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HomePopularHow Does Simvastatin Work To Lower Cholesterol

How Does Simvastatin Work To Lower Cholesterol

Effect On Mipomersen On Lipid And Lipoprotein Levels

How Statins Work to Reduce Cholesterol

In the pivotal trial, 51 patients with Homozygote Familial Hypercholesterolemia on treatment were randomized to additional treatment with mipomersen or placebo and followed for 26 weeks . Mipomersen lowered LDL-C levels by 21% and apolipoprotein B levels by 24% compared to placebo. In addition, non-HDL-C was decreased by 21.6%, triglycerides by 17%, and Lp by 23% while HDL and apolipoprotein A-I were increased by 11.2% and 3.9% respectively.

Mipomersen has also been studied in patients with Heterozygous Familial Hypercholesterolemia. In a double-blind, placebo-controlled, randomized trial, patients on maximally tolerated statin therapy were treated weekly with subcutaneous mipomersen 200 mg or placebo for 26 weeks . LDL-C levels decreased by 33% in the mipomersen group compared to placebo. Additionally, mipomersen significantly reduced apolipoprotein B by 26%, triglycerides by 14%, and Lp by 21% compared to placebo with no significant changes in HDL-C levels. In an extension follow-up study the beneficial effects of mipomersen were maintained for at least 2 years .

In a meta-analysis of 8 randomized studies with 462 subjects with either non-specified hypercholesterolemia or Heterozygous Familial Hypercholesterolemia, Panta and colleagues reported that mipomersen decreased LDL-C levels by 32% compared to placebo . Additionally, non-HDL-C was decreased by 31%, apolipoprotein B by 33%, triglycerides by 36%, and Lp by 26% with no effect on HDL levels.

Get Relief From Statin Side Effects

Your doctor may be able to suggest some ways to relieve the side effects you have with statins. These changes may help, but talk to your doctor first:

  • Take a break from statins, which can help you know if the drugs are the cause of muscle aches or other side effects
  • Try a different statin drug or dose
  • Change your exercise routine gradually and skip intense workouts if youâre not used to them
  • Try another type of medication to lower your cholesterol
  • Take coenzyme Q10 supplements, which may stave off side effects in some people

The statin medications that are approved for use in the U.S. include:

  • Lipitor

Who Should Avoid Taking Zocor

Although Zocor can help lower your high cholesterol, certain medical conditions may prevent you from taking this medication. Therefore, your doctor may need to recommend an alternative treatment option to lower your high fat levels.

These medical conditions include

  • Severe allergies: Although taking Zocor may help lower your high cholesterol levels, you should not take this medication if you have ever had an allergic reaction to it.
  • Liver problems: If you have active liver disease or very high levels of liver enzymes, it is best not to take Zocor.
  • Medications: It is best to avoid taking Zocor if you are taking medications that are known to inhibit metabolic pathways in the body.
  • Waiting: Studies have shown that taking Zocor during pregnancy may increase the likelihood that this drug will cross the placental barrier. Therefore, if you are considering trying to have a baby, or are currently pregnant, it is best to tell your doctor immediately. They will then decide if the benefits of this drug outweigh the possible risks.
  • Feeding: Studies have shown that Zocor passes easily from the blood to the breast milk, so it is best not to use this drug if you are breastfeeding.

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What Are Some Examples Of Statins

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

Most individuals are placed on statins because of high levels of cholesterol. Though reduction of cholesterol is important, heart disease is complex and, as discussed previously, other factors such as inflammation may play a role. Thirty-five percent of individuals who develop heart attacks do not have high blood cholesterol levels, yet most of them have atherosclerosis. This means that high levels of cholesterol are not always necessary for atherosclerotic plaques to form.

Because it is not clear which effect of statins is responsible for their benefits, the goal of treatment with statins should not be only the reduction of cholesterol to normal levels, but rather the prevention of the complications of atherosclerosis . This concept is important because it allows for individuals who have or are at risk for atherosclerosis, but do not have high levels of cholesterol to be considered for treatment with statins. Statins, like angiotensin converting enzyme inhibitors , are an important class of drugs because they have been shown to reduce the incidence of heart attacks, strokes, and death.

