For people with high cholesterol, lifestyle modifications such as eating better, getting more exercise, losing weight and reducing stress can help curb cardiovascular risk…to some extent. But to substantially lower elevated cholesterol and its attendant risk for heart attack and stroke, long-term use of a prescription cholesterol-lowering medication may be necessary, says Cleveland Clinic cardiovascular disease expert Steven Nissen, MD.
Our bodies produce two main types of cholesterol—high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol. Elevated levels of LDL cholesterol (sometimes referred to as “bad” cholesterol) raise the risk for heart attack and stroke by causing circulation-blocking waxy deposits to form in arteries. For that reason, it’s the primary target of cholesterol-lowering drugs.
High levels of HDL cholesterol (sometimes called “good” cholesterol) are associated with lower cardiovascular disease risk, which was previously attributed to removing cholesterol from artery walls. But this effect is more uncertain than once thought, and doctors now consider HDL cholesterol levels to be less important in assessing cardiovascular risk. HDL cholesterol is not a primary target of cholesterol-lowering drugs.
Statin drugs are, by far, the most prescribed cholesterol-lowering drugs, having largely supplanted older drugs. Statins help stop waxy LDL cholesterol from accumulating in and clogging arteries by curbing its synthesis in the liver and promoting its removal from the bloodstream. Taken orally, statins are much more effective than older oral medications and have an excellent safety profile, though they generally aren’t prescribed for people with severe liver disease such as cirrhosis.
Seven statins have been approved for treatment of high LDL cholesterol. Which one makes sense for you depends upon several factors, including how high your cholesterol levels are, other medications you are taking and whether you have already suffered a heart attack or stroke.
Moderate-intensity statins. There are five moderate-intensity statins, including atorvastatin (at a dose of 10 mg to 20 mg)…rosuvastatin (5 mg to 10 mg)…simvastatin (20 mg to 40 mg)…pravastatin (40 mg to 80 mg)…and pitavastatin (2 mg to 4 mg). These are best for people whose elevated cholesterol levels and medical history place them at moderate cardiovascular risk.
High-intensity statins atorvastatin (Lipitor, 40 mg or 80 mg) and rosuvastatin (Crestor, 20 mg or 40 mg) often are good options for people who already have had a cardiovascular event and others at especially high risk.
At their maximum dosages, statins can cut LDL cholesterol by up to 55%. When a statin alone isn’t enough to do the trick, adding the cholesterol-absorption inhibitor ezetimibe (Zetia) can get levels even lower.
Caution: Statin drugs can cause a range of mild side effects, including headache, nausea and fatigue. Some people who take a statin develop muscle pain (myalgia)…and perhaps one in 10,000 people who take a statin develop the potentially serious condition rhabdomyolysis, in which muscle tissue breaks down.
Good news: Switching from one statin to another often can ease side effects if they arise.
If switching statins fails to bring relief from bothersome side effects—or if cholesterol levels remain high despite the use of a statin—doctors sometimes add or substitute the oral drug bempedoic acid (Nexletol) or one of a class of injectable drugs known as PCSK9 inhibitors.
Bempedoic acid isn’t quite as effective as statins at lowering cholesterol levels, but it is better tolerated. PCSK9 inhibitors also are better tolerated than statins and equally effective at reducing cholesterol levels. (PCSK9 inhibitors cost much more than statins and so generally are not used as initial treatment.)
PCSK9 inhibitors are often added to statins for people with familial hypercholesterolemia, a particularly severe, inherited form of stubbornly high cholesterol.
Two PCSK9 traditional inhibitors are available: Alirocumab (Praluent) and evolocumab (Repatha). A newer injectable medication called inclisiran (Leqvio) is a PCSK9 inhibitor but works by blocking production of the PCSK9 protein and is administered every six months. It’s another good option when statins and PCSK9 inhibitors aren’t enough or are causing troublesome side effects.
LDL cholesterol below 100 milligrams/deciliter is considered healthy. Individuals whose levels or a history of cardiovascular disease place them at high cardiovascular risk should generally aim for a much lower number to keep heart trouble at bay. The National Lipid Association, a nonprofit medical society that helps doctors optimize the management of cholesterol and other lipids, now recommends getting LDL cholesterol below 55 mg/dl for very high-risk patients…and still lower levels can bring greater risk reduction.
When setting LDL cholesterol targets for their patients, cardiologists often check for so-called risk-enhancing factors, including rheumatoid arthritis, high levels of an inflammatory marker called C-reactive protein and increased levels of a particularly dangerous of cholesterol particle known as lipoprotein(a).
