What are statins? How do they work? What are the uses of statins? Who can take statins? What are the safety considerations and side effects of statins? Get answers to these questions and more in this comprehensive guide.

Understanding Statins: An Overview

Statins, also known as HMG-CoA reductase inhibitors, are a class of medications that are primarily used to help lower cholesterol levels. These drugs work by blocking the production of a liver enzyme responsible for creating cholesterol, which leads to a reduction in total cholesterol levels in the bloodstream. Statins can lower LDL (bad) cholesterol by 30% to 50%, making them an effective tool in the management of high cholesterol and the prevention of cardiovascular complications.

The Role of Cholesterol in Heart Health

Cholesterol is a type of fat molecule, or lipid, that is found in the blood. There are two main types of cholesterol: LDL (low-density lipoprotein) and HDL (high-density lipoprotein). LDL cholesterol is often referred to as “bad” cholesterol, as it can contribute to the buildup of plaque in the arteries, a condition known as atherosclerosis. This buildup can block the flow of blood, increasing the risk of heart attack and stroke. Conversely, HDL cholesterol is considered “good” cholesterol, as it helps to remove LDL cholesterol from the arteries. Statins primarily focus on lowering LDL cholesterol levels.

The Mechanism of Action: How Statins Work

Statins work by inhibiting the activity of the HMG-CoA reductase enzyme, which plays a crucial role in the production of cholesterol in the liver. By blocking this enzyme, statins effectively reduce the amount of cholesterol that the liver can produce, leading to a decrease in total cholesterol levels in the bloodstream. This reduction in cholesterol helps to prevent the buildup of plaque in the arteries, reducing the risk of cardiovascular events.

The Diverse Uses of Statins

Statins are primarily used to treat high cholesterol levels (hyperlipidemia), but their benefits extend beyond just lowering cholesterol. Statins may also be prescribed to prevent complications in individuals who have experienced a heart attack or stroke, or those who have diabetes. By reducing the risk of future cardiovascular events, statins can play a crucial role in the management of these conditions.

Eligibility for Statin Therapy

The American Heart Association recommends that adults at high risk for a heart attack and stroke take a statin. This includes individuals with an LDL cholesterol level of 190 mg/dL or higher, those with existing coronary heart disease, individuals aged 40 to 75 years old with Type 2 diabetes, and those aged 40 to 75 years old with a 7.5% or higher risk of heart disease. Statin therapy may also be approved for children with a family history of very elevated cholesterol levels (familial hypercholesterolemia).

Safety Considerations and Side Effects

Statins are generally well-tolerated, but like any medication, they can have potential side effects. The most common side effects of statins include muscle aches, fatigue, and increased liver enzymes. In rare cases, more serious side effects such as liver damage or a condition called rhabdomyolysis (severe muscle damage) may occur. It is important for individuals taking statins to be monitored by their healthcare provider and report any adverse effects immediately.

Exploring the Statin Landscape

There are several different statin medications available, each with their own brand names and unique characteristics. Some of the most commonly prescribed statins include Lipitor (atorvastatin), Zocor (simvastatin), Crestor (rosuvastatin), Pravachol (pravastatin), and Mevacor (lovastatin). Healthcare providers will consider factors such as a patient’s individual risk factors, cholesterol levels, and response to treatment when determining the most appropriate statin medication.

In conclusion, statins are a crucial class of medications that play a vital role in the management of high cholesterol and the prevention of cardiovascular complications. By understanding the mechanisms of action, uses, and safety considerations of statins, individuals can work closely with their healthcare providers to make informed decisions about their treatment options and achieve optimal heart health.

List of statin uses, brands, and safety recommendations

Statins help to lower cholesterol levels and treat people who have had a heart attack or stroke, or those who have diabetes

Statins list | What are statins? | How they work | Uses | Who can take statins? | Safety | Side effects | Costs

Statins are a class of medications that are used to treat elevated cholesterol levels. However, lowering cholesterol levels is not the only benefit associated with taking a statin. Statins may also be prescribed to prevent complications in those who have experienced a heart attack or stroke, or those who have diabetes. 

Continue reading to learn more about statins, their uses, and their side effects.

Other statins

• Altoprev (lovastatin)
• Altocor (lovastatin)
• Livalo (pitavastatin)

What are statins?

Statins, or HMG-CoA reductase inhibitors, are a class of drugs that are used to help lower cholesterol levels. Individuals who have elevated cholesterol levels may be prescribed a statin. A buildup of cholesterol in the arteries can block the flow of blood, which can increase the risk of a heart attack or stroke. 

Fat molecules, or lipids, in the blood, can encompass LDL cholesterol, HDL cholesterol, and triglycerides. LDL, or low-density lipoprotein cholesterol, is what is considered “bad” cholesterol while HDL, or high-density lipoprotein cholesterol, is what is considered “good” cholesterol. High levels of HDL cholesterol are associated with protective effects on heart health. High levels of triglycerides may increase the risk of heart attacks and strokes. Statins generally target LDL cholesterol levels.

Statins are cholesterol-lowering drugs that have been found to reduce the risk of heart attacks and strokes. They may be given as a preventative treatment to those with a high risk of heart attack or stroke. They may also be prescribed to prevent the recurrence of a cardiovascular event in individuals who have already had a heart attack or stroke.  

How do statins work?

Statins work by blocking the production of a liver enzyme that creates cholesterol. HMG-CoA reductase plays an important role in cholesterol production in the liver. When this enzyme is blocked, total cholesterol levels in the bloodstream are lowered. Statins can also lower LDL cholesterol levels by 30% to 50%. 

Statin drugs also help your body reabsorb cholesterol that has been deposited in the walls of the blood vessels (atherosclerosis). Your body needs some cholesterol to perform functions, such as digestion, hormone production, and vitamin absorption. As less cholesterol is produced from the liver, your body must seek alternate sources. This leads to the reabsorption of LDL-containing plaques in your arteries, which can help lower overall blood cholesterol levels. 

A healthcare provider may recommend lifestyle changes, such as eating a healthy diet low in saturated fats, regularly exercising, quitting smoking, and decreasing alcohol consumption, before prescribing a statin. These lifestyle changes are also recommended while being treated with a statin to help lower cholesterol levels. 

What are statins used for?

Statins are primarily used to treat high cholesterol levels (hyperlipidemia), which can help decrease the risk of cardiovascular complications from the following:

If you don’t currently have a history of any of these conditions, your healthcare provider may recommend a statin for preventative measures if you are considered a high-risk individual. Statins are recommended if you have at least a 10% chance of developing cardiovascular disease over the next ten years. Your provider can provide screening that will help determine your risk level. Risk factors may include a poor diet, smoking, and low physical activity levels.

Who can take statins?

Adults

The American Heart Association recommends that adults at high risk for a heart attack and stroke take a statin. A blood test will be conducted to determine current cholesterol levels. Individuals with an LDL level of 190 mg/dL or higher, existing coronary heart disease, an age of 40 to 75 years old with Type 2 diabetes, or ages 40 to 75 years old with a 7.5% or higher risk of heart disease may be recommended to take a statin. 

Children

Statin therapy is approved for children with a family history of very elevated cholesterol levels (familial hypercholesterolemia). In general, statin use can be started in children aged 8 to 10 years of age but should be monitored carefully by a specialist. Currently, Mevacor (lovastatin), Zocor (simvastatin), Pravachol (pravastatin), Crestor (rosuvastatin), and Lipitor (atorvastatin) are approved for use in children by the U.S. Food and Drug Administration (FDA). Statin therapy should be started in tandem with lifestyle changes, including diet modification and increased physical activity. 

Seniors

Older individuals can safely take statins, and those with established cardiovascular disease should continue therapy with a statin medication. The dosage of some statin medications may be lower for seniors than for other age groups. 

Are statins safe?

In general, statins are safe to take. However, a few groups of people should avoid statins, and some medications should not be mixed with statins. 

Grapefruit juice should be avoided while taking statins. Grapefruit juice can block a liver enzyme that is responsible for processing and clearing statins from the body. This could lead to increased levels of the statin in the body. Increased statin levels in the body could increase the risk of adverse effects, such as myopathy (muscle weakness) and rhabdomyolysis (muscle tissue breakdown). In addition, the risk of adverse effects may be increased when statins are taken with the following medications: 

• Sporanox (itraconazole)
• Erythrocin (erythromycin)
• Serzone (nefazodone) 
• Sandimmune (cyclosporine) 
• Cardizem (diltiazem) 
• Calan (verapamil) 

Medications classified as bile acid sequestrants (examples include Colestid and Questran) may interfere with the absorption of statins. Take statins at least one hour before or four hours after taking a medication like Colestid or Questran. 

