Anticholesterol drug is 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 (primary prevention)
The medications for dyslipidemia can be grouped into five categories: fibrates, bile acid resins, hydroxymethylglutaryl co-enzyme A (HMG-CoA) reductase inhibitors (known collectively as statins), proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and miscellaneous agents.
The statins are divided into two groups: fermentation-derived and synthetic. They include, along with brand names, which may vary between countries:
| Statin | Image | Brand name | Derivation | Metabolism |
|---|---|---|---|---|
| Atorvastatin |
 |
Lipitor, Ator | Synthetic | CYP3A4 |
| Cerivastatin |
 |
Lipobay, Baycol (withdrawn from the market in August, 2001 due to risk of serious rhabdomyolysis) | Synthetic | various CYP3Aisoforms |
| Fluvastatin |
 |
Lescol, Lescol XL | Synthetic | CYP2C9 |
| Lovastatin |
 |
Mevacor, Altocor, Altoprev | Naturally occurring, fermentation-derived compound. It is found in oyster mushroomsand red yeast rice | CYP3A4 |
| Mevastatin |
 |
Compactin | Naturally occurring compound found in red yeast rice | CYP3A4 |
| Pitavastatin |
 |
Livalo, Livazo, Pitava | Synthetic | CYP2C9 and CYP2C8(minimally) |
| Pravastatin |
 |
Pravachol, Selektine, Lipostat | Fermentation-derived (a fermentation product of bacterium Nocardia autotrophica) | Non-CYP |
| Rosuvastatin |
 |
Crestor | Synthetic | CYP2C9 and CYP2C19 |
| Simvastatin |
 |
Zocor, Lipex | Fermentation-derived (simvastatin is a synthetic derivate of a fermentation product of Aspergillus terreus) | CYP3A4 |
| Simvastatin + ezetimibe | Vytorin, Inegy | Combination therapy: statin + cholesterol absorption inhibitor | ||
| Lovastatin + niacin extended-release | Advicor, Mevacor | Combination therapy | ||
| Atorvastatin + amlodipine | Caduet, Envacar | Combination therapy: statin + calcium antagonist | ||
| 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 Cerivastatin is the most potent, (withdrawn from the market in August 2001 due to the risk of serious rhabdomyolysis) followed by (in order of decreasing potency), rosuvastatin, atorvastatin,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 bile acid resins or sequestrants are the oldest and safest lipid lowering agents, but are less potent than other classes now available and are not always well tolerated. The bile acid sequestrants are highly positively charged and bind to the negatively charged bile acids in the intestine, inhibiting their lipid solubilizing activity and thus reducing cholesterol absorption. They also inhibit the reabsorption of bile acids (absorption of which is typically 95%) and thus cause a contraction of the bile acid pool, which leads to increased bile acid synthesis that competes with cholesterol synthesis in the liver; this may also contribute to a lowering of cholesterol.
The bile acid resins or sequestrants are the oldest and safest lipid lowering agents, but are less potent than other classes now available and are not always well tolerated. The bile acid sequestrants are highly positively charged and bind to the negatively charged bile acids in the intestine, inhibiting their lipid solubilizing activity and thus reducing cholesterol absorption. They also inhibit the reabsorption of bile acids (absorption of which is typically 95%) and thus cause a contraction of the bile acid pool, which leads to increased bile acid synthesis that competes with cholesterol synthesis in the liver; this may also contribute to a lowering of cholesterol.
Fibrates are fibric acid derivative agents and are used to lower plasma lipids and particularly triglyceride levels. Their mechanism of action is believed to be via activation of the hepatic peroxisome proliferator activated receptors (PPARs), which regulate gene transcription of enzymes involved in lipid synthesis and secretion.
PCSK9 inhibitors – PCSK9 inhibitors attach to a particular liver cell surface protein, which results in lowered LDL (“bad”) cholesterol. You can take this class of drug with statins. A provider can inject PCSK9 inhibitors for you. They’re usually for people at high risk of heart disease who haven’t been able to lower their cholesterol enough in other ways.
