Statins, also known as
HMG-CoA reductase inhibitors, are a class of
lipid-lowering medications. Statins have been found to reduce
cardiovascular disease (CVD) and mortality in those who are at high
risk of cardiovascular disease. The evidence is strong that statins
are effective for treating CVD in the early stages of the disease
(secondary prevention) and in those at elevated risk but without CVD
Side effects of statins include muscle pain, increased risk of
diabetes mellitus, and abnormalities in liver enzyme tests.
Additionally, they have rare but severe adverse effects, particularly
muscle damage. They inhibit the enzyme
HMG-CoA reductase which
plays a central role in the production of cholesterol. High
cholesterol levels have been associated with cardiovascular disease
As of 2010[update], a number of statins are on the market:
atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin,
rosuvastatin, and simvastatin. Several combination preparations of
a statin and another agent, such as ezetimibe/simvastatin, are also
available. In 2005, sales were estimated at US$18.7 billion in
the United States. The best-selling statin is atorvastatin also
known as Lipitor, which in 2003 became the best-selling pharmaceutical
in history. The manufacturer
Pfizer reported sales of
US$12.4 billion in 2008. Due to patent expirations, several
statins became available in 2016 as less expensive generics.
1 Medical uses
1.1 Primary prevention
1.2 Secondary prevention
1.3 Comparative effectiveness
1.5 Familial hypercholesterolemia
1.6 Contrast induced nephropathy
2 Adverse effects
2.1 Cognitive effects
2.5 Drug interactions
3 Mechanism of action
3.1 Inhibiting cholesterol synthesis
3.3 Decreasing of specific protein prenylation
3.4 Other effects
4 Available forms
6 Society and culture
10 External links
Clinical practice guidelines
Clinical practice guidelines generally recommend people try "lifestyle
modification", including a cholesterol-lowering diet and physical
exercise, before statin use. Statins or other pharmacologic agents may
be recommended for those who do not meet their lipid-lowering goals
through diet and lifestyle changes. Statins appear to work
equally well in males and females.
In 2016 the
United States Preventive Services Task Force recommended
statins for those who have at least one risk factor for coronary heart
disease, are between 40 and 75 years old, and have at least a 10%
10-year risk of heart disease. The risk factors for coronary heart
disease included abnormal lipid levels in the blood, diabetes
mellitus, high blood pressure, and smoking. The risk of heart
disease is estimated using the ACC/AHA Pooled Cohort equation.
They recommended selective use of low-to-moderate doses statins in the
same adults who have a calculated 10-year CVD event risk of 7.5–10%
Most evidence suggests that statins are effective in preventing heart
disease in those with high cholesterol, but no history of heart
disease. A 2013
Cochrane review found a decrease in risk of death and
other poor outcomes without any evidence of harm. For every 138
people treated for 5 years one fewer dies and for every 49 treated one
fewer has an episode of heart disease. A 2011 review reached
similar conclusions. And a 2012 review found benefits in both
women and men. A 2010 review concluded that treating people with
no history of cardiovascular disease reduces cardiovascular events in
men but not women, and provides no mortality benefit in either
sex. Two other meta-analyses published that year, one of which
used data obtained exclusively from women, found no mortality benefit
in primary prevention.
National Institute for Health and Clinical Excellence
National Institute for Health and Clinical Excellence (NICE)
recommends statin treatment for adults with an estimated 10 year risk
of developing cardiovascular disease that is greater than 10%.
Guidelines by the
American College of Cardiology
American College of Cardiology and the American
Heart Association recommend statin treatment for primary prevention of
cardiovascular disease in adults with
LDL cholesterol ≥
190 mg/dL or those with diabetes, age 40–75 with LDL-C
70–190 mg/dl; or in those with a 10-year risk of developing
heart attack or stroke of 7.5% or more. In this latter group, statin
assignment was not automatic, but was recommended to occur only after
a clinician-patient risk discussion with shared decision making where
other risk factors and lifestyle are addressed, the potential for
benefit from a statin is weighed against the potential for adverse
effects or drug interactions and informed patient preference is
elicited. Moreover, if a risk decision was uncertain, factors such as
family history, coronary calcium score, ankle-brachial index, and an
inflammation test (hs-CRP ≥ 2.0 mg/L) were suggested to inform
the risk decision. Additional factors that could be used were an LDL-C
≥ 160 or a very high lifetime risk. However, critics such as
Steven E. Nissen say that the AHA/ACC guidelines were not properly
validated, overestimate the risk by at least 50%, and recommend
statins for patients who will not benefit, based on populations whose
observed risk is lower than predicted by the guidelines. The
European Society of Cardiology and the European Atherosclerosis
Society recommend the use of statins for primary prevention, depending
on baseline estimated cardiovascular score and
Statins are effective in decreasing mortality in people with
pre-existing CVD. They are also advocated for use in people at
high risk of developing coronary heart disease. On average,
statins can lower
LDL cholesterol by 1.8 mmol/l (70 mg/dl),
which translates into an estimated 60% decrease in the number of
cardiac events (heart attack, sudden cardiac death) and a 17% reduced
risk of stroke after long-term treatment. They have less effect
than the fibrates or niacin in reducing triglycerides and raising
HDL-cholesterol ("good cholesterol").