There may be an increased risk of bleeding when statins are taken with Coumadin (warfarin). However, this risk may be lower with the following statins compared to other statins:

• Lipitor (atorvastatin)
• Pravachol (pravastatin)

There is an increased risk of liver failure or rhabdomyolysis when statins are taken with Niaspan (niacin) or fibrates (Lopid or Tricor).

Taking St. John’s Wort with Mevacor (lovastatin) or Zocor (simvastatin) may lead to reduced statin levels, which can lead to decreased effectiveness of the statin treatment. 

Statin recalls

Pravastatin recall, 2/6/2018

Statin restrictions

Adults with active liver disease or abnormal liver enzyme levels should not take statins. Talk to a healthcare provider about other possible warnings and precautions associated with the use of statins.  

Can you take statins while pregnant or breastfeeding?

Statin therapy is contraindicated during pregnancy. Women who may become pregnant will want to take precautions against pregnancy or avoid taking a statin if they wish to become pregnant. Women who are breastfeeding should also avoid taking statins. 

Are statins controlled substances?

No, statins are not controlled substances. 

Common statin side effects

The most common side effects of statins include:

• Headache
• Muscle aches
• Fatigue
• Fever
• Diarrhea
• Nausea
• Vomiting
• Stomach upset
• Rash

More severe but rare side effects of statins include:

• Severe muscle pain
• Rhabdomyolysis, or muscle breakdown
• Serious liver problems

Although rare, statins can cause a condition called rhabdomyolysis. Rhabdomyolysis results in life-threatening muscle damage. The breakdown of muscle tissue can lead to the release of a certain protein called myoglobin into the bloodstream, which can damage the kidneys. Symptoms of rhabdomyolysis include severe muscle pain, liver damage, and kidney failure.

The use of statins, especially in high doses, has also been associated with memory loss. However, this side effect is rare, and it is reversible after discontinuation of therapy. On the other hand, some studies have shown that statins are protective against dementia and Alzheimer’s disease. 

Serious side effects associated with statins are often rare and associated with high doses. This list of side effects is not comprehensive. Speaking with a healthcare professional is the best way to get a complete list of side effects in order to determine whether taking a stain is suitable for you. If you experience side effects with a certain statin, your doctor may recommend a different statin.

Tell your doctor if you have a history of any of the following before taking a statin:

• A known allergy to statins
• Liver disease or raised liver enzyme levels
• Other medications you are currently taking
• Pregnancy or a desire to become pregnant in the near future
• Breastfeeding

How much do statins cost?

Statins are generally affordable medications that are available in brand-name and generic formulations. Almost all Medicare and insurance plans will cover statins. Costs will vary depending on your insurance plan. Without insurance, the price can vary widely depending on the medication and quantity of tablets prescribed. However, using a prescription discount card from SingleCare may help reduce the cost of statins. 

Statins – NHS

Statins are a group of medicines that can help lower the level of low-density lipoprotein (LDL) cholesterol in the blood.

LDL cholesterol is often referred to as “bad cholesterol”, and statins reduce the production of it inside the liver.

Why have I been offered statins?

Having a high level of LDL cholesterol is potentially dangerous, as it can lead to a hardening and narrowing of the arteries (atherosclerosis) and cardiovascular disease (CVD).

CVD is a general term that describes a disease of the heart or blood vessels. It’s the most common cause of death in the UK.

The main types of CVD are:

• coronary heart disease – when the blood supply to the heart becomes restricted
• angina – chest pain caused by reduced blood flow to the heart muscles
• heart attacks – when the supply of blood to the heart is suddenly blocked
• stroke – when the supply of blood to the brain becomes blocked

A doctor may recommend taking statins if either:

• you have been diagnosed with a form of CVD
• your personal and family medical history suggests you’re likely to develop CVD at some point over the next 10 years and lifestyle measures have not reduced this risk

Find out more about when statins may be recommended.

Taking statins

Statins come as tablets that are taken once a day.

For some types of statin it does not matter what time of day you take it, as long as you stick to the same time.

Some types of statin should be taken in the evening.

Check with your doctor whether there’s a particular time of day you should take your statin.

You usually have to continue taking statins for life because if you stop taking them, your cholesterol will return to a high level within a few weeks.

If you forget to take your dose, do not take an extra one to make up for it. Just take your next dose as usual the following day.

If you accidentally take too many statin tablets (more than your usual daily dose), contact a doctor or pharmacist for advice or call NHS 111.

Cautions and interactions

Statins can sometimes interact with other medicines, increasing the risk of unpleasant side effects, such as muscle damage.

Some types of statin can also interact with grapefruit juice.

It’s very important to read the information leaflet that comes with your medicine to check if there are any interactions you should be aware of.

If in doubt, contact a GP or pharmacist for advice.

Find out more things to consider when taking statins.

Side effects of statins

Many people who take statins experience no or very few side effects.

Others experience some troublesome, but usually minor, side effects, such as diarrhoea, a headache or feeling sick.

Your doctor should discuss the risks and benefits of taking statins if they’re offered to you.

The risks of any side effects also have to be balanced against the benefits of preventing serious problems. 

A review of scientific studies into the effectiveness of statins found around 1 in every 50 people who take the medicine for 5 years will avoid a serious event, such as a heart attack or stroke, as a result.

Find out more about the side effects of statins.

Alternatives to statins

If you’re at risk of developing CVD in the near future, your doctor will usually recommend lifestyle changes to reduce this risk before they suggest that you take statins.

Lifestyle changes that can reduce your cholesterol level and CVD risk include:

Statins may be recommended if these measures do not help.

Read more about treating high cholesterol and preventing CVD.

Types of statin

There are 5 types of statin available on prescription in the UK:

Page last reviewed: 19 November 2018
Next review due: 19 November 2021

Tips From Other Journals – American Family Physician

Tips

From Other Journals

Am Fam Physician. 2002 Mar 15;65(6):1211-1215.

Statins (also known as 3-hydroxy-3-methyl-glutaryl coenzyme A [HMG-CoA] reductase inhibitors) are generally recognized as the treatment of choice in patients with hypercholesterolemia because they are easy to use, effective, and well tolerated. However, there are currently five statins on the market: synthetic statins (atorvastatin and fluvastatin), and three natural statins—(lovastatin, pravastatin, and simvastatin). Cerivastatin was recently withdrawn from the market. Chong and colleagues reviewed the various statins to determine if there are clinical advantages to choosing one over the others. The statins have different abilities to lower low-density lipoprotein (LDL) cholesterol levels, differing pharmacokinetics, differing interactions with drugs and foods, and variable costs.

Statins lower cholesterol levels through inhibition of HMG-CoA reductase. The synthetic and natural statins have essentially equivalent efficacy at improving the lipid profile. However, in patients who do not achieve their LDL goals, atorvastatin and simvastatin may be the best choices for initial therapy.

Statins also have antiproliferative effects on smooth muscle cells and antioxidant and anti-inflammatory effects, all of which may help to reduce coronary events. Current research does not clearly suggest that one statin is better than another at causing these effects.

Bioavailability varies widely among the statins: simvastatin is less than 5 percent bioavailable, while fluvastatin is approximately 24 percent bioavailable. The agents are also absorbed at rates ranging from about 30 percent with lovastatin to 98 percent with fluvastatin. First-pass metabolism occurs in all statins except pravastatin. Pravastatin is also the least protein-bound of the statins (about 50 percent), compared with the others, which are more than 90 percent protein-bound.

View/Print Figure

Statin Selection or Substitution

FIGURE.

Simplified flow chart of major considerations for statin selection or substitution. The cost-effective statin choices in the last stage are based on an analysis using AWP and may depend on the specific heath care setting. (LDL = low-density lipoprotein cholesterol; AWP = average wholesale price.)

Adapted with permission from Chong PH, Seeger JD, Franklin C. Clinically relevant differences between the statins: implications for therapeutic selection. Am J Med 2001;111:396.

Statin Selection or Substitution

FIGURE.

