Complete Guide to Cholesterol-Lowering Medications

April 8, 2025/Andrew Le

High cholesterol often develops without noticeable symptoms, earning it the reputation of a “silent killer.” In 2019, elevated levels of LDL, or “bad” cholesterol, were linked to roughly 4.4 million deaths worldwide. This accounted for 12.6% of all deaths associated with risk factors.

In the US, an estimated 86 million adults aged 20 and older have total cholesterol levels above the recommended range. Among them, nearly 25 million have levels considered significantly elevated.

The good news is that high cholesterol can be managed through consistent lifestyle adjustments, such as healthier eating habits, regular physical activity, and, when necessary, cholesterol-lowering medications. It’s possible to reduce LDL, support better artery function, and lower the chances of severe cardiovascular events.

🔑 Key Takeaways

➤ Statins effectively lower LDL-C and significantly reduce the risk of death and major heart events. Their benefits apply to both men and women across a range of cardiovascular risk levels.

➤ Drugs like ezetimibe, PCSK9 inhibitors, and bempedoic acid are used when statins alone don’t lower cholesterol enough or when side effects limit statin use.

➤ Using lower doses of multiple medications, such as statins plus ezetimibe or bempedoic acid, can achieve strong LDL reductions with fewer side effects than high-dose monotherapy.

➤ Treatments like ACLY inhibitors, MTTP inhibitors, and ANGPTL3 inhibitors work through novel pathways. These offer more options for people with hard-to-treat or genetic cholesterol disorders.

➤ Liver function, kidney health, blood sugar, and muscle symptoms should be checked regularly to ensure treatment remains effective and safe over time.

➤ Some triglyceride-lowering drugs, like fibrates and omega-3s, can affect LDL levels slightly, but the impact varies and may even cause an increase in certain cases.

What Are Cholesterol-Lowering Medications?

Cholesterol is a fat-like substance made by the liver. It supports several important functions in the body, such as building cell membranes, producing hormones, and helping digest fat. There are two main types:

  • Low-density lipoprotein cholesterol (LDL-C): Often called “bad” cholesterol
  • High-density lipoprotein cholesterol (HDL-C): Often called “good” cholesterol

Too much LDL-C in the blood can lead to hypercholesterolemia or high cholesterol. When this happens, cholesterol may stick to the walls of your arteries. Over time, the buildup forms plaque, which can narrow or block blood flow–a condition known as atherosclerosis.

If this narrowing affects the arteries that supply the heart or brain, it can lead to serious outcomes like heart attacks or strokes. These conditions fall under a broader category called atherosclerotic cardiovascular disease (ASCVD).

Cholesterol-lowering medications are prescribed to reduce these risks. They work in different ways. Some block the production of cholesterol in the liver, and others help the body remove it from the blood more efficiently. These drugs are often recommended for people with ASCVD or those at high risk, such as individuals with diabetes, high blood pressure, or a family history of heart disease.

LDL Cholesterol Levels

Here’s how LDL-C levels are typically categorized under US guidelines:

LDL-C LevelHealthy IndividualsIndividuals with Heart Disease or Other Forms of Atherosclerosis
Below 70 mg/dL–Optimal. In some individuals, the desired value could be below 55 mg/dL.
Below 100 mg/dLOptimalNear-optimal
100-129 mg/dLNear-optimalBorderline High
130-159 mg/dLBorderline HighHigh
160-189 mg/dLHighVery High
190 mg/dL and aboveVery HighSeverely High

List of Cholesterol-Lowering Medications

There are several different classes of cholesterol-reducing medications available. These are:

1. Statins (HMG-CoA Reductase Inhibitors)

Statins work by blocking the enzyme HMG-CoA reductase, which is responsible for cholesterol production in the liver.

By blocking this enzyme, the liver produces less cholesterol. Since cholesterol is essential for various bodily functions, the liver responds by making more LDL receptors. These tiny “catchers” grab LDL from your bloodstream and pull it into the liver.

With less cholesterol being made and more LDL being cleared, overall LDL cholesterol levels drop. This helps reduce the risk of plaque buildup in arteries and lowers the chances of heart disease.

Statins are particularly effective because about 80% of the cholesterol in your body comes from the liver, not your diet. That’s why they are considered the first-line therapy for lowering cholesterol levels.