Nicotinic acid, or niacin, is a B-complex vitamin. You can get over-the-counter (OTC) versions of this, but some versions are prescription-only. Niacin decreases LDL cholesterol and triglycerides and increases HDL. If you have gout or severe liver disease, you shouldn’t take niacin.
The miscellaneous medications used for hypercholesterolemia or dyslipidemia include niacin, omega-3 fatty acids, ezetimibe, mipomersen and lomitapide. Niacin is a water soluble B vitamin (vitamin B3, nicotinic acid), but when used to treat dyslipidemia, it is given in doses far in excess of the minimal requirements as a vitamin. Niacin acts by reducing triglyceride synthesis via inhibition of synthesis and esterification of free fatty acids. Niacin favorably affects all aspects of dyslipidemia and is the most potent agent available for increasing HLD cholesterol levels. Niacin is available in multiple generic forms and as a combination with various statins (lovastatin: Advicor and simvastatin: Simcor). High doses of niacin are associated with a high rate of acute liver injury particularly if taken as slow release forms.
Omega-3 fatty acids are essential polyunsaturated fatty acids that have several functions in normal metabolism and health. Commonly referred to as “fish oil”, many formulations of omega-3 fatty acids are available over-the-counter as nutritional supplements in support of general health. High doses of omega-3 fatty acids can lower serum triglyceride levels and several formulations have been developed as prescription medications for therapy of severe hypertriglyceridemia including omega-3 acid ethyl esters (Lovaza 2004), icosapent ethyl (Vascepa, 2012) and omega-3 carboxylic acids (Epanova, 2014). These agents have occasionally been associated with transient and mild serum enzyme elevations during treatment but have not been linked to cases of clinically apparent liver injury.
Ezetimibe (Zetia: 1999) is a lipid lowering agent that acts by inhibition of cholesterol absorption, via binding to the intestinal protein known as Neiman Pick C1 like protein 1, the major cholesterol transport protein in the intestine. Inhibition of cholesterol absorption is usually followed by an increase in hepatic cholesterol synthesis, which can be blocked by HMG-CoA reductase inhibitors. For these reasons, ezetimibe is usually used in conjunction with statins and it is often used in fixed combinations (Vytorin). Ezetimibe has been linked to a low rate of mild-to-moderate serum aminotransferase elevations during therapy and rare instances of clinically apparent acute liver injury.
Adenosine triphosphate-citric lyase (ACL) inhibitors (bempedoic acid) – Bempedoic acid works in your liver to slow down cholesterol production. You should take it with statin medications, but you’ll need to limit your dosage if you take it with simvastatin or pravastatin.
Selective cholesterol absorption inhibitors (ezetimibe) – This class of antihyperlipidemic works in your intestine to stop your body from absorbing cholesterol. These inhibitors reduce LDL cholesterol, but may also reduce triglycerides and increase HDL, or “good,” cholesterol. You can combine them with statins.
The following medications for dyslipidemia and hypercholesterolemia are discussed individually in LiverTox:
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Bile Acid Resins/Sequestrants
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Cholestyramine
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Colesevelam
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Colestipol
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Fibrates
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Clofibrate
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Fenofibrate
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Gemfibrozil
-
-
Monoclonal Antibodies
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Alirocumab (Anti-PCSK9)
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Evinacumab (Anti-ANGPTL3)
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Evolocumab (Anti-PCSK9)
-
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Niacin (Nicotinic Acid)
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Omega-3 Fatty Acids,
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Icosapent Ethyl
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Omega-3 Acid Ethyl Esters
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Omega-3 Carboxylic Acids
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Statins
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Atorvastatin
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Fluvastatin
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Lovastatin
-
Pitavastatin
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Pravastatin
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Rosuvastatin
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Simvastatin
-
-
Miscellaneous
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Bempedoic Acid
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Ezetimibe
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Inclisiran
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Lomitapide
-
Mipomersen
-
Resmetirom
-
The oyster mushroom, a culinary mushroom, naturally contains lovastatin.
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 | – |
| 56–60% | – | – | – | – | 40 mg | – |
| * 80-mg dose no longer recommended due to increased risk of rhabdomyolysis | ||||||
| Starting dose | ||||||
| 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 |
References
