An alternative to statins may help reduce deaths from heart disease among people with high levels of LDL, or “bad” cholesterol, new research finds.
When taken as a daily pill, bempedoic acid lowered LDL cholesterol and showed a significant 39% reduction in heart disease deaths and heart attacks, researchers reported Saturday at the American Diabetes Association’s annual meeting. The findings were simultaneously published in JAMA.
“What we saw really surprised me,” said the study’s lead author, Dr. Steven Nissen, chief academic officer of the Heart, Vascular & Thoracic Institute at the Cleveland Clinic. “I hope this will be a wake-up call for patients and physicians.”
Right now, fewer than half the people who should be prescribed a cholesterol-lowering medication because of heart disease risk are getting it, according to Nissen. That needs to change, he said.
“Treating people who have risk factors before their first cardiovascular event would have large benefits,” not just in preventing complications but also in preventing deaths, he said.
What is a healthy level of cholesterol?
Bempedoic acid, which was approved in 2020 by the Food and Drug Administration, is not as effective as statins, which are considered the gold standard in treating high cholesterol. However, many people stop or refuse to take statins because of possible side effects such as muscle pain, headaches, sleep problems and digestive problems.
Recent research found that about 20% of people at high risk for heart disease refuse to take statins when prescribed by their doctor. Women in particular were less likely to accept a statin prescription, according to the study published in JAMA Network Open.
Although the new study looked at only the impact of bempedoic acid on people who had adverse reactions to statins, it found that lowering cholesterol resulted in a significant decrease in heart attacks and heart-disease related deaths.
What’s most important is to get blood cholesterol to healthy levels, whether by taking a statin or bempedoic acid or other lipid-lowering medication, Nissen said in an interview.
More on heart health
LDL, or low density lipoprotein, is the type of cholesterol that contributes to the buildup of fatty deposits in the arteries and raises the risk of cardiovascular events, such as heart attack and stroke. 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.
The 4,206 patients enrolled in the new study are part of a larger group described in a New England Journal of Medicine article in March. The NEJM study included both patients who had experienced a cardiovascular event, such as a stroke or heart attack, as well as those who only had risk factors.
In the new research, Nissen and his colleagues focused only on participants who had never been diagnosed with heart disease, but were at high risk because of factors such as high LDL, diabetes and hypertension.
The average age of the participants in the new study was 68, and 59% were women. Two-thirds had diabetes. At the outset, the average LDL level in the participants was 142.5 mg/dL.
Six months into the study, compared with patients taking a placebo, participants who received a daily dose of bempedoic acid experienced a 23.2% reduction in LDL cholesterol and a 22.7% decrease in inflammation caused by a protein in the blood associated with heart and stroke risk.
Other key findings of the study, which tracked most participants for a little more than three years, showed that:
- Risk of heart attacks among people who received the medication were cut by 39%.
- Risk of heart disease-related death had been reduced by 39%.
- The combined risk of a patient dying, having a heart attack or a stroke had been cut by 36%.
There was a small increased risk of complications in those who were treated with bempedoic acid versus placebo, including the development of gout and gallstones.
Statins as ‘first-line therapy’
While bempedoic acid may not cause as many muscle-related symptoms, it is more expensive than generic statins, Dr. Druv S. Kazi, a cardiologist, noted in an editorial accompanying the JAMA study.
“Patients are likely to face substantially higher out-of-pocket costs for bempedoic acid than for a generic statin,” Kazi wrote.
Sheldon Koenig, CEO and president of Esperion, which makes the medication sold as Nexletol and funded the study, said the drug is now covered by many insurance companies.
“For Medicare, the company has preferred status and the copay is generally only $45 per month,” Koenig said.
The new findings are “exciting and very promising,” said Dr. Marc Eisenberg, a cardiologist and an associate professor of medicine at Columbia University’s Vegelos College of Physicians and Surgeons. “But statins should still be offered and tried as a first-line therapy.” Eisenberg was not associated with the new study.
While the study is “well designed,” Eisenberg said, “we still need more studies.”
These “are very important findings,” said Dr. Robert Rosenson, director of metabolism and lipids for the Mount Sinai Health System and a professor of medicine at the Icahn School of Medicine at Mount Sinai.
The benefits seen in the new study are greater than you would expect simply based on the reductions seen in LDL level, said Rosenson, who was not associated with the research.
The new study reinforces the idea that “targeting LDL cholesterol reduces cardiovascular risk,” said Dr. Jeffrey Berger, director of the Center for the Prevention of Cardiovascular Disease at NYU Langone Health.
Patients with risk factors, such as high LDL and diabetes, but who haven’t yet been diagnosed with cardiovascular disease “are the largest group of patients we take care of,” Berger said. Berger was not part of the new study.
For people who can’t or won’t take statins, bempedoic acid offers an alternative, Berger said.
“But I do think it’s important to recognize that there are important side effects with this drug. Like everything in medicine, there are risks and benefits,” Berger said.
