Log in to MyACC
Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction - PACMAN-AMI
Contribution To Literature:
Highlighted text has been updated as of November 7, 2024.
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.
Description:