Effect On Bempedoic On Lipid And Lipoprotein Levels

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EFFECT WITHOUT STATINS

In a study that randomized 345 patients with hypercholesterolemia .and a history of intolerance to statin to bempedoic acid or placebo bempedoic acid decreased LDL-C by 21.4%, non-HDL-C by 17.9%, and apolipoprotein B by 15% . One third of patients were on background non-statin therapy most commonly ezetimibe and fish oil. Triglyceride levels were not altered but there was a small decrease in HDL-C levels that was statistically significant .

IN COMBINATION WITH STATINS

Notably, the addition of bempedoic acid to atorvastatin 80mg per day was still capable of significantly decreasing LDL-C , non-HDL-C , and apolipoprotein B compared to placebo . The addition of bempedoic acid to high dose atorvastatin therapy did not cause meaningful changes in atorvastatin pharmacokinetics.

IN COMBINATION WITH STATIN AND EZETIMIBE

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Mechanisms Accounting For The Ezetimibe Induced Lipid Effects

NPC1L1 is highly expressed in the intestine with the greatest expression in the proximal jejunum, which is the major site of intestinal cholesterol absorption . Knock out animals deficient in NPC1L1 have been shown to have a decrease in intestinal cholesterol absorption . Ezetimibe binds to NPC1L1 and inhibits cholesterol absorption . In animals lacking NPC1L1, ezetimibe has no effect on intestinal cholesterol absorption, demonstrating that ezetimibeâs effect on cholesterol absorption is mediated via NPC1L1 . Thus, a major site of action of ezetimibe is to block the absorption of cholesterol by the intestine . Cholesterol in the intestinal lumen is derived from both dietary cholesterol and biliary cholesterol ; thus the majority is derived from the bile . As a consequence, even in patients that have very little cholesterol in their diet, ezetimibe will decrease cholesterol absorption. While ezetimibe is very effective in blocking intestinal cholesterol absorption it does not interfere with the absorption of triglycerides, fatty acids, bile acids, or fat-soluble vitamins including vitamin D and K.

What Are Warnings And Precautions For Simvastatin

Warnings

  • This medication contains simvastatin. Do not take Zocor if you are allergic to simvastatin or any ingredients contained in this drug.
  • Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

Effects of Drug Abuse

  • There are no known effects of drug abuse.

Short-Term Effects

  • See “What Are Side Effects Associated with Using Simvastatin?”

Long-Term Effects

  • See “What Are Side Effects Associated with Using Simvastatin?”

Cautions

  • Non-serious and reversible cognitive side effects may occur.
  • Increased blood sugar and glycosylated hemoglobin levels were reported with statin intake.
  • Heavy alcohol use, history of liver disease, renal failure.
  • Monitor LFTs before initiating treatment and thereafter when clinically indicated; reports of fatal and nonfatal hepatic failure in people taking statins.
  • Discontinue if markedly elevated CPK levels occur or myopathy is diagnosed or suspected.
  • Increases in HbA1c and fastingserumglucose levels were reported with simvastatin.
  • Severe electrolyte, endocrine, or metabolic disorders.
  • Grapefruit juice increases simvastatin systemic exposure; avoid large quantities of grapefruit juice .

Simvastatin and myopathy risk:

Pregnancy and Lactation

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What Statins Are Available To Treat High Cholesterol

Available statin drugs

  • Increased blood glucose levels.
  • Reversible memory issues.

If youre unable to take statins because of the side effects, youre said to be statin-intolerant. If you are taking a statin, you should avoid grapefruit products because they can increase side effects. You should limit the amount of alcohol that you drink because combining alcohol and statin usage can increase your risk of liver damage. You may want to talk with your provider or pharmacist if you are concerned about any other types of interactions.

PCSK9 inhibitors

PCSK9 inhibitors are designed to attach to a particular liver protein, which results in lowered LDL cholesterol. This class of drug can be given with statins and is usually for people at high risk of heart disease who have not been able to lower their cholesterol enough through other means.

What Are Statins And Why Are They Used In The Treatment Of Lupus

How does Simvastatin (Statins) work?