⚠️ Important Considerations
Not everyone responds to statins the same way. Genetic differences influence LDL-C reduction and susceptibility to side effects. Genome-wide association studies (GWAS) have identified candidate genes, including BAAT, BCL3, and CMTM6, that directly impact total cholesterol levels and LDL production, affecting statin response.

Types of Statins

Different statins have slightly different FDA-approved uses, but in general, they are prescribed to prevent or treat heart-related conditions caused by blocked arteries. This includes preventing heart attacks and strokes, whether you already have heart disease or are at high risk of developing it.

Statins are classified into three groups:

Statin IntensityLDL-C ReductionStatin DosagesWho They’re For
Low-Intensity StatinsLess than 30%Fluvastatin (20-40 mg)Lovastatin (20 mg)Pitavastatin (1 mg)Pravastatin (10-20 mg)Simvastatin (10 mg)– If you need only a slight reduction in cholesterol.
– If you cannot tolerate higher doses due to side effects.
Moderate-Intensity Statins30-50%Atorvastatin (10-20 mg)Fluvastatin (80 mg)Lovastatin (40 mg)Pitavastatin (2-4 mg)Pravastatin (40-80 mg)Rosuvastatin (5-10 mg)Simvastatin (20-40 mg)– Adults aged 40-75 with at least one risk factor for heart disease and a 10% or greater likelihood of a cardiovascular event within 10 years (as per USPSTF).
High-Intensity StatinsMore than 50%Atorvastatin (40-80 mg)Rosuvastatin (20-40 mg)– If you have a 10-year risk of heart-related complications due to clogged arteries above 20%.
– If you have very high cholesterol levels (LDL-C ≥ 190 mg/dL).

Side Effects

Statins are generally safe and well-tolerated, but some side effects can occur. The most common side effect of statin therapy is muscle-related symptoms, with myalgia (muscle pain) being the most frequent, affecting 1% to 10% of individuals taking statins.

Types of muscle problems caused by statins include:

  • Myopathy (muscle weakness)
  • Myositis (muscle inflammation)
  • Myonecrosis (serious muscle damage that can progress to rhabdomyolysis)
  • Rhabdomyolysis (severe muscle breakdown, rare but life-threatening)

Other side effects of statin therapy are:

  • Liver injury
  • Kidney damage (proteinuria and hematuria)
  • Increased risk of diabetes mellitus

Pravastatin and fluvastatin have the lowest risk of muscle-related side effects. Meanwhile, rosuvastatin and simvastatin are more likely to cause kidney injury. High-intensity statins increase the risk of developing diabetes mellitus.

Safety and Effectiveness

Numerous studies across diverse patient populations have consistently shown that statin therapy is effective for hypercholesterolemia and reduces the risk of cardiovascular diseases caused by blocked arteries. The benefits of statins far outweigh the risks, making them one of the most widely used cholesterol-lowering medications.

A large meta-analysis of 14 randomized statin trials involving 90,056 individuals found that the risk of cardiovascular events significantly decreased:

  • Every 1.0 mmol/L drop in LDL-C reduced the risk of dying from any cause by 12%
  • Deaths from coronary heart disease (CHD) dropped by 19%
  • 21% lower risk of major vascular events (like heart attacks, strokes, or needing bypass surgery)
  • 23% lower risk of heart attacks or death from coronary disease
  • 17% lower risk of stroke
  • 24% lower risk of needing coronary revascularization (bypass or stents)

The greater the LDL-C reduction, the lower the risk of vascular events.

Historically, there was debate about whether statins were as effective for women as for men, particularly in primary prevention. However, a 2015 meta-analysis of 27 randomized trials involving 174,000 participants confirmed that statins provide equal cardiovascular benefits for both sexes.

2. Cholesterol Absorption Inhibitors

These medications lower cholesterol by blocking its absorption in the small intestine, reducing how much enters the bloodstream. In response, the liver pulls more cholesterol from the blood, helping to lower LDL-C levels.

Types of Cholesterol Absorption Inhibitors

Currently, ezetimibe (brand name Zetia®) is the only FDA-approved cholesterol absorption inhibitor available. It specifically blocks NPC1L1, a protein in the intestine responsible for cholesterol absorption, reducing LDL-C levels by 13% to 20%.

