April 6, 2024 — The first trial of a new strategy to remove cholesterol from patients’ arteries reduced the risk of death within three months of a previous heart attack, heart attack, Annual Scientific Sessions did not reduce risk of stroke. However, our findings suggest that this strategy may be beneficial with longer follow-up.

Dr. C. Michael Gibson

“We found no statistically significant reductions in the risk of primary endpoints such as death, heart attack, or stroke at 90 days, and no reduction in stroke risk at any time point,” he said. said C. Michael Gibson, MD. M.D. at Harvard Medical School and lead author of the study. However, an exploratory analysis of outcomes showed that treated patients had fewer heart attacks and deaths from heart attacks at six months than patients in the control group, he said.

“Although the primary endpoint was not met, our data support the hypothesis that HDL cholesterol plays a role in reducing subsequent coronary plaque rupture events, such as heart attacks, by enhancing cholesterol efflux. ,” Gibson said.

Gibson said people who have had a heart attack are at a higher risk of having one, especially in the next 90 days. The study showed that patients received an infusion of ApoA-I, a component of HDL (“good”) cholesterol, immediately after a heart attack, with the aim of stabilizing coronary artery plaques and reducing adverse cardiovascular events. This is the first study. The investigational drug used in this study, CSL112, is a type of ApoA-I extracted from human plasma, the liquid component of blood.

High LDL cholesterol levels can cause plaque to build up in the arteries that carry blood to the heart, increasing the risk of artery blockage that can lead to a heart attack. HDL cholesterol removes cholesterol from the arteries and transports it to the liver, where it is excreted. ApoA-I, the main component of HDL cholesterol, helps initiate the process of removing cholesterol from the body. Previous studies showed that a single infusion of CSL112 reduced the amount of LDL cholesterol in arterial plaques by as much as 50%.

Other studies have shown that high levels of HDL cholesterol are associated with a lower risk of heart attack. However, recent research suggests that HDL cholesterol levels may be more important than how effective cholesterol removal is in reducing heart attack risk. Gibson said.

“We know that when a heart attack occurs, HDL cholesterol helps move large amounts of cholesterol out of the arteries, leading to better outcomes for patients,” he said.

Gibson and his colleagues hypothesized that injecting CSL112 immediately after a heart attack could reduce a patient’s risk of having a repeat heart attack during the next critical 90 days by increasing the body’s ability to process cholesterol. Ta. The international AEGIS-II trial, conducted in 49 countries, was designed to test this hypothesis.

The study included 18,219 patients (median age 65.5 years, 74% men, 84.5 % white) were registered. They also had other risk factors, such as having had a heart attack in the past, taking medication for diabetes, and being over 65 years old. Patients were randomly assigned to receive an infusion of either CSL112 or placebo for 4 weeks, with the first infusion given within 5 days of admission.

The study’s primary endpoint was 90 days to the first major adverse cardiovascular event (MACE, i.e., heart attack, stroke, or death from heart disease or stroke). Secondary endpoints included time to first occurrence of his MACE within 6 months to 1 year and time to occurrence of each specific event within 90 days, 6 months, and 1 year. I was there.

At 90 days, the risk of death, heart attack, or stroke was reduced by 4.8% in patients treated with CSL112 compared with 5.2% in patients treated with placebo, but this difference was not statistically significant. Ta. However, in an exploratory analysis, patients treated with CSL112 were 14% less likely to have a heart attack or die from a heart attack after 180 days. Additionally, patients treated with CSL112 were 32% less likely to have a heart attack at 90 days due to a blood clot in a stent (a small mesh tube inserted into an artery to prevent artery blockage). At 90 days, it was 29% lower. 180 days.

Another potentially important finding was that patients whose LDL cholesterol levels were 100 mg/dL or higher at the start of the study experienced a 30% reduction in the primary endpoint, although this was a statistically significant finding. In contrast, patients whose LDL cholesterol levels were 100 mg/dL or higher at the start of the study did not, Dr. Gibson said. No reduction in the primary endpoint was observed below 100 mg/dL.

“Baseline LDL modulated the treatment effect,” Dr. Gibson said.

“Overall, our findings are consistent with ApoA-I having a role in stabilizing heart blockages and reducing the risk of blockages rupturing beyond 90 days and causing a heart attack.” said Mr. Gibson. “Administering ApoA-1 to remove cholesterol from the body and then treating patients with cholesterol-lowering drugs to keep LDL cholesterol levels low may reduce deaths and heart attacks in the long term. I can think of it.”

Future research will focus on identifying high-risk patients who may benefit from this approach, he said. He said the antiplatelet effect of CSL112, or the reduction in cholesterol in the arteries due to treatment with CSL112, could also explain the significant reduction in the number of heart attacks caused by blood clots in stents. The reason strokes are not decreasing, he said, is because strokes can be caused by mechanisms other than rupturing artery blockages.

A limitation of the study is that women, Black people and people of Asian descent were underrepresented, which could reduce the generalizability of the findings, Gibson said.

This research was funded by CSL Behring, the manufacturer of CSL112.

The study was published online in the New England Journal of Medicine upon publication. The results of the exploratory analysis are Journal of the American College of CardiologyJack.

Gibson will present a presentation entitled “ApoA-I Event Reduction in Acute Myocardial Infarction Patients (Ischemic Syndrome II (AEGIS-II) Study): Primary Study Results” on Saturday, April 6, the first day of the ongoing ACC Scientific Sessions. Published research. In Atlanta, GA through April 8th.

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