Statins are medications that lower the level of cholesterol in your blood by reducing the production of cholesterol in the liver. Cholesterol is a natural component of the fats in your blood stream and the cells of your body. However, people with high levels of cholesterol in their blood face an increased risk of cardiovascular disease, which can lead to chest pain, heart attack, stroke, and peripheral vascular disease.

When too much cholesterol circulates in the blood, the substance can cause deposits to form on your artery walls. Plaque is dangerous because it can block the flow of blood to various parts of your body, including your heart and brain. Studies have shown that people with lupus are more likely to have clogged arteries that can lead to heart attack and stroke at a younger age. This increased risk is caused by elevated cholesterol levels, high blood pressure, diabetes, and inflammation, conditions that occur often in people with lupus. Certain medications, such as corticosteroids can provoke or compound these symptoms. For this reason, the cholesterol-lowering properties of statins are commonly called upon for lupus patients.

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Serious Side Effects Of Statins

Statins are linked to a few rare but potentially serious side effects, including:

  • Myositis, which is inflammation of the muscles. The risk of muscle injury increases when certain other medications are taken with statins. For example, if you take a combination of a statin and a fibrate — another cholesterol-reducing drug — the risk of muscle damage increases greatly compared to someone who takes a statin alone.
  • Elevated levels of CPK, or creatine kinase, a muscle enzyme that when elevated, can cause muscle pain, mild inflammation, and muscle weakness. This condition, though uncommon, can take a long time to resolve.
  • Rhabdomyolysis, extreme muscle inflammation and damage. With this condition, muscles all over the body become painful and weak. The severely damaged muscles release proteins into the blood that collect in the kidneys. The kidneys can become damaged trying to eliminate a large amount of muscle breakdown caused by statin use. This can ultimately lead to kidney failure or even death. Fortunately, rhabdomyolysis is extremely rare. It happens in less than one in 10,000 people taking statins.

If you have any unexplained joint or muscle pain, tenderness, or weakness while taking statins, you should call your doctor immediately.

Some studies link statin use with birth defects. Doctors advise pregnant women not to use these drugs.

How Are Doctors Sure That Statins Really Are Safe And Beneficial

Statins have been studied more than nearly any other drug that people take. In fact, more than 170,000 people who take statins have been studied in detail and for extended periods of time. We certainly know the benefits of statins.We also understand the risks of statins. In some instances, after doctors have prescribed a drug for 10 years or more, it is taken off the market because of unforeseen, adverse side effects. Weve been prescribing statins since the 1990s for patients at high risk for stroke and heart disease. With statins, the side effects actually are well known. But how can we put that in perspective?Any focus on statin side effects needs to be counterbalanced by the fact that statins reduce peoples risk of dying from heart attack, heart disease, or stroke. Data from the 2008 JUPITER Trial suggest a 54 percent heart attack risk reduction and a 48 percent stroke risk reduction in people at risk for heart disease who used statins as preventive medicine. The data are not speculative; rather, they reflect statins real potential to save lives and avoid illness.There are many varieties of brand name and generic statins available. All statins work in more or less the same way to lower bad cholesterol in patients at high risk for cardiac events.Below are a few of the common brand names you may recognize, along with their generic counterparts:

  • Lipitor
  • Vytorin

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Isolated Hypercholesterolemia In Primary Prevention

In patients with isolated hypercholesterolemia without cardiovascular disease initial drug therapy is with a statin. The statin dose should be chosen based on the percent reduction in LDL-C required to lower the LDL-C level to below the target goal . As discussed earlier, the side effects of statin therapy increase with higher doses so one should not automatically start with high doses, but instead should choose a dose balancing the benefits and risks. Generic statins are inexpensive drugs and are very effective in both lowering LDL-C levels and reducing cardiovascular events. Additionally, they have an excellent safety profile. If the initial statin dose does not lower LCL-C sufficiently, one can then increase the dose. If the maximal statin dose does not lower LDL-C sufficiently adding ezetimibe is a reasonable next step if the LDL-C level is in a reasonable range and an additional 20-25% reduction in LDL will be sufficient. High dose statin and ezetimibe will lower LDL-C by as much as 70%, which will lower LDL-C to goal in the majority of patients who do not have a genetic basis for their elevated LDL-C levels. If the combination of statin plus ezetimibe does not lower the LDL-C to goal one can add a third drug, such as bempedoic acid or colesevelam. If the patient has diabetes with a moderately elevated A1c level using colesevelam instead of ezetimibe or in combination with ezetimibe could improve both glycemic control and further lower LDL-C levels.