Statins have been studied for improving operative outcomes in cardiac
and vascular surgery. Mortality and adverse cardiovascular events
were reduced in statin groups.
While no direct comparison exists, all statins appear effective
regardless of potency or degree of cholesterol reduction. There do
appear to be some differences between them, with simvastatin and
pravastatin appearing superior in terms of side-effects.
A comparison of simvastatin, pravastatin, and atorvastatin, based on
their effectiveness against placebos, found, at commonly prescribed
doses, no differences among the statins in reducing cardiovascular
morbidity and mortality, and lipids.
In children statins are effective at reducing cholesterol levels in
those with familial hypercholesterolemia. Their long term safety
is, however, unclear. Some recommend that if lifestyle changes
are not enough statins should be started at 8 years old.
Statins may be less effective in reducing
LDL cholesterol in people
with familial hypercholesterolemia, especially those with homozygous
deficiencies. These people have defects usually in either the LDL
receptor or apolipoprotein B genes, both of which are responsible for
LDL clearance from the blood. Statins remain a first-line
treatment in familial hypercholesterolemia, although other
cholesterol-reducing measures may be required. In people with
homozygous deficiencies, statins may still prove helpful, albeit at
high doses and in combination with other cholesterol-reducing
Contrast induced nephropathy
A 2014 meta-analysis found that statins could reduce the risk of
contrast-induced nephropathy by 53% in people undergoing coronary
angiography/percutaneous interventions. The effect was found to be
stronger among those with preexisting kidney dysfunction or diabetes
Choosing a statin for people with special considerations
Commonly recommended statins
Kidney transplantation recipients taking ciclosporin
Pravastatin or Fluvastatin
Drug interactions are possible, but studies have not shown that these
statins increase exposure to ciclosporin.
HIV-positive people taking protease inhibitors
Pravastatin or Fluvastatin
Negative interactions are more likely with other choices
Persons taking gemfibrozil, a non-statin cholesterol-lowering drug
Combining gemfibrozil and a statin increases risk of rhabdomyolysis
and subsequently kidney failure
Persons taking the anticoagulant warfarin
The statin use may require that the warfarin dose be changed, as some
statins increase the effect of warfarin.
The most important adverse side effects are muscle problems, an
increased risk of diabetes mellitus, and increased liver enzymes in
the blood due to liver damage. Over 5 years of treatment
statins result in 75 cases of diabetes, 7.5 cases of bleeding stroke,
and 5 cases of muscle damage per 10,000 people treated. This could
be because, as statins inhibit the enzyme (
HMG-CoA reductase) that
makes cholesterol, statins also inhibit the other processes of this
enzyme, such as CoQ10 production, and CoQ10 production is important
for muscle cells and in blood sugar regulation.
Other possible adverse effects include neuropathy, pancreatic and
liver dysfunction, and sexual dysfunction. The rate at which such
events occur has been widely debated, in part because the risk/benefit
ratio of statins in low-risk populations is highly dependent on the
rate of adverse events. A Cochrane meta-analysis of statin
clinical trials in primary prevention found no evidence of excess
adverse events among those treated with statins compared to
placebo. Another meta-analysis found a 39% increase in adverse
events in statin treated people relative to those receiving placebo,
but no increase in serious adverse events. The author of one study
argued that adverse events are more common in clinical practice than
in randomized clinical trials. A systematic review concluded that
while clinical trial meta-analyses underestimate the rate of muscle
pain associated with statin use, the rates of rhabdomyolysis are still
"reassuringly low" and similar to those seen in clinical trials (about
1–2 per 10,000 person years). A systematic review co-authored by
Ben Goldacre concluded that only a small fraction of side effects
reported by people on statins are actually attributable to the
There are reports of cognitive decline with statins. In 2012, in
recognition of an increase in reports and increasing concerns over the
relationship between statins and memory loss (including reports of
transient global amnesia), forgetfulness and
Food and Drug Administration
Food and Drug Administration (FDA) added to its
required labeling on statin medications a warning about possible
cognitive impacts. The effects are described as rare, non-serious,
and reversible upon cessation of treatment.
