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What’s the safest cholesterol medication?

Statins are the first-line option, but another medication may have fewer side effects for certain people

Key takeaways

  • Lipitor (atorvastatin) is typically the first-line drug to treat high cholesterol because it has fewer side effects than other statins.

  • Statins are the drug class of choice to manage high cholesterol for people with a risk of cardiovascular disease.

  • Medications like Zetia, fibrates, niacin, bile acid sequestrants, or PCSK9 inhibitors may be better for certain patients.

Cholesterol medicines, such as statins, continue to play a pivotal role in helping reduce deaths from heart disease, which currently kills 1 person every 33 seconds in the United States. Statins, lauded for their cholesterol-lowering capabilities, are taken by more than 90 million Americans. Their primary function is to combat the dangerous levels of low-density lipoprotein (LDL) cholesterol, otherwise known as “bad” cholesterol.

“Statins are the most commonly prescribed cholesterol drugs because extensive research shows their effectiveness in reducing heart attack and stroke,” explains Renee Akers, Pharm.D., a pharmacist based in Asheville, North Carolina. “Statins help lower blood cholesterol levels by blocking your body’s ability to make its own cholesterol.”

When people are diagnosed with high cholesterol, they often wonder what the safest cholesterol medication is. The answer, however, is not straightforward. There isn’t a universal safest statin or other cholesterol-lowering Rx. The best choice hinges on various factors, including individual side effects and interaction with other medications. The journey to finding the right cholesterol medication is as personalized as the treatment for heart disease itself.

Which cholesterol drug is the safest?

Lipitor (atorvastatin) is typically the first-line drug used to treat high cholesterol, says Dr. Akers. “The drug is generally well-tolerated by most people,” explains Kate Byrd, Pharm.D., former community pharmacist with Long Drugs. Additionally, decades of research support its long-term safety and effectiveness, reinforcing its place at the top.

Statins, in general, are the first drug class of choice for managing cholesterol due to their robust efficacy in reducing heart attack and stroke risk. The National Lipid Association’s Statin Safety Task Force 2014 report explains that the benefits of statins are closely tied to an individual’s risk for cardiovascular disease. For those with a very low risk, the risks of adverse events may outweigh the benefits. 

“Overall, the key to effective statin use, as well as reducing muscle problems, is keeping doses as low as possible and avoiding drug interactions with the statin,” Dr. Akers says. It’s crucial to discuss the best approach with a cardiologist, considering personal risk factors and other medical conditions to determine the best medication for you.

Common types of cholesterol drugs 

Cholesterol management is a key aspect of preventing cardiovascular disease and stroke. Medications that can help keep levels in a healthy range include:

  • Statins
  • Fibrates
  • Niacin
  • Bile acid sequestrants
  • PCSK9 inhibitors
  • Zetia (ezetimibe)

Typically, statins are the first-line option in individuals with cardiovascular disease risk factors due to their proven effectiveness in lowering LDL (bad) cholesterol and reducing the risk of heart attacks and other cardiovascular events. However, the choice of medication is influenced by individual health history, potential side effects, and specific cholesterol issues.

This is not an exhaustive list, and other drugs may be used to treat high cholesterol depending on individual needs and health conditions. It’s always best to talk with your healthcare provider about your specific circumstances.


Statins are the most commonly prescribed drugs for cholesterol management. “They work by helping the liver reduce the amount of cholesterol produced and also help the liver remove cholesterol that is already in the bloodstream,” says Alexander Olumese, Pharm.D., a clinical pharmacist with the University of Maryland Medical System in Baltimore, Maryland. “This is important because, in situations where cholesterol is high, plaque (atherosclerosis) begins to form in the blood vessels. Increased plaque can lead to the narrowing of arteries and the blockage of blood flow.” 

Some of the most common statins include Lipitor (atorvastatin), Crestor (rosuvastatin), Zocor (simvastatin), Lescol XL (fluvastatin), Pravachol (pravastatin), and Mevacor (lovastatin), among others. Although statin therapy is generally safe, it may cause side effects, which may lead to treatment cessation for some. According to the most recent studies, these side effects and adverse events include but are not limited to:

  • Muscle pain, muscle aches, and muscle weakness
  • Increased liver enzyme levels
  • Increased risk of Type 2 diabetes
  • General abdominal discomfort
  • Headaches
  • Sleep problems

It’s important to note that some statin medication holds specific warnings related to adverse events and drug interactions. Simvastatin, one of the most commonly used statin drugs, interacts with grapefruit juice, leading to increased levels of simvastatin in the body, which can, in turn, lead to more side effects. Lovastatin is another statin that may interact with grapefruit juice. Typically, these types of interactions occur with high doses of a statin. If you enjoy vitamin C through grapefruit or grapefruit juice, check with your healthcare provider about any possible restrictions.

