“Statins are still the cornerstone,” said Steven Nissen, chairman of cardiovascular medicine at the Cleveland Clinic and lead author of the study. “But if you can’t tolerate statins, and there are millions of people like that, then we’ve put in place an effective alternative to reduce morbidity.”
The research, published Saturday in the New England Journal of Medicine, was funded by the drug’s maker, Esperion Therapeutics, based in Ann Arbor, Michigan.
Fewer heart attacks and surgeries
The study recruited 13,970 patients, about half of whom were randomized to a group taking bempedoic acid and the other half to a placebo group. The average LDL or “bad” cholesterol in both groups at the start of the study was 139 mg per deciliter. Almost half of the study subjects were women.
In this study, bempedoic acid reduced cholesterol by 21%. People who took the drug had a 23% lower risk of myocardial infarction and a 19% lower risk of having a revascularization procedure.
“The benefits of bempedoic acid are now clearer,” wrote John H. Alexander, director of cardiovascular research at the Duke Clinical Research Institute, in an accompanying editorial. “It is now our responsibility to translate this information into better primary and secondary prevention for the patients most at risk, who will thus benefit from fewer cardiovascular events.”
The drug’s ability to lower cholesterol and heart attack risk without creating muscle pain may be because it targets an enzyme in the liver, not the muscles.
Muscle pain was actually more common in the placebo group (6.8%) than in the drug group (5.6%). Patients in the bempedoic acid group had a slight increased risk of gout, which is caused by a buildup of uric acid in the blood. , a condition that causes severe pain in the big toe. The study reported gout in 2.1% of patients in the placebo group and 3.1% of patients in the study group.
Bempedoic acid is not a brand new drug; it was approved by the Food and Drug Administration in 2020 based on studies that showed it reduced LDL cholesterol by 28% in patients who could not tolerate statins. When given to patients already taking moderate or high dose statins, the drug lowers cholesterol by an additional 18%.
Proving that a drug helps the heart
But proving a drug lowers cholesterol doesn’t mean it will prevent heart attacks or other cardiovascular events. One of the big disappointments in cardiovascular drug development was a drug called evacetrapib, made by Eli Lilly, which dramatically lowered LDL cholesterol, doubled “good” HDL cholesterol, and yet did not prevent heart attacks.
Without “outcome data” showing that bempedoic acid reduces heart attacks, doctors are less likely to prescribe the drug and insurers may not pay for it, Nissen said.
“In today’s era where we have other cholesterol-lowering drugs, people won’t use a drug that hasn’t shown benefits on outcomes,” Nissen said. “People want proof. Everyone was waiting for this trial.
Another type of drug, called a PCSK9 inhibitor, also lowers cholesterol and heart risk, but is given by injection. Although drug prices vary widely, the going price for PCSK9 is around $112 per week. Bempedoic acid costs about $70 per week. By comparison, statins, which are available in generic forms, can cost anywhere from 50 cents to $7 a week.
But the research needed to prove that bempedoic acid could prevent heart attacks was a challenge. A large body of research already shows that statins, which were introduced in the 1980s and are taken by 1 in 4 adults, have been proven to reduce heart attacks in patients at risk and prevent heart attacks. extra for those who have already had it. A. Denying at-risk patients a proven treatment to study a new drug would be unethical.
But many patients have tried statins but stopped taking them due to adverse side effects – most often due to muscle pain, but some have also complained of cognitive effects, including fuzzy thoughts or gaping. memory.
The bempedoic acid study, conducted at 1,250 sites in 32 countries, enrolled nearly 14,000 of these patients. They were counseled on the proven benefits of statins and the risks of not taking them.
“To do it ethically, we had to get people to sign a pretty scary statement,” Nissen said. “They had to agree that they could get a placebo for five years. Patients are phenomenal in their willingness to contribute to studies like this.
Solve the problem of intolerance to statins
For years, doctors have been skeptical of patient complaints about statin side effects, speculating that the problem was psychological — the “nocebo effect” — or that pain from another condition was mistakenly attributed to the statin. But a 2016 study, which tested patients who complained of side effects with statins and a placebo, finally showed that statin intolerance is real.
Nissen said most patients have no problem taking statins, but for the minority of patients who have statin intolerance, the problem is concerning.
“Statin intolerance is controversial, but for people who have it, it’s just infuriating,” Nissen said. “We now have a new tool in the tool chest.”