Multiple systematic reviews and meta-analyses have concluded that the
available evidence does not support an association between statin use
and cognitive decline.
In observational studies 10–15% of people who take statins
experience muscle problems; in most cases these consist of muscle
pain. These rates, which are much higher than those seen in
randomized clinical trials have been the topic of extensive debate
Rare reactions include myopathies such as myositis (inflammation of
the muscles) or even rhabdomyolysis (destruction of muscle cells),
which can in turn result in life-threatening kidney injury. The risk
of statin-induced rhabdomyolysis increases with older age, use of
interacting medications such as fibrates, and hypothyroidism.
Coenzyme Q10 (ubiquinone) levels are decreased in statin use;
CoQ10 supplements are sometimes used to treat statin-associated
myopathy, though evidence of their efficacy is lacking as of
2007[update]. The gene
SLCO1B1 (Solute carrier organic anion
transporter family member 1B1) codes for an organic anion-transporting
polypeptide that is involved in the regulation of the absorption of
statins. A common variation in this gene was found in 2008 to
significantly increase the risk of myopathy.
Records exist of over 250,000 people treated from 1998 to 2001 with
the statin drugs atorvastatin, cerivastatin, fluvastatin, lovastatin,
pravastatin, and simvastatin. The incidence of rhabdomyolyis was
0.44 per 10,000 patients treated with statins other than cerivastatin.
However, the risk was over 10-fold greater if cerivastatin was used,
or if the standard statins (atorvastatin, fluvastatin, lovastatin,
pravastatin, or simvastatin) were combined with a fibrate (fenofibrate
or gemfibrozil) treatment.
Cerivastatin was withdrawn by its
manufacturer in 2001.
Some researchers have suggested hydrophilic statins, such as
fluvastatin, rosuvastatin, and pravastatin, are less toxic than
lipophilic statins, such as atorvastatin, lovastatin, and simvastatin,
but other studies have not found a connection.
the expression of gene atrogin-1, which is believed to be responsible
in promoting muscle fiber damage. Tendon rupture does not appear
The relationship between statin use and risk of developing diabetes
remains unclear and the results of systematic reviews and
meta-analyses are mixed. Higher doses have a greater
effect, but the decrease in cardiovascular disease outweighs the risk
of developing diabetes. Use in postmenopausal women is associated
with an increased risk for diabetes. The exact mechanism
responsible for the possible increased risk of diabetes mellitus
associated with statin use is unclear. Statins are thought to
decrease cells' uptake of glucose from the bloodstream in response to
the hormone insulin. One way this is thought to occur is by
interfering with cholesterol synthesis which is necessary for the
production of certain proteins responsible for glucose uptake into
cells such as GLUT1.
Several meta-analyses have found no increased risk of cancer, and some
meta-analyses have found a reduced risk.
Statins may reduce the risk of esophageal cancer, colorectal
cancer, gastric cancer, hepatocellular carcinoma, and
possibly prostate cancer. They appear to have no effect on the
risk of lung cancer, kidney cancer, breast cancer,
pancreatic cancer, or bladder cancer.
Combining any statin with a fibrate or niacin (other categories of
lipid-lowering drugs) increases the risks for rhabdomyolysis to almost
6.0 per 10,000 person-years. Monitoring liver enzymes and creatine
kinase is especially prudent in those on high-dose statins or in those
on statin/fibrate combinations, and mandatory in the case of muscle
cramps or of deterioration in kidney function.
Consumption of grapefruit or grapefruit juice inhibits the metabolism
of certain statins. Bitter oranges may have a similar effect.
Furanocoumarins in grapefruit juice (i.e. bergamottin and
dihydroxybergamottin) inhibit the cytochrome P450 enzyme CYP3A4, which
is involved in the metabolism of most statins (however, it is a major
inhibitor of only lovastatin, simvastatin, and to a lesser degree,
atorvastatin) and some other medications (flavonoids (i.e.
naringin) were thought to be responsible). This increases the levels
of the statin, increasing the risk of dose-related adverse effects
(including myopathy/rhabdomyolysis). The absolute prohibition of
grapefruit juice consumption for users of some statins is
The FDA notified healthcare professionals of updates to the
prescribing information concerning interactions between protease
inhibitors and certain statin drugs.
