Compared to a placebo, adding the injectable cholesterol-lowering drug alirocumab to high-intensity statin therapy in patients who had a heart attack resulted in twice the reductions in three key measures of vulnerability of plaque that signal the risk of future cardiac events, according to research presented at the American College of Cardiology’s 71st Annual Scientific Session.
The trial is the first to examine the effect of alirocumab, a PCSK9 inhibitor, on ‘vulnerable plaques’ (fatty deposits in the arteries that are thought to cause future cardiac events) using three imaging tests that assess the likelihood of future cardiac events in patients recovering from a heart attack. The study met its primary endpoint – a reduction in percent atheroma volume (PAV), which is a measure of cholesterol plaque buildup in the coronary arteries.
Following early initiation of alirocumab in addition to high-intensity statin therapy in a population at high risk of acute myocardial infarction, we observed dual regression of coronary atherosclerosis and stabilization of plaques high risk compared to treatment with statins alone. »
Lorenz Räber, MD, PhD, professor of cardiology and director of the catheterization laboratory at the University Hospital of Bern in Switzerland and principal investigator of the trial
Most heart attacks are caused by cholesterol deposits in the coronary artery that are covered by a thin fibrous cap. A rupture of this plug can potentially lead to coronary blockage which results in a heart attack.
About 1 in 5 people who have had a heart attack will be readmitted to hospital with a second cardiac event within five years.
PCSK9 inhibitors boost the liver’s ability to remove low-density lipoprotein (LDL) cholesterol – or “bad” cholesterol – from the body, thereby lowering LDL cholesterol levels in the blood. Alirocumab, which is injected under the skin, was the first drug in its class to be approved by the United States Food and Drug Administration for use alone or in combination with other cholesterol-lowering drugs such as statins.
The current trial, known as PACMAN-AMI, recruited 300 patients who had a heart attack and were treated with a stent (a small mesh tube) to open up the blocked artery. The average patient age was 58.5 years and 81.3% were male. All patients received a high daily dose of rosuvastatin (20 mg), and they were randomly assigned to receive injections of alirocumab or a placebo every two weeks as additional treatment. The first injection was given less than 24 hours after stent insertion, while the patients were still in hospital for their heart attack.
Within 24 hours of stent placement, patients underwent three types of imaging in two other heart arteries (not including the one that caused the heart attack). These imaging tests measured the amount of plaque accumulation (PAV, the primary endpoint) by intravascular ultrasound; the amount of cholesterol in the plaques by near-infrared spectroscopy; and the thickness of the hard outer layer, or cap, covering the plaques by optical coherence tomography (a light-based imaging technique that provides microscopic images of the artery). The thinner the hard cap, the more likely it is to rupture, which could allow plaques to block the artery and cause another heart attack.
“VAP, plaque cholesterol content, and cap thickness are key features of vulnerability to future cardiac events,” Räber said. “This kind of detailed information could previously only be obtained at autopsy. Nowadays, it can be visualized in living patients using these imaging tests. Our study was the first to use three intracoronary imaging tests in combination to provide a complete picture of plaque size, composition and morphology [shape and structure].”
Patients continued on their assigned treatment for 50 weeks. At 52 weeks, the three imaging tests were repeated and the researchers analyzed the differences between the images before and after treatment. On all three imaging measures, patients who received alirocumab performed significantly better than those who received placebo. The overall plaque material and lipid deposits on their arterial walls regressed to a greater extent (double reduction) and the hard caps covering the plaques became thicker (double thickening), meaning they were less likely to break. Patients who received alirocumab also required significantly fewer repeat stenting procedures. No significant adverse events occurred in relation to the imaging tests.
Patients receiving the combination of alirocumab and a statin achieved a mean LDL level of 23.6, the lowest level ever achieved in a major trial of cholesterol-lowering drugs in patients with acute myocardial infarction, Raber said. The study drug was generally well tolerated (6.4% injection site reactions and 3.4% allergic reactions).
“These results provide information to support more frequent, earlier, and targeted use of alirocumab in addition to high-intensity statin therapy in patients who have had a heart attack and are at high risk of having one. a second,” Räber said.
A limitation of the study, he said, is that it was not designed to measure whether adding alirocumab to statin therapy resulted in fewer cardiac events compared to statin therapy. Alone. Instead, the study used changes in all three imaging markers of heart attack risk as surrogates.
This study was simultaneously published online in the Journal of the American Medical Association at the time of presentation. The study was an academic, investigator-initiated trial funded by grants from Sanofi and Regeneron, the co-developers of alirocumab, and Infraredx, the maker of near-infrared spectroscopy imaging catheters.
Räber will be available to the media at a press conference on Sunday, April 3 at 9:30 a.m. ET / 1:30 p.m. UTC in room 103AB.
Räber will present the study, “Effects of Alirocumab on Coronary Atherosclerosis Assessed by Serial Multimodality Intracoronary Imaging in Patients with Acute Myocardial Infarction: A Double-blind, Placebo-controlled, Randomized Trial (PACMAN-AMI),” on Sunday, April 3, at 8:00 a.m. ET / 12:00 p.m. UTC in the main tent, Hall D.