Ezetimibe has been FDA-approved since 2002 and is the most commonly used non-statin agent. It is mainly added to statin therapy when statins alone do not adequately reduce LDL-C levels or when patients can only tolerate a low-dose statin.

In fact, fixed-dose combination therapies that pair ezetimibe with a statin are available. These include:

  • Vytorin® (ezetimibe + simvastatin)
  • Roszet® (ezetimibe + rosuvastatin)

Ezetimibe can also be used on its own (monotherapy), particularly for patients who cannot tolerate statins. In some cases, it may be combined with other cholesterol-lowering medications.

🩺 Medical Insight

Ezetimibe is the preferred treatment for sitosterolemia, a rare genetic disorder (1 in 50,000 people) where the body absorbs too much plant sterol from food and fails to remove it properly. Since plant sterols are similar to cholesterol, their buildup increases the risk of artery-clogging plaques and heart disease.

Side Effects

Ezetimibe is generally well tolerated, with no major side effects reported. The most frequently observed side effects include:

  • Headache
  • Runny nose
  • Sore throat

Less common reactions include:

  • Body aches
  • Back pain
  • Chest discomfort
  • Diarrhea
  • Joint pain
  • Fatigue
  • Weakness

Safety and Effectiveness

Several studies have examined whether ezetimibe improves heart health, either alone or in combination with statins. Some trials focused on whether ezetimibe provides additional benefits beyond statins, while others looked at its effects in specific patient groups.

Here are the key findings from major trials:

TrialPopulationResults
SEAS TrialPatients with aortic stenosis (narrowed heart valve)Ezetimibe-simvastatin lowered LDL by 61%, but did not significantly reduce major heart-related events compared to placebo. However, there was a small reduction in ischemic cardiovascular events like bypass surgeries.
SHARP TrialPatients with kidney disease (some on dialysis)Ezetimibe-simvastatin lowered LDL by about 34 mg/dL and reduced major atherosclerotic events by 17%.
IMPROVE-IT TrialPatients with recent heart attack or unstable anginaEzetimibe-simvastatin reduced LDL to 54 mg/dL, compared to 70 mg/dL with statins alone. This led to a 6.4% reduction in major heart events.
EWTOPIA 75 Trial (Japan)Elderly patients (75+ years) with high cholesterol who had never had heart diseaseEzetimibe alone lowered LDL by 26% and reduced major heart events by 34%.
RACING Trial (South Korea)Patients with ASCVDCompared moderate-intensity statin + ezetimibe vs. high-intensity statin alone. LDL was slightly lower in the combination group (58 mg/dL vs. 66 mg/dL). Heart event rates were similar, but fewer side effects were seen with the ezetimibe combination.

3. PCSK9 Inhibitors

PCSK9 is a protein that attaches to LDL receptors and causes them to get destroyed. Remember those? They’re the little “grabbers” on liver cells that pull cholesterol out of your blood. When too many receptors are destroyed, more LDL cholesterol stays in your bloodstream.

PCSK9 inhibitors are medications that stop the PCSK9 protein from interfering with LDL receptors. This allows more receptors to stay active and continue clearing cholesterol.

These drugs are especially helpful for people who:

  • Have genetic high cholesterol (like familial hypercholesterolemia),
  • Can’t tolerate statins,
  • Or need more cholesterol-lowering medications than statins alone can provide.

Types of PCSK9 Inhibitors

There are two types of PCSK9 inhibitors:

Monoclonal Antibodies

These drugs attach directly to the PCSK9 protein and prevent it from interacting with LDL receptors. By doing so, they help preserve the receptors.

Two fully human monoclonal antibodies have been approved by the FDA for this purpose:

  • Alirocumab (Praluent®)
  • Evolocumab (Repatha®)

These medications can be used on their own or in combination with statins. In either case, they typically lower LDL-C levels by 50% to 60%.

Small Interfering RNA (siRNA)

Unlike monoclonal antibodies, this form works inside the liver cells. Inclisiran (Leqvio®), the only approved siRNA-based PCSK9 inhibitor, reduces PCSK9 production at the genetic level. It does this by using RNA interference (RNAi) to suppress the gene responsible for producing PCSK9.