Protease inhibitors and statins
taken together may increase the blood levels of statins and increase
the risk for muscle injury (myopathy). The most serious form of
myopathy, rhabdomyolysis, can damage the kidneys and lead to kidney
failure, which can be fatal.
Mechanism of action
Atorvastatin bound to
HMG-CoA reductase: PDB entry 1hwk
HMG-CoA reductase pathway, which is blocked by statins via
inhibiting the rate limiting enzyme
Statins act by competitively inhibiting
HMG-CoA reductase, the
rate-limiting enzyme of the mevalonate pathway. Because statins are
similar in structure to
HMG-CoA on a molecular level, they will fit
into the enzyme's active site and compete with the native substrate
(HMG-CoA). This competition reduces the rate by which HMG-CoA
reductase is able to produce mevalonate, the next molecule in the
cascade that eventually produces cholesterol. A variety of natural
statins are produced by
Aspergillus fungi as secondary
metabolites. These natural statins probably function to inhibit
HMG-CoA reductase enzymes in bacteria and fungi that compete with the
Inhibiting cholesterol synthesis
HMG-CoA reductase, statins block the pathway for
synthesizing cholesterol in the liver. This is significant because
most circulating cholesterol comes from internal manufacture rather
than the diet. When the liver can no longer produce cholesterol,
levels of cholesterol in the blood will fall.
appears to occur mostly at night, so statins with short
half-lives are usually taken at night to maximize their effect.
Studies have shown greater
LDL and total cholesterol reductions in the
short-acting simvastatin taken at night rather than the
morning, but have shown no difference in the long-acting
In rabbits, liver cells sense the reduced levels of liver cholesterol
and seek to compensate by synthesizing
LDL receptors to draw
cholesterol out of the circulation. This is accomplished via
proteases that cleave membrane-bound sterol regulatory element binding
proteins, which then migrate to the nucleus and bind to the sterol
response elements. The sterol response elements then facilitate
increased transcription of various other proteins, most notably, LDL
LDL receptor is transported to the liver cell membrane
and binds to passing
LDL and V
LDL particles (colloquially, "bad
cholesterol"), mediating their uptake into the liver, where the
cholesterol is reprocessed into bile salts and other byproducts. This
results in a net effect of less
LDL circulating in blood.
Decreasing of specific protein prenylation
Statins, by inhibiting the HMG CoA reductase pathway, simultaneously
inhibit the production of both cholesterol and specific prenylated
proteins (see diagram).This inhibitory effect on protein prenylation
may be involved, at least partially, in the improvement of endothelial
function, modulation of immune function, and other pleiotropic
cardiovascular benefits of statins, as
well as in the fact that a number of other drugs that lower
not shown the same cardiovascular risk benefits in studies as
statins, and may also account for certain of the benefits seen in
cancer reduction with statins. In addition, the inhibitory effect
on protein prenylation may also be involved in a number of unwanted
side effects associated with statins, including muscle pain
(myopathy) and elevated blood sugar (diabetes).
As noted above, statins exhibit action beyond lipid-lowering activity
in the prevention of atherosclerosis. The
ASTEROID trial showed direct
ultrasound evidence of atheroma regression during statin therapy.
Researchers hypothesize that statins prevent cardiovascular disease
via four proposed mechanisms (all subjects of a large body of
Improve endothelial function
Modulate inflammatory responses
Maintain plaque stability
Prevent blood clot formation
In 2008, the JUPITER study showed benefit in those who had no history
of high cholesterol or heart disease, but only elevated C-reactive
protein levels. The conclusions of this study are, however,
Click on genes, proteins and metabolites below to link to respective
articles. [§ 1]
Statin Pathway edit]]
Statin Pathway edit
^ The interactive pathway map can be edited at WikiPathways:
The statins are divided into two groups: fermentation-derived and
synthetic. They include, along with brand names, which may vary
Lipobay, Baycol (withdrawn from the market in August, 2001 due to risk
of serious rhabdomyolysis)
Lescol, Lescol XL
Mevacor, Altocor, Altoprev
Naturally occurring, fermentation-derived compound. It is found in
oyster mushrooms and red yeast rice
Naturally occurring compound found in red yeast rice
Livalo, Livazo, Pitava
Pravachol, Selektine, Lipostat
Fermentation-derived (a fermentation product of bacterium Nocardia
CYP2C9 and CYP2C19
Fermentation-derived (simvastatin is a synthetic derivate of a
fermentation product of
Simvastatin + ezetimibe
Combination therapy: statin + cholesterol absorption inhibitor
Lovastatin + niacin extended-release
Atorvastatin + amlodipine
Combination therapy: statin + calcium antagonist
Simvastatin + niacin extended-release
LDL-lowering potency varies between agents.
