What You Need To Know About Statins

Why Doctors Prescribe Statins

Doctors prescribe statins to lower cholesterol and reduce the risk of heart disease. However, in November of 2023, the American Heart Association released a new model for calculating the risk of heart attack or stroke based on cholesterol levels. The mode hasn’t been incorporated into official guidelines yet, but experts say that if it does, 38.1% fewer people may be prescribed statins. The researchers also emphasized the importance of lifestyle factors in helping to prevent cardiovascular disease. In light of the news, it’s even more important to discuss your overall risk of heart attack and stroke with your healthcare provider and decide together whether statins—and their side effects—are a good option for you.

What are Statins?

Most of the cholesterol in your blood doesn’t come from butter, cheese, and egg yolks, but instead from your body’s own liver. Statins are drugs that prevent your liver from making the cholesterol that can clog your arteries. Statins work by blocking the activity of an enzyme known as HMG-CoA reductase, which is involved in the body’s production of cholesterol. 

Do Statins Work?

Statins do seem to lower cholesterol for most people who take them. However, how much the cholesterol is reduced and whether or not this translates to better health and lower risk of heart disease, varies between individuals and is a frequent topic of debate.

A 2016 review in The Lancet said the benefits of using statins greatly outweigh any risks associated with them. The authors described an ongoing benefit, as risks of cardiovascular events get lower as people continue to take the drugs and cholesterol levels continue trending downwards. For example, they found evidence in randomized controlled trials (RCTs) that a two-point reduction in LDL (low-density lipoprotein) cholesterol, typically considered “bad” cholesterol, while taking 40mg of Lipitor daily is linked to a nearly 50% reduction in the risk for a major cardiovascular event. The authors expressed concerns that exaggerated side effects caused people to stop taking statins, and subsequently raise their risk for cardiovascular issues.

A study published in the Annals of Internal Medicine found that people who continued with statins, despite side effects, had slightly better outcomes than those who didn’t. People who stopped taking statins, because of side effects, were found to be slightly more likely to die or have a heart attack or stroke according to the study. Among those who continued taking statins despite side effects, 12.2% had a heart attack or stroke within four years, compared to 13.9% of those who stopped statins after a possible side effect. The study did not take into account other methods of lowering cholesterol, such as adding more exercise into their days.

Statins Impact People Differently

There’s wide variety in how people respond to statins. According to a 2019 study published in the journal Heart, after two years of taking statins, fewer than half of the people monitored had what’s considered an “optimal reduction in LDL cholesterol levels” (40%). 

Those who responded well to statins had a 13% reduced risk of developing cardiovascular disease. Those who did not experience at least a 40% reduction in LDL, still saw a moderately lower risk of cardiovascular issues, but were 22% more likely to develop cardiovascular disease compared to those who did achieve optimal reduction. 

Additionally, evidence of statins benefitting in people over 75 years old without vascular disease is limited. A study in JAMA Internal Medicine finds that statins do not appear to reduce the risk of heart attack in patients over 65 who had moderately high cholesterol, but no evidence of hardening arteries (atherosclerosis).

In 2016, U.S. guidelines recommended that statins be prescribed to those between the ages of 40 and 75 who have a 10% or greater risk of having a heart attack within the next 10 years and who have one or more risks for cardiovascular disease (CVD), such as high cholesterol, high blood pressure, diabetes, or smoking. The experts in the study stated there was not enough evidence to recommend the drugs for those over the age of 75. The guidelines were refreshed, but largely remained the same, in 2022.

With those guidelines, as many as 40% of older Americans should take a statin to curtail their risk of developing heart disease or having a cardiovascular event. 

But in 2018, researchers argued in Annals of Internal Medicine, that the guidelines for recommending statins are too broad, and use should be restricted to far fewer people with higher risk for cardiovascular disease. Their computer model suggested, for example, that there was no net benefit to prescribing statins for men between 70 and 75 unless their 10-year cardiovascular disease risk was at least 21%. Among men 40 to 44, the benefit was not greater than risk unless their cardiovascular disease risk was at least 14%.

Milo Puhan, MD, PhD, a senior author of the Annals of Internal Medicine study with the University of Zurich, told NPR that, as people age, the benefits of statins diminish compared to the harm they may cause. He added that only 15% to 20% of older adults should be taking statins, much less than the 40% recommended under the current guidelines.

