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A new study reinforces the importance of lowering cholesterol in people at risk for, but who haven’t had a heart attack or stroke.
The study looked at a statin alternative, called bempedoic acid, and found that as it reduced levels of LDL cholesterol, it also lowered the risk for heart attack, stroke and death.
Researchers are quick to say bempedoic acid shouldn’t be used instead of statins.
It’s far more expensive and doesn’t have the decades-long track record of safety and effectiveness. But for people who can’t tolerate statins or a high enough dose to bring their cholesterol levels down adequately, the new study suggests it’s important to find alternatives, and that bempedoic acid can be at least part of the solution.
Having high cholesterol along with diabetes, obesity, tobacco use or high blood pressure puts people at risk for heart attack and stroke. But less than half of those at high risk are taking appropriate medication, said Dr. Steven Nissen, the Cleveland Clinic cardiologist who led the new research, which is being presented Saturday at the American Diabetes Association annual conference in San Diego.
“I think this is a wake-up call to the medical community and to patients that people who have high cholesterol and risk factors need to be treated,” Nissen said.
Dr. Christie Ballantyne, director of the center for cardiometabolic disease prevention at Baylor College of Medicine in Houston, said he sees the study as “good news.”
“You can get your LDL down if you can’t get a statin,” said Ballantyne, who was not involved in the research. “I think that’s an important message to the public.”
Take the findings with a grain of salt
The research was a follow-on to a large study looking at bempedoic acid Nissen published earlier this year. That finding showed in 14,000 patients that bempedoic acid was a viable alternative to statins for people who can’t take the cheaper, more established drugs.
The study looked at a subset of 4,200 of those people, who hadn’t yet had a major cardiac event like a heart attack or stroke. The half who took bempedoic acid were 39% less likely to die from a cardiac event over the next three-and-a-half years than those who received a placebo, a result Nissen called “simply stunning.”
Preventive cardiologist Dr. Salim Virani, who was not involved in the study, agreed with Nissen’s message but was more cautious about the current findings.
Virani, who is affiliated with Texas Heart Institute and is vice provost for research at Aga Khan University in Pakistan, puts less stock in the details of the results because it relied on a subset of trial participants, who might not be representative.
In the group who hadn’t had a heart attack or stroke, more people dropped out of the trial if they received a placebo than if they received bempedoic acid.
Those people might also be less likely to follow healthy lifestyle recommendations and therefore be more likely to have a heart attack or stroke, Virani said, perhaps accounting for what looks like a better outcome among those who took the drug.
“These groups are inherently a little different,” he said.
Drawing conclusions from a subgroup can be misleading, agreed Dr. Rita Redberg, a cardiologist at the University of California, San Francisco and editor-in-chief of the journal “JAMA Internal Medicine.” She cited a famous 2011 study where researchers found aspirin prevented heart attacks among participants overall, but not in those who were born under the astrological signs of Gemini or Libra ‒ a distinction that was clearly meaningless.
Redberg said the study wasn’t representative of the average American, because most participants were from Eastern Europe where they likely had unhealthier diets lower physical activity levels and other differences.
“I will continue to recommend a healthy diet and regular physical activity (and no smoking) as the best way to prevent heart disease and live longer,” Redberg said via email.
Bempedoic acid
Bempedoic acid, approved by the Food and Drug Administration in 2020, is sold by Esperion Therapeutics of Ann Arbor, Michigan, under the brand name Nexletol and often in combination with another cholesterol-lowering drug ezetimibe as Nexlizet. Both drugs cost about $400 a month.
Statins are known to cause muscle aches in a subset of people, which can usually be minimized by reducing the dose. Bempedoic acid can increase the risk of gout, muscle pain and gallstones.
People should not take the study as license to use bempedoic acid instead of statins, Virani said. Statins have a 40- to 45-year safety record, which is important for a drug meant to be taken for the rest of someone’s life. “I hope it does not take people away from statin therapy. That’s my concern,” he said.
Nissen agreed his findings don’t argue in favor of using bempedoic acid specifically. Statins are still better drugs for people who can tolerate them. In the past, he has “taken on the pharmaceutical industry over drugs I thought did not provide a benefit over its risk,” but in this case, he thinks the benefits far outweigh the risks.
Importance of prevention
The last study that looked at the potential health benefits of lowering cholesterol for people who haven’t had a heart attack or stroke was 17 years ago. It was stopped early because it showed people who lowered their cholesterol lived longer, but because it was never completed, some of its findings remained controversial.
Other studies had failed to show a benefit in this group and it’s cheaper and easier to study people who’ve already had a heart attack or stroke to see if treatment can prevent a second event. For them, it’s clear that lowering cholesterol can be helpful.
“If you have a fire in your house and somebody puts it out, that’s great,” Ballantyne said. But it would be better to prevent the fire ‒ or in this case, a heart attack or stroke ‒ in the first place, he said. “Once you have damage, it’s always harder to treat.”
In his own family, Ballantyne’s aunt and brother never got a chance to have a second event. Both died from their first heart attack. He’s happy to have the new study confirm that there’s a benefit to LDL-lowering in people who are at high risk but haven’t had a heart attack or stroke.
During his career, Ballantyne said he’s seen a lot of progress against heart disease, but recently, that has started to reverese.
“We have tremendous tools for prevention and we’re not using them that well,” he said. “Unfortunately, we get reactive, rather than proactive with our health.”
The bottom line for lowering cholesterol, Nissen said, is “the benefits are large, the risks are small and the number of people out there (who could benefit) is enormous. It’s literally tens of millions of people.”
Contact Karen Weintraub at kweintraub@usatoday.com.
Health and patient safety coverage at USA TODAY is made possible in part by a grant from the Masimo Foundation for Ethics, Innovation and Competition in Healthcare. The Masimo Foundation does not provide editorial input.
