Insights from latest CCS & ACS guidelines on lipid management
05 Jun 2025
byKanas Chan
The advent of new lipid-lowering agents, such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, has led to guideline updates on management of chronic coronary syndrome (CCS) and acute coronary syndrome (ACS). In addition to potent LDL-cholesterol (LDL-C) reduction, alirocumab may mitigate atherosclerotic cardiovascular disease (ASCVD) risk by inducing plaque stabilization and exerting protective vascular effects.
Accumulation of LDL-C is a major casual driver of atherosclerosis. Recent European Society of Cardiology (ESC) guidelines on ACS and CCS both recommended that “lower is better for longer” and “the earlier, the better” regarding LDL-C levels and goal achievement. [Eur Heart J 2020;41:2313-2330; Eur Heart J 2024;45:3415-3537; Eur Heart J 2023;44:3720-3826]
According to ESC’s 2024 guidelines, CCS patients are considered at very high ASCVD risk. The LDL-C goal for very high-risk patients is <1.4 mmol/L and a ≥50 percent reduction from baseline (Class IA). Addition of a PCSK9 inhibitor (eg, alirocumab) is recommended for patients who do not achieve the LDL-C goal on the maximum tolerated dose of statin and ezetimibe (Class IA). [Eur Heart J 2024;45:3415-3537]
“It is important not only to prevent the progression of atherosclerosis, but also to induce plaque regression in these [very] high-risk patients,” said Professor Hung-Fat Tse of the Department of Medicine, University of Hong Kong.
The ALTAIR study evaluated the effect of adding alirocumab to rosuvastatin on plaque stabilization in patients with coronary artery disease and thin-cap fibroatheroma (ie, at high risk of plaque rupture). Compared with rosuvastatin alone, adding alirocumab to rosuvastatin led to greater reduction in LDL-C (64.6 vs 17.4 percent), as well as greater changes in fibrous cap thickness (median, 212.3 vs 88.6 percent; p=0.006) and lipid volume (-30.8 vs -2.1 percent; p=0.015), confirming alirocumab’s enhanced plaque stabilization effect. [Circ J 2024;88:1809-1818]
“Importantly, the ESC guidelines specified that although stable for a long period, CCS are frequently progressive and may destabilized at any moment with the development of ACS,” pointed out Tse. [Eur Heart J 2024;45:3415-3537]
Patients with ACS are at the highest risk for recurrent cardiovascular events within 1 year after the index event. Therefore, ESC’s 2023 guidelines recommend intensifying lipid-lowering therapy during the index ACS hospitalization (Class I). [Eur Heart J 2024;45:3415-3537]
The ODYSSEY OUTCOMES trial focused on patients hospitalized for ACS (ie, MI or unstable angina) within the past year. In these patients, alirocumab reduced LDL-C level by 54.7 percent at 48 months and significantly reduced the risk of death from coronary heart disease, nonfatal MI, fatal or nonfatal ischaemic stroke, or unstable angina requiring hospitalization (hazard ratio [HR], 0.85; 95 percent confidence interval [CI], 0.78–0.93; p<0.001) vs placebo. [J Am Heart Assoc 2022;11:e022198; N Engl J Med 2018;379:2097-2107]
Alirocumab was associated with a lower risk of chest pain vs placebo (HR, 0.919; 95 percent, 0.845–0.998; p=0.046) in patients after ACS. [Am J Prev Cardiol 2024;20:100900] “It is likely that plaque regression or stabilization resulted in symptom relief,” explained Tse.
The PACMAN-AMI trial showed that alirocumab and high-intensity statin induced substantially greater atheroma volume (PAV) regression than described in previous vessel-level analyses (-4.86 vs -2.13 percent), and was associated with more frequent reclassification of high-risk plaque phenotype into more stable, less lipid-rich plaque phenotypes. These findings highlight protective vascular effects with early initiation (<24 hours) of alirocumab in patients with acute MI. [JAMA Cardiol 2024;9:1082-1092]
