cardiovascular disease involving a total of 2152 patients with no toxicity or
drug interactions reported in the CoQ10 group
as compared to the placebo group. Most of these controlled trials have been
reviewed [33,34]. In addition to these controlled trials there have been many
open-label long term trials in cardiovascular disease using CoQ10
doses up to 600 mg per day with up to eight year follow up, again with a
complete lack of toxicity. In heart failure alone there have been at least 39
open trials with supplemental CoQ10 published
involving a total of 4498 patients again with remarkable safety with the only
reported side-effects being rare cases of mild nausea.
safety and tolerability of CoQ10 was
documented by Langsjoen in 1990 [http://www.pnas.org/content/87/22/8931.full.pdf]
in a six year study of 126
heart failure patients . Later, in
1993, Morisco published a double blind controlled trial on 641 heart failure
patients treated with either placebo or CoQ10 for
one year . The investigators found a
signiﬁcant reduction of hospitalizations for worsening of heart failure in the
CoQ10 group and no evidence of
In 1994 Baggio published an open-label multi-center trial on 2664 patients with
heart failure, treated with 150 mg CoQ10 per
day for three months and reported good tolerability . Also in 1994 Langsjoen
published long term observations on 424 cardiac patients, treated with 75 to
600 mg of CoQ10 per day for up to eight years with no adverse
effects or drug interactions . One out of the 424 patients experienced
There have been
two case reports published claiming potential interaction between CoQ 10 and
coumadin (warfarin), suggesting that CoQ10 has
a vitamin K-like effect [31,64]. This has not been corroborated by other
investigators and was the subject of a prospective trial . Physicians
wisely and routinely follow prothrombin times very closely in patients on
coumadin, particularly after any change in diet, medication or over-the-counter
supplements. In this author’s 18 year experience with the use of CoQ10 in
many thousands of cardiac patients we have yet to see a single case of CoQ 10-coumadin
interaction at doses up to 600 mg of CoQ10 per
day (unpublished observations).
prescribed HMG CoA-reductase inhibitors block the endogenous biosynthesis both of cholesterol and of coenzyme
Q10, and the decrease in
both substances is related to the dose as well as the potency of these drugs.
The depletion of coenzyme Q10 appears
to be well tolerated in younger and healthier patients, particularly in the
short term, but the data reveal detrimental cardiac effects in several animal
models, particularly in older animals, and there is good evidence to support a detrimental effect in humans with pre-existing
cardiac dysfunction when subjected to this statin-induced coenzyme Q 10 depletion. CoQ10 is
known to be deﬁcient in congestive heart failure, with the
degree of deﬁciency in blood and cardiac tissue correlating with the severity
of the CHF [19,28]. Normal whole blood levels of CoQ10 are
about 1.0 ± 0.2 µg/ml
with deﬁciency in the range of 0.6 ± 0.2
µg/ml. [40% less]. It is
also known that CoQ10
levels steadily fall after the age of 40
[27,63]. Statin drugs
produce a depletion in coenzyme Q 10,
which in settings of pre-existing CoQ10 deﬁciency,
such as in CHF [18,19,28,39,40] and ageing , has the ability to worsen
As the potency of statin drugs increases and
as the target LDL cholesterol level decreases, the severity of CoQ10
will increase with an increasing
likelihood of impairment in heart
muscle function. This tragic scenario may very well be prevented by using
supplemental CoQ10 with all HMG CoA reductase inhibitors.
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M. Tomasetti, S. Bompadre and G.P. Littarru,
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