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Alirocumab significantly reduces high-risk coronary plaques

Presented By
Prof. Lorenz Räber, Bern University Hospital, Switzerland
Conference
ACC 2022
Trial
Phase 3, PACMAN-AMI
orig text:

Adding the PCSK9 inhibitor alirocumab to high-intensity statin therapy shortly after an acute myocardial infarction (MI) promoted coronary plaque regression better than high-intensity statin therapy alone, based on serial intracoronary imaging performed in the PACMAN-AMI trial. Prof. Lorenz Räber (Bern University Hospital, Switzerland) reported the PACMAN-AMI (NCT03067844) results at the ACC 2022 Scientific Session, which were simultaneously published in JAMA [1,2]. Prof. Räber explained that the unmet need being addressed by PACMAN-AMI was that it is not well known what the impact of PCSK9 inhibition is on high-risk atherosclerotic plaque characteristics, particularly lipid content and fibrous cap thickness. PACMAN-AMI randomised 300 patients with acute ST-elevation myocardial infarction (STEMI) (53%) or non-STEMI (47%) who had undergone successful percutaneous coronary intervention (PCI) of the culprit vessel and in whom at least 2 proximal non-infarct-related arteries had been found with non-obstructive atherosclerosis (20% to 50% diameter stenosis). Half the patients received subcutaneous 150 mg/mL alirocumab and half the patients received placebo, starting within 24 hours after PCI, and then every 2 weeks for 1 year. Only 12% of patients were on statins at baseline; LDL-cholesterol level was >125 mg/dL (3.2 mmol/L) in statin-naïve patients and >70 mg/dL (1.8 mmol/L) in statin-treated patients. The primary endpoint was the percentage change in atheroma volume. At baseline and 1 year, participants had coronary plaque characteristics in the non-infarct-related arteries assessed using intravenous ultrasound, near-infrared spectroscopy, and optical coherence tomography. The primary endpoint at 1 year was met; a significantly greater reduction in atheroma volume was measured in the alirocumab arm compared with placebo (2.13% vs 0.92%; P<0.001; see Figure). Furthermore, while no differences were seen between trial arms in all-cause mortality and MI, a significant reduction was measured in non-infarct-related revascularisation in the alirocumab arm (8.2% vs 18.5%; P<0.001). Evidence of PCSK9 inhibition was observed in the 1 year LDL-cholesterol reduction, which averaged 50.7% in the placebo arm and 84.8% in the alirocumab arm. Key secondary endpoints also favoured the alirocumab arm: the reduction in maximum lipid core burden index within 4 mm (79.42 vs 37.60; P=0.006), as well as change in mean minimal fibrous cap thickness (62.67 μm vs 33.19 µm; P=0.001). Figure: Primary endpoint of PACMAN-AMI [1] Prof. Räber noted that the “changes were greatest in patients with lower on-treatment LDL-cholesterol levels <50 mg/dL, which suggests that we should achieve very, very low LDL levels in our patients at very high risk.” Safety results were similar in both trial arms, although there was a slightly higher occurrence of general allergic reactions in the alirocumab arm (3.4% vs 0%, respectively). Prof. Räber suggested that the findings of PACMAN-AMI could be useful when counselling patients with atherosclerosis.
    1. Räber L, et al. 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). Abstract 405–12, ACC 2022, 2–4 April, Washington DC, USA.
    2. Räber L, et al. JAMA. 2022;327(18):1771-1781.
  Copyright ©2022 Medicom Medical Publishers


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Adding the PCSK9 inhibitor alirocumab to high-intensity statin therapy shortly after an acute myocardial infarction (MI) promoted coronary plaque regression better than high-intensity statin therapy alone, based on serial intracoronary imaging performed in the PACMAN-AMI trial. Prof. Lorenz Räber (Bern University Hospital, Switzerland) reported the PACMAN-AMI (NCT03067844) results at the ACC 2022 Scientific Session, which were simultaneously published in JAMA [1,2]. Prof. Räber explained that the unmet need being addressed by PACMAN-AMI was that it is not well known what the impact of PCSK9 inhibition is on high-risk atherosclerotic plaque characteristics, particularly lipid content and fibrous cap thickness. PACMAN-AMI randomised 300 patients with acute ST-elevation myocardial infarction (STEMI) (53%) or non-STEMI (47%) who had undergone successful percutaneous coronary intervention (PCI) of the culprit vessel and in whom at least 2 proximal non-infarct-related arteries had been found with non-obstructive atherosclerosis (20% to 50% diameter stenosis). Half the patients received subcutaneous 150 mg/mL alirocumab and half the patients received placebo, starting within 24 hours after PCI, and then every 2 weeks for 1 year. Only 12% of patients were on statins at baseline; LDL-cholesterol level was >125 mg/dL (3.2 mmol/L) in statin-naïve patients and >70 mg/dL (1.8 mmol/L) in statin-treated patients. The primary endpoint was the percentage change in atheroma volume. At baseline and 1 year, participants had coronary plaque characteristics in the non-infarct-related arteries assessed using intravenous ultrasound, near-infrared spectroscopy, and optical coherence tomography. The primary endpoint at 1 year was met; a significantly greater reduction in atheroma volume was measured in the alirocumab arm compared with placebo (2.13% vs 0.92%; P<0.001; see Figure). Furthermore, while no differences were seen between trial arms in all-cause mortality and MI, a significant reduction was measured in non-infarct-related revascularisation in the alirocumab arm (8.2% vs 18.5%; P<0.001). Evidence of PCSK9 inhibition was observed in the 1 year LDL-cholesterol reduction, which averaged 50.7% in the placebo arm and 84.8% in the alirocumab arm. Key secondary endpoints also favoured the alirocumab arm: the reduction in maximum lipid core burden index within 4 mm (79.42 vs 37.60; P=0.006), as well as change in mean minimal fibrous cap thickness (62.67 μm vs 33.19 µm; P=0.001). Figure: Primary endpoint of PACMAN-AMI [1] Prof. Räber noted that the “changes were greatest in patients with lower on-treatment LDL-cholesterol levels <50 mg/dL, which suggests that we should achieve very, very low LDL levels in our patients at very high risk.” Safety results were similar in both trial arms, although there was a slightly higher occurrence of general allergic reactions in the alirocumab arm (3.4% vs 0%, respectively). Prof. Räber suggested that the findings of PACMAN-AMI could be useful when counselling patients with atherosclerosis.
    1. Räber L, et al. 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). Abstract 405–12, ACC 2022, 2–4 April, Washington DC, USA.
    2. Räber L, et al. JAMA. 2022;327(18):1771-1781.
  Copyright ©2022 Medicom Medical Publishers

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