Cerivastatin is the most
potent, (withdrawn from the market in August, 2001 due to risk of
serious rhabdomyolysis) followed by (in order of decreasing potency),
rosuvastatin, atorvastatin, simvastatin, lovastatin, pravastatin, and
fluvastatin. The relative potency of pitavastatin has not yet
been fully established.
The oyster mushroom, a culinary mushroom, naturally contains
Some types of statins are naturally occurring, and can be found in
such foods as oyster mushrooms and red yeast rice. Randomized
controlled trials have found these foodstuffs to reduce circulating
cholesterol, but the quality of the trials has been judged to be
low. Due to patent expiration, most of the block-buster branded
statins have been generic since 2012, including atorvastatin, the
largest-selling branded drug.
Statin equivalent dosages
LDL reduction (approx.)
* 80-mg dose no longer recommended due to increased risk of
10 mg; 5 mg if hypothyroid, >65 yo, Asian
LDL reduction goal
40 mg if >45%
40 mg if >25%
20 mg if >20%
20 mg if
LDL >190 mg/dL (4.87 mmol/L)
40 mg if >45%
With evening meals
In 1971, Akira Endo, a Japanese biochemist working for the
pharmaceutical company Sankyo, began the search for a
cholesterol-lowering drug. Research had already shown cholesterol is
mostly manufactured by the body in the liver, using the enzyme HMG-CoA
reductase. Endo and his team reasoned that certain microorganisms
may produce inhibitors of the enzyme to defend themselves against
other organisms, as mevalonate is a precursor of many substances
required by organisms for the maintenance of their cell walls
(ergosterol)[dubious – discuss] or cytoskeleton (isoprenoids).
The first agent they identified was mevastatin (ML-236B), a molecule
produced by the fungus
A British group isolated the same compound from Penicillium
brevicompactum, named it compactin, and published their report in
1976. The British group mentions antifungal properties, with no
HMG-CoA reductase inhibition.
Mevastatin was never marketed, because of its adverse effects of
tumors, muscle deterioration, and sometimes death in laboratory dogs.
P. Roy Vagelos, chief scientist and later CEO of Merck & Co, was
interested, and made several trips to Japan starting in 1975. By 1978,
Merck had isolated lovastatin (mevinolin, MK803) from the fungus
Aspergillus terreus, first marketed in 1987 as Mevacor.
A link between cholesterol and cardiovascular disease, known as the
lipid hypothesis, had already been suggested.
Cholesterol is the main
constituent of atheroma, the fatty lumps in the wall of arteries that
occur in atherosclerosis and, when ruptured, cause the vast majority
of heart attacks. Treatment consisted mainly of dietary measures, such
as a low-fat diet, and poorly tolerated medicines, such as clofibrate,
cholestyramine, and nicotinic acid.
Cholesterol researcher Daniel
Steinberg writes that while the Coronary Primary Prevention Trial of
1984 demonstrated cholesterol lowering could significantly reduce the
risk of heart attacks and angina, physicians, including cardiologists,
remained largely unconvinced.
Society and culture
To market statins effectively, Merck had to convince the public of the
dangers of high cholesterol, and doctors that statins were safe and
would extend lives. As a result of public campaigns, people in the
United States became familiar with their cholesterol numbers and the
difference between "good" and "bad" cholesterol, and rival
pharmaceutical companies began producing their own statins, such as
pravastatin (Pravachol), manufactured by Sankyo and Bristol-Myers
Squibb. In April 1994, the results of a Merck-sponsored study, the
Simvastatin Survival Study, were announced. Researchers
tested simvastatin, later sold by Merck as Zocor, on 4,444 patients
with high cholesterol and heart disease. After five years, the study
concluded the patients saw a 35% reduction in their cholesterol, and
their chances of dying of a heart attack were reduced by 42%.
In 1995, Zocor and Mevacor both made Merck over US$1 billion.
