Impact of Triple Regression of Coronary Atheroma in Response to Lipid-Lowering Therapy

Patients with acute myocardial infarction (AMI) still experience a substantial rate of adverse events, mostly due to disease progression in non–infarct-related arteries (IRAs). Previous studies have shown that lipid-lowering therapy is able to halt disease progression or even induce regression in non-IRAs according to the achieved LDL-C levels. In the randomized controlled trial PACMAN-AMI, treatment with a PCSK9 inhibitor (alirocumab) in addition to high-intensity statin therapy was associated with atheroma volume reduction, plaque lipid content reduction, and fibrous cap thickening in non-IRAs of patients with AMI after 52 weeks of drug treatment. However, how frequently concordant changes in regression/stabilization occur and whether the concomitant presence of atheroma volume reduction and stabilization of plaque composition (lipid component reduction and fibrous cap thickening) are associated with a lower incidence of cardiovascular events remained unknown.

Now published in JACC and simultaneously presented at the ESC Congress 2023, a new subanalysis of the PACMAN-AMI trial investigated the characteristics and clinical outcomes of patients with concomitant atheroma volume reduction, lipid component reduction, and fibrous cap thickening (named “triple regression” in the manuscript) after 1 year of treatment with high-intensity lipid-lowering therapy. Among 265 patients (537 non-IRAs) undergoing serial multimodality intracoronary imaging at baseline and 52 weeks, the investigators found that 1) triple regression occurred in one-third of the patients with AMI treated with high-intensity lipid-lowering therapy, 2) alirocumab treatment was the strongest independent predictor of triple regression in addition to a higher baseline lipid accumulation, and 3) patients with triple regression were at lower risk of adverse cardiovascular events — mainly ischemia-driven revascularization — at the 1 year follow-up period. Triple regression occurred in 41% and 23% of the patients treated with alirocumab/statin and placebo/statin, respectively.

This study filled the knowledge gap on the rates and characteristics of patients with AMI who "fully respond"" to high-intensity lipid-lowering therapy, demonstrating net vascular benefits resulting in lower rates of future cardiovascular events. Triple regression was not predicted by specific clinical features at baseline but rather by the presence of lipid-rich plaques and treatment with potent lipid-lowering therapy (ie, PCSK9 inhibitors). Of note, patients with triple regression showed very low LDL-C levels at follow-up compared with patients without triple regression (mean LDL-C level, 38.4 vs 55.7 mg/dL). As a main message, triple regression in patients with AMI is possible when very low LDL-C levels are achieved, and patients with lipid-rich atherosclerosis might benefit more from high-intensity lipid-lowering therapy; however, further research is needed to test this latter hypothesis in a dedicated randomized controlled trial.