Common Names of Statins

• Lipitor (atorvastatin)
• Crestor (rosuvastatin)
• Zocor (simvastatin)
• Pravachol (pravastatin)
• Mevacor (lovastatin)
• Lescol (fluvastatin)
• Livalo (pitavastatin)
• Altoprev (lovastatin extended release)

Side Effects of Statins and What to Do About Them

One of the reasons there’s ongoing debate about the efficacy of statins and when to use them is because they’ve been associated with many side effects, despite their broad use.

In an editor’s note that accompanied the JAMA Internal Medicine study on older adults, Gregory Curfman, MD, editor-in-chief of Harvard Health Publications, noted that, since statins have been associated with musculoskeletal disorders and cognitive dysfunction, which can boost the risk for falls and have a large impact on older adults, physicians should carefully consider the risk before prescribing or continuing statins in this population, in particular. Still, anyone can experience side effects from medication, and it’s important to discuss the risks and any alternatives with your healthcare provider before taking any prescribed medications.

Muscle Aches and Pains with Statins

As many as 30% of people taking statins report muscle aches and pains, but the side effect hasn’t always been well-understood. Some researchers suggested it was a “nocebo effect” or a negative placebo. Their work* had shown that, when people and their doctors were told they were taking statins, they were more likely to report muscle aches than those who thought they might be taking a placebo. (*Editor’s note: the study was funded by Pfizer, Lipitor’s manufacturer.) 

However, in 2023, researchers found some clues as to why some people who took statins had muscle aches and even severe weakness. It may be because the drugs interfere with an important enzyme. People with genetic mutations in this enzyme can develop a rare, but devastating type of muscular dystrophy.

Although it’s rare, some people on statins have experienced myositis (inflammation of the muscles), or rhabdomyolysis (breakdown of muscle cells), which can result in potentially life-threatening kidney injury. People taking Zocor, Lipitor, or Mevacor appear to be most likely to experience muscle symptoms, according to a 2019 report in the journal Circulation Research. The researchers suggest trying a different statin or lowering your dose if you experience these pains, though the latter could mean less cholesterol-lowering efficacy.

On April 2, 2024, the FDA added a warning to Lipitor’s label that it had received reports of new or worsening myasthenia gravis, a rare autoimmune form of muscular dystrophy.

A study in the journal JAMA Internal Medicine suggests that older men taking statins appear to be slightly less active than those who do not take them, probably due to muscle pain. According to the study, statin users logged about 40 fewer minutes of moderate activity each week compared to nonusers. Researchers examined data on 14,000 adults, more than 30 years old, who were enrolled in TRICARE, the military’s health care program. Half had taken a statin drug an average of 3.7 years while the others had never taken one. Zocor was the most commonly taken statin in the study. Statin users had a higher likelihood of back disorders, such as spondylosis and intervertebral disc disorder, the researchers reported in JAMA Internal Medicine.

The American Heart Association (AHA) points out that there are many causes of muscle pain in people who are most likely to be taking statins. In a 2018 analysis, the organization recommended checking vitamin D levels and possibly sending the individual to a neuromuscular specialist.

If you experience muscle aches, talk to your doctor about trying a lower dose, a different statin, or discontinuing statin treatment and finding an alternative therapy. 

Risk of Diabetes with Statins

Taking statins can raise your risk of developing type 2 diabetes, according to a 2023 review, and that risk increases with the dose and intensity of the statin you are prescribed. The reasons for this are unclear, but research suggests that statins may increase insulin resistance, and they also appear to inhibit the pancreas’ ability to secrete insulin.

However, the extent to which the drugs contribute to new onset diabetes is hotly debated, with previous studies showing wide ranges of increased risk. Additionally, your risk is higher if you have other additional risk factors for diabetes.

Cancer Risk with Statins

A number of early studies pointed to potential association between statin use and increased cancer risk in certain people. Older people, those who take statins for a long time, and people with a history of breast cancer or prostate cancer, appeared to be at higher risk. 

A study at the Fred Hutchinson Cancer Research Center in Seattle found that women 55 to 74 years old who took statins for 10 or more years have double the risk of being diagnosed with invasive ductal carcinoma and invasive lobular carcinoma, two common types of breast cancer. 

In a Taiwanese study published in Clinical Endocrinology, regular use of statins, particularly among women, was associated with an increased risk of thyroid cancer. Compared with controls, patients who routinely used statins had a 40% increased risk of having thyroid cancer. 

Meanwhile, a 2023 study in Asian women found that women who had been taking statins for at least six months before having been diagnosed with breast cancer were less likely to die from cancer-related causes than those who weren’t taking the drugs. Another study in a journal called “Medicine” found that previous use of any statin was associated with a reduction in the risk of brain cancer. For more on potential benefits of statins for brain cancer protection, see MedShadow’s Statins May Lower Glioma Risk Over Time.

