Statins Drugs for Cholesterol: Mode of Action, Side Effects and Examples

Definition

Statins are a group of drugs that are prescribed to lower the raised cholesterol levels in the blood.

They are the most preferred and effective of the cholesterol reducing medicines. Statins lower LDL cholesterol by 30 to 55%. They also modestly reduce triglycerides and slightly increase HDL.

Besides lowering the bad cholesterol, they reduce the plaques in the arterial walls by breaking them up and improving blood flow through the arteries. As a result, they significantly reduce the risk of cardiovascular disease. Besides this proven benefit, they also possibly have beneficial effects in prevention of certain cancers and metabolic syndrome.

New guidelines for statin therapy: Indications

The American College of Cardiology and American Heart Association have identified four categories of people who may have to be put on statins:

  • People with a very high LDL cholesterol levels of 190 mg/dL (4.9 mmol/L) or higher.
  • Those with high LDL cholesterol levels and history of its cardiovascular complications such as a heart attack, stroke or peripheral vascular disease or a corrective surgery such an angioplasty or bypass.
  • People with raised cholesterol more than 70 to 189 mg/dL and accompanying diabetes.
  • People with an LDL above 100 mg/dL and a high 10-year risk of 7.5 percent or more of developing a heart attack. This risk is measured by an online tool developed by American College of Cardiology and the American Heart Association after you have filled in your present and past medical history details.

How do statins lower cholesterol in the body? Mode of action

Statins are a class of drugs which are used to lower cholesterol. They also act to reduce triglyceride levels.

Statins primarily act by lowering cholesterol production in the liver by inhibiting the action of the enzyme, HMG-CoA reductase that plays a major role in cholesterol synthesis. They are, therefore, also called also HMG-CoA reductase inhibitors

They raise LDL receptor activity and stimulate the liver to remove the LDL and VLDL cholesterol from the blood.

Due to its action on HMG-CoA reductase, statins are usually prescribed to be taken at night because that is when this enzyme is most active in the synthesis of cholesterol in the liver.

Statins are directly associated with reducing the risk of cardiovascular events such as a heart attack and stroke by helping to reduce any cholesterol plaque that has built up in your arterial walls

They are well tolerated – rarely side effects are seen.

Dosage

Statins are usually recommended once a day. Again, some statins may be recommended twice a day because of the dosage requirement.

  • Usual dose ranges from 5 to 40 mg orally once a day in the evening.
  • For patients with existing coronary artery disease (CHD) or at a high risk for it, the initial dose prescribed is 10 to 20 mg orally once a day in the evening along with “Therapeutic Lifestyle Changes” (TLC).
  • For patients at high risk of CHD along with other risk factors such as a current CHD, diabetes, or history of a peripheral vascular disease, stroke,  initial dose prescribed is 40 mg orally once a day in the evening.
  • Some statins are more effective than others in reducing elevated cholesterol and triglyceride levels. Crestor (rosuvastatin) 40 mg and Lipitor (atorvastatin) 80 mg at those doses are the most potent in reducing high TG levels.

List of statin examples with generic and brand names

The generic names are followed by the brand names in brackets:

  • Atorvastatin (Lipitor)
  • Fluvastatin (Lescol)
  • Lovastatin (Mevacor)
  • Pravastatin (Pravachol)
  • Simvastatin (Zocor)
  • Rosuvastatin (Crestor)

The different types of statins mentioned above differ in various ways. The most glaring difference is their potency to reduce cholesterol. Presently, atorvastatin (Lipitor) and rosuvastatin (Crestor) are the most potent, and fluvastatin (Lescol) is the least.

Side effects

As mentioned above, side effects are rare and include generalized muscle pain, weakness, constipation, abdominal cramps, headache and interference with liver function causing dark colored urine. High blood sugar and type 2 diabetes is another possible occurrence but is rare.

On these side effects presenting themselves, you must stop statins immediately and report to your doctor who will take the necessary action. There are other choices of drugs besides statins to lower your cholesterol.

Some people have reported memory loss, which however recovers a few weeks after stopping the drug. But, this is still uncertain.

Muscle damage

Some people on statins commonly complain of muscle pain and weakness. However, switching over to another statin, possibly of a milder potency can relieve this problem.

Statins are known to cause a more serious form of myopathy (muscle damage). This is called rhabdomyolysis and can be life threatening.  The skeletal muscles are involved, which break down rapidly and in the process, the muscle cells release protein myoglobin into the bloodstream.

These proteins have a toxic effect on the kidneys and can even cause them to fail. Rhabdomyolysis can even lead to permanent paralysis.

However, rhabdomyolysis is extremely rare affecting a few cases among millions and is seen in people who take high doses of statins over prolonged periods of time.

Screening for liver damage when on statins

Two liver enzymes, alanine aminotransferase or ALT, and aspartate aminotransferase or AST may be mildly elevated due to statin therapy.

The risk of liver dysfunction is found to be highest with Fluvastatin. Higher the dose more is the risk of liver damage.

However, it is safe to continue treatment unless the rise of these enzyme levels is three times the upper limit of their normal levels.  Secondly, the liver damage is not permanent and when statins are stopped the liver values return to normal.

