How Statin Drugs Protect The Heart
More than 200 million people around the world take statin drugs for theirheart health. Shifting ideas about the risks and benefits of statins overthe years, however, have left some new patients confused about whetherthese drugs are rightor safefor them.
Traditionally, statins were viewed as purely cholesterol-lowering drugs. So it made sense just to use them for people with high cholesterol, explains Johns Hopkins cardiologist Michael Blaha, M.D. But weve learned that they also benefit people with lower levels of cholesterol who are at a high risk of heart disease. So we now think of statins as risk-reducing drugs.
This dramatic change in thinking means that people who once were not candidates for statins are now prescribed them to lower their risk of heart attack and stroke.
Help For Your Cholesterol When The Statins Won’t Do
If you are one of the many, but also one of the few…
After a routine check-up, your doctor says that you are one of the many, the 100 million Americans with an unhealthy cholesterol level. Since you are already pretty careful about your diet and you walk every day, medication is the next step. Like most physicians, your doctor prescribes one of the statin drugs. It’s a good choice these widely popular drugs can lower LDL cholesterol levels by 20%60%, thus reducing the risk of cardiac events by 24%37%. If that’s not enough reason to start therapy with a statin drug, consider that it appears to reduce the risk of stroke by 24%31% and it may even protect you against osteoporosis and dementia.
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Table 1: Cholesterol goals for healthy adults |
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60 mg/dL or above |
Optimal |
It’s a long list of side effects, but it shouldn’t stop doctors from turning to a statin first when medication is needed to bring cholesterol into range. Fortunately, most side effects are mild and disappear promptly when the statin is stopped. In some cases, the problems will resolve simply by reducing the dose or switching to another statin, but care is required. Still, all in all, the statins are the safest and best tolerated of all cholesterol-lowering medications.
Demographic Factors And Statin Side Effects
Because most research on statins has involved middle-aged, white participants, there is less information available about side effects in people of color and older adult groups.
Some studies have indicated that people of East Asian descent may be more likely to experience side effects from statins.
But a large 2016 study with racially and ethnically diverse participants found that Asian people and Hispanic people experienced the same cholesterol-lowering benefits as white participants, as well as no increase in side effects.
The same study also grouped participants into categories of male and female, finding that the statin lowered LDL cholesterol equally well for both categories.
If youre over age 75, some research suggests you may be at of muscle problems related to statins. But for many older adults, the benefits of statins for preventing heart attack and stroke outweigh this risk.
One study found that 75-year-olds who stopped taking statins had a 33 percent higher risk of being hospitalized for a cardiovascular event, versus those of the same age who continued to take statins.
Its best to discuss potential benefits and side effects with your doctor to find out whether statins are right for you.
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Alzheimer’s Disease Protection By Statins Disproved
Some evidence indicates that statin therapy could inhibit the progression of Alzheimer’s disease. In a 2007 study. A study published a year later, however, followed living patients over 12 years, found no significant difference in Alzheimer’s rates between those who took statins and those who didn’t. A 2014 review of four studies, including two large randomized controlled trials, found no evidence that statins helped with cognitive decline in dementia.
How Do Statins Work
Statins work by slowing down the production of LDL-cholesterol in the liver, where its made. Because the liver isnât making so much cholesterol, it then takes cholesterol out of your blood to make bile with, so your blood cholesterol levels fall.
Statins slow down LDL-cholesterol production by blocking an enzyme called HMG-CoA-Reductase the medical name for statins is HMG-CoA Reductase inhibitors. Enzymes are proteins in the body which speed up normal processes. In this case, LDL production.
Statins can lower your triglycerides
As well as lowering your LDL-cholesterol, statins can lower your triglycerides too, and high triglycerides are linked to liver disease, heart disease and diabetes.
Statins can raise HDL cholesterol
Statins can sometimes raise your HDL-cholesterol the type of cholesterol which helps to clear the fat from of your arteries.
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Muscle Pain And Weakness
The most common side effect is muscle pain and weakness, a condition called rhabdomyolysis, most likely due to the depletion of Co-Q10, a nutrient that supports muscle function. Dr. Beatrice Golomb of San Diego, California is currently conducting a series of studies on statin side effects. The industry insists that only 2-3 percent of patients get muscle aches and cramps but in one study, Golomb found that 98 percent of patients taking Lipitor and one-third of the patients taking Mevachor suffered from muscle problems.4 A message board devoted to Lipitor at forum.ditonline.com contained more than 800 posts, many detailing severe side effects. The Lipitor board at www.rxlist.com contains more than 2,600 posts .
