The results of two subanalyses of the PACMAN-AMI trial were presented on the final day (2 September) of the European Society of Cardiology (ESC) 2024 Congress.

Coronary heart disease is the most frequent cause of mortality in the industrialised world, and hypercholesterolaemia is a major risk factor. Statins are the first-line therapy, but are often not wholly effective.

Several studies have demonstrated low-density lipoprotein cholesterol (LDL-C) reduction with PCSK9 inhibition, in addition to decreased adverse cardiovascular events. The Phase III PACMAN-AMI trial (NCT03067844) investigated the effect of Regeneron Pharmaceutials’ PCSK9 inhibitor Praluent (alirocumab), a PCSK9 inhibitor, in patients with acute myocardial infarction (AMI).

Some data from the study was presented earlier at the conference during a session outlining the efficacy of antibodies like Praluent in reducing LDL-C levels.

In the study, patients received Praluent or placebo every two weeks alongside statin therapy. After 52 weeks, PCSK9 inhibition significantly reduced percent atheroma volume (PAV), the difference between vessel and lumen volumes, and other measures of blood vessel occlusion compared to statin therapy alone.

Subanalyses provide more insights

Dr. Yasushi Ueki from Shinshu University Hospital in Japan first presented a subanalysis of the PACMAN-AMI trial. His team used risk stratification to identify patients with the greatest potential for benefit from plaque regression.

Ueki explained his group divided patients into three groups based on risk factors for chronic coronary disease—those with none, with one, or with two or more major risk factors. Blood vessel imaging for these patients was compared before and after 52 weeks of Praluent treatment or placebo between risk-stratified groups.

Ueki’s team found PAV was only significantly reduced among patients with one or no risk factors, with, “no significant difference between patients with two or more risk factors”. This was also true regarding changes in maximum lipid core burden index and macrophage angle.

According to Ueki, “among AMI patients with no or one atherothrombotic risk factors, the addition of alirocumab to high-intensity statin demonstrated greater coronary plaque regression; patients with fewer risk factors thus appear to be more susceptible for atheroma regression”.

Dr. Flavio Biccirè from the University Hospital of Bern in Switzerland then spoke about his team’s subanalysis. They focused on vessel lesions, regions at which plaque buildup is most pronounced, as opposed to the PACMAN-AMI trial’s wider, vessel-level analysis.

Identifying vessel lesions using imaging data from 245 patients, Biccirè and his colleagues remeasured clinical outcomes. They found that at the lesion level, PAV change with Praluent at 52 weeks was -4.9 compared to placebo, far greater than the -2.1 change stated in the original analysis.

Biccirè concluded, “LDL-C lowering induced an extensive atheroma burden reduction at lesion-level”, and that, “significant changes in coronary lesions, rather than mild effects described at vessel-level, underlie the protective vascular effects of contemporary lipid-lowering therapies”.