What are statins and how do they work?

Statin pills
Statins are used for treating hyperlipidemia and heterozygous familial hypercholesterolemia for the primary and secondary prevention of coronary heart disease, (angina, heart attack), stroke, peripheral arterial disease (intermittent claudication).

Statins (or HMG-CoA reductase inhibitors) are a class of drugs that reduce cholesterol in individuals who have dyslipidemia (abnormal fats in the blood) and thus are at risk for cardiovascular disease.

  • Dyslipidemia may involve an elevation of total cholesterol, a reduction of low-density lipoprotein (LDL) cholesterol and/or triglycerides, or a reduction of high-density lipoprotein (HDL) cholesterol in the blood.
  • Statins work by blocking the enzyme in the liver that is responsible for making cholesterol. This enzyme is called hydroxy-methylglutaryl-coenzyme A reductase (HMG-CoA reductase).

Cholesterol is described as a soft wax-like fatty substance that is found in the bloodstream and in cells. It is important to note that cholesterol is a naturally existing substance in all individuals from birth and its presence is actually necessary for promoting an overall healthy body.

  • About 75% of cholesterol is produced by the liver and other cells in the body, and 25% comes from food.

Cholesterol can have a negative impact on health when there is too much bad LDL cholesterol circulating in the blood system.

  • Contributing factors to high LDL levels may be unhealthy foods, genetics, lack of physical activity, and smoking.

Triglycerides are a form of body fat that increases due to being overweight or obese, and physical inactivity, amongst others factors.

  • High triglycerides levels may contribute to heart disease and diabetes.
  • HDL cholesterol is known as good cholesterol as it protects the heart against heart attacks: it is important to have an HDL level greater than 40 mg/dL.

As previously mentioned, cholesterol contributes to cardiovascular disease as well as neurological and peripheral vascular disease.

  • The way this occurs is by atherosclerosis, a condition, where over the course of time, cholesterol builds up in arteries and forms hardened plaques.
  • If plaques rupture, blood clots may form on the plaque and block the arteries.
  • The clots also may dislodge and circulate within the body, block distant arteries, and ultimately reduce the flow of blood and oxygen through the arteries and to organs.
  • Clots situated in the coronary arteries may give rise to angina or a heart attack.
  • Clots in the carotid artery (the artery that supplies blood to the brain) may result in a stroke, and clots affecting the lower extremities such as the legs may result in peripheral arterial disease.

For what conditions are statins used?

Statins are used for treating

  • hyperlipidemia and heterozygous familial hypercholesterolemia for the primary and secondary prevention of coronary heart disease,
  • angina (heart attack), 
  • stroke, and
  • peripheral arterial disease (intermittent claudication).

Statins have unapproved uses including

Are there differences among statins?

There are a variety of ways that statins differ. One of the differences involves potency in the ability to reduce cholesterol plasma levels.

Statins also differ in how strongly they interact with other drugs; this is due to drug metabolism.

  • Of the statins, neither pravastatin (Pravachol) nor rosuvastatin (Crestor) undergo extensive CYP450 metabolism and are likely to produce muscle toxicity such as myalgia, myopathies, and inflammation of the muscles due to increased plasma levels and subsequent interactions with other drugs.

In patients who have renal disease,

  • dosages of pravastatin (Pravachol), lovastatin (Mevacor, Altocor), rosuvastatin (Crestor), and simvastatin (Zocor) should be adjusted to prevent increased plasma concentration.
  • No adjustment is necessary for atorvastatin (Lipitor) or fluvastatin (Lescol).

The statins differ in their ability to cause side effects.

  • Skeletal muscle toxicity such as rhabdomyolysis may occur when certain drugs are given with statins which causes an increase in the concentration of statins.
  • Cerivastatin (Baycol) was withdrawn from pharmacies worldwide because it caused rhabdomyolysis 10 to 100 times more often than other statins.

What are side effects of statins?

Common side effects include

The serious side effects include

  • extreme muscle pain,
  • rhabdomyolysis, and
  • serious liver problems.

What are the drug interactions with statins?

  • Statins [atorvastatin (Lipitor), lovastatin (Mevacor, Altocor), fluvastatin (Lescol), and simvastatin (Zocor)] when taken together with itraconazole (Sporanox), erythromycin (for example, Benzamycin, Emgel, Ilotycin, Staticin), protease inhibitors, nefazodone (Serzone), cyclosporine (Sandimmune, Neoral, Restasis), diltiazem (Cardizem LA, Cardizem Injection, Tiazac), verapamil (Covera-HS, Verelan PM, Calan), and grapefruit juice could cause an interaction that blocks the enzymes in the liver that eliminate statins from the body.
    • This causes an increased level of statins that could result in an increased risk of myopathies and rhabdomyolysis.
  • Bile acid sequestrants [colestipol (Colestid) and cholestyramine (Questran, Questran Light)] prevent the absorption of statins into the body by binding to them in the intestine. It is recommended that statins be ingested one hour before or four hours after cholestyramine (Questran, Questran Light) or colestipol (Colestid).
  • Statins [fluvastatin (Lescol), lovastatin (mevacor, Altocor), rosuvastatin (Crestor), and simvastatin (Zocor)], when taken with warfarin (Coumadin), may cause an increased risk of bleeding. Atorvastatin (Lipitor) and pravastatin (Pravachol) do not have a clinically significant effect when given warfarin (Coumadin).
  • An increased risk of rhabdomyolysis or liver failure can occur when statins are taken with niacin [nicotinic acid (Niaspan, Niacor)], or fibric acids [gemfibrozil (Lopid), clofibrate (Atromid-S), and fenofibrate (Tricor)].
  • St John’s Wort decreases the levels of lovastatin (Mevacor, Altocor) and simvastatin (Zocor) and could possibly reduce the efficacy of the specified statins.

What are some examples of statins approved by the FDA in the U.S.?

Statins that are approved for use in the U.S. include:

  • atorvastatin (Lipitor),
  • fluvastatin (Lescol),
  • lovastatin (Mevacor, Altocor)
  • pravastatin (Pravachol),
  • rosuvastatin (Crestor),
  • simvastatin (Zocor ), and
  • pitavastatin (Livalo).
Reviewed by:
Robert J. Bryg, MD
Board Certified Internal Medicine with subspecialty in Cardiovascular Disease

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