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Secrets to a Healthy Heart

Debunking Statin Myths

The truth about side effects — and how to get more out of these cholesterol-lowering medications

Box of statin drugs against a background of an EKG and cholesterol panel..

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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 recent 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 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 this “bad” cholesterol, 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 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, stroke and peripheral artery disease are being prescribed the recommended statin therapy, according to a 2020 study in JAMA Network Open. And only slightly more than half (or 43 million) adults who could benefit from cholesterol medication are currently taking it, according to the Centers for Disease Control and Prevention (CDC).

Some of the hesitation comes from 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 watch and report back if they have muscle problems, which appear in about five percent of patients. But awareness of the potential for this symptom and other symptoms like digestive problems have its own affects, 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 recent 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 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., president-elect of the American Heart Association and 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 largest 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.

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,” he adds.

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 they 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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A patient's perspective: Having success with a PCSK9 inhibitor

Roberta Sutter, 63, says she long worried that she'd suffer a heart attack, like her father. With a genetic mutation that contributes to her high cholesterol, she had reason to worry. After her total cholesterol hit 300 and her LDL 200, medications helped bring down those numbers to 166 and 100.

Already on the maximum dose of a statin, her doctor recommended last year that she start on the medication evolocumab (Repatha). It's one of two, easy-to-use non-statin medications on the market that help the liver break down excess cholesterol.

Sutter administers the injection to herself once every month with a device like an EpiPen, pushing a button to trigger the needle to penetrate her skin, which expels the medicine.

Three months after Sutter started taking the medicine in addition to her statin, her LDL dropped to 34, something she says she's grateful for. “I planned my whole life thinking I would have a short life span because I had this cholesterol problem … but I actually got to meet my grandson,” she says.

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 their 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 five 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 a high LDL that can't be controlled by statins, or 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, which 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 to use.

  • Leqvio was just approved for use in Europe in December 2020, but it is not approved yet in the U.S. It can be used alone or in combination with statins to lower LDL. It completely blocks the production of PCSK9 (that problematic liver protein that otherwise raises cholesterol.) “It's a potential revolution in cholesterol control” because it can be given every six months at your doctor's office, after two starter doses 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. It's not yet known if it will reduce cardiac events as much as the PCSK9 inhibitors do, but ongoing clinical trials that wrap up in March 2022 will hopefully determine that. Lloyd-Jones calls this medication a “niche drug” and says “it's always good to have more in the armamentarium for patients who can't tolerate other drugs."