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18th May 2022
The PCSK9 inhibitor, alirocumab, given twice weekly in combination with a statin, to patients who underwent urgent percutaneous coronary intervention (PCI) after an acute myocardial infarction (MI) resulted in significantly greater coronary plaque regression in non-infarct-related arteries after 52 weeks compared to placebo. This was the conclusion of a randomised clinical trial by teams from Switzerland and Denmark.
It has been previously shown that the use of maximal dose statin therapy can produce a significant regression of coronary atherosclerosis when measured by the percent atheroma volume. Patients who have experienced an MI continue to be at risk of a subsequent event, highlighting the continued need for statin therapy. For example, one study of post-MI patients found how such individuals continue to be at risk of cardiovascular events beyond the first year after their initial MI. A further reason to continue statin therapy and to hopefully see regression of coronary atherosclerosis, comes from a study in those with acute coronary syndrome. The study revealed that subsequent major adverse cardiovascular events were equally attributable to recurrence at the site of initial or culprit lesions and to non-culprit or non-infarct-related arteries. It has also been shown that the combination of alirocumab and high dose statins in patients who experienced acute coronary syndrome 1 to 12 months earlier, reduces the risk of recurrent ischaemic cardiovascular events compared to placebo.
Although combining alirocumab with a statin reduces subsequent recurrent adverse cardiovascular events, little is known about how this combination impacts on plaque burden and composition. As a result, for the present study, the researchers undertook the Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction (PACMAN-AMI) randomised trial. The study recruited adult patients (> 18 years) who underwent urgent percutaneous coronary intervention (PCI) of the culprit lesion for treatment of ST-elevation MI. Patients were randomised 1:1 to biweekly subcutaneous alirocumab (150mg) or placebo and which was started less than 24 hours after the PCI and given in combination with rosuvastatin 20mg daily for a total of 52 weeks. The availability of various imaging modalities enabled the team to take a closer look at how the combination therapy affected plaques. They used intravascular ultrasonography (IVUS), near-infrared spectroscopy and optical coherence tomography (OCT) on two non-infarct-related coronary arteries both at baseline and at the end of the study. The IVUS was used to assess changes in percent atheroma volume (PAV), whereas near-infrared provided a measure of the maximum lipid core burden index. This latter metric, provides an assessment of the lipid content of a plaque, such that lower values are associated with a reduced risk of adverse events. OCT can be used to assess minimal fibrous cap thickness with a thicker plaque being more stable and therefore less likely to rupture.
The primary outcome for the study was the change in IVUS PAV from baseline to week 52 and two secondary outcomes were changes in maximum lipid core burden index and OCT-derived minimal fibrous cap thickness.
Alirocumab and changes in percent atheroma volume
A total of 300 patients with a mean age of 58.5 years (18.7% women) and an overall mean LDL cholesterol level of 3.94mmol/l were randomised to alirocumab or placebo.
After 52 weeks of therapy, the mean LDL cholesterol level was 1.91mmol/l in the placebo group and 0.60mmol/l in the alirocumab group (p < 0.001).
For the primary endpoint, the change in mean PAV was significantly greater for alirocumab compared to placebo (-2.13% vs -0.92%, p < 0.001). The lipid core burden was also significantly reduced with alirocumab (mean change -79.4 vs -37.60, alirocumab vs placebo, p = 0.006). Finally, fibrous cap thickness also significantly increased with alirocumab compared to placebo (p = 0.01).
Based on these findings, the authors concluded by calling for future studies to examine whether the changes observed with alirocumab would lead to an improvement of clinical outcomes for patients.
Räber L et al. Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction: The PACMAN-AMI Randomized Clinical Trial. JAMA 2022