When used in patients already receiving the maximum tolerated dose of statins,inclisiran can reduce LDL-C by about 50%. Its main advantage is the twice-a-year dosing, making it easier to stay on treatment.

Side Effects

Since evolocumab and alirocumab are biologic drugs (made from living cells), the immune system may sometimes see them as foreign and react to them as if they were harmful. This immune response can range from mild symptoms like:

  • Rash
  • Itching
  • Swelling at the injection site

More serious reactions like hypersensitivity or deep swelling, especially around the eyes, lips, or throat (angioedema), can also happen. Other side effects include:

  • Muscle and joint pain
  • Headache
  • Upper respiratory symptoms
  • Diarrhea

Inclisiran, so far, has not been linked to any severe adverse effects. The most frequent side effects include:

  • Injection site reactions
  • Joint pain
  • Urinary tract infections
  • Bronchitis
  • Diarrhea
  • Limb pain
  • Shortness of breath

Safety and Effectiveness

In studies involving people with heterozygous familial hypercholesterolemia (one faulty gene causing high cholesterol levels), alirocumab and evolocumab lowered LDL cholesterol by over 50% and 60%, respectively, with effects sustained throughout their study periods. Inclisiran reduced LDL by nearly 40%, although the reduction was 38.1% by the end of the study.

Among those with homozygous familial hypercholesterolemia (two faulty genes), evolocumab and alirocumab led to LDL reductions of about 31% and 27%. Inclisiran, however, did not lower LDL levels in this high-risk group, despite successfully reducing PCSK9 levels as intended.

These results reflect the complexity of treating this disorder. People with this condition usually can’t get their LDL to healthy levels, even when they take strong cholesterol-lowering medications like statins or ezetimibe.

4. Bile Acid Sequestrants

Our body uses cholesterol to make bile acids, which help digest fat. After digestion, most of these bile acids are recycled back into the liver to be used again.

Bile acid sequestrants work by attaching to bile acids in the intestines, preventing them from being reabsorbed. Instead, the bound bile acids leave the body through stool. To replace the lost bile acids, the liver makes more–and to do that, it needs more cholesterol.

To meet this demand, the liver pulls cholesterol from the bloodstream, which helps lower LDL cholesterol levels. Although the body may respond by making more cholesterol, much of it is redirected into bile acid production, so blood cholesterol levels still go down.

Types of Bile Acid Sequestrants

There are three bile acid sequestrants approved for use in the US, each with a slightly different range of effectiveness depending on the dose:

Bile Acid SequestrantsLDL-C Reduction
Colesevelam (Welchol®)15%-18% decrease
Colestipol (Colestid®)12%-24% decrease
Cholestyramine (Prevalite®, Questran®)7%-28% decrease

They can be taken on their own or combined with other cholesterol-lowering medications like statins or ezetimibe. Some people may even use them as part of a more intensive three- or four-drug plan.

One of the reasons these medications stand out is their compatibility with diabetes treatment. They’re safe to use alongside most anti-diabetic medications, and in some cases, they can also help improve blood sugar levels. This matters, especially since type 2 diabetes and high cholesterol often go hand in hand.

Colesevelam has been studied the most in this area. Not only did it bring down LDL-C, but it also led to improvements in HbA1c (a marker of long-term blood sugar control). These findings helped support its FDA approval for use in people with type 2 diabetes.

Side Effects

Bile acid sequestrants generally stay in the gut and are not absorbed into the bloodstream, so most side effects are limited to the digestive system. Common issues include:

  • Constipation
  • Bloating
  • Stomach pain
  • Indigestion
  • Nausea
  • Heartburn
  • Loss of appetite
  • Upset stomach

Constipation is especially common, affecting up to 28% of people taking cholestyramine and around 10% of those using colestipol.

These drugs can also reduce the absorption of fat-soluble vitamins, especially vitamin K. Over time, or with higher doses, this can lead to a deficiency. Since vitamin K is needed to produce clotting factors in the liver, low levels may increase the risk of bleeding.

Safety and Effectiveness

The Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT) was the first major trial to test whether lowering LDL cholesterol could prevent heart disease. Over 3,800 middle-aged men with high cholesterol but no symptoms were enrolled. One group took 24 g of cholestyramine a day, while the other got a placebo, and they were followed for about seven years.