Elevated Liver Enzymes with Statins

According to a study in the journal Clinics in Liver Disease, it is common for people taking statins to have elevated liver enzymes, which could indicate liver damage. The increase in liver enzymes is dose-related, with higher doses of statins leading to a greater risk of increased enzyme levels. However, in multiple studies, enzyme levels in people taking statins were not consistently different than in people taking a placebo, and irreversible liver damage was extremely rare. Research shows that the risk of liver injury caused by statin is estimated to be about 1%, similar to the risk in people taking a placebo.

After a review of post-marketing data and liver outcome studies from organizations submitting reports of drug-associated liver injury, the Food and Drug Administration (FDA) revised statin labeling requirements to remove the recommendation for periodic liver enzyme monitoring. Healthcare professionals are advised to perform liver enzyme tests before starting a patient on statin treatment, with follow up tests only if clinically indicated as necessary. Patients are advised to notify their healthcare provider if they experience unusual fatigue, loss of appetite, yellowing of skin or eyes, upper belly pain, or dark colored urine. 

And as always, contact your doctor if you have any questions or concerns about potential liver problems of any kind. 

Cognitive Effects with Statins

Some studies show statins can hinder your cognition while others claim to show a benefit.

The Case for Cognitive Impairment with Certain Statins

One type of statin may increase the risk for memory loss and other cognitive issues, according to a study presented at the Alzheimer’s Association International Conference in 2018. The drugs in question are known as “lipophilic statins.” Common brands include Lipitor, Zocor, and Mevacor. Compared to other types of statins, these three medications tend to cross the blood-brain barrier more easily, which can lead to potential central nervous system complications.

For the study, researchers at the University of Toronto looked at data from patients seen at a memory disorders clinic. Patients were divided into three groups. The first was a control group not taking a statin. The second group was taking Lipitor. And the final group was taking Crestor, which is known as a hydrophilic statin. Data showed that those in the Lipitor group had slightly lower cognitive and neurology assessment scores on a series of tests compared to those in the control or Crestor groups. Results also showed that there were no significant differences in test evaluations between the Crestor group and the control group. 

The Case for Cognitive Improvement with Statins

In contrast, in a 2018 study published in the American Journal of Epidemiology, researchers note that the authors of several review articles have concluded that there is no strong evidence that statins have adverse cognitive effects, and that short-term statin use does not adversely affect cognitive function, while long-term statin use may have a beneficial effect. 

Another study, published in 2021 found no difference in the likelihood that statin users would develop dementia or cognitive changes compared to those who didn’t use statins. The researchers also looked specifically at lipophilic statins—the ones previously associated with cognitive impairment—alone, and did not find any increased risk there.

Although there have been reports of cognitive issues associated with statins, as well as analyses finding no significant evidence that statins lead to dementia or mild cognitive impairment, the FDA mandated that a warning of possible cognitive effects be added to the labeling of statins. If you experience memory loss or other negative cognitive effects after taking a statin, talk to your healthcare provider immediately.

Do Statins Cause Depression? 

Researchers have questioned whether the use of statins could lead to depression. Some research has shown the possibility that low cholesterol levels may trigger depression, but there is also contradictory evidence, suggesting that statins could be protective against depression. 

It’s crucial to monitor your mood, along with other symptoms, as you start to take any new drug. Consider using a symptom tracker for a few months when you start taking statins, and share what you notice with your healthcare provider.

Dry Skin with Statins

While it’s not common, statins have been associated with a variety of skin irritations. According to a 2021 study, people taking statins have reported:

• Dry skin
• Rashes
• Hives
• Increased skin sensitivity
• Skin discoloration
• Swelling
• Eczema

Drugs That Interact with Statins

Doctors and patients need to be aware of drug interactions between statins and medications used to treat heart disease, according to recommendations from the AHA.

Statins are prescribed to patients who have clogged arteries, a condition known as atherosclerosis, or those at risk for it. So in many cases, these people are also taking other heart meds.

The AHA published a list of drugs often given to heart patients that can interact with statins. These include:

• Blood pressure-lowering medications known as calcium channel blockers. These include Norvasc (amlodipine), Cardizem (diltiazem), and Calan (verapamil).
• Drugs to treat irregular heartbeat, such as Multaq (dronedarone), Cordarone (amiodarone), and Digox (digoxin).
• Heart failure medications, including Entresto (sacubitril/valsartan) and Corlanor (ivabradine).
• Drugs known as fibrates, which are used to lower triglycerides, another type of lipid (fat) in the blood, such as Lopid (gemfibrozil).
• Blood thinners, such as Coumadin (warfarin) and Brilinta (ticagrelor).