Simplified flow chart of major considerations for statin selection or substitution. The cost-effective statin choices in the last stage are based on an analysis using AWP and may depend on the specific heath care setting. (LDL = low-density lipoprotein cholesterol; AWP = average wholesale price.)

Adapted with permission from Chong PH, Seeger JD, Franklin C. Clinically relevant differences between the statins: implications for therapeutic selection. Am J Med 2001;111:396.

Pravastatin and fluvastatin are hydrophilic, which may cause less insomnia than the other statins (which are lipophilic). This may not be a clinically important distinction, so selection on this criterion alone is probably not warranted. However, if a patient develops insomnia, switching to a different agent is an option. Renal elimination occurs in greater proportions with pravastatin, and a dose reduction may be reasonable in patients with moderate or greater renal dysfunction. If creatinine clearance is less than 60 mL per minute (1.00 mL per second), the medication should be started at one half the usual starting dosage and titrated according to response. Atorvastatin and fluvastatin do not require dosage adjustments in patients with renal impairment.

All statins are associated with drug interactions, mainly because of their effects on the cytochrome P450 enzymatic pathway. However, pravastatin does not undergo metabolism by this pathway. Fluvastatin is metabolized by the CYP2C9 isoenzyme, while the other statins are metabolized by the CYP3A4 isoenzyme. Because a number of other medication interactions may occur, it is prudent to check these interactions before prescribing one of these medications.

Food interactions may also occur; grapefruit juice increases levels of atorvastatin, lovastatin, and simvastatin. Food increases the bioavailability of lovastatin, so this medication should be taken with food. Conversely, the bioavailability of pravastatin, atorvastatin, and fluvastatin is decreased by food, but this effect is not thought to change the lipid-lowering effects. Therefore, these three statins can be taken at any time.

In the accompanying figure, the authors offer an approach to determining which statin is appropriate for each patient.

Most Statin Users Won’t Have Major Side Effects – WebMD

By Serena Gordon

HealthDay Reporter

TUESDAY, July 9 (HealthDay News) — Statins — the widely used cholesterol-lowering drugs — have few serious side effects, although they do slightly raise the risk of type 2 diabetes, according to a large new evidence review.

In the analysis of 135 previous studies, which included nearly 250,000 people combined, researchers found that the drugs simvastatin (Zocor) and pravastatin (Pravachol) had the fewest side effects in this class of medications. They also found that lower doses produced fewer side effects in general.

“As with any drugs, statins have both benefits and harms,” said study lead author Huseyin Naci, a doctoral candidate at the London School of Economics and Political Science.

“We show that harmful side effects of statins are not common, and they are greatly outweighed by their benefits,” said Naci, also a research fellow in the department of population medicine at Harvard Medical School in Boston.

Results of the study, which received no drug company funding, were released online July 9 in the journal Circulation: Cardiovascular Quality and Outcomes.

Statins are medications used to lower the amount of LDL cholesterol or “bad” cholesterol — in your blood. LDL levels can be lowered through dietary changes and exercise, but many people find it difficult to maintain these lifestyle changes.

Moreover, statins may be useful for stabilizing plaque in the blood vessels (plaque can break off and cause a heart attack or a stroke) and reducing inflammation, according to Dr. Suzanne Steinbaum, a preventive cardiologist and director of Women and Heart Health at Lenox Hill Hospital in New York City. She was not involved with the new study.

In the analysis, the researchers reviewed data from randomized clinical trials, some of which compared statins to each other, while some compared statins to an inactive placebo pill. The average follow-up time for the studies included in the analysis was 1. 3 years.

The review included data from the seven statins currently on the market. Atorvastatin (Lipitor), simvastatin and pravastatin were the most commonly used statins among participants.

Simvastatin and pravastatin had the best safety profile, according to this review.

Overall, the researchers found a 9 percent increased risk of type 2 diabetes in people taking statins. Naci said it’s possible that statins may impair the secretion of insulin, although this study didn’t examine potential mechanisms for why statins might increase diabetes risk.

“The slight increase in diabetes risk is greatly outweighed by the cardiovascular benefits of statins,” he said.

Statins were not linked to any increase in the risk of cancer, according to the review. “There is conclusive evidence that statins do not raise cancer risk,” Naci said.

The use of statins, particularly atorvastatin, was linked to an increase in liver enzyme irregularities. Naci said these blood test changes don’t cause any symptoms, and are reversible when the drug is stopped. “If monitored closely, there is no cause for concern, and no specific precautions are warranted based on our study,” he said. “Switching to a statin associated with fewer elevations may be appropriate.”

The researchers also found that the higher the dose, the more likely people were to stop participating in a trial due to side effects.

“Side effects do tend to go up with higher doses,” cardiologist Steinbaum said. “You want to use as little medication as possible, and combine the use of statins with lifestyle management. There’s no medication that’s a quick fix and a cure, but it’s worth taking statins if you can manage the side effects.”

She added that while simvastatin and pravastatin may have the most favorable side effect profiles, “they tend to be the least potent statins. The statins with the greatest effects tend to have the most side effects,” Steinbaum said.

“Not all statins are the same,” noted study author Naci. “Our study provides evidence that the side effect profiles of individual statins vary, which should be considered when making prescribing decisions. “

Comparative effectiveness of generic and brand-name statins on patient outcomes: a cohort study

Background:

Statins are effective in preventing cardiovascular events, but patients do not fully adhere to them.

Objective:

To determine whether patients are more adherent to generic statins versus brand-name statins (lovastatin, pravastatin, or simvastatin) and whether greater adherence improves health outcomes.

Design:

Observational, propensity score-matched, new-user cohort study.

Setting:

Linked electronic data from medical and pharmacy claims.

Participants:

Medicare beneficiaries aged 65 years or older with prescription drug coverage between 2006 and 2008.

Intervention:

Initiation of a generic or brand-name statin.

Measurements:

Adherence to statin therapy (measured as the proportion of days covered [PDC] up to 1 year) and a composite outcome comprising hospitalization for an acute coronary syndrome or stroke and all-cause mortality. Hazard ratios (HRs) and absolute rate differences were estimated.

Results:

A total of 90,111 patients who initiated a statin during the study was identified; 83,731 (93%) initiated a generic drug, and 6380 (7%) initiated a brand-name drug. The mean age of patients was 75.6 years, and most (61%) were female. The average PDC was 77% for patients in the generic group and 71% for those in the brand-name group (P<0.001). An 8% reduction in the rate of the clinical outcome was observed among patients in the generic group versus those in the brand-name group (HR, 0.92 [95% CI, 0.86 to 0.99]). The absolute difference was -1.53 events per 100 person-years (CI, -2.69 to -0.19 events per 100 person-years).

Limitation:

Results may not be generalizable to other populations with different incomes or drug benefit structures.

Conclusion:

Compared with those initiating brand-name statins, patients initiating generic statins were more likely to adhere and had a lower rate of a composite clinical outcome.

Primary funding source:

Teva Pharmaceuticals.

The ABCs of statin prescriptions

Statins are frequently prescribed to patients with high cholesterol.

If you have high cholesterol, your doctor may prescribe a type of drug called a statin. What do you need to know about this medication?

Overall, remember one thing: Never start and then stop taking any medicine without consulting your physician.

Why do I need to take a statin?                        

You may have high levels of cholesterol or other fats in your blood. Cholesterol can stick to the walls of your arteries, which narrows or blocks them.

Think of your arteries as a highway, your blood as traffic and cholesterol as orange construction barrels. Too much cholesterol can act as those large barrels and block the flow of your blood, resulting in heart disease, heart attack or stroke.

Statins work by slowing your body’s production of cholesterol, which can keep your arteries open and your blood moving more freely. This type of drug is often the first medical treatment to lower your cholesterol.  

Which statin is right for me?

Your doctor may prescribe one of many different brands of statin drugs, including less expensive or generic forms. Some common brand names include Lipitor, Lescol, Altoprev, Livalo, Pravachol, Crestor or Zocor.

A statin may also be prescribed along with other medicines to manage another condition such as high blood pressure. Read the label and the information that accompanies your prescription carefully. Some brands should be taken only at night or with food. If you have questions, consult your pharmacist.

What do I need to talk about with my physician?

