HMG-CoA reductase inhibitor
- limit, block, or decrease the action or function of; "inhibit the action of the enzyme"; "inhibit the rate of a chemical reaction"
- control and refrain from showing; of emotions, desires, impulses, or behavior (同)bottle up, suppress
- limit the range or extent of; "Contact between the young was inhibited by strict social customs"
- the 3rd letter of the Roman alphabet (同)c
- (music) the keynote of the scale of C major
- a general-purpose programing language closely associated with the UNIX operating system
- a substance that retards or stops an activity
- the 8th letter of the Roman alphabet (同)h
- an enzyme that catalyses the biochemical reduction of some specified substance
- 〈感情・欲望・行動・作用など〉‘を'抑制する / (…しないように)〈人〉‘を'抑制する,妨げる《+『名』+『from』+『名』(do『ing』)》
- 抑制する人(物) / 化学反応抑制剤
- 鉛筆の硬度 / 《俗》heroin
Lovastatin, a compound isolated from Aspergillus terreus, was the first statin to be marketed.
|Biological target||HMG-CoA reductase|
Statins (or HMG-CoA reductase inhibitors) are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver, which produces about 70 percent of total cholesterol in the body. High cholesterol levels have been associated with cardiovascular disease (CVD). Statins have been found to prevent cardiovascular disease and mortality in those who are at high risk. The evidence is strong that statins are effective for treating CVD in the early stages of a disease (secondary prevention) and in those at elevated risk but without CVD (primary prevention). 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.
As of 2010, a number of statins are on the market: atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Mevacor, Altocor), pitavastatin (Livalo), pravastatin (Pravachol), rosuvastatin (Crestor) and simvastatin (Zocor). Several combination preparations of a statin and another agent, such as ezetimibe/simvastatin, are also available. In 2005 sales were estimated at $18.7 billion in the United States. The best-selling statin is atorvastatin, 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 are now available as less expensive generics.
- 1 Medical uses
- 1.1 Primary prevention
- 1.2 Secondary prevention
- 1.3 Comparative effectiveness
- 1.4 Children
- 1.5 Prevention of contrast induced nephropathy
- 2 Adverse effects
- 2.1 Cognitive effects
- 2.2 Muscles
- 2.3 Diabetes
- 2.4 Cancer
- 2.5 Drug interactions
- 3 Mechanism of action
- 3.1 Inhibiting cholesterol synthesis
- 3.2 Increasing LDL uptake
- 3.3 Decreasing of specific protein prenylation
- 3.4 Other effects
- 4 Available forms
- 5 History
- 6 Research
- 7 References
- 8 External links
Clinical practice guidelines generally recommend people to 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.
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.
The 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 and the American Heart Association recommend statin treatment for primary prevention of cardiovascular disease in adults with LDL cholesterol > 190 mg/dL. 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 LDL thresholds.
Statins are effective in decreasing mortality in people with pre-existing CVD. They are also currently advocated for use in patients at high risk of developing 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 atorvastatin, pravastatin and simvastatin, based on their effectiveness against placebos, found, at commonly prescribed doses, no statistically significant differences among agents in reducing cardiovascular morbidity and mortality.
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.
Prevention of contrast induced nephropathy
A recent meta-analysis of randomized controlled trials 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 mellitus.
|Choosing a statin for people with special considerations|
|Condition||Commonly recommended statins||explanation|
|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||Atorvastatin, Pravastatin or Fluvastatin||Negative interactions are more likely with other choices|
|persons taking gemfibrozil, a non-statin cholesterol-lowering drug||Atorvastatin||Combining gemfibrozil and a statin increases risk of rhabdomyolysis and subsequently kidney failure|
|persons taking the anticoagulant warfarin||any statin||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 increased concentrations of liver enzymes, muscle problems, and an increased risk of diabetes. Other possible adverse effects include cognitive loss, neuropathy, pancreatic and hepatic 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 group 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 by the Canadian Working Group Consensus Conference that considered published meta analyses of clinical trials, spontaneous adverse event reports to the FDA, and published cohort studies 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 patient years). A systematic review co-authored by Ben Goldacre concluded that only a small fraction of side effects reported by patients on statins are actually attributable to the statin.