How Does Zocor Work

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Zocor is a cholesterol-lowering drug that works by binding to the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase. This enzyme is one of the main enzymes in the cholesterol biosynthesis pathway. Therefore, when the drug binds to the enzyme, it ultimately reduces the amount of cholesterol produced in the liver.

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Pharmacokinetics And Drug Interactions

Statins have different pharmacokinetic properties which can explain clinically important differences in safety and drug interactions . Most statins are lipophilic except for pravastatin and rosuvastatin, which are hydrophilic. Lipophilic statins can enter cells more easily but the clinical significance of this difference is not clear. Most of the clearance of statins is via the liver and GI tract . Renal clearance of statins in general is low with atorvastatin having a very low renal clearance making this particular drug the statin of choice in patients with significant renal disease. The half-life of statins varies greatly with lovastatin, pravastatin, simvastatin, and fluvastatin having a short half-life while atorvastatin, rosuvastatin, and pitavastatin having a long half-life . In patientâs intolerant of statins, the use of a long-acting statin every other day or 2 times per week has been employed. Short acting statins are most effective when administered in the evening when HMG-CoA reductase activity is maximal while the efficacy of long-acting statins is equivalent whether given in the AM or PM . In patients who prefer to take their statin in the morning one should use a long-acting statin.

Thus, despite the excellent safety record of statins, careful attention must be paid to the potential drug-drug interactions. For additional information see Kellick et al .

Dangers Of Statin Drugs: What You Havent Been Told About Popular Cholesterol

Hypercholesterolemia is the health issue of the 21st century. It is actually an invented disease, a problem that emerged when health professionals learned how to measure cholesterol levels in the blood. High cholesterol exhibits no outward signsunlike other conditions of the blood, such as diabetes or anemia, diseases that manifest telltale symptoms like thirst or weaknesshypercholesterolemia requires the services of a physician to detect its presence. Many people who feel perfectly healthy suffer from high cholesterolin fact, feeling good is actually a symptom of high cholesterol!

Doctors who treat this new disease must first convince their patients that they are sick and need to take one or more expensive drugs for the rest of their lives, drugs that require regular checkups and blood tests. But such doctors do not work in a vacuumtheir efforts to convert healthy people into patients are bolstered by the full weight of the US government, the media and the medical establishment, agencies that have worked in concert to disseminate the cholesterol dogma and convince the population that high cholesterol is the forerunner of heart disease and possibly other diseases as well.

The drugs that doctors use to treat the new disease are called statinssold under a variety of names including Lipitor , Zocor , Mevacor and Pravachol .

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How Do You Take Them

Both simvastatin and atorvastatin typically require once-a-day dosing. Be sure to confirm the size of your dose with your provider or pharmacist before taking it.;

Splitting the pills in half

Atorvastatin tablets, especially the 40 mg and 80 mg tablets, can be large. While the FDA-approved labeling for atorvastatin advises against splitting tablets, studies since atorvastatin was approved have not found any problems with doing so. If you would like to split your atorvastatin tablets, check with your provider first. Simvastatin tablets are usually smaller, but its OK to split them and swallow one half at a time to get your full dose.

What time you should take them

Atorvastatin stays in the body longer than simvastatin does, and this might make atorvastatin more convenient for some people. Your body makes most of your cholesterol at night. So simvastatin should be taken at night for the greatest benefit. Atorvastatin offers the same benefit when taken at any time of day. Both medications are not affected by whether or not you take them with food.

If you miss a dose

If you forget to take atorvastatin, and its been less than 12 hours since you were supposed to take it, take the dose as soon as you can. Then take your next dose on schedule. If its been more than 12 hours, skip the dose entirely do not double-up on your next dose.;

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