Statins with Other Heart Drugs

The most common interaction when taking heart drugs and statins in combination with a statin is that it can increase the level of the statin in the blood, which can lead to muscle weakness or pain. However, the benefits of taking the medications outweigh the risks, which are relatively minor, the AHA recommendations state. To minimize the risks, a doctor should adjust the dose of the statin.

But there are some drug combinations that should be avoided. For example, Lopid should never be taken with the statins Mevacor, Pravachol, or Zocor, because Lopid prevents your body from metabolizing the statins, leading to high levels of them in the blood that can damage the muscles causing weakness, organ damage and even death. 

The AHA statement notes that niacin, which is also used to lower lipids in the blood either as monotherapy or combination therapy with statins, does not provide benefits and is potentially harmful. The researchers conclude that “there are currently no clear indications for the routine use of niacin preparations in combination with statins.”

In 2016, the FDA withdrew the approval of Niaspan (niacin extended-release) and the fibrate Trilipix (fenofibric acid) to be used in combination with a statin. Niaspan and Trilipix were supposed to be taken along with statins to reduce the risk of cardiovascular events, but studies showed that the combinations did not have any significant cardiovascular benefit.

Statins with Antibiotics

Taking a statin with certain antibiotics may not mix well. In a study in the Annals of Internal Medicine, researchers warn that if you are taking statins, you should avoid erythromycin and clarithromycin. Both can increase the concentration of the statin in your bloodstream, leading to muscle or kidney damage, and possibly death. If you need an antibiotic, azithromycin is a better choice. 

Statins and Antiviral Drugs

The FDA issued a warning about interactions between statins and protease inhibitors, drugs for human immunodeficiency virus (HIV) or hepatitis C virus (HCV). Again, the risk for muscle injury, and even rhabdomyolysis, may be increased due to a rise in the blood levels of statins when these drugs are taken at the same time. 

Statins and Grapefruit Juice

While not a drug, grapefruit is often noted as a food that, when consumed, can interact with statins. Another FDA report notes that eating grapefruit or drinking grapefruit juice can impact how statins work. 

Eating a grapefruit or having a glass of grapefruit juice in the morning can be a healthy way to start your day – the fruit is high in vitamin C and potassium. But the FDA is reminding consumers that grapefruit can interact with many drugs and how they work in the body, especially if you have high blood pressure or an irregular heartbeat.

When grapefruit interacts with certain medications, the juice causes too much of the drug to enter the bloodstream, similar to what happens when statins are taken with some heart drugs. This can lead to more side effects. For example, drinking grapefruit juice while taking statins such as Zocor and Lipitor, can lead to too much of the drug remaining in your system, increasing your risk for liver and muscle damage that can lead to kidney failure.

For a further list of drugs that interact with grapefruit, click here.

You can also read the medication guide or patient information sheet that comes with your prescription drugs to see if there is a grapefruit juice warning. For OTC (over-the-counter) drugs, check out the Drug Facts label on the bottle.

If you have to avoid grapefruit and grapefruit juice, pay attention to the labels of other fruit juices as they may contain grapefruit juice. Seville oranges, pomelos, and tangelos can have the same effect on drugs as grapefruit, so best to avoid them if you know your drug can interact with grapefruit.

Research also shows that the impact of grapefruit or grapefruit juice varies depending on the statin in use and the quantity and timing of ingestion of grapefruit or juice. So before giving up your grapefruit habit, talk to your doctor about how you might be able to safely keep grapefruit in your diet while taking a statin.   

Always discuss with your doctor or pharmacist all the medicines, herbal supplements, vitamins and even foods or drinks you are consuming to avoid drug interactions.

Alternatives to Statins

There is a large variety of alternatives for people who don’t want to take drugs (See MedShadow’s 5 Things to Know About Statin Alternatives).

According to the National Heart, Lung, and Blood Institute (NHLBI) the most common cause of high cholesterol is an unhealthy lifestyle. In many cases, changes in diet and exercise can make a big difference in reducing cholesterol levels.

The NHLBI offers a three-part program called TLC, or Therapeutic Lifestyle Changes, that uses diet, physical activity, and weight loss to lower high cholesterol. The program offers advice on how to make heart-healthy lifestyle changes for everyone, no matter what your heart disease risk is currently. 