There are anecdotal reports of cognitive decline with statins. A systematic review by the Canadian Working Group Consensus Conference concluded that the available evidence "is not strongly supportive of a major adverse effect of statins". Another meta-analysis reported concluded that there is moderate quality evidence of no increase in dementia, mild cognitive impairment or cognitive performance scores, although the strength of the evidence is limited, particularly for high doses. In 2012, in recognition of an increase in anecdotal reports and increasing concerns over the relationship between statins and memory loss (including reports of transient global amnesia), forgetfulness and confusion, the FDA added to its required labeling on statin drugs a warning about possible cognitive impacts. The effects are described as rare, non-serious, and reversible upon cessation of treatment.
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 and discussion.
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.
Graham et al. (2004) reviewed records of over 250,000 patients 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 fibrate (fenofibrate or gemfibrozil) treatment. Cerivastatin was withdrawn by its manufacturer in 2001.
All commonly used statins show somewhat similar results, but the newer statins, characterized by longer pharmacological half-lives and more cellular specificity, have had a better ratio of efficacy to lower adverse effect rates. 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 risk of myopathy was suggested to be lowest with pravastatin and fluvastatin, probably because they are more hydrophilic and as a result have less muscle penetration. Lovastatin induces the expression of gene atrogin-1, which is believed to be responsible in promoting muscle fiber damage.
Statins are associated with a slightly increased risk of diabetes (2-17% in one review). Higher doses have a greater effect, but the decrease in cardiovascular disease outweighs the risk of developing diabetes.
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, another category 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 controversial.
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
Statins act by competitively inhibiting HMG-CoA reductase, the first committed enzyme of the HMG-CoA reductase pathway. Because statins are similar to HMG-CoA on a molecular level, they take the place of HMG-CoA in the enzyme and reduce the rate by which it is able to produce mevalonate, the next molecule in the cascade that eventually produces cholesterol, as well as a number of other compounds. This ultimately reduces cholesterol via several mechanisms. A variety of statins are produced by Penecillium and Aspergillus fungi as secondary metabolites. These natural statins probably function to inhibit HMG-CoA reductase enzymes in bacteria and fungi that compete with the producer.
Inhibiting cholesterol synthesis
By inhibiting 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. Cholesterol synthesis 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 atorvastatin.
Increasing LDL uptake
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 protease enzymes that cleave a protein called "membrane-bound sterol regulatory element binding protein", which migrates to the nucleus and causes increased production of various other proteins and enzymes, including the LDL receptor. The LDL receptor then relocates to the liver cell membrane and binds to passing LDL and VLDL particles (the "bad cholesterol" linked to disease). LDL and VLDL are drawn out of circulation into the liver, where the cholesterol is reprocessed into bile salts. These are excreted, and subsequently recycled mostly by an internal bile salt circulation.
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 LDL have 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 biomedical research):
- Improve endothelial function
- Modulate inflammatory responses
- Maintain plaque stability
- Prevent thrombus 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. These conclusions of this study are, however, controversial.
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
- The interactive pathway map can be edited at WikiPathways: "Statin_Pathway_WP430".
The statins are divided into two groups: fermentation-derived and synthetic. They include, along with brand names, which may vary between countries:
||Lipobay, Baycol. (Withdrawn from the market in August, 2001 due to risk of serious rhabdomyolysis)||Synthetic||various CYP3A isoforms|
||Lescol, Lescol XL||Synthetic||CYP2C9|
||Mevacor, Altocor, Altoprev||This is a naturally occurring, fermentation-derived compound. It is found in oyster mushrooms and red yeast rice.||CYP3A4|
||Compactin||This is a naturally occurring compound found in red yeast rice.||CYP3A4|
||Pravachol, Selektine, Lipostat||Fermentation-derived. (A fermentation product of bacterium Nocardia autotrophica).||Non CYP|
||Crestor||Synthetic||CYP2C9 and CYP2C19|
||Zocor, Lipex||Fermentation-derived. (Simvastatin is a synthetic derivate of a fermentation product ofAspergillus terreus.)||CYP3A4|
|Lovastatin+Niacin extended-release||Advicor||Combination therapy|
|Atorvastatin+Amlodipine Besylate||Caduet||Combination therapy – Cholesterol+Blood Pressure|
|Simvastatin+Niacin extended-release||Simcor||Combination therapy|
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.
