Bempedoic acid may be an alternative for people who need to lower their cholesterol but can’t or won’t take statins, according to a large study published Saturday in the New England Journal of Medicine.
Statins are the most commonly prescribed cholesterol-lowering drugs that help lower so-called “bad” cholesterol, or low-density lipoprotein (LDL) cholesterol in the blood; more than 90% of adults who take cholesterol-lowering medication use a statin, according to the US Centers for Disease Control and Prevention.
Statins are considered safe and effective, but there are millions of people who can’t or won’t take them. In some people, this causes intense muscle pain. Previous research has shown that between 7% and 29% of patients who need to lower their cholesterol do not tolerate statins, according to Dr. Steven Nissen, a cardiologist and researcher at the Cleveland Clinic and co-author of the new study.
“I see heart patients coming in with terrible histories, multiple myocardial infarctions, sometimes bypass surgery, lots of stents and they say, ‘Doctor, I’ve tried several statins, but every time I take a statin, my muscles hurt, or they’re weak. I can’t get upstairs. I just can’t tolerate these drugs,” Nissen said. “We need alternatives for these patients.”
Doctors have a few options, including ezetimibe and a monoclonal antibody called proprotein convertase subtilisin/kexin type 9, or PCSK9 inhibitors for short.
Bempedoic acid, sold as Nexletol, was designed specifically to treat patients intolerant to statins. The FDA approved it for this purpose in 2020, but the drug’s effects on heart health had not been fully evaluated before this large trial. The new study was funded in part by Esperion Therapeutics, the maker of Nexletol.
For the study, which was presented Saturday at the American College of Cardiology’s annual scientific session with the World Congress of Cardiology, Nissen and his colleagues recruited 13,970 patients from 32 countries.
All patients were statin intolerant, usually due to musculoskeletal adverse effects. Patients had to sign an agreement that they could not tolerate statins “even though I know they would reduce my risk of heart attack, stroke, or death,” and providers signed a similar statement.
The patients were then randomized into two groups. One was treated with bempedoic acid, the other was given a placebo, which did nothing. The researchers then followed these patients for almost five years. The number of men and women in the trial was mostly evenly split, and most participants, about 91%, were white and 17% were Hispanic or Latino.
The drug works in a similar way to statins, drawing cholesterol out of a waxy substance called plaque that can build up in artery walls and interfere with blood flow to the heart. If there is too much plaque buildup, it can lead to a heart attack or stroke.
But bempedoic acid is only activated in the liver, unlike a statin, so it’s unlikely to cause muscle pain, Nissen said.
In the trial, researchers found that bempedoic acid was well tolerated and that the percentage reduction in “bad” cholesterol was 21.7% greater with bempedoic acid than placebo.
The risk of cardiovascular events – including death, stroke, heart attack and coronary revascularization, a procedure or surgery to improve blood flow to the heart – was 13% lower with bempedoic acid compared to placebo over a median of 3.4 years.
“The drug worked in both primary and secondary prevention patients – that is, patients who had had an event and patients who were at very high risk for a first event. There were a lot of diabetics. they were people at very high risk,Nissen said. “So the drug lived up to his expectations and probably did a lot better than a lot of people thought it would.”
In the group that took bempedoic acid, there were a few more cases of gout and gallstones, compared to people who took a placebo.
“The number is small, and comparing it to a heart attack, I think most people would say, ‘OK, I’d rather have a little gout attack,'” Nissen said.
Bempedoic acid had no observed effect on mortality, but that may be because the observation period was too short to say whether it had that kind of impact. Previous statin trials have shown the same; it was only after several studies on statins that scientists were able to show an impact on mortality.
Dr. Howard Weintraub, a cardiologist at NYU Langone Health who did not work on this study, said that while he knows some people won’t see a drug as effective unless it reduces mortality, he thinks that is shortsighted.
“I think there’s more to doing medicine than counting body bags,” Weintraub said. this is a good thing.”
He was thrilled to see the results of this trial, especially since the people in this study are often what he calls “forgotten individuals” – the millions who could benefit from lowering their cholesterol, but who cannot take statins.
“It’s not like their LDL is 180 or 190 or 230, their LDL is 139. That’s about the average in our country,” Weintraub said. He said doctors often just tell these patients to watch their diet, but he thinks that suggests they would benefit from medication.
“Both the primary and secondary prevention groups achieved benefits, which I think is impressive with the modest amount of LDL reduction,” Weintraub said.
There are some limitations to this test. It was narrowly focused on patients with known intolerance to statins. Nissen said the lawsuit was not designed for to determine whether bempedoic acid could be an alternative to statins.
“Statins are the gold standard. They are the cornerstone. The purpose of this study was not to replace statins, but to provide an alternative therapy for people who simply cannot take them,” said Nissen said.
Bempedoic acid is a much more expensive drug than a statin. There are generic versions of statins and some cost just a few dollars. Bempedoic acid, on the other hand, has no generic alternative and a 30-day supply can cost upwards of $400, according to GoodRx.
“I think insurance companies need to recognize that while this drug will cost more than statins, having a heart attack or stroke or needing a stent is expensive. A 23% reduction (in myocardial infarctions) is a huge reduction,” Weintraub said.
In an editorial in the New England Journal of Medicine that accompanied the study, Dr. John H. Alexander, who works in the division of cardiology at the Duke Clinical Research Institute, Duke Health, Durham said physicians should take these findings into consideration. during processing. patients with high cholesterol who cannot take statins.
“The benefits of bempedoic acid are now clearer, and it is now our responsibility to translate this information into better primary and secondary prevention for patients most at risk, who will thus benefit from fewer cardiovascular events”, Alexander wrote.
Dr. Manesh Patel, a cardiologist and American Heart Association volunteer who was not part of the study, said providers already prescribe bempedoic acid to some patients, but with this new research, he thinks they will soon be used with more patients intolerant to statins.
“We continue to see that if we can significantly lower your LDL levels, we improve people’s cardiovascular health. And so we need so many different arrows in our quiver to try to achieve that,” Patel said.
Heart disease is the leading cause of death for men and women worldwide. One person dies every 34 seconds in the United States from cardiovascular disease, according to the CDC. About 697,000 people in the United States died of heart disease in 2020 alone, roughly the same number as the population of Oklahoma City.
“Given the number of people eligible for statins, which are already tens of millions of patients, the number of people who cannot tolerate statins is in the millions,” Nissen said. “It’s a big public health issue and I think we’ve found something that directly addresses it.”