Secrets to a Healthy Heart
Debunking Statin Myths
The truth about side effects — and how to get more out of these cholesterol-lowering medications
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En español | You know high cholesterol is not a good thing. But just how dangerous it can be was driven home in a 2019 study in the Journal of the American Heart Association. Scientists following 3,875 adults for 35 years found that those with long exposure to high LDL cholesterol — often called “bad” cholesterol — had five times the rate of cardiovascular disease and four times the mortality of individuals with optimal LDL levels.
While the best way to lower LDL, which clogs arteries and is a significant cause of heart attack and stroke, is through diet and exercise, statins are the accepted second line of defense. And with good reason, says Nihar Desai, M.D., associate professor of medicine at the Yale School of Medicine in New Haven, Connecticut. “The data to support their use is overwhelming,” he says. “They’re highly effective at reducing the risk of cardiac disease and cardiac events like a heart attack.”
Yet only about 60 percent of people with coronary artery disease and peripheral artery disease, or who have had a stroke, are being prescribed the recommended statin therapy, according to a 2020 study in JAMA Network Open. And only slightly more than half (or 47 million) the adults who could benefit from cholesterol medication are currently taking it, according to the Centers for Disease Control and Prevention.
Some of the hesitation comes from concerns about potential side effects, which many doctors say have been overblown. Here’s a closer look at common concerns with statins like atorvastatin (Lipitor), pravastatin (Pravachol), rosuvastatin (Crestor) and simvastatin (Zocor) — and when you need to worry, or not.
CONCERN: Statins can have a lot of side effects, including muscle pain, digestive problems and liver damage.
REALITY: Patients who take statins are often told by their doctors to report back if they have muscle problems, which appear in about 5 percent of patients. But awareness of the potential for this symptom and others, like digestive problems, can have its own effect, says Roger S. Blumenthal, M.D., professor of medicine at the Johns Hopkins University School of Medicine and director of the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease in Baltimore, who explains that what may be at play is a kind of twist on the placebo effect, called the nocebo effect.
A study reported in The New England Journal of Medicine in November 2020 found evidence for this idea. Researchers conducted a blinded trial of statins versus a placebo, or no treatment, among 60 patients who had abandoned statins because they had what they judged to be serious side effects. In patients who discontinued statin therapy because of side effects, 90 percent of the symptoms caused by the statins were also caused by the placebo.
When patients complain of muscle problems, Blumenthal often stops their medication for a bit and then restarts it to see if it is still intolerable. Some patients will do better taking statins every other day, or at a lower dose, he says.
Donald Lloyd-Jones, M.D., chair of the Department of Preventive Medicine at Northwestern University Feinberg School of Medicine in Chicago, says that in general, atorvastatin (Lipitor) and rosuvastatin (Crestor) are among the best-tolerated statins and also have the greatest LDL-lowering effect and best safety profile.
Liver issues are another reported side effect of statins. Lloyd-Jones says that this problem occurs in patients who already have fatty liver, a metabolic disorder that causes fat buildup in the liver. Rarely do patients get earlier, mild liver inflammation from statins, he says.
The U.S. Department of Health and Human Services notes that serious risks are rare with statins, and that studies involving thousands of people show no differences in muscle aches and liver abnormalities between those taking a statin and those on an inactive pill.
CONCERN: Statins cause diabetes.
REALITY: Statins can increase the risk of developing diabetes by about 30 percent in people already at risk for the disease or who have prediabetes, according to a 2017 study in a British medical journal.
“People with normal blood sugar do not develop diabetes because you put them on a statin. These people were going to become diabetic anyway. Maybe we accelerated their diabetes slightly,” says Lloyd-Jones. “We don’t prevent diabetes by withholding statins. We do it with lifestyle changes.”
CONCERN: Statins cause dementia, or cognitive dysfunction.
REALITY: There have been many studies on the use of statin medications to prevent heart attacks that have shown that the statins don’t cause cognitive problems, including dementia. In fact, they have been shown to prevent dementia with long-term use.
In a study reported in Scientific Reports in 2018, researchers found that statin users without baseline cognitive problems had between a 15 and 26 percent reduced risk of developing dementia and mild cognitive dysfunction.
“It’s extremely rare that statins are associated with a change in mental status, quite rare in fact, because statins prevent little strokes that add up to dementia,” says Lloyd-Jones.
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Getting Better Results With a Second Rx
If you’re taking a statin as prescribed to lower your bad cholesterol, cheers to you. But you should also know that statins are no longer your only Rx option. Designed either to work with statins or on their own, newer PCSK9 inhibitors lower LDL even further — and don’t have to be taken every day. They also appear to have very few side effects, one reason cardiologists we talked to called them “exciting” and “revolutionary” for their field.
How much more bang do they give for the buck? When used alongside statins, they can lower cholesterol by as much as 70 percent compared to the 50 to 60 percent reduction statins alone provide.
These medications — called alirocumab (Praluent), evolocumab (Repatha) and inclisiran (Leqvio) — could also be a good option on their own if you’re one of the 5 to 10 percent of patients who can’t tolerate statins.
Here is what they can do for you.
• Repatha and Praluent. These drugs were approved for use in 2015 and are the most potent non-statin drugs to come to market, says Lloyd-Jones. Studies have shown that they can lower the risk of serious cardiac events, such as heart attack and stroke, by 15 percent compared with a placebo. They’re recommended for people with high LDL levels that can’t be controlled by statins, or those who have a genetic condition called familial hypercholesterolemia, which can cause dangerously high cholesterol levels. They’re novel monoclonal antibodies, or proteins made in the lab, that target and inactivate a protein in the liver that can block your body from sweeping away excess LDL cholesterol. A bonus is that both drugs, known as PCSK9 inhibitors, can be self-administered by an easy injection once or twice a month. The hitch is that they can be expensive.
• Leqvio. Federally approved in the U.S. in December 2021, this drug completely blocks the production of PCSK9 (that problematic liver protein that otherwise raises cholesterol). “It’s a potential revolution in cholesterol control” because after two starter doses, it can be given every six months at your doctor’s office, says Lloyd-Jones. In addition, its efficacy is comparable to other medications.
• Nexletol. This is an oral, once-daily non-statin medication for lowering LDL cholesterol. It’s not technically a PCSK9 inhibitor but works in a similar way by limiting your liver from producing cholesterol. It’s not as effective as the above injectable medications — when combined with Zetia, another non-statin, it lowered cholesterol by 36 percent. However, it is very well tolerated by patients, with minimal side effects, such as muscle aches. A new study published in The New England Journal of Medicine in March 2023 found that treatment with Nexletol was associated with a lower risk of major cardiac events.
Editor’s note: This story was updated with new information on March 31, 2023.