The American Food and Drug Administration (FDA), now recommends that liver function tests and CPK levels should be performed before starting therapy with statins and there is no need to periodically perform these tests while on statin therapy.

The reason given is that serious liver injury with statins is rare and unpredictable and there does not appear to be any advantage in the follow-up tests unless there are clinical signs of liver damage.

These signs can include unusual weakness, loss of appetite, pain in the abdomen, dark-colored urine, or yellowing of your eyes.

Erectile dysfunction

There is a misconception that statins cause erectile dysfunction.  You should know that an erection is the direct result of extra blood flow into the penis.

High LDL cholesterol levels cause the formation of cholesterol plaques on the inner walls of the arteries reducing the arterial lumen and blood flow. This causes the erection power to reduce.

Statins reduce LDL levels and even break up the plaques, thereby increasing the blood flow.

Therefore, if at all, statins improve erectile dysfunction.

Dementia

There have been reports of cognitive deterioration from statin use for+ several years.

The reports indicate memory loss, forgetfulness, and confusion in people of all age groups. This problem is not confined to any one type but from use of all statins.

This side effect could arise after taking the statin for a day or after use for several years. However, it is rare and reversible. It disappears within a few weeks after stopping the medicine.

Furthermore, that statins can cause dementia is still uncertain. In fact, research indicates that statin use may help to prevent Alzheimer’s disease.

Johns Hopkins researchers found that statins do not disturb short-term memory or cognition. They further add that when the drugs are taken for more than one year, the risk of dementia is reduced by 29 percent.

The FDA warns that you should not stop taking the medicines but talk to your health provider who may suggest an alternative drug besides statin.

Diabetes risk 

Should you worry? Does the use of statins induce diabetes? Here’s the take.

According to the National Center for Biotechnology Information (NCBI), high-intensity statins, such as atorvastatin 80 mg and rosuvastatin 20 mg, are associated with an increased risk of diabetes.

Research indicates that statins are associated with an almost 50 percent higher risk of type 2 diabetes.

The risk with moderate-intensity statins such as atorvastatin 10 mg, simvastatin 20-40 mg, or pravastatin 40 mg does exist but it is less.

This shows that the diabetes risk increased with higher statin doses.

Statins increase diabetes risk by raising the insulin resistance and it appears that the cholesterol-lowering drugs impair the pancreas from secreting insulin.

However, weighing the pros against the cons, the impact of diabetes is not important according to NCBI. The lowered risk of cardiovascular disease by taking statins far outweighs any diabetic risk.

However, do consult your doctor for a solution. In all probability, he would want to reduce your statin dose by advising you to go stricter on your “Therapeutic Lifestyle Changes” (TLC); meaning choosing your diet very carefully, increasing your exercise intensity and following strictly the lifestyle rules.

He will likely monitor your sugar levels closely, try to lower the statin dose or change to a statin alternative.

Do statins cause gallstones?

Gallstones are the result of supersaturation of the bile with cholesterol. The major component of gallstones is cholesterol.

Statins, by their cholesterol reducing property, have a direct action on the composition of bile and prevent the formation of cholesterol gallstones.

They reduce the cholesterol saturation of bile thereby preventing the formation of gallstones and even dissolving any existing ones.

People on statins have an 11% to 24% decreased risk of developing gallstones.

Therefore, it will be wrong to say that use of statins leads to gallstone formation.

Precaution: Statins and grapefruit

There is one precaution to take when on statins. Avoid taking grapefruit because it reduces the efficacy of the drug.

Grapefruit juice deactivates an enzyme in the liver, which is responsible for metabolizing statins.

As a result, statins accumulate in the blood and can cause statin toxicity. Avoid alcohol too, while on statins as there can be liver problems and alcohol will only worsen or augment this problem.

Kidney and liver function tests have to be carried out before starting statins and then periodically when taking statins.

How long should you take statins? Can they be stopped?

Once your doctor has put you on statins for your cholesterol problem, consider it as a lifelong commitment. If you stop the drug, your cholesterol levels will rise and put you at a risk of cardiovascular events.

However, according to Mayo clinic, there can be exceptions where the individual has made changes in his diet, lost a good amount of weight and made substantial changes for the better in his lifestyle.

Secondly, family history of cardiovascular disease should be looked into to see the quantum of risk.

In a case that looks favorable, the dose can be reduced initially, cholesterol levels monitored every six weeks and if the response is encouraging, the drug can be stopped. Following up with your doctor will be the key issue.

In the case of side effects such as liver and muscle damage, if stopping statins is not possible, your doctor will switch you over to other nonstatin cholesterol-lowering drugs.

How often to screen for cholesterol when on statins?

With statins, reduction in cholesterol levels is seen in about two months’ time, when cholesterol levels should be checked again for comparison with the previous report.

This helps in two ways. It shows the amount of success and also enables your doctor to determine whether any change in dosage is required or not.

Screening should thus be done every six to eight weeks till blood levels normalize. After that, some doctors recommend testing every six months and some advise once a year.

According to the FDA, the benefits of using statins far outweigh the risks and the side effects because the possibility of the risks is small.

In other words, weighing the pros against the cons, the FDA favors going in for the stains rather than against it in spite of the side effects, which are very rare.

 

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