PCSK9 inhibition
PACMAN-AMI substudy shows high baseline Lp(a) blunts plaque lipid-core regression despite alirocumab plus high-intensity statins (Circ Cardiovasc Imaging 2024)
Original title: Association of Lipoprotein(a) With Changes in Coronary Atherosclerosis in Patients Treated With Alirocumab
In the phase 3 PACMAN-AMI trial, 300 acute myocardial infarction patients were randomised to biweekly alirocumab 150 mg or placebo added to high-intensity statins, with serial intravascular imaging at baseline and 52 weeks. Among 265 patients with serial intravascular ultrasound data, alirocumab produced greater overall reductions in atheroma volume and lipid-core burden than placebo. However, within the alirocumab group, patients in the highest Lp(a) quartile (98 nmol/L or above) showed a markedly smaller reduction in lipid-core burden index (-40.2 vs. -91.4, P = 0.01 after adjustment) than lower-quartile patients, a reduction comparable to placebo overall, a pattern that held at alternative Lp(a) cutoffs of 75 and 125 nmol/L. Elevated baseline Lp(a) blunts plaque lipid-core regression despite intensive alirocumab-plus-statin therapy, offering a mechanistic explanation for residual cardiovascular risk in patients with high Lp(a).
Original abstract
Background: Elevated Lp(a) (lipoprotein[a]) is a risk marker for atherosclerotic disease, but the underlying mechanisms remain elusive. We examined the association of Lp(a) with changes in coronary atherosclerosis following intensive lipid-lowering therapy.
Methods: In the PACMAN-AMI trial (Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction), 300 patients with acute myocardial infarction were randomized to receive biweekly alirocumab 150 mg or placebo in addition to high-intensity statins. Patients underwent serial 2-vessel intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy in the non-infarct-related arteries at baseline and after 52 weeks. The main end points were percent atheroma volume by intravascular ultrasound, minimum fibrous cap thickness by optical coherence tomography, and maximum lipid core burden index within 4 mm (maxLCBI4mm) by near-infrared spectroscopy.
Results: A total of 265 patients had serial intravascular ultrasound data (mean age, 58±9 years; 16% women). Alirocumab resulted in greater reductions in percent atheroma volume and maxLCBI4mm, as well as a greater increase in minimum fibrous cap thickness, compared with placebo. In the alirocumab group, the reduction in maxLCBI4mm was smaller in patients with higher baseline Lp(a), defined by the highest quartile (Q4, ≥98 nmol/L; n=30), than in those with lower baseline Lp(a) (Q1-Q3, <98 nmol/L; n=99; -40.2 [-91.1 to 10.7] versus -91.4 [-113.9 to -68.9], respectively; P=0.01 after adjustment for clinically relevant baseline variables), and was comparable to the maxLBI4mm reduction in the placebo group (-37.60 [-57.40 to -17.80]; n=134). These findings were consistent when higher baseline Lp(a) was defined by cut-off values of ≥75 versus <75 nmol/L (n=35 versus 94, respectively, in the alirocumab group) and ≥125 versus <125 nmol/L (n=23 versus 106, respectively). Changes in percent atheroma volume and minimum fibrous cap thickness did not differ in relation to baseline Lp(a).
Conclusions: In patients with acute myocardial infarction, elevated Lp(a) at baseline is associated with attenuation of plaque lipid regression despite intensive treatment with alirocumab plus high-intensity statin. This finding may explain the residual cardiovascular risk associated with high Lp(a) despite optimal control of lipid levels.
Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03067844.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.