There are also warnings of a rare side effect of statins called rhabdomyolysis. “Sometimes, muscle aches develop into muscle breakdown, which may lead to kidney failure,” Dr. Akers says. “It’s important to notify your doctor if you develop severe muscle pain, dark brown urine, and fever while taking a statin.”

Zetia (ezetimibe)

Zetia (ezetimibe) is a commonly used non-statin anti-lipid medicine that works by reducing cholesterol absorption in the small intestine, thus lowering LDL cholesterol. While statins are the backbone of cholesterol-lowering treatments, millions of individuals can still have elevated LDL levels despite taking statins. There, it is common for ezetimibe to be used in combination with statins to elicit a better effect.

Ezetimibe has fewer side effects than other cholesterol-lowering medicines. “Diarrhea is the most common side effect, affecting up to 10% of people taking ezetimibe,” Dr. Byrd says. However, increasing water and fiber in one’s diet can often help manage this gastrointestinal upset.


Fibrates, such as Lopid (gemfibrozil) and Tricor (fenofibrate), are another class of cholesterol-lowering drugs. They mainly target triglycerides—another type of fat in the blood—by decreasing the liver’s release of triglycerides and increasing the production of an enzyme that breaks down triglycerides. 

“Fibrates increase your body’s ability to break down and remove triglycerides from your bloodstream; they also slightly raise ‘good’ high-density lipoprotein (HDL) cholesterol levels, which statins don’t typically affect,” Dr. Byrd says. “Side effects of fibrates can include stomach pain, gallstones, and muscle damage, especially when taken with statins. Muscle aches (myalgia) are the most frequent side effect of fibrates, affecting up to 10% of patients.”

Studies report that the most common adverse effects of fibrates include altered liver enzyme levels, altered kidney function, and muscle pains and aches. However, fibrates are generally safe to use and do not need frequent monitoring unless a patient is susceptible to any of the known side effects.


Niacin, or nicotinic acid, is a B vitamin that boosts HDL (good) cholesterol and lowers triglycerides and LDL cholesterol. However, unlike statins and fibrates, it takes slightly longer to exert its effects. Niacin is naturally found in many foods, like fish, beef, chicken, and turkey. In the body, niacin is converted to nicotinamide adenine dinucleotide (NAD), a vital molecule used for energy production and numerous other physiological functions.

Niacin has been studied both as a standalone treatment and in combination with statin therapy for cholesterol management. However, despite studies proving its effectiveness in managing cholesterol levels, it’s important to note that results have varied, and some individuals have experienced adverse effects such as flushing, itching, increased blood sugar, and, in rare cases, liver damage.

Therefore, the American College of Cardiology and the American Heart Association have provided guidance indicating a preference for statins over non-statin therapies like niacin in reducing cardiovascular risk. This advisory is primarily based on the consistent and significant benefits statins have shown in large-scale clinical trials compared to the mixed results and potential side effects associated with niacin.

Bile acid sequestrants

“Bile acid sequestrants like Questran (cholestyramine) … bind to bile acids in your digestive system, preventing them from being reabsorbed into your bloodstream,” Dr. Byrd explains. “These medicines force your liver to use cholesterol to make new bile acids, thus lowering your overall cholesterol levels.”

Bile acid sequestrants can help lower LDL cholesterol but may cause gastrointestinal issues and reduce the absorption of other medications. Dr. Byrd says that “constipation, bloating, and gas can affect up to 20% of users.”

PCSK9 Inhibitors

Newer to the scene are PCSK9 inhibitors like Praluent (alirocumab) and Repatha (evolocumab). “These injectable medications block the PCSK9 protein, which removes LDL receptors from your liver,” Dr. Byrd says. “This leads to more LDL receptors available to remove LDL cholesterol from your bloodstream.” They are typically used in patients with genetic conditions leading to high cholesterol or those who don’t respond to statins.

However, like all medicines, they come with their own side effects. Some using PCSK9 inhibitors may experience injection site reactions, which range from mild redness and swelling to pain and itching. Side effects such as fatigue, chills, muscle aches, and headaches may occur, but these effects usually resolve within a day or two.

The bottom line: Take statins with lifestyle changes

While statins are generally considered the most safe and effective cholesterol medications, there is no one-size-fits-all approach. Choosing the right cholesterol medication involves considering several factors:

  • Individual health profile: A person’s overall health, including any existing conditions and whether they have a high risk of cardiovascular disease, plays a crucial role in determining the most suitable cholesterol medication.
  • Side effects: Patients should discuss the potential side effects of different medications with their healthcare providers and weigh them against their benefits.
  • Lifestyle modifications: Integrating lifestyle changes as part of cholesterol management is crucial.

“The best way to lower cholesterol without having to take a medication is to stop smoking, exercise, follow a healthy diet, and limit alcohol intake,” Dr. Akers says. Consulting with a cardiologist is essential to tailor a plan that suits individual health needs and risks.