Greater plaque regression and stabilization with PCSK9i in patients with acute MI
Effects Of Alirocumab On Coronary Atherosclerosis Assessed By Serial Multimodality Intracoronary Imaging In Patients With Acute Myocardial Infarction: A Double-blind, Placebo-controlled, Randomized Trial (PACMAN AMI)
Presented at ACC.22 by Prof. Lorenz Räber, MD (Bern, Switzerland)
Introduction and methods
High-risk vulnerable plaques in coronary arteries are characterized by large plaque burden, large lipid content, and thin fibrous caps. It is known that statins can halt the progression of atherosclerosis. However, the effects of PCSK9 inhibitors on coronary plaques remain unknown.
Aim of the study
This double-blind, multicenter, placebo-controlled trial investigated the effects of alirocumab on plaque burden, composition and fibrous cap thickness in patients with an acute MI.
A total of 299 patients with acute MI were randomized in a 1:1 ratio to receive either biweekly alirocumab (150 mg) or placebo for 50 weeks in addition to high-intensity statin therapy (rosuvastatin 20 mg daily). Treatment was started <24 hours after PCI of the culprit lesion. Imaging tests were performed immediately after the stenting procedure and at 52 weeks. The following imaging tests were performed in two non-infarct related arteries at both timepoints: Intravascular ultrasound (IVUS) to measure the plaque volume, near-infrared spectroscopy (NIRS) to measure the amount of cholesterol within the plaques and optical coherence tomography (OCT) to measure the thickness of the fibrous cap.
The primary endpoint was primary endpoint was change in IVUS-derived percent atheroma volume. Secondary endpoints were change in NIRS-derived maximum lipid core burden index within 4 mm and OCT-derived minimal fibrous cap thickness.
- Patients in the alirocumab group (alirocumab + statin) achieved an average LDL-c level of 23.6 mg/dL (0.6 mmol/L) at week 52 (reduction of 84.8% compared to baseline). In the placebo group (placebo + statin), patients achieved an average LDL-c level of 74.4 mg/dL (1.9 mmol/L) at week 52 (reduction of 50.7% compared to baseline).
- Treatment with alirocumab resulted in a larger decrease in percent atheroma volume (-2.1%) compared with placebo (-0.9%; difference -1.2%, 95% CI -1.77% to -0.65%, P<0.001).
- Reduction in maximum lipid core burden index within 4mm was greater with alirocumab (-79.4) compared with placebo (-37.6; Difference -41.2, 95% CI -70.7 to -11.8, P=0.006).
- The increase in minimal fibrous cap thickness was also greater in the alirocumab group (62.7 µm) compared with the placebo group (33.2 µm; difference 29.7 µm, 95% CI 11.8 to 47.6 µm, P=0.001).
- The benefit of plaque regression and stabilization was higher at lower achieved LDL-c levels.
This study showed that treatment with alirocumab, compared with placebo, in addition to high-intensity statin therapy resulted in greater coronary plaque regression, greater cholesterol core reduction and a higher increase in the protective fibrous cap after 52 weeks in non-infarct related coronary arteries in patients with acute MI.
-Our coverage of ACC.22 is based on the information provided during the congress-