The most widely used cholesterol medications are statins, and they dominate the top of any prescribing list. Atorvastatin (Lipitor) and rosuvastatin (Crestor) are the two most commonly prescribed cholesterol drugs in the United States, followed by simvastatin (Zocor), ezetimibe (Zetia), and several newer options that work through entirely different mechanisms. Here are the 10 cholesterol medications you’re most likely to encounter, how they work, and what sets each one apart.
1. Atorvastatin (Lipitor)
Atorvastatin is the single most prescribed cholesterol medication in the country. It’s a high-intensity statin, meaning it can lower LDL (“bad”) cholesterol by 41% to 55% depending on the dose. At its highest dose, it falls into the 51-55% reduction range. Your liver produces most of your body’s cholesterol, and atorvastatin works by blocking the enzyme responsible for that production. With less cholesterol being made, your liver pulls more LDL out of your bloodstream to compensate.
2. Rosuvastatin (Crestor)
Rosuvastatin is the most potent statin available. At its highest dose, it can reduce LDL cholesterol by 56-60%, making it the go-to choice when aggressive lowering is needed. Even at a moderate dose, it achieves reductions of 41-50%. It’s typically prescribed for people with established heart disease, very high cholesterol (190 mg/dL or above), or diabetes with additional risk factors. Rosuvastatin and atorvastatin together account for the vast majority of statin prescriptions.
3. Simvastatin (Zocor)
Simvastatin is an older, less potent statin that lowers LDL by roughly 26-50% across its dose range. It was once one of the most prescribed cholesterol drugs in the world, and it remains widely used today, particularly at lower doses. One important note: the FDA recommends against starting new patients on the highest dose (80 mg) due to an increased risk of muscle injury. People who’ve already been taking that dose for over 12 months without problems can continue, but doctors generally won’t prescribe it to someone new at that level.
4. Pravastatin
Pravastatin is a lower-intensity statin often chosen for people who need a gentler option. It’s less likely to interact with other medications because it’s processed differently by the body than most other statins. This makes it a common choice for people taking multiple prescriptions.
5. Ezetimibe (Zetia)
Ezetimibe works in a completely different way from statins. Instead of blocking cholesterol production in the liver, it blocks cholesterol absorption in your small intestine. On its own, ezetimibe lowers LDL by about 18%, which is modest compared to statins. Its real power comes from combining it with a statin, where it adds another 21-30% reduction on top of what the statin already achieves. Current guidelines recommend adding ezetimibe for people whose LDL stays at 100 mg/dL or higher despite being on the strongest statin dose they can tolerate.
6. Evolocumab (Repatha)
Evolocumab belongs to a newer class called PCSK9 inhibitors. Your liver has receptors on its surface that grab LDL particles and pull them out of your blood. A protein called PCSK9 normally breaks down those receptors, reducing their numbers. Evolocumab blocks that protein, so more receptors stay active and more LDL gets cleared. The result is dramatic: LDL reductions of roughly 50%, and up to 70% in some studies. Evolocumab is given as an injection, either every two weeks or once a month.
7. Alirocumab (Praluent)
Alirocumab works through the same PCSK9-blocking mechanism as evolocumab and achieves similar LDL reductions. It’s also a self-administered injection given every two to four weeks. Both PCSK9 inhibitors are generally reserved for people with very high cardiovascular risk, familial (inherited) high cholesterol, or those who can’t tolerate statins well enough to reach their cholesterol goals.
8. Inclisiran (Leqvio)
Inclisiran is the newest entry on this list and represents a different approach to the same target. Rather than blocking the PCSK9 protein after it’s made, inclisiran uses a technology called small interfering RNA to prevent liver cells from producing PCSK9 in the first place. In clinical trials, it lowered LDL by 48-52% compared to placebo. The biggest practical advantage is the dosing schedule: after an initial injection and a second one at three months, you only need an injection every six months. That means just two or three shots a year, administered in a clinic rather than self-injected at home.
9. Bempedoic Acid (Nexletol)
Bempedoic acid is a daily pill designed for people who can’t tolerate statins. It blocks an enzyme involved in cholesterol production, similar to how statins work, but at an earlier step in the process. Because of where it acts, it’s only active in the liver and not in muscle tissue, which is why it’s less likely to cause the muscle pain that drives many people away from statins. Side effects can include back pain, muscle spasms, and pain in the hands or feet. Less commonly, it can trigger gout flares or tendon problems. A combination pill that pairs bempedoic acid with ezetimibe (sold as Nexlizet) is also available for people who need both.
10. Fenofibrate (Antara, Lipofen)
Fenofibrate is a fibrate, a class of drugs that primarily targets triglycerides rather than LDL cholesterol. It speeds up the breakdown of triglyceride-rich particles in the blood and can also raise HDL (“good”) cholesterol, particularly in people whose HDL is low to begin with. Fenofibrate is often prescribed alongside a statin for people whose triglycerides remain elevated even after LDL is under control. Its close relative, gemfibrozil (Lopid), works similarly but is used less often because it has more drug interactions with statins.
Statin Side Effects and Intolerance
Since seven of the medications above are statins or statin-related, muscle symptoms deserve a closer look. Muscle aches and weakness are reported by 5-25% of statin users in real-world studies, though the rate in controlled trials is lower. The spectrum ranges from mild soreness to, very rarely, a serious condition where muscle tissue breaks down. Doctors define statin intolerance as experiencing side effects that go away when the dose is reduced or stopped, after trying at least two different statins including one at its lowest available dose. If you fall into that category, options like ezetimibe, bempedoic acid, or PCSK9 inhibitors can still bring your cholesterol down significantly without statins.
How Doctors Choose Between Them
The decision starts with your cardiovascular risk. Current guidelines use a risk calculator that estimates your chance of a heart attack or stroke over the next 10 years, placing you in a low (under 3%), borderline (3-5%), intermediate (5-10%), or high (10% or above) risk category. People at intermediate or high risk are typically started on a statin. Those at borderline risk may be offered one if they have additional factors like elevated inflammation markers or calcium buildup in their coronary arteries detected on a CT scan.
For most people, a statin alone is enough. If it’s not, ezetimibe is usually added next. PCSK9 inhibitors or inclisiran come into play when LDL remains stubbornly high despite those first two steps, or when someone has inherited a genetic form of high cholesterol. Bempedoic acid fills the gap for people who genuinely can’t take statins. Fenofibrate addresses a different problem altogether, targeting triglycerides when they’re the main concern.