Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction - PACMAN-AMI
Contribution To Literature:
The PACMAN-AMI trial showed that, compared with placebo, administration of alirocumab 150 mg biweekly within 24 hours after PCI for AMI results in a greater reduction in plaque burden and plaque regression at 52 weeks in the nonculprit vessel. All patients were also on high-dose rosuvastatin.
The goal of the trial was to demonstrate the efficacy of early administration of alirocumab on plaque characteristics among patients undergoing percutaneous coronary intervention (PCI) for an acute myocardial infarction (AMI).
After PCI of the culprit lesion in the infarct-related artery (IRA), eligible patients underwent intracoronary imaging of the two non-IRAs and, if successful, they were randomly allocated in a 1:1 fashion to receive either 150 mg alirocumab (n = 148) or placebo (n = 152), administered biweekly via subcutaneous injection for 52 weeks. The first dose of the study drug was administered within 24 hours after PCI, without dose adjustment during the study period. Patients in both treatment groups received 20 mg of rosuvastatin daily, without change in type or dose of statin during the course of the study.
- Total screened: 1,636
- Total number of enrollees: 300
- Duration of follow-up: 1 year
- Mean patient age: 58 years
- Percentage female: 18%
- Percentage with diabetes: 10%
- Age ≥18 years
- Successful PCI of culprit vessel for AMI (non–ST-segment elevation myocardial infarction [NSTEMI] or STEMI)
- Suitable for intracoronary imaging with angiographic stenosis >20% but <50% in proximal portion of two non-IRAs
- Low-density lipoprotein cholesterol (LDL-C) at baseline ≥125 mg/dl if not on statin for 4 weeks, ≥70 mg/dl if on stable dose of statin for 4 weeks
- Left main or three-vessel disease
- History of coronary artery bypass grafting
- Severe chronic kidney disease or liver disease
- Known statin intolerance
Other salient features/characteristics:
- Statin use: 12%
- Index event: STEMI 53%, NSTEMI 47%
The primary endpoint, change in mean percent atheroma volume (PAV) from baseline, for alirocumab vs. placebo, was -2.13% vs. -0.92% (p < 0.001).
Secondary outcomes for alirocumab vs. placebo:
- Normalized total atheroma volume: -26.12 mm3 vs. -14.97 mm3 (p < 0.001)
- Patients with % PAV regression: 84.6% vs. 65.9% (p < 0.001)
- Total lipid core burden index (on near-infrared spectroscopy imaging): -29.3 vs. -12.38 (p = 0.004)
- Change in LDL-C from baseline: -131.2 vs. -76.5 mg/dl (p < 0.001)
- Change in HDL-C from baseline: 7 vs. 3.7% (p < 0.001)
- Clinical events: all-cause mortality: 1.4% vs. 0.7% (p > 0.05); ischemia-driven coronary revascularization: 8.2% vs. 18.5%
The results of this trial indicate that compared with placebo, administration of alirocumab 150 mg biweekly within 24 hours after PCI for AMI results in a greater reduction in plaque burden and plaque regression at 52 weeks in the nonculprit vessel. All patients were also on high-dose rosuvastatin. LDL-C levels were reduced by nearly 85% with alirocumab + rosuvastatin compared with 51% with rosuvastatin alone. Clinical events were low.
These are important data and provide further data regarding the utility of PCSK9 monoclonal antibodies for secondary prevention in high-risk patients (such as those with AMI) as combination therapy with high-dose statin therapy. In the ODYSSEY OUTCOMES trial, a similar reduction in LDL-C was noted with alirocumab, with a significant reduction in major adverse cardiovascular events when initiated 1-12 months (median 2.6 months) after an ACS presentation. This trial suggests that earlier initiation of the medication could be considered in high-risk patients.
Räber L, Ueki Y, Otsuk T, et al., on behalf of the PACMAN-AMI Collaborators. Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction: The PACMAN-AMI Randomized Clinical Trial. JAMA 2022;Apr 3:[Epub ahead of print].
Presented by Dr. Lorenz Raber at the American College of Cardiology Annual Scientific Session (ACC 2022), Washington, DC, April 3, 2022.
Clinical Topics: Acute Coronary Syndromes, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Stable Ischemic Heart Disease, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Nonstatins, Novel Agents, Statins, Interventions and ACS, Interventions and Coronary Artery Disease, Interventions and Imaging, Interventions and Vascular Medicine, Angiography, Nuclear Imaging, Chronic Angina
Keywords: ACC22, ACC Annual Scientific Session, Acute Coronary Syndrome, Cholesterol, LDL, Constriction, Pathologic, Coronary Angiography, Coronary Artery Disease, Diagnostic Imaging, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Non-ST Elevated Myocardial Infarction, PCSK9 protein, human, Percutaneous Coronary Intervention, Plaque, Atherosclerotic, Proprotein Convertase 9, Rosuvastatin Calcium, Secondary Prevention, Spectroscopy, Near-Infrared, ST Elevation Myocardial Infarction
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