Effect of alirocumab on coronary plaque stratified by atherothrombotic risks

Abstract Background Previous clinical studies have shown that high-risk subgroups including patients with major atherosclerotic cardiovascular disease (ASCVD) events and multiple atherothrombotic risk factors derive enhanced cardiovascular benefit from proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition. To date, the effect of alirocumab on coronary plaque regression stratified by the number of atherothrombotic risk factors remains unknown. Purpose To investigate the utility of atherothrombotic risk stratification to identify patients with acute myocardial infarction (AMI) who have the greatest potential for benefit on plaque regression as assessed by intracoronary imaging from the addition of alirocumab to high-intensity statin therapy. Methods This was a substudy of the PACMAN trial, a randomized, double-blind trial comparing biweekly alirocumab (150 mg) versus placebo in AMI patients undergoing percutaneous coronary intervention. Intravascular ultrasound (IVUS) was serially performed in non-infarct-related coronary arteries at baseline and after 52 weeks. Atherothrombotic risk factors defined in the 2018 ACC/AHA cholesterol guidelines include myocardial infarction, ischemic stroke, peripheral artery disease, age ≥65 years, familial hypercholesterolemia, coronary revascularization, diabetes, hypertension, chronic kidney disease, current smoking, LDL-C ≥100 mg/dL despite maximum tolerated statin therapy, and history of heart failure. The key endpoint was the change in IVUS-derived percent atheroma volume (PAV) from baseline to 52 weeks. Results A total of 263 patients available for serial IVUS data were analyzed for the current study. The most prevalent atherothrombotic risk factors were current smoking (49%), hypertension (43%), and age ≥65 years (24%). Patients were divided into 3 groups according to the number of risk factors (0 risk factor: n=52, 1 risk factor: n=101, ≥2 risk factors: n=100). Patients with risk factors had greater PAV at baseline compared with those with 0 risk factor (39.0% vs. 42.6% vs. 42.8%, P=0.008). The addition of Alirocumab to high-intensity statin therapy demonstrated a significant reduction in PAV among patients with 0 risk factor (-2.66% vs. -1.02%, P=0.009) and those with 1 risk factor (-2.36% vs. -0.76%, P<0.001) (Figure 1). In contrast, patients with ≥2 risk factors had no significant PAV reduction by alirocumab (-1.72% vs. -1.12%, P=0.076, P for interaction=0.009). Conclusions Among AMI patients with no or 1 atherothrombotic risk factor, the addition of alirocumab to high-intensity statin therapy demonstrated greater coronary plaque regression. Patients with fewer risk factors thus appear to be more susceptible for atheroma regression.Change in PAV stratified by risk factors