Give your health care provider a list of all other medications, supplements, herbs or vitamins you’re taking. And tell your doctor if you start taking any new medicine, whether or not it’s distributed over the counter or with a prescription.

Before you start taking statins, tell your provider if:

• You are pregnant, plan to become pregnant or are breastfeeding
• You have allergies
• You have diabetes
• You have any sort of acute or chronic liver disease

What happens once I take this drug?

• Severe muscle problems
• Weakness
• Fever
• Dark urine

Your provider might schedule regular blood tests to measure how well the statin is working and monitor for any side effects.

When you first start taking a statin, you may experience mild side effects including:

If a side effect persists, let your doctor know. There may be another, more comfortable option for you.

Never start — and then stop — taking any medication without consulting your physician.

Sources:
“How to Take Statins.” nih.gov, National Institutes of Health, U.S. National Library of Medicine, 24 January 2020.

“Controlling Cholesterol with Statins. ” fda.gov, U.S. Food & Drug Administration, 16 February 2017

Considerations in the Approach to Appropriate Statin Selection

US Pharm. 2018;43(7):22-26.

ABSTRACT: Statins are a class of medications widely used for primary and secondary prevention of cardiovascular events. With six statins available generically, the selection of an appropriate agent may be determined based on drug-specific factors, including dosing considerations, drug interactions, and adverse events. Individualized patient-care plans can be developed based on data from important clinical studies, differences in guidelines, and current management recommendations for two major adverse events associated with statin use.

The cornerstone of dyslipidemia treatment involves the use of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, more commonly known as statins. With a variety of generic options on the market and strong evidence backing their use, statins are some of the most widely prescribed medications in the world. ¹ However, frequent use of these agents has led to continual scrutiny of their safety and ongoing debate about their role in therapy. This article, which focuses on generic statins, will highlight the debate about statins’ role in therapy, discuss proper use, and explore evidence surrounding two major adverse events.

Of the seven different statins on the market, six are available generically (TABLE 1).^2-7 Three available branded formulations are pitavastatin (Livalo), simvastatin oral suspension (FloLipid), and lovastatin extended-release (Altoprev).^8-10 The role of branded agents in therapy is limited given the widespread availability of generic options.

Atorvastatin and simvastatin are also available generically in several combination products. These include the combination of atorvastatin and amlodipine, a calcium channel blocker (CCB) indicated for hypertension, and the combination of simvastatin and ezetimibe, an intestinal cholesterol-absorption inhibitor also indicated for hypercholesterolemia. ^11,12 Coformulated statin and niacin products (niacin/lovastatin and niacin/simvastatin) were removed from the market in 2016 based on a lack of evidence that adding niacin in statin-treated patients further reduces cardiovascular (CV) outcomes beyond what is seen with statins alone.¹³

Statins have repeatedly been proven effective for reducing LDL-cholesterol (LDL-C) and triglyceride levels while raising HDL-cholesterol (HDL-C) levels.¹⁴ Additionally, they have been shown to improve meaningful patient-oriented outcomes, such as major CV events (CVEs), in both primary and secondary prevention.^15-19

Several heavily debated treatment guidelines discuss the role of statins in treating hyperlipidemia. These include the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline and the 2017 American Academy of Clinical Endocrinology (AACE) guideline.^14,20 Both guidelines suggest that after implementation of lifestyle modifications, including smoking cessation, adhering to an exercise regimen, and following a heart-healthy diet, statins are first-line therapy for both primary and secondary prevention of CV disease (CVD). ^14,20 The guidelines differ, however, in how to determine which statins are appropriate for which patients.

The 2013 ACC/AHA guideline introduced four treatment groups to be targeted for statin therapy:

1. Patients with prior atherosclerotic CVD (ASCVD), including those with a prior event (i.e., acute coronary syndromes, history of myocardial infarction, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack, or peripheral arterial disease of presumed atherosclerotic origin).
2. Patients with no history of an ASCVD event who have an LDL-C level of 190 mg/dL or higher. Age is not a basis for exclusion from this criterion.
3. Patients aged 40 to 75 years with diabetes but no history of an ASCVD event, and an LDL-C level between 70 and 189 mg/dL.
4. Patients aged 40 to 75 years without diabetes who have no history of an ASCVD event and an LDL-C level between 70 and 189 mg/dL.²⁰

The ACC/AHA guideline also introduced the idea of grouping statins by intensity (i. e., their expected LDL-C–lowering ability) (TABLE 2).²⁰ Based on the treatment group (as defined above), the guideline recommends specific statin intensities for particular clinical situations (TABLE 3).²⁰ Several treatment groups require calculation of an ASCVD risk score using an ASCVD risk estimator. This online tool takes into account the patient’s age, sex, race, systolic blood pressure, total cholesterol, HDL-C, and past medical history significant for hypertension treatment, diabetes, or smoking.²¹ Once all inputs have been entered, the patient’s 10-year risk of experiencing an ASCVD event is calculated.

These recommendations do not automatically apply to certain subgroups of patients. For instance, the use of statins in older adults should be approached cautiously. Although statin use for secondary prevention in elderly patients confers significant benefit, its use for primary prevention is unclear.^22-24 Additionally, patients with heart failure have not been found to experience the same benefits from statin therapy as those without heart failure. ²⁵ Based on these findings, treatment recommendations include limiting initiation of high-intensity statins to patients aged younger than 75 years and possibly avoiding statins in patients with heart failure.²⁰ Overall, the decision to use statins in these groups is not clear-cut and should involve an ongoing conversation between provider and patient about potential risks and benefits of therapy.²⁰

Contrary to the 2013 ACC/AHA recommendation to initiate therapy according to treatment-group classification, the 2017 AACE guideline recommends that individual patients be treated based on laboratory findings.¹⁴ According to this guideline, patient risk is determined by a variety of major, additional, and nontraditional risk factors. Individuals are then classified into one of five risk groups, each with a corresponding LDL-C and non–HDL-C goal (TABLE 4). Based on current levels and individualized goals, statins alone or in combination with other agents should be initiated based on expected LDL-C– or non–HDL-C–lowering ability. ¹⁴

Combination treatment involving the addition of a second agent to ongoing statin therapy remains a somewhat controversial topic. Whereas earlier trials and guidelines minimized the addition of other agents to background statin therapy, recent studies and consensus statements—including one from the ACC/AHA—support the use of ezetimibe, evolocumab, or alirocumab, the last two of which are proprotein convertase subtilisin/kexin type 9 inhibitors, as add-on therapy for secondary prevention.^20,26-31 That said, statins remain universal first-line therapy in both primary and secondary prevention; the definitive role of other specific agents remains unclear.

The choice of statin therapy begins with the clinician’s preferred treatment approach, whether that is the ACC/AHA method of statin treatment groups or the AACE method of LDL-C or non–HDL-C goals. From there, properties of each statin must be taken into account to determine the best option for the individual patient. Not all statins are equal, and several key differences exist that may influence patient selection, including dosing considerations, drug interactions, and adverse events (AEs).

Dosing

Although most statins may be taken without regard to meals, immediate-release (IR) lovastatin should be taken with the evening meal because of increased bioavailability.⁴ However, the opposite is true for extended-release lovastatin, which should not be taken with food owing to decreased bioavailability.⁸ Further, although all statins may be dosed once daily, IR fluvastatin and lovastatin may require twice-daily dosing.^3,4 Finally, whereas atorvastatin, pravastatin, and rosuvastatin may be administered at any time of day, fluvastatin, lovastatin, and simvastatin should be taken in the evening.^3,4,7 Simvastatin, in particular, was shown to have significantly different efficacy when taken in the evening as opposed to the morning.³²

Drug Interactions

Each statin has different concerns regarding drug-drug and drug-food interactions because of the specific pathways through which each is metabolized (TABLE 5). Too many drug interactions exist to discuss each in detail; therefore, only a selected few are described below.

