The body uses ACL further upstream in the same cholesterol synthesis process that also employs the enzyme targeted by statins, known as HMGCR, researchers said in background notes.
A study of nearly 655,000 people found that people’s ACL and HMGCR scores were associated with similar patterns in LDL cholesterol levels and similar effects on heart disease risk based on those levels, researchers reported. Ference led this study.
Further, people who carry genetic variants that inhibit ACL have lower LDL cholesterol levels and lower risk of heart health problems, researchers found.
Based on this, researchers decided to test how well a drug that blocks ACL would lower cholesterol levels in average people.
That drug, bempedoic acid, was randomly assigned to 1,488 people with high LDL cholesterol despite being on high-intensity statin therapy. Another 742 statin users were given a placebo.
After a year, bempedoic acid lowered LDL cholesterol levels by 18 percentage points, researchers found.
The most troubling adverse event was the incidence of gout, which led 18 bempedoic acid patients to quit the trial, compared to three placebo patients, Holmes and Eckel said.
Gout occurs when uric acid levels rise in the bloodstream beyond the kidneys’ ability to remove the harmful byproduct. High uric acid levels cause crystals to form in joints, producing inflammation and arthritis.
“This discontinuation because of gout is something that needs to be explored further by additional study,” Eckel said. “That could end up to be something on the package insert that could influence prescribing patterns.”
For example, bempedoic acid might not be best prescribed to people with gout or with already elevated uric acid levels, he said.
The American Heart Association/American College of Cardiology’s updated cholesterol treatment guidelines in 2018 kept the main focus on statins, which are cheap and proven effective.
But the AHA and ACC also allowed that ezetimibe and PCSK9 inhibitors could play a role for people whose cholesterol remains elevated despite statin therapy.
“In the setting of patients at high risk of disease who are on maximal doses of statins, additional lipid-lowering drugs will lead to a further reduction in cardiovascular disease risk, as we have seen with PCSK9 inhibitors,” said Holmes.
“There is therefore a potential role for drugs that inhibit AC