The test for muscle wasting or rhabdomyolysis is elevated levels of a chemical called creatine kinase . But many people experience pain and fatigue even though they have normal CK levels.5
John Altrocchi took Mevacor for three years without side effects then he developed calf pain so severe he could hardly walk. He also experienced episodes of temporary memory loss.
Active people are much more likely to develop problems from statin use than those who are sedentary. In a study carried out in Austria, only six out of 22 athletes with familial hypercholesterolemia were able to endure statin treatment.9 The others discontinued treatment because of muscle pain.
Medical Guidelines And Recommendations
In 2015, the United States Department of Agriculture Dietary Guidelines Advisory Committee recommended that Americans eat as little dietary cholesterol as possible, because most foods that are rich in cholesterol are also high in saturated fat and thereby may increase the risk of cardiovascular disease. For over 2 decades, the Dietary Guidelines for Americans recommended that dietary cholesterol be no more than 300 mg per day. In a 2014 draft, DGAC dropped this recommendation because evidence showed no appreciable relationship between dietary and serum cholesterol. This caught the eye of the Physicians Committee for Responsible Medicine , which sued DGAC due to concerns of conflicts of interest which prompted the final draft to recommend eating “as little dietary cholesterol as possible”. A 2013 report by the American Heart Association and the American College of Cardiology recommended to instead focus on healthy dietary patterns rather than cholesterol limits as they are hard for clinicians and consumers to implement. They recommend the DASH and Mediterranean diet, which are low in cholesterol. A 2017 review by the American Heart Association recommends switching saturated fats for polyunsaturated fats to reduce cardiovascular disease risk.
| > 6.2 | High risk |
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Effect On Mipomersen On Lipid And Lipoprotein Levels
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.
What Are The Side Effects
All medicines can have side effects. With statins, the most common one is muscle pain. Anywhere from 5% to 20% of people who take statins report having it. And it’s more common among people taking high doses. But it’s not clear if those muscle symptoms are actually related to statins, or if something else is to blame.
“Most people can tolerate these drugs, but a handful of my patients do have muscle aches,” Steinbaum says. If that happens, switching to a different statin, lowering your dose, or taking your pill every other day instead of daily might help.
In very rare cases, statins can cause severe muscle damage that can be life-threatening. This may happen with certain statins, especially if it interacts with another drug that you take. Be sure to review all your prescription and over-the-counter medications and supplements with your doctor.
Other rare side effects include liver injury, so ask your doctor how often your liver enzymes should be tested. Ongoing liver monitoring is no longer recommended, but Steinbaum still advises it: “I still do liver checks often, because if you’re taking a statin along with even something like Tylenol, you could have damage.”
Memory loss or confusion and neuropathy have also been reported, though they seem to be rare and more likely at very high doses. The FDA hasnât concluded that statins cause those problems.
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Mechanisms Accounting For Bempedoic Acid Induced Lipid Effects
Bempedoic acid is a potent inhibitor of ATP-citrate lyase, which catalyzes the formation of acetyl-CoA in the cytoplasm . Acetyl-CoA is a precursor for the synthesis of cholesterol . The inhibition of ATP-citrate lyase by bempedoic acid decreases cholesterol synthesis in liver reducing hepatic intracellular cholesterol levels . Of note, bempedoic acid is a pro-drug and conversion to its CoA-derivative by very-long-chain acyl-CoA synthetase-1 is required for inhibition of cholesterol synthesis . Very-long-chain acyl-CoA synthetase-1 is highly expressed in the liver but is not expressed in adipose tissue, kidney, intestine or skeletal muscle . The inability of bempedoic acid to be activated in muscle and inhibit cholesterol synthesis suggests that bempedoic acid is unlikely result in muscle toxicity.
Effect Of Bile Acid Sequestrants On Lipid And Lipoprotein Levels
The major effect of bile acid sequestrants is to lower LDL-C levels in a dose dependent fashion. Depending upon the specific drug and dose the decrease in LDL-C ranges from approximately 5 to 30% . The effect of monotherapy with bile acid sequestrants on LDL-C levels observed in various studies is shown in .
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Effect Of Lomitapide On Clinical Outcomes
There are no clinical outcome trials but it is presumed that lowering LDL-C levels in patients with Homozygous Familial Hypercholesterolemia will reduce cardiovascular events. After initiating lomitapide therapy 1.7 cardiovascular events per 1000 patient months on treatment was observed vs. 26.1 cardiovascular events per 1000 patient months in a comparison cohort .
Who Should Take Statins To Lower Cholesterol
Having low LDL and total cholesterol reduces your risk of heart disease. But not everyone needs to take statins to lower cholesterol.