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.)||Atorvastatin||Fluvastatin||Lovastatin||Pravastatin||Rosuvastatin||Simvastatin|
|10–20%||–||20 mg||10 mg||10 mg||–||5 mg|
|20–30%||–||40 mg||20 mg||20 mg||–||10 mg|
|30–40%||10 mg||80 mg||40 mg||40 mg||5 mg||20 mg|
|40–45%||20 mg||–||80 mg||80 mg||5–10 mg||40 mg|
|46–50%||40 mg||–||–||–||10–20 mg||80 mg*|
|50–55%||80 mg||–||–||–||20 mg||–|
|* 80-mg dose no longer recommended due to increased risk of rhabdomyolysis|
|Starting dose||10–20 mg||20 mg||10–20 mg||40 mg||10 mg; 5 mg if hypothyroid, >65 yo, Asian||20 mg|
|If higher 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%|
|Optimal timing||Anytime||Evening||With evening meals||Anytime||Anytime||Evening|
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) or cytoskeleton (isoprenoids). The first agent they identified was mevastatin (ML-236B), a molecule produced by the fungus Penicillium citrinum.
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 mention of 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.
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 Scandinavian 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 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 cancer.
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- table adapted from the following source, but check individual references for technical explanations
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- Zhang XL, Geng J, Zhang XP, Peng B, Che JP, Yan Y, Wang GC, Xia SQ, Wu Y, Zheng JH (April 2013). "Statin use and risk of bladder cancer: a meta-analysis.". Cancer causes & control : CCC 24 (4): 769–76. doi:10.1007/s10552-013-0159-3. PMID 23361339.
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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)
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- 1. スタチン：作用、副作用、および投与 statins actions side effects and administration
- 2. 筋系に生じるスタチン系薬剤の副作用 statin muscle related adverse events
- 3. 心血管疾患の二次予防としての低比重リポタンパク（LDL-C）高値の管理 management of elevated low density lipoprotein cholesterol ldl c in primary prevention of cardiovascular disease
- 4. 心血管疾患の二次予防としての低比重リポタンパク（LDL-C）の管理 management of low density lipoprotein cholesterol ldl c in secondary prevention of cardiovascular disease
- 5. スタチン：心血管系以外に利益をもたらす可能性 statins possible noncardiovascular benefits
- A population-based case-control study on statin exposure and risk of acute diverticular disease.
- Sköldberg F1, Svensson T2, Olén O2,3,4, Hjern F5, Schmidt PT6, Ljung R7.
- Scandinavian journal of gastroenterology.Scand J Gastroenterol.2016 Feb;51(2):203-10. doi: 10.3109/00365521.2015.1081274. Epub 2015 Sep 10.
- OBJECTIVE: A reduced risk of perforated diverticular disease among individuals with current statin exposure has been reported. The aim of the present study was to investigate whether statins reduce the risk of acute diverticular disease.MATERIAL AND METHODS: A nation-wide population-based case-contr
- PMID 26357870
- Atherogenic Lipoprotein Subfractions Determined by Ion Mobility and First Cardiovascular Events After Random Allocation to High-Intensity Statin or Placebo: The Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) Trial.
- Mora S1, Caulfield MP2, Wohlgemuth J2, Chen Z2, Superko HR2, Rowland CM2, Glynn RJ2, Ridker PM2, Krauss RM2.
