heartdiseasefacts.com
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April 6, 2024
3 minute read
Important points:
- Four weekly infusions of apolipoprotein AI did not reduce the risk of cardiac-related events in cases of acute myocardial infarction.
- The treatment was well tolerated.
ATLANTA — Four weekly infusions of a novel formulation of human apolipoprotein AI did not reduce combined CV endpoints at 90 days in adults with acute myocardial infarction, multivessel disease, or additional CV risk factors, researchers found. researchers reported.
The AEGIS II trial, presented at the American College of Cardiology Scientific Sessions, was designed to test the evolution of the so-called HDL hypothesis. In short, improved HDL function after MI stabilizes atherosclerotic plaques, thereby reducing the risk of major adverse CV events. Dr. C. Michael Gibson, MS, said the interventional cardiologist, cardiovascular researcher, and CEO of the combined nonprofit research institute Baim and PERFUSE at Harvard Medical School, during a recent clinical trial presentation. The investigational infusion He CSL112 (CSL Behring) was designed to increase levels of apolipoprotein AI, increase cholesterol efflux capacity, and potentially improve the “quality” of HDL particles.
“This has been a 20-year journey. The HDL hypothesis is one of the great remaining questions in cardiology,” Gibson said during his presentation. “There have been many attempts to raise HDL, but they haven’t had much success. Why? Part of it is because of off-target toxicity… Another problem is that even if we [HDL] Maybe your “good” cholesterol levels weren’t all that great. Maybe it was just “OK” cholesterol. Maybe it was “meh” cholesterol. So we turned around and started researching what it really means to have good cholesterol. ”
Hints of “modest” benefits for some
C. Michael Gibson
Gibson et al. analyzed data from 18,219 adults with acute MI, multivessel CAD, and additional CV risk factors. Participants were enrolled from 49 countries, average age was 66 years, and 74.1% were male. Researchers randomly assigned participants to four weekly infusions of CSL112 6 g (n = 9,112) or placebo (n = 9,107), with the first infusion administered within 5 days after the first medical contact for acute MI. was administered. The primary endpoint was a composite of MI, stroke, and cardiovascular death during 90 days of follow-up. Secondary endpoints were the same at 180 and 365 days.
The survey results were announced at the same time New England Medical Journal.
At 90 days, researchers reported no significant difference between groups on the primary endpoint, 4.8% vs. 5.2% in the intervention and placebo groups, respectively (HR = 0.93, 95% CI, 0.81-1.05, 95% CI, 0.81-1.05, P = .24). The CSL112 group had numerically fewer MI and CV-related deaths than the placebo group, which is consistent with previous analyzes suggesting a biological effect of plaque stabilization, Gibson said.
The non-significant difference persisted at 180 days (HR = 0.91; 95% CI, 0.81-1.01; P = .077) and 1 year later (HR = 0.93; 95% CI, 0.85-1.02; P = .137).
Gibson also said that as participants’ baseline LDL increased, the potential treatment effect of CSL112 also increased when analyzed as a continuous variable. However, this observation requires further research.
Adverse events were similar in both groups. The number of patients with hypersensitivity or anaphylactoid reactions that led to drug discontinuation was small, but more in her CSL112 group than in the placebo group (14 patients vs. 4 patients; 14 patients vs. 4 patients). . P = .02), Gibson said.
“Testing the HDL hypothesis in the context of successful introduction of LDL-lowering therapy is becoming increasingly difficult,” Gibson et al. write. NEJM. “Patients in this study demonstrated excellent adherence to treatment based on evidence-based guidelines, including dual antiplatelet therapy. The benefit in mitigating MI appears to be small, if any.”
Is it time to shelve HDL drugs?
Christy M. Baranton
In a related editorial published in NEJM, Christy M. Ballantyne, MD, FACC, FACP, FAHA, FNLA, Director of Cardiovascular Research and Professor of Medicine at Baylor College of Medicine. Vijay Nambi, MD; Michael E. DeBakey, an associate professor of medicine at Baylor College of Medicine and a staff cardiologist at the Veterans Affairs Hospital, says many of the early events after an acute myocardial infarction can be related to stent thrombosis, and the impact of cholesterol efflux. It was pointed out that there is a possibility that it will not be accepted. Additionally, most lipid-altering therapies begin to take effect after about 12 months.
“The AEGIS II trial is the final curtain call to characterize HDL function, which can be used in conjunction with genomics and metabolomics, before declaring the end of therapies targeting ‘very unfortunate lipoproteins.’ A reconceptualization focused on the development of better assays, utilizing proteomics and transcriptomics, may be needed to identify new targets and correct targets for testing therapeutics that improve cholesterol efflux and HDL function. identify the population,” Ballantine and Nambi wrote. “Until then, it may be time to shelve HDL drugs and put them on the ‘backlist’ of cardiovascular disease preventive therapies.”
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Gibson MC et al. American College of Cardiology/Journal of American College of Cardiology joint latest clinical trial. Presentation location: American College of Cardiology Scientific Sessions. April 6-8, 2024. Atlanta.
Disclosure: CSL Behring sponsored the AEGIS II study. Ballantyne has received institutional grant/research support from Abbott Diagnostic, Akcea, Amgen, Arrowhead, Eli Lilly, Ionis, Merck, New Amsterdam, Novartis, Novo Nordisk, Regeneron, Roche Diagnostic, and from Abbott Diagnostic, Alnylam Pharmaceuticals, Amgen , has reported receiving consulting fees from Arrowhead. , AstraZeneca, Denka Seiken, Eli Lilly, Esperion, Genentech, Illumina, Ionis, Merck, New Amsterdam, Novartis, Novo Nordisk, Roche Diagnostics, Ten Sixteen Bio. Mr. Gibson reports financial ties to numerous pharmaceutical and medical device companies. For relevant financial disclosures of all other authors, please see the research paper and editorial.
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