Those on cholestyramine saw a 20% drop in LDL and a 19% lower risk of major heart events, including fewer deaths from coronary disease and fewer nonfatal heart attacks.

In patients with familial type II hyperlipoproteinemia (another genetic disorder causing very high LDL), colestipol reduced total cholesterol from about 413 mg/dL to 270 mg/dL and LDL from 331 mg/dL to 188 mg/dL. Many also experienced a decrease in xanthoma size (fat deposits under the skin) and showed stable artery plaque on follow-up scans, suggesting the condition had slowed.

⚠️ Important Considerations
One drawback of bile acid sequestrants is that they can interfere with how other medications are absorbed in the gut. To avoid unwanted interactions, other medications should be taken at least 4 hours before or after taking a bile acid sequestrant.

5. ACLY Inhibitors

ATP-citrate lyase (ACLY) is an enzyme that helps produce acetyl-CoA, a building block the liver uses to make cholesterol. ACLY inhibitors block this enzyme, leading to less cholesterol production in the liver.

To compensate, the liver pulls more LDL cholesterol from the bloodstream. This process works similarly to how statins lower LDL.

Types of ACLY Inhibitors

Bempedoic acid (Nexletol®) became the first ACLY inhibitor approved in the US in February 2020. It’s also available as a combination pill with ezetimibe under the brand name Nexlizet®. Bempedoic acid can lower LDL cholesterol by around 15% to 25%, whether taken on its own or alongside other cholesterol-lowering medications.

This drug is typically added to a statin regimen, especially for people with atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) who still need help getting their LDL levels down.

For those with diabetes who can’t tolerate statins, the American Diabetes Association’s 2024 guidelines recommend bempedoic acid as an effective alternative to help lower the risk of future heart events.

Side Effects

Bempedoic acid is a pro-drug, meaning it needs to be activated in the liver to work. It doesn’t get activated in muscle tissue, so it’s less likely to cause muscle side effects.

Mild symptoms may include:

  • Upper respiratory infections
  • Bronchitis
  • Muscle spasms
  • Back or abdominal pain

Serious side effects like hyperuricemia, gout, and tendon rupture can occur, but they’re uncommon.

Safety and Effectiveness

On its own, bempedoic acid lowers LDL cholesterol by about 21%. When paired with ezetimibe, the drop is even greater (around 36.2%).

In patients with HeFH already taking the highest statin dose they could tolerate, bempedoic acid lowered LDL cholesterol by 21%. By week 12, about 32% of those patients reached a healthy LDL level below 100 mg/dL.

⚠️ Important Considerations

When taking bempedoic acid or bempedoic acid/ezetimibe with other medications, certain interactions may affect safety or how well the drug works. Here are some key precautions:

➤ Statins: Avoid using with simvastatin doses over 20 mg or pravastatin over 40 mg, as this may increase the risk of muscle-related side effects.

➤ Cyclosporine (immunosuppressant): Co-use can raise cyclosporine levels in the blood. If both are prescribed, close monitoring is advised.

➤ Bile Acid Sequestrants: These may reduce the absorption of ezetimibe. To prevent this, take bempedoic acid/ezetimibe at least 2 hours before or 4 hours after bile acid sequestrants.

6. MTTP Inhibitors

MTTP is a protein found in the liver and intestines that helps the body package fats and release them into the bloodstream. MTTP inhibitors block this process, so the body produces fewer fat-carrying particles. This helps reduce LDL cholesterol and other blood fats linked to heart disease.

Types of MTTP Inhibitors

Lomitapide (Juxtapid®) is currently the only FDA-approved MTTP inhibitor. It’s used alongside a low-fat diet and other cholesterol-lowering medications to help reduce LDL, total cholesterol, apo B, and non-HDL cholesterol in adults with homozygous familial hypercholesterolemia (HoFH).

However, its safety and effectiveness haven’t been confirmed in people with high cholesterol who don’t have HoFH, including those with HeFH.