Fibrates: Although the combination of a fibrate and a statin has not been shown to meaningfully alter clinical outcomes, patients may still be prescribed gemfibrozil, fenofibrate, or fenofibric acid together with a statin to target severely uncontrolled hypertriglyceridemia.^14,20,26,33 Because both of these classes are associated with muscle-related toxicity, combination therapy significantly increases this risk compared with either therapy alone.³³ This additive toxicity is more frequently seen with gemfibrozil than with other fibrates.³³ Therefore, gemfibrozil use is contraindicated with simvastatin and should be avoided with other statins.^7,20 If a statin and a fibrate will be used together, fenofibrate or fenofibric acid is preferred.^20,33 However, if gemfibrozil must be used, fluvastatin—or, with careful monitoring, atorvastatin or rosuvastatin (maximum 10 mg daily)—is the agent of choice. ³³

Amiodarone: This antiarrhythmic agent indicated for ventricular fibrillation is a known inhibitor of P-glycoprotein (Pgp) and the CYP450 enzyme system, specifically CYP3A4 and, to a lesser extent, CYP2C9.^33,34 As a result, maximum recommended dosages exist for lovastatin (maximum 40 mg daily) and simvastatin (maximum 20 mg daily) when used with amiodarone.^4,7,33 Although atorvastatin is metabolized through CYP3A4, no dosage adjustment is necessary (similarly to other statins) because data do not suggest serious AEs when atorvastatin and amiodarone are used concomitantly.^2,33

CCBs: Both dihydropyridine (amlodipine) and nondihydropyridine CCBs (diltiazem, verapamil) have been shown to have meaningful drug interactions with statins. Similarly to amiodarone, amlodipine, diltiazem, and verapamil inhibit CYP3A4.^33,35-37 Amlodipine also has an inhibitory effect on Pgp.^33,35 Based on AEs reported in the literature, a maximum daily dosage of 20 mg for lovastatin is recommended when used with amlodipine, diltiazem, or verapamil. ^4,33 It is also recommended that simvastatin not exceed 20 mg when used with amlodipine, but a lower dose of 10 mg should be administered when used with diltiazem and verapamil.^7,33 No specific dosing recommendations exist with atorvastatin, although caution should be exercised when it is administered with either of the nondihydropyridine CCBs.^2,33

Adverse Drug Reactions

Statins are generally well tolerated; however, discontinuation rates remain high.³⁸ Discontinuation of statin therapy and failure to resume statin therapy after the occurrence of adverse drug reactions are associated with increased rates of CVEs.³⁹ Patients’ concerns about statin safety in light of two major statin-related AEs—myotoxicity and new-onset diabetes—may lead to statin discontinuation.

Myotoxicity: Statins have long been associated with muscle-related toxicity, including myalgia (muscle pain without elevated creatine kinase [CK]), myopathy (general term for muscle disease), and myositis (muscle inflammation), the last two of which involve significant CK elevations. ^40,41 All statins share a warning for the rare but serious side effect of rhabdomyolysis.^2-7 Often, however, myotoxicity attributed to statins is due to the nocebo effect; that is, a person believes that a medication will cause harm and subsequently the medication causes the anticipated harm.^42,43 Therefore, to ensure the best outcome, pharmacists must be well versed in this commonly reported side effect and its proper management.

It is incorrect to assume that all reports of muscle symptoms are due to the nocebo effect; proper vetting of the patient’s past medical history (PMH), description of the pain, and association with statin therapy is imperative.⁴⁴ First, an examination of PMH for CK elevations and other potential causes of muscle pain or weakness allows the clinician to treat alternative underlying pathophysiology or correct factors that may alter statin metabolism. Common causes include old age, drug interactions, impaired renal or hepatic function, increased physical activity, and vitamin D deficiency. ^20,41

Next, the clinician should compare the patient’s presentation with commonly seen statin-induced symptoms. Statin-induced muscle toxicity usually presents as pain, tenderness, cramps, and weakness, usually in the leg muscles.^20,41 These symptoms are typically worse after exercise and do not resolve without discontinuation of the offending agent.⁴¹

The last step is to determine whether a causal relationship between symptoms and statin use exists. When a statin is suspected as the cause of mild-to-moderate symptoms, temporary withdrawal is recommended. If the symptoms do not resolve after approximately 2 weeks, the statin is likely not the cause and should be reinitiated at the original dose. However, if the symptoms resolve, a retrial of the same statin at the same or a lower dose should be undertaken. If similar symptoms are then experienced, the statin should be presumed the cause and discontinued. Upon symptom resolution, a low dose of an alternative statin should be initiated and titrated to the maximum tolerated dose. ^20,41 Patient acceptance and understanding of this process are important because the nocebo effect may otherwise lead to further perceived reactions.

Several other strategies exist for managing and preventing these symptoms. First, owing to a higher likelihood of symptoms, the clinician may choose to avoid the most lipophilic statins (lovastatin and simvastatin) in favor of more hydrophilic statins (fluvastatin, pravastatin, and rosuvastatin).⁴⁴ Simvastatin 80 mg should never be initiated as new therapy in any patient because of an unusually high frequency of statin-associated muscle symptoms.^7,45 Alternative therapies, such as coenzyme Q10, have not demonstrated consistent benefit but may be considered in patients experiencing psychologically induced symptoms.^41,44,46 Finally, extended-interval dosing, which involves dosing statin medications several times weekly rather than once daily, may be considered. This approach improves adherence and lipid profiles in patients with prior statin intolerance. ^47-49

New-Onset Diabetes: An important AE associated with statin use is new-onset diabetes. Statins have been shown to increase the risk of diabetes development, although several important caveats exist.⁵⁰ First, although this can be considered something of a class effect, the true risk of each specific statin is still unknown.^51,52 In the largest meta-analysis to date, pravastatin had the lowest risk, simvastatin and atorvastatin had a moderate risk, and rosuvastatin had the highest risk of causing new-onset diabetes.⁵³ None of these findings was statistically significant, however.⁵³ Additionally, the finding that diabetes risk increases as the dose of statin increases has been inconsistent.⁵⁴

Statin-induced diabetes is most prevalent in persons already at high risk for developing diabetes.^50,54 This includes older patients and those with prediabetes or metabolic syndrome.^50,55 One consistent finding has been that, for each new case of incident diabetes caused by statins, several CVEs can be prevented in higher-risk patients. ⁵⁰ Therefore, pharmacists should counsel anxious statin users at moderate or high risk for CV complications that the risk of developing diabetes is more than offset by the CV risk-reduction benefits. However, the risk-benefit ratio is unclear in patients with a very low risk of CVEs.⁵⁰

Although statin therapy is not without risks, its benefits in reducing CV outcomes have made it the cornerstone of CVE prevention. Available guidelines differ widely, but the one constant is that statins should be first-line therapy for primary and secondary prevention in nearly every patient. The widespread generic availability of statins has made these agents increasingly more accessible. By understanding that not all statins are the same, the pharmacist can help ensure the best possible outcome for each patient.

