Statin drugs are the gold standard when it comes to reducing LDL, or ‘bad’ cholesterol, but many patients at risk for heart disease refuse to take them because of severe side effects, such as muscle pain or weakness.
An alternative medication, bempedoic acid, significantly lowers cholesterol and the risk of heart attacks, as well as reducing the need for a procedure that unblocks clogged arteries, according to a large clinical trial presented Saturday at the annual meeting of the American College of Cardiology. The research was published Saturday in the New England Journal of Medicine.
“Statins are the cornerstone of cardiovascular disease prevention, and they are recommended to a large number of people who either have or are at risk for cardiovascular disease,” said the study’s lead author, Dr. Steven E. Nissen, chief academic officer of the Heart and Vascular Institute at the Cleveland Clinic. “Anywhere from 7% to 29% of patients experience adverse effects they can’t tolerate. The primary problem is muscle pain.”
These patients won’t do well if they can’t get their cholesterol down, Nissen said. Bempedoic doesn’t cause muscle side effects because it’s not activated in the muscle and other tissues around the body, he explained. Until the medication gets to the liver, it’s not activated at all.
LDL, or low density lipoprotein, cholesterol contributes to fatty buildups in the arteries, raising the risk of heart attacks and strokes. Lowering LDL is a major way of protecting against heart disease, the leading cause of death for men and women in the United States. According to the American Heart Association, the optimal total cholesterol level for an adult is about 150 mg/dL, with LDL levels at or below 100 mg/dL.
Bempedoic acid, which is already approved by the Food and Drug Administration, has been previously shown to lower cholesterol when used in combination with statins.
In the new trial, Nissen and his colleagues recruited 13,970 patients who couldn’t tolerate statins and randomly assigned them to receive a daily dose of bempedoic acid or a placebo. At the beginning, the patients’ average LDL cholesterol level was 139.0.
At the end of six months, LDL cholesterol levels had dropped by 29.2 points. At the end of the follow-up period, which lasted a median of 40.6 months, the risk of heart attacks among the patients who received the medication had been cut by 23%, while the risk of needing cardiac revascularization (the procedure to clear clogged arteries) was cut by 19%.
There was a small increased risk of complications, including gout and gall stones, in patients who got the medication versus those who received placebos.
The researchers found that, compared with people in the placebo group, patients who took bempedoic acid had a combined 13% lower risk of death from cardiovascular disease, nonfatal strokes and nonfatal heart attacks.
Rather than focusing simply on cholesterol levels, the researchers were looking at data that might be more meaningful to patients — the risk of heart attacks, for example — which Nissen hopes will encourage more patients to take a cholesterol-lowering drug.
Esperion, the company that makes and markets bempedoic acid, sells it alone or coupled with a second cholesterol-lowering medication, called ezetimibe. Both versions are priced at $395 per month, said Dr. JoAnne Foody, a cardiologist and chief medical officer at Esperion.
”We are not looking to supplant statins,” Foody said. “They are the first-line therapy. Anyone who can get on statins, should.”
Bempedoic acid may not be as effective as statins, but could be a life-saving medication for people at risk for cardiovascular disease but who can’t or won’t take statins, said Dr. Howard Weintraub, clinical director of the Center for the Prevention of Cardiovascular Disease at the Leon H. Cheney Division of Cardiology at NYU Langone Health.
Dr. Marc Eisenberg welcomed the new research.
“This is an exciting study, but at this time statins are still the best treatment for most people with high cholesterol and cardiovascular risk factors,” said Eisenberg, a cardiologist and associate professor of medicine at Columbia University Vagelos College of Physicians and Surgeons.
“More studies comparing bempedoic acid and established medications like statins and ezetimibe in head to head trials will be very useful in the future,” Eisenberg said in an email.
Dr. Robert Rosenson cautioned against doctors and patients seeing bempedoic as equivalent to statins.
“Bempedoic acid is not a replacement for statin therapy,” Rosenson, a professor of medicine at the Icahn School of Medicine at Mount Sinai in New York, said. "The LDL-lowering efficacy and reductions in cardiovascular events were modest and less than with statins.”