Side Effects

As expected, based on how it works, lomitapide often causes side effects in the digestive system and liver. Among the most reported adverse reactions are:

  • Diarrhea
  • Nausea
  • Vomiting
  • Indigestion
  • Abdominal pain

Safety and Effectiveness

Research showed that lomitapide lowered LDL cholesterol by an average of 50% after 26 weeks in adults with HoFH already taking the highest doses of cholesterol-lowering treatment, including LDL apheresis. The effect remained steady over time, with a 44% reduction at week 56 and 38% at week 78.

LDL apheresis is a medical procedure that filters LDL cholesterol directly out of the blood, similar to how dialysis filters waste in people with kidney failure.

⚠️ Important Considerations

Before starting and during lomitapide treatment:

➤ Check liver function: Measure ALT, AST, alkaline phosphatase, and total bilirubin to screen for potential liver toxicity, a known risk with lomitapide.

➤ Confirm a negative pregnancy test: Lomitapide can harm an unborn baby, so pregnancy must be ruled out before starting treatment.

➤ Start a low-fat diet: Limit fat intake to less than 20% of total daily calories to help reduce gastrointestinal side effects.

➤ Take daily nutritional supplements: To prevent deficiencies, patients should take supplements that include 400 IU of vitamin E, at least 200 mg of linoleic acid, 210 mg of alpha-linolenic acid (ALA), 110 mg of eicosapentaenoic acid (EPA), and 80 mg of docosahexaenoic acid (DHA).

7. ANGPTL3 Inhibitors

ANGPTL3 is a protein that gets in the way of how your body clears fats from the blood. When it’s active, fat particles, like those that carry cholesterol, stick around in the bloodstream longer than they should. ANGPTL3 inhibitors block this protein, allowing those fat-clearing enzymes to work normally again.

The exact mechanism of how it lowers LDL cholesterol isn’t completely clear.

Types of ANGPTL3 Inhibitors

Evinacumab (Evkeeza®) is the first and only FDA-approved ANGPTL3 inhibitor, initially approved in 2021 for use in adults and adolescents (aged 12 and older) with HoFH. In 2023, its approval was expanded to include pediatric patients aged 5 and older.

Like lomitapide (Juxtapid®), evinacumab is not approved for other forms of high cholesterol, such as HeFH. However, it has been studied in people with refractory hypercholesterolemia, a condition in which LDL levels remain high despite multiple cholesterol-lowering medications and lifestyle changes.

In one trial, subcutaneous and intravenous evolocumab reduced LDL cholesterol by 47% and 50% after 16 weeks, respectively.

Side Effects

Some people taking evinacumab have reported mild to moderate side effects, including:

  • Allergic reactions
  • Cold-like symptoms (like runny nose and sore throat)
  • Nausea
  • Flu-like feelings
  • Dizziness
  • Pain in arms or legs

Injection site reactions are also common and may include:

  • Redness
  • Pain
  • Bruising
  • Swelling
  • Itchiness where the shot was given

The most serious side effect reported in clinical trials was a severe allergic reaction (anaphylaxis), although this was rare.

Safety and Effectiveness

A 2020 study looked at patients with very high LDL cholesterol, averaging around 255 mg/dL, despite being on the strongest treatments available. After 24 weeks of evinacumab therapy, their LDL levels fell by 47%, while those on placebo saw a 2% increase.

Side effect profiles were comparable between groups, suggesting the treatment was generally well tolerated.

8. Triglyceride Lowering Drugs

Triglyceride-lowering drugs are used to bring down levels of triglycerides–a type of fat that circulates in your blood. When elevated, triglycerides can increase the risk of heart disease, pancreatitis, and metabolic syndrome.

While these medications mainly target triglycerides, many also reduce LDL cholesterol to some extent. Common options include:

Fibrates (Fibric Acid Derivatives)

Fibrates are commonly used to treat atherogenic dyslipidemia–a condition marked by high triglycerides, low HDL (good cholesterol), and sometimes elevated LDL.

In the US, available fibrates include:

  • Gemfibrozil (Lopid®)
  • Fenofibrate (Tricor®, Trilipix®, Lipofen®, and others)
  • Fenofibric acid (Fibricor®)

Fibrate therapy can affect LDL cholesterol in different ways. In people with very high triglyceride levels, it may temporarily raise LDL-C. However, when triglycerides aren’t severely elevated, LDL-C typically drops by 10-30%.