- Circulation.Circulation.2015 Dec 8;132(23):2220-9. doi: 10.1161/CIRCULATIONAHA.115.016857. Epub 2015 Sep 25.
- BACKGROUND: Cardiovascular disease (CVD) can occur in individuals with low low-density lipoprotein (LDL) cholesterol (LDL-C). We investigated whether detailed measures of LDL subfractions and other lipoproteins can be used to assess CVD risk in a population with both low LDL-C and high C-reactive pr
- PMID 26408274
- Statin therapy and plasma vitamin E concentrations: A systematic review and meta-analysis of randomized placebo-controlled trials.
- Sahebkar A1, Simental-Mendía LE2, Ferretti G3, Bacchetti T4, Golledge J5.
- Atherosclerosis.Atherosclerosis.2015 Dec;243(2):579-88. doi: 10.1016/j.atherosclerosis.2015.09.028. Epub 2015 Oct 9.
- BACKGROUND: Vitamin E is one of the most important natural antioxidants, and its plasma levels are inversely associated with the progression of atherosclerosis. There have been reports suggesting a potential negative effect of statin therapy on plasma vitamin E levels. The aim of this meta-analysis
- PMID 26539697
- Effects of Pitavastatin on Pressure Overload-Induced Heart Failure in Mice
- KAMEDA Yoshihito,HASEGAWA Hiroshi,KUBOTA Akihiko,TADOKORO Hiroyuki,KOBAYASHI Yoshio,KOMURO Issei,TAKANO Hiroyuki
- Circulation journal : official journal of the Japanese Circulation Society 76(5), 1159-1168, 2012-04-25
- … biBackground:/i/b 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), which are widely used to lower plasma cholesterol levels, have been reported to have various pleiotropic effects such as protective effect of endothelial cells, angiogenic effect, antioxidant effect and anti-inflammatory effect. …
- NAID 10030132534
- 兵庫 秀幸,田妻 進,茶山 一彰
- 消化と吸収 34(3), 206-211, 2012-03-31
- NAID 10030560853
- HMG-CoA reductase inhibitor any of a group of drugs that competitively inhibit the enzyme catalyzing the rate-limiting step in cholesterol biosynthesis and are used to lower plasma lipoprotein levels in the treatment of ...
- Competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase are the rate limiting enzymes in cholesterol biosynthesis. By blocking the conversion of HMG-CoA to the cholesterol precursor mevalonate, these ...
|拡張検索||「HMG-CoA reductase inhibitors」|
- HMG-CoA reductase inhibitor
- ヒドロキシメチルグルタリルコエンザイムA還元酵素阻害薬 hydroxymethylglutaryl-CoA reductase inhibitor。スタチン statin
- 高脂血症治療薬、高脂血症、コレステロールの生合成。HMG-CoA還元酵素 HMG-CoA reductase
- TG250-350mg/dl 380
- TG350-450mg/dl 470
|ロスバスタチン||クレストール||水溶性||ー 5)||未変化体 5)||29||10 5)||15～19 5)|
|1)Prog Med, 18:957-962,1998. 2)Heart, 85:259-264,2001. 3)PHarmacol Ther, 80:1-34 改変 4)興和(株)社内資料 5)添付文書|
- HMG-CoA reductaseを競合阻害→肝内コレステロール産生↓→肝LDL受容体発現↑→血中LDL↓
- 1. 横紋筋融解症
- 2. CYPを介する薬物相互作用
- 3. 肝障害
- 4. CK上昇
- This was suggested by a study showing greater increases in post-marathon CK levels in individuals receiving statins; older runners receiving statins exhibited more susceptibility to CK elevations than younger runners. These elevations in CK were, however, mild and subclinical, which suggests that trained individuals need not discontinue statin therapy prior to a race.(uptodate)
- 炭素 carbon
- シトシン cytosine
- システイン cysteine
- セルシウス度 摂氏 degrees Celsius degree C
- 産婦人科領域で「子宮外頚 子宮外頚部 exocervix」を表現するための略語