Endo was awarded the 2006 Japan Prize, and the Lasker-DeBakey Clinical
Medical Research Award in 2008. For his "pioneering research into a
new class of molecules" for "lowering cholesterol," Endo was
inducted into the
National Inventors Hall of Fame
National Inventors Hall of Fame in Alexandria,
Virginia in 2012. Michael C. Brown and Joseph Goldstein, who won the
Nobel Prize for related work on cholesterol, said of Endo: "The
millions of people whose lives will be extended through statin therapy
owe it all to Akira Endo."
Research continues into other areas where specific statins also appear
to have a favorable effect, including dementia, lung cancer,
nuclear cataracts, hypertension, and prostate
Statins are perhaps the most widely prescribed drug-type, and related
patents are beginning to expire.
In 2014 The Federal Drug Administration (FDA) issued a report of the
side effects of statin usage, which found that some patients reported
cognitive problems, including issues with forgetfulness, memory loss,
and confusion. Other patients, who run a risk of raised blood sugar
levels that statins can lead to Type-2 Diabetic Mellitus were also of
concern. There was a further report released in March 2015, which
states Finnish researchers had determined that patients using statins
have a significant risk of developing Type 2 diabetes mellitus.
The publication of a report entitled "
Cholesterol confusion and statin
controversy" by Robert DuBroff (a research cardiologist, University Of
New Mexico) and Michel de Lorgeril (a medical researcher at the French
Centre National de Recherche Scientifique
Centre National de Recherche Scientifique specialized in cardiology
and nutrition – and a member of the European Society of Cardiology)
presented to the
World Congress of Cardiology
World Congress of Cardiology merely suggested than
association between cholesterol levels does not necessarily indicate a
cause of Coronary Heart Disease, but may be also simply a coincidence
or an incidental consequence.
The public controversy over cholesterol medication use resulted from
authoritative medical journals which ran scientific articles (such as
the one quoted above) questioning the widespread prescriptions of
statins. Popular interpretation in Britain is said to have prompted an
estimated 200,000 people to stop using statins over a six-month period
to mid 2016, according to the authors of a study funded by the British
Heart Foundation. They conclude there could be up to 2,000 extra heart
attacks or strokes over the following 10 years as a consequence, but
admit that it is impossible to be certain.
National Institute for Health and Care Excellence
National Institute for Health and Care Excellence asserts that
statins could prevent up to 28,000 heart attacks and 16,000 strokes
each year in Britain. That guidance, which was based on evidence from
the group led by Prof
Rory Collins at the clinical trials service unit
at Oxford University, was questioned by the British Medical Journal,
which is campaigning against the over-use of medicines and medical
An unintended effect of the academic statin controversy is the spread
of scientifically questionable alternative therapies. Cardiologist
Steven Nissen at
Cleveland Clinic commented "We are losing the battle
for the hearts and minds of our patients to Web sites..."
promoting unproven medical therapies.
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Statin page at Bandolier, an evidence-based medicine journal (little
content after 2004)
NHS Choices: High
Cholesterol Prevention (dietary measures etc)
Pharmacology: major drug groups
Proton pump inhibitors
Blood and blood
forming organs (B)
Calcium channel blockers
Angiotensin II receptor antagonists
Bile acid sequestrants
Thyroid hormones/Antithyroid agents
infestations (J, P, QI)
Antimicrobials: Antibacterials (Antimycobacterials)
and joints (M)
nervous system (N)
Sensory organs (S)
Other ATC (V)
Lipid modifying agents (C10)
Cholesterol absorption inhibitors, NPC1L1
Bile acid sequestrants/resins (LDL)
HMG-CoA reductase, LDL)
Niacin and derivatives (HDL and LDL)
MTTP inhibitors (VLDL)
CETP inhibitors (HDL)
PCSK9 inhibitors (LDL)
Magnesium pyridoxal 5-phosphate glutamate
‡Withdrawn from market
§Never to phase III
Pharmacology: enzyme inhibition
Oxidoreductase (EC 1)
1.1 Aldose reductase
1.4 Monoamine oxidase
1.5 Dihydrofolate reductase
1.17 Xanthine oxidase
Transferase (EC 2)
2.5 Dihydropteroate synthetase
2.6 GABA transaminase
Hydrolase (EC 3)
3.4 Protease: Exopeptidase
3.5 Histone deacetylase
Lyase (EC 4)
4.1 Dopa decarboxylase
4.2 Carbonic anhydrase