Most side effects are mild and tend to affect the digestive system or muscles. Common complaints include:

  • Upset stomach or indigestion
  • Nausea
  • Diarrhea
  • Abdominal discomfort
  • Back pain
  • Headache

However, fibrates are generally not recommended alongside statins, as they can interfere with how statins are broken down in the body. This interaction may increase the risk of muscle-related side effects, such as myopathy.

Niacin

Niacin, or vitamin B3, is a mix of nicotinic acid and nicotinamide. It’s been around since 1955, making it the oldest lipid-lowering medication. In fact, it was the first medication approved specifically for treating dyslipidemia.

Currently, Niacor® is the only brand-name prescription niacin still available in the US. However, there are also generic versions of both:

  • Immediate-release niacin
  • Extended-release niacin

In one study involving people with metabolic syndrome who weren’t taking statins, niacin lowered LDL cholesterol by 17%.

The most frequent side effect is flushing, which affects up to 85% of users. It typically shows up as redness and warmth, often across the face and neck, and may come with itching, tingling, or a burning feeling.

Niacin can also affect your blood sugar levels, even if you don’t have diabetes. If you’re not diabetic, using niacin long-term (around five years) may raise your risk of developing diabetes by about 34%. If you already have diabetes, niacin can increase your fasting blood sugar.

Because of these effects, it’s usually not recommended if you have diabetes and should be used with caution in metabolic syndrome.

Omega-3 Fatty Acid Ethyl Esters

The lipid-lowering effects of fish oil come from two omega-3 fatty acids–eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In the US, there are two FDA-approved prescription products that contain these compounds in different amounts:

  • Lovaza® – a combination of EPA and DHA
  • Vascepa® – contains only EPA

In patients with moderate hypertriglyceridemia already taking statins, Vascepa lowered LDL cholesterol by 6.2%. However, in other studies with very high triglyceride levels, fish oil was associated with a modest increase in LDL-C.

Common side effects of fish oil include:

  • Nausea
  • Diarrhea
  • Indigestion
  • Abdominal discomfort
  • Burping (eructation)

At very high doses, omega-3 fatty acids can reduce blood clotting, which might increase the risk of bleeding.

⚠️ Important Considerations

Niacin and omega-3 fatty acids (fish oil) are available both as prescription medications and over-the-counter supplements, but the two are not interchangeable. Supplement forms should not be used in place of prescription drugs, as they can carry serious risks and are not regulated in the same way.

Unlike prescription versions, dietary supplements aren’t monitored by the FDA. The actual amount of the active ingredient may differ significantly from what the label says. Even different batches from the same brand can vary.

Always consult your healthcare provider before starting any treatment, whether it’s for cholesterol or anything else.

Summary

Cholesterol-lowering medications help reduce the risk of heart attacks and strokes by lowering LDL (bad) cholesterol levels. Statins are the most commonly used and effective drugs for this purpose. If statins aren’t enough or aren’t well tolerated, other options like ezetimibe, PCSK9 inhibitors, bile acid sequestrants, ACLY inhibitors, MTTP inhibitors, and ANGPTL3 inhibitors may be added.

Each medication works differently. Some block cholesterol production, others prevent absorption, and some help remove it from the blood. Side effects vary, and some drugs may interact with others or require specific precautions.

The choice of treatment depends on how high your cholesterol is, your health conditions, and how you respond to medication. Always talk to your doctor to find the best and safest option for you.

FAQs About Cholesterol-Lowering Medications

What is the best medicine to reduce cholesterol?

Statins are widely regarded as the most effective drugs for lowering LDL cholesterol and reducing the risk of heart disease. In the studies referenced earlier, statins can lower LDL cholesterol by up to 50% or more, significantly reducing cardiovascular events. In some cases, additional medications like ezetimibe or PCSK9 inhibitors may be used if statins alone aren’t enough. Treatment choice depends on your risk factors and response to therapy.

What is the safest cholesterol-lowering medication?

Safety often depends on how you respond to a particular treatment. Among statins, pravastatin and fluvastatin are generally linked to a lower risk of muscle-related side effects. If you have trouble tolerating statins, options like ezetimibe or PCSK9 inhibitors might be considered, depending on your overall health. The safest and most suitable choice is best determined in consultation with your healthcare provider.

Sources

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