Your health care provider will decide on your treatment based on:
- Your total, HDL , and LDL cholesterol levels
- Your age
- Your history of diabetes, high blood pressure, or heart disease
- Other health problems that may be caused by high cholesterol
- Whether or not you smoke
- Your risk of heart disease
- Your ethnicity
You should take statins if you are 75 or younger, and you have a history of:
- Heart problems due to narrowed arteries in the heart
- Stroke or TIA
- Aortic aneurysm
- Narrowing of the arteries to your legs
If you are older than 75, your provider may prescribe a lower dose of a statin. This may help lessen possible side effects.
You should take statins if your LDL cholesterol is 190 mg/dL or higher. You should also take statins if your LDL cholesterol is between 70 and 189 mg/dL and:
- You have diabetes and are between ages 40 and 75
- You have diabetes and a high risk of heart disease
- You have a high risk of heart disease
You and your provider may want to consider statins if your LDL cholesterol is 70 to 189 mg/dL and:
- You have diabetes and a medium risk for heart disease
- You have a medium risk for heart disease
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Possible Side Effects And Interactions
Always talk to your doctor if you experience any side effects or unusual symptoms. Statin medication can have possible side effects or interact with food or other drugs. It is good practice to keep a list of all the medications, supplements and over-the-counter drugs you are taking, so you can let your doctor know.
If you have taken a statin before and experienced any side effects, let your doctor know. Your doctor may be able to switch you to another statin with a lower risk of side effects.
An Extremely Common Solution
If you are looking at starting a statin prescription, you might take some comfort in knowing that you are far from alone. Millions of people across the United States use medication to lower their cholesterol levels.
Elevated LDL levels are very common in the United States, and a statin prescription is a common option used to improve those numbers and reduce the patients risk for negative health outcomes.
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Antiviral And Antibacterial Effects
One of the more surprising effects of statin use has been its apparent bug-fighting properties. A 2004 Canadian study found that statins suppressed the attachment of the HIV virus to potential host cells.
A 2005 study of more than 700 hospital patients being treated for pneumonia found that the death rate was more than twice as high among those who were not using statins.
In 2006, a Canadian study examined the rate of , a deadly blood infection, among patients who had been hospitalized for heart events. In the two years after their hospitalization, the statin users had a rate of sepsis 19% lower than that of the non-statin users.
A 2009 review of 22 studies found that statins appeared to have a beneficial effect on the outcome of infection, but they couldn’t come to a firm conclusion.
See If Youre At Risk For A Heart Attack By Taking Our Risk Assessment
You don’t want your first sign of heart disease to be a heart attack. That’s why it’s so important to know what your risk of heart disease may bethe leading cause of death in this country for both men and women.
Answer the following questions to learn more about your risk for a heart attack.
Disclaimer: This material is provided for informational use only and should not be construed as medical advice or used in place of consulting a licensed medical professional. You should consult with your doctor to determine what is right for you.
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Side Effects Of Cholesterol Medications
To minimize side effects of cholesterol-lowering drugs, its important to take them in the manner prescribed. Because some cholesterol-lowering drugs affect your liver, you may need to have your liver function tested occasionally.
Let your doctor know if you have any problems after starting a new medication. They may be able to adjust your dosage or switch you to an alternative medication.
Contact your doctor immediately if your symptoms are severe or seem life-threatening.
How Long Does It Take Cholesterol To Go Down
People who need to use medications such as statins to lower their cholesterol should see their cholesterol levels fall quickly.
These medications may work in a matter of weeks, and they generally work to a larger degree than lifestyle changes.
However, because diet affects the levels of cholesterol in the body, doctors commonly recommend that people make changes to their diet and lifestyle in addition to taking medications.
Making simple changes to the diet and lifestyle can help reduce cholesterol.
These changes vary depending on how strictly a person adheres to their diet, as well as other factors, such as exercise and weight loss.
Some dietary changes may cause minor reductions in cholesterol in as little as
Dietary and lifestyle changes and medications can all help lower blood cholesterol levels.
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Are Statins Right For You
If you have high cholesterol, your healthcare provider may prescribe you a statin drug. Still, statins may not be appropriate for everyone, so talk with a practitioner about whether or not they are suitable in your case, why, and what your other treatment options might be.
Lamarche F, Agharazii M, Nadeau-fredette AC, Madore F, Goupil R. Central and brachial blood pressures, statins, and low-density lipoprotein cholesterol: A mediation analysis. Hypertension. 2018 71:415-421. doi:10.1161/HYPERTENSIONAHA.117.10476
Mcguinness B, Craig D, Bullock R, Malouf R, Passmore P. Statins for the treatment of dementia. Cochrane Database Syst Rev. 2014 :CD007514. doi:10.1002/14651858.CD007514.pub3
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 .
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