REFERENCES

1. IMS Institute for Healthcare Informatics. Medicines use and spending in the U.S.: a review of 2015 and outlook to 2020. https://morningconsult. com/wp-content/uploads/2016/04/IMS-Institute-US-Drug-Spending-2015.pdf. Accessed March 18, 2018.
2. Lipitor (atorvastatin) package insert. New York, NY: Pfizer, Inc; June 2017.
3. Lescol/Lescol XL (fluvastatin) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corp; August 2017.
4. Mevacor (lovastatin) package insert. Whitehouse Station, NJ: Merck & Co, Inc; February 2014.
5. Pravachol (pravastatin) package insert. Princeton, NJ: Bristol-Myers Squibb Company; July 2016.
6. Crestor (rosuvastatin) package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; August 2017.
7. Zocor (simvastatin) package insert. Whitehouse Station, NJ: Merck & Co, Inc; February 2015.
8. Altoprev (lovastatin) package insert. Zug, Switzerland: Covis Pharma; April 2017.
9. FloLipid (simvastatin) package insert. Brooksville, FL: Salerno Pharmaceuticals LP; July 2017.
10. Livalo (pitavastatin) package insert. Montgomery, AL: Kowa Pharmaceuticals America, Inc; November 2016.
11. Caduet (amlodipine/atorvastatin) package insert. New York, NY: Pfizer Inc; October 2017.
12. Vytorin (ezetimibe/simvastatin) package insert. Whitehouse Station, NJ: Merck & Co, Inc; February 2018.
13. AbbVie Inc.; withdrawal of approval of new drug applications for Advicor and Simcor. www.federalregister.gov/documents/2016/04/18/2016-08894/abbvie-inc-withdrawal-of-approval-of-new-drug-applications-for-advicor-and-simcor. Accessed March 18, 2018.
14. Jellinger PS, Handelsman Y, Rosenblit PD, et al. American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease. Endocr Pract. 2017;23(suppl 2):1-87.
15. LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352:1425-1435.
16. Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195-2207.
17. Mihaylova B, Emberson J, Blackwell L, et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012;380:581-590.
18. Baigent C, Landray MJ, Reith C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet. 2011;377:2181-2192.
19. Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350:1495-1504.
20. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 suppl 2):S1-S45.
21. American College of Cardiology. ASCVD Risk Estimator Plus. http://tools.acc.org/ASCVD-Risk-Estimator. Accessed March 18, 2018.
22. Wenger NK, Lewis SJ, Herrington DM, et al. Outcomes of using high- or low-dose atorvastatin in patients 65 years of age or older with stable coronary heart disease. Ann Intern Med. 2007;147:1-9.
23. Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360:1623-1630.
24. Teng M, Lin L, Zhao YJ, et al. Statins for primary prevention of cardiovascular disease in elderly patients: systematic review and meta-analysis. Drugs Aging. 2015;32:649-661.
25. Kjekshus J, Apetrei E, Barrios V, et al. Rosuvastatin in older patients with systolic heart failure. N Engl J Med. 2007;357:2248-2261.
26. Ginsberg HN, Elam MB, Lovato LC, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362:1563-1574.
27. Kastelein JJ, Akdim F, Stroes ES, et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med. 2008;358:1431-1443.
28. Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387-2397.
29. Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376:1713-1722.
30. Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 2017 focused update of the 2016 ACC Expert Consensus Decision Pathway on the role of non-statin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: a report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol. 2017;70:1785-1822.
31. ODYSSEY Outcomes: results suggest use of PCSK9 inhibitor reduces CV events, LDL-C in ACS patients. American College of Cardiology. www.acc.org/latest-in-cardiology/articles/2018/03/05/15/53/sat-9am-odyssey-outcomes-cv-outcomes-with-alirocumab-after-acs-acc-2018. Accessed June 20, 2018.
32. Wallace A, Chinn D, Rubin G. Taking simvastatin in the morning compared with in the evening: randomised controlled trial. BMJ. 2003;327:788.
33. Wiggins BS, Saseen JJ, Page RL, et al. Recommendations for management of clinically significant drug-drug interactions with statins and select agents used in patients with cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2016;134:e468-e495.
34. Pacerone (amiodarone) package insert. Maple Grove, MN: Upsher-Smith Laboratories LLC; July 2017.
35. Norvasc (amlodipine) package insert. New York, NY: Pfizer Inc; October 2017.
36. Cardizem (diltiazem) package insert. Bridgewater, NJ: Valeant Pharmaceuticals; November 2016.
37. Calan (verapamil) package insert. New York, NY: Pfizer Inc; September 2017.
38. Riaz H, Khan AR, Khan MS, et al. Meta-analysis of placebo-controlled randomized controlled trials on the prevalence of statin intolerance. Am J Cardiol. 2017;120:774-781.
39. Zhang H, Plutzky J, Shubina M, Turchin A. Continued statin prescriptions after adverse reactions and patient outcomes: a cohort study. Ann Intern Med. 2017;167:221-227.
40. Tomaszewski M, Stepien KM, Tomaszewska J, Czuczwar SJ. Statin-induced myopathies. Pharmacol Rep. 2011;63:859-866.
41. Stroes ES, Thompson PD, Corsini A, et al. Statin-associated muscle symptoms: impact on statin therapy—European Atherosclerosis Society Consensus Panel Statement on assessment, aetiology and management. Eur Heart J. 2015;36:1012-1022.
42. Gupta A, Thompson D, Whitehouse A, et al. Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase. Lancet. 2017;389:2473-2481.
43. Pedro-Botet J, Rubiés-Prat J. Statin-associated muscle symptoms: beware of the nocebo effect. Lancet. 2017;389:2445-2446.
44. Laufs U, Filipiak KJ, Gouni-Berthold I, et al. Practical aspects in the management of statin-associated muscle symptoms (SAMS). Atheroscler Suppl. 2017;26:45-55.
45. FDA Drug Safety Communication: new restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury. www.fda.gov/Drugs/DrugSafety/ucm256581.htm. Accessed March 18, 2018.
46. Banach M, Serban C, Sahebkar A, et al. Effects of coenzyme Q10 on statin-induced myopathy: a meta-analysis of randomized controlled trials. Mayo Clin Proc. 2015;90:24-34.
47. Goldberg AS, DeGorter MK, Ban MR, et al. Efficacy and plasma drug concentrations with nondaily dosing of rosuvastatin. Can J Cardiol. 2013;29:915-919.
48. Matalka MS, Ravnan MC, Deedwania PC. Is alternate daily dose of atorvastatin effective in treating patients with hyperlipidemia? The Alternate Day Versus Daily Dosing of Atorvastatin Study (ADDAS). Am Heart J. 2002;144:674-677.
49. Copher HR, Stewart RD. Daily dosing versus alternate-day dosing of simvastatin in patients with hypercholesterolemia. Pharmacotherapy. 2002;22:1110-1116.
50. Rochlani Y, Kattoor AJ, Pothineni NV, et al. Balancing primary prevention and statin-induced diabetes mellitus prevention. Am J Cardiol. 2017;120:1122-1128.
51. Corrao G, Ibrahim B, Nicotra F, et al. Statins and the risk of diabetes: evidence from a large population-based cohort study. Diabetes Care. 2014;37:2225-2232.
52. Lim S, Oh PC, Sakuma I, Koh KK. How to balance cardiorenometabolic benefits and risks of statins. Atherosclerosis. 2014;235:644-648.
53. Navarese EP, Buffon A, Andreotti F, et al. Meta-analysis of impact of different types and doses of statins on new-onset diabetes mellitus. Am J Cardiol. 2013;111:1123-1130.
54. Crandall JP, Mather K, Rajpathak SN, et al. Statin use and risk of developing diabetes: results from the Diabetes Prevention Program. BMJ Open Diabetes Res Care. 2017;5:e000438.
55. Ganda OP. Statin-induced diabetes: incidence, mechanisms, and implications. F1000Res. 2016;5.

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90,000 Statins for the primary prevention of cardiovascular diseases

Cardiovascular diseases (CVD), which include heart attacks (myocardial infarction), angina pectoris and strokes, are the leading causes of death and the leading cause of morbidity worldwide. High blood cholesterol levels are associated with cardiovascular events and are an important risk factor. Thus, lowering high blood cholesterol levels is an important way to reduce the chances of suffering from cardiovascular events.Statins are drugs that lower cholesterol levels – (eg, simvastatin, pravastatin, atorvastatin) are the treatment of first choice. Following the emergence of the results of early randomized controlled trials in the 1990s, reviews of the effects of statins have been published highlighting their benefits, especially in individuals with a history of cardiovascular events. Benefits include a decrease in the incidence of cardiovascular events. Statins have also been shown to reduce the risk of a first event in healthy individuals at high risk for cardiovascular disease (primary prevention), but information on possible dangerous effects has not been fully reported.The aim of this updated systematic review is to evaluate the effects, in terms of both benefits and harms, of statins in the primary prevention of CVD. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE until 2011. We found 18 randomized controlled trials with 19 groups of trials (56,934 patients) between 1994 and 2008. All were randomized controlled trials comparing statins to conventional treatment or placebo.The median age of participants was 57 (range 28-97), 60.3% were males, and in the eight trials that reported ethnicity, 85.9% were European (white). The duration of treatment was at least one year with a follow-up period of at least six months. All-cause mortality, fatal and non-fatal cardiovascular events have been reduced with statin use, as has the need for revascularization (restoration of adequate blood supply to the heart) by surgery (coronary artery bypass grafting) or angioplasty (PTCA). Of the 1,000 people who received statins for five years, 18 could have avoided a serious cardiovascular event, which compares well with other therapies used to prevent cardiovascular disease. Taking statins did not increase the risk of serious adverse effects such as cancer. Statins can be cost effective in primary prevention.

Two injections a year will lower cholesterol: a new generation drug was recommended in England

September 1, 2021

Photo author, Getty Images

Residents of England and Wales may soon have access to an expensive but very effective drug, lowering cholesterol levels.And through the National Health Service (NHS) – that is, free.

The drug (marketed under the Leqvio brand) costs about £ 2,000 ($ 2,750) per dose, but Novartis, which manufactures the drug, has agreed to supply it at an undisclosed discount.