In fact, experts recommend that people who have high cholesterol and have not had a heart attack try changes in diet and getting lots of exercise before taking a statin. 

Foods and Supplements to Lower Cholesterol

The National Institute on Complementary and Integrative Medicine offers the following guidelines on natural products that may be helpful in treating high cholesterol:

• Stanols and sterols. Studies show that stanol or sterol supplements, taken with meals, can reduce cholesterol levels. The FDA permits some foods and dietary supplements that contain stanols or sterols to carry a health claim saying that they may reduce the risk of heart disease when consumed in appropriate amounts.
• Soy. Some research shows that some soy products have a small cholesterol-lowering effect. Soy foods appear to be more effective in lowering cholesterol than soy protein supplements. 
• Flaxseed. Studies suggest that some types of flaxseed supplements, including whole flaxseed and flaxseed lignans, have possible beneficial effects in lowering cholesterol. These potential benefits have not been shown for flaxseed oil.  
• Garlic. An analysis of the research on garlic supplements concluded that they can lower cholesterol if taken for more than two months. 
• Green tea. Evidence for green tea is limited, but there is some research that suggests it may have a modest cholesterol-lowering effect.
• Oats and oat bran. Studies suggest that long-term intake of oats or oat bran can reduce the risk of cardiovascular disease by lowering total and LDL cholesterol.    

Best Exercises to Lower Cholesterol

Studies show that increasing your physical activity is one of the best things you can do to lower your cholesterol. Researchers suggest a combination of moderate and high intensity cardiovascular activities, such as running, swimming, biking, walking, or dancing, and moderate-intensity resistance training, such as lifting weights work best. 

Non-Statin Medications for Cholesterol

Other medications to lower cholesterol include Zetia (ezetimibe), which works by limiting the absorption of cholesterol. However, Zetia is often taken in combination with a statin. Prevalite (cholestyramine), Welchol (colesevelam), and Colestid (colestipol) help to lower cholesterol by binding directly to bile acid, which is used in digestion. As a result, your liver uses cholesterol to make more bile acid, which reduces cholesterol levels in the blood.

A study published in JAMA indicates that some of these methods to lower cholesterol may be just as effective as statins in also reducing cardiovascular events. Researchers analyzed 49 trials involving more than 300,000 people that looked at different ways of lowering cholesterol. 

The trials were sorted into four groups: Those that examined statins; non-statin treatments that work to lower LDL “bad” cholesterol levels, such as diet and Zetia; fibrates and niacin; and a newer class of cholesterol-lowering drugs known as PCSK9 inhibitors. Statins and nonstatin interventions lead to similar reductions in the risk of a heart attack, stroke, or need for a stent, according to the study. Fibrates and niacin also worked to mitigate the risk, though the reduction was not as great as with statins and non-statin treatments. The PCSK9 inhibitors also showed some benefit, but there have been few studies conducted to determine their long-term effects.

Lastly, Nexletol (bempedoic acid) was approved by the FDA in 2020 to be used alongside statins for individuals with heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease (ASCVD) who require additional lowering of LDL-C

The new drug, bempedoic acid, works by targeting the enzyme ATP citrate lyase, which is involved in the production of LDL cholesterol. In a new study, adding bempedoic acid plus a statin led to a greater reduction in LDL cholesterol compared with just increasing the dosage of a statin.

Researchers conducted a one-year trial, enrolling 2,000 patients that had atherosclerotic cardiovascular disease, a genetically-inherited high cholesterol, or both conditions. All patients continued to take the highest dose of a statin they could tolerate and were randomized to receive either bempedoic acid or a placebo.

The results showed that adverse events occurred at similar rates in both groups. But those in the bempedoic arm saw their LDL decline by an average of 19.2 md/dL. An LDL level between 130 and 159 mg/DL is considered borderline high, 160-189 high, and 190 and above very high.

*Editor’s Note: The study was sponsored by Esperion Therapeutics, the developers of bempedoic acid.

Some of the adverse events seen in the trial were uric acid and gout, though researchers noted those can be managed and treated by healthcare providers. There were also more deaths in the bempedoic than the placebo group, though the authors said the deaths were likely unrelated to the drug and more likely the results of cancer and cardiac death due to cardiovascular disease.

Be aware that many people who stop taking statins due to side effects have better luck with the drugs the second time around. Most patients who stop statin treatment are able to tolerate them when they go back on statin therapy, according to a study that followed patients for 9 years. For more on this see MedShadow’s Statins Often Tolerated on the Second Try.

 

This article was originally published Dec 4, 2019. It was updated on Oct 13, 2023.