A preliminary version of the National Institute of Clinical Excellence (NICE) guidelines notes that Incliziran reduces the level of bad fats in the blood when other, cheaper drugs, such as statins, do not work or do not work well enough.

NICE, which certifies drugs in England and Wales, recommends it as an option for people who have had a stroke or heart attack who are not helped by other cholesterol-lowering drugs.

Experts hope this will help reduce the risk of further life-threatening cardiovascular problems.

Although there is still no evidence of long-term efficacy of the drug, doctors believe that it can be used, relying on the data already available.

NICE guidelines state that Inclysiran injections should be given by a nurse, for example, at a general practitioner’s clinic.

What is cholesterol?

• Cholesterol is a fat derivative, lipid, found in some foods and also produced in the liver.
• There are different types, but too much “bad” cholesterol – low-density lipoprotein – can clog your arteries, increasing your risk of heart disease and stroke.
• The main causes of low-density lipoprotein formation are fatty foods, lack of exercise, being overweight, smoking and drinking alcohol. Heredity also plays a role.
• If cholesterol levels do not decrease after diet and lifestyle changes, medication may be needed.

While commonly used statins slow down the production of cholesterol in the liver, then Incliziran works in a different way: it stimulates the liver to remove harmful cholesterol.

Incliziran shuts down or mutes the PCSK9 gene, causing the liver to absorb more LDL cholesterol from the blood and break it down.

The drug can also be used in conjunction with statins.

“Incliziran has the potential to be a watershed moment in preventing the premature death of thousands of people from heart attacks and strokes,” says Meindert Boysen, deputy head of NICE and director of the Center for Health Technology Assessment. “.

“Cardiovascular disease continues to be a leading cause of death, so it’s great that we now have such an effective and convenient medicine for people living with dangerously high cholesterol,” said Amanda Pritchard, executive director of the National Health Service. “Implementing an Incliserant will save many lives while being fair to taxpayers.”

The British National Health Service is funded directly from the government budget.Every resident of the United Kingdom has access to free medicine. Prescription drugs are available at pharmacies in England free of charge, apart from a flat remuneration fee of £ 9.35 each.

How to reduce the side effects of statins?

Millions of people take statins to lower their cholesterol levels. And many of them face excruciating side effects: muscle aches and cramps; weakness growing every day – such that the legs do not hold, and there is no strength to rise; liver damage; increased risk of developing diabetes – and this is not the whole list. In August 2001, a well-known pharmaceutical company was forced to recall a popular cholesterol-lowering drug used by about 700,000 Americans after 31 people died of severe myopathy – progressive muscle wasting ¹ .

But the statins prescribed by the doctor cannot be canceled! They must be taken continuously, often for life. Therefore, the question arises: is it possible to somehow neutralize their dangerous side effects?

Scientists have found that along with lowering cholesterol, statins also lower the level of coenzyme Q ₁₀ , which is vital for every cell in our body, especially the cardiovascular system and muscles; besides, it slows down the aging process.Within a month of taking statins, the level of coenzyme Q ₁₀ in the body drops by 50-80% ² ! With such a sharp decrease in the level of coenzyme, the body begins to age prematurely, wither, weaken, and become weak. In the United States, more and more experts recommend coenzyme Q ₁₀ ³ when prescribing statins. It has been proven that a daily intake of 100 mg of coenzyme Q ₁₀ reliably reduces the severity of muscle pain ² and neutralizes the changes associated with side effects of statins ⁴ .

How to choose the right coenzyme Q

₁₀ ?

On the shelves of pharmacies, you can find a variety of types and forms of coenzyme – tablets, water-based drops, suspensions, etc. But we must remember that coenzyme Q ₁₀
– the substance is fat-soluble, that is, it is absorbed as much as possible in the form of an oil solution. Therefore, carefully read the composition on the package – oil should come first. Soy is most often used – it is cheap and has an unpleasant aftertaste; a little less often – olive.But the company “Evalar” for better assimilation of its Coenzyme Q ₁₀ chose not any oil, but coconut, which in itself is just a storehouse of nutrients necessary for our body. In each capsule of Coenzyme Q ₁₀ Evalar – maximum ⁵ dosage of coenzyme (100 mg), dissolved in coconut oil of the first cold pressed, from the leading manufacturer in Japan. At the same time, Coenzyme Q ₁₀ Evalar is 2 times more profitable than its analogue ⁶ !

Coenzyme Q ₁₀ Evalar can be taken not only to reduce the side effects of statins – it contributes to:

NOT A DRUG

¹ https: // info-farm.ru / alphabet_index / c / cerivastatin.html
² Atmosphere. Cardiology. 2008, No. 3
³ Nutrition Journal. 2013, No. 12: p. 142
⁴ Alternative and Complementary Therapies Vol. 9, No. 4
⁵ Evalar assortment
⁶ Price benefit according to DSM Group data for the 1st half of 2019

90,000 How to lower cholesterol without side effects *

Perhaps one of the most unpleasant news that you can hear – “you have high cholesterol levels”….

It immediately becomes clear what health problems may follow: high blood pressure, unstable heart function, the development of atherosclerosis, an increased risk of heart attacks and strokes …

Where does excess cholesterol come from?

Depending on the degree of risk, different cholesterol lowering methods are used:

• giving up bad habits;
• physiotherapy exercises;
• weight loss;
• special diets;
• drug treatment.

Among medications, the most common way to combat excess cholesterol is the use of statins.However, they can have a lot of side effects: pain and cramps in the muscles, fatigue that grows every day, etc.

What to do? How to lower cholesterol without side effects

Probiotics – the new word for lowering cholesterol

Recently, a growing number of people are looking for natural and safe solutions to their cardiovascular problems. The most natural way to normalize cholesterol levels is to take probiotics.Among more than 550 different strains, clinical studies have identified 3 (CECT7527, CECT7528, CECT7529). They belong to the species Lactobacillus plantarum and have a positive effect on lipid reduction. The research results are revolutionary! It has been proven that the strains have a unique ability to remove bile acids that the liver synthesizes from cholesterol ² . They break down bile salts, preventing their reabsorption and increasing excretion. Thanks to this process, the liver is forced to start working again and use the available cholesterol reserves to form new bile acids, which leads to a decrease in total cholesterol and LDL (low density lipoprotein) cholesterol in blood plasma ³ .In addition, bacteria synthesize short-chain fatty acids, which in turn can cause a decrease in lipid levels in the systemic circulation. Lactobacillus plantarum is also able to trap cholesterol in the intestines, promoting its excretion ⁴ .

In addition, probiotic organisms are able to lower triglyceride levels, which statins do not. This is due to the fact that the split salts of bile acids can also be converted into secondary bile acids, which activate receptors in various tissues, increasing energy expenditure, and hence the level of triglycerides ³ .

Probiotics and Statins

Lactobacillus plantarum has been clinically proven to increase the effectiveness of statins, reduce dosage and minimize the risk of side effects, and help lower cholesterol in people with statin intolerance ² .

Which probiotic should you choose?

The only targeted probiotic in Russia for lowering cholesterol levels is Multiflora Cholesterol Evalar , which contains the special strains of beneficial bacteria Lactobacillus plantarum CECT7527, CECT7528, CECT7529 necessary for the health of the cardiovascular system.

Multiflora Cholesterol Evalar
Is a specially developed probiotic of European quality for lowering the level of total cholesterol and low density lipoproteins (“bad” cholesterol), as well as for enhancing the action of statins in order to reduce their dosage.

Benefits of Multiflora Cholesterol Evalar

• The only targeted probiotic in Russia for lowering cholesterol.
• A number of clinical studies of the active ingredient have been carried out.
• Quality – designed in Europe. Produced by Evalar – the number 1 company in Russia.
• Safety – no side effects, except for individual intolerance.
• Ease of use – only 1 capsule per day

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¹ Holm, R., Mul ̈lertz, A. & Mu, H. Bile salts and their importance for drug absorption. International Journal of Pharmaceutics vol. 453 44–55 (2013).
² Espadaler, J. Demographic and Clinical Characteristics influencing the effects of a cholesterol-lowering probiotic. Ann Nutr Metab 74, 1-31 (2019).
³ Bosch, M. et al. Lactobacillus plantarum CECT 7527, 7528 and 7529: Probiotic candidates to reduce cholesterol levels. J. Sci. Food Agric. 94, 803-809 (2014).
⁴ Ichim, T. E., Patel, A. N. & Shafer, K. A. Experimental support for the effects of a probiotic / digestive enzyme supplement on serum cholesterol concentrations and the intestinal microbiome. J. Transl. Med. 14, (2016).

What you shouldn’t eat if you are taking medication – Rossiyskaya Gazeta

Food can help you heal faster, or, on the contrary, slow down your recovery or even make it worse.Sometimes habitual foods become poisonous – if you take certain medications at the same time.

Why is this happening? Some substances that make up certain foods, due to their biochemical characteristics, can interfere with the timely removal of the drug from the body and increase its dose in the blood. And sometimes, on the contrary, the effect of the drug is weakened, blocked. We think: pills do not help, but in fact, their incorrect combination with food is “to blame”.

What kind of food are drugs “not friendly” with

Ibuprofen and soda

Ibuprofen is a commonly used pain reliever that belongs to the group of non-steroidal anti-inflammatory drugs.Trademarks: Nurofen, Faspik, Advil, Dolgit, Burana, etc. Non-steroidal anti-inflammatory drugs also include diclofenac, voltaren.

All of these drugs are often taken without a prescription or prescription. For example, elderly people who have joint pain are forced to drink them almost on a regular basis.

Ibuprofen and other non-steroidal anti-inflammatory drugs are incompatible with sodas.

Carbon dioxide and acid, which are contained in soda, enhance absorption and increase the concentration of the drug in the blood.In this case, it is impossible to control the dose, and there is a threat that a toxic effect will appear – primarily on the kidneys. Their filtering mechanism is damaged. In the worst case, kidney failure can even occur.

Clotrimazole and milk

Antifungal drugs – clotrimazole, ketonazole and others, which, in particular, are used to treat thrush, are not combined with milk. Dairy products should be temporarily excluded from the diet during treatment.Milk reduces the absorption of drugs, which means that the effectiveness of treatment decreases. You also need to limit milk and cottage cheese while taking antibiotics – from the group of tetracyclines and quinolones.

Amiodarone, statins and grapefruit

The antiarrhythmic drug amiodarone has been well studied, as it has been used for many decades. The good thing is that it has a wide spectrum of action and is suitable for many patients. There are a lot of trade names: cordaron, sedakoron, rhythmorest and others.

But in parallel with taking this medicine, you cannot eat grapefruit and pomelo, drink grapefruit juice. These citrus fruits contain a special substance that slows down the excretion of amiodarone from the body. The drug accumulates and begins to act aggressively, suppressing not only “unnecessary” electrical impulses in the heart muscle, but also suppressing the normal heart rhythm. This leads to bradycardia, and in extreme cases, cardiac arrest can occur.

You should not eat grapefruit and people taking drugs to lower cholesterol – a group of statins.The same thing happens as with amiodarone: the drug is excreted from the body worse, its concentration in the blood increases, there is a risk of a sharp decrease in pressure and tachycardia.

Anti-hypertension drugs and salt

There are many antihypertensive drugs. There is a group of diuretics that enhance the excretion of fluid from the body, a group of beta-blockers, a group of calcium antagonists. The mechanism of action of these drugs is different, although they are all aimed at lowering blood pressure.Therefore, depending on the patient’s condition, the doctor selects the drug that will be most effective, and sometimes combines drugs from different groups. A common property of all antihypertensive drugs is that they act more effectively if the patient follows an anti-salt diet. Therefore, during treatment, it is necessary to minimize the amount of salt entering the body. This means that canned food, sausages, all kinds of pickles and smoked meats, fast food and instant semi-finished products – dry soups, bouillon cubes – should be ignored.

Another group of antihypertensive drugs – ACE inhibitors. Trade names – enalapril, captopril, lisinopril and others. They retain potassium in the body, which is actually very necessary and supports the normal functioning of the heart and blood vessels. But, taking medicines from this group constantly, you need to be careful with foods in which there is a lot of potassium: dried apricots and apricots, bananas, oranges, eggplants, beans, spinach. In this case, you do not need to use potassium-fortified salt when preparing food (which, in fact, cardiologists usually recommend for hypertensive patients in order to reduce sodium intake).”Excessive” potassium is fraught with heart rhythm disturbances.

By the way

There are a lot of pills, and it is very difficult to remember what is combined with what and what is harmful to a person. Therefore, there are several simple rules that always “work”: during treatment you need to become a teetotaler (in some cases, for example, when taking paracetamol, even a very small dose of ordinary red wine can be fatal). Do not drink tea or coffee with tablets – the caffeine contained in them is quite aggressive in itself.In the vast majority of cases, the best option is to drink a tablet or pill with a glass of plain clean (non-carbonated!) Water. And it is also important to strictly observe the intake regimen: it is said in the instructions – to take one hour before meals, this interval must be maintained.

Atherosclerosis can be cured

For the first time in the history of medicine, scientists managed to find a way to clean the walls of blood vessels from the deposits accumulating on them. The consequence of this discovery could be a decrease in the number of heart attacks in millions of people and an increase in their life expectancy.

Over time, fat and calcium are deposited on the walls of human blood vessels. This process can be compared to the pollution of drainpipes, and its consequences are by no means harmless. Plaque on the inner walls of blood vessels, called atheroma, narrows them and interferes with the blood supply to the organs. But the most important danger is that deposits can detach from the walls of blood vessels, move along them and form blood clots, which cause strokes and heart attacks.

Although it is believed that some people have a genetic predisposition to vascular occlusion, it can be avoided by following a healthy lifestyle.However, the statistics of this disease are disappointing: in the UK alone, nearly 2 million people suffer from vascular degeneration.

On Monday at the annual meeting of the American College of Cardiology in Atlanta, a paper was presented, on which scientists from around the world have worked. They found a way not only to stop, but also to reverse the process of atheroma formation.

Previously it was believed that the “pollution” of blood vessels is irreversible, and doctors concentrated their efforts only on how to slow it down. Neal Uren, a cardiologist in the UK who took part in the study, said: “It used to be that if a diagnosis of atherosclerosis was made, the patient was sentenced to life. Now we have evidence that the walls of the vessels can be cleaned. ”

Tests of the drug rosuvastatin, known under the trademark Crestor, showed that the patients who took it cleanse the walls of blood vessels and restore their performance, for which the drug was christened the “Holy Grail” in the medical environment.

Cardiologists followed up 349 patients at 53 cardiac centers in the USA, Canada, Europe and Australia. Patients took large doses of rosuvastatin, the most potent statin, daily, with a daily dose of at least 40 mg of the drug, while the usual dose of statins taken on a daily basis does not exceed 10-20 mg.

Today cardiologists suggest that if you regularly take the drug for two years, then the already narrowed artery demonstrates the effect of “rejuvenation” for 3-4 years.After a ten-year intake, the artery “sheds” 12-15 years.

Tests showed that after intensive administration of the drug, the volume of deposits decreased by 10%, the level of LDL or “bad” cholesterol in the blood fell by 50%, and the level of HDL of “good” cholesterol rose by 15%. The full results of the clinical trials will be published in the Journal of the American Medical Association on April 5.

Scottish cardiologist Neal Uren said, “For the first time, we have the ability to turn back the clock for people with diseased arteries.”

Rosuvastatin is not currently used to treat atherosclerosis, but it is sometimes prescribed to lower cholesterol. The drug is manufactured by AstraZeneca. After the results of the study were made public, the company’s share price increased by 3%. Rosuvastatin will cost the patient about £ 30 a month.

These studies are not the first to show positive results from statins. In January of this year, the British National Institute for Health and Clinical Excellence made a recommendation for all people over 45 years of age who are at risk of developing cardiovascular diseases to take these drugs constantly. Side effects – muscle flaccidity and slight deterioration of liver function – were seen in only a small number of patients.

Professor Peter Weissberg, director of the British Heart Foundation, says the study is “very encouraging,” but he cautiously adds that doctors have yet to figure out whether cleaning blood vessels will reduce the number of heart attacks and strokes. “Whether this drug can save lives is a separate question, and it was not the goal of the study,” he explained.

Galina Antonova

GZT

Clinical Study Myopathy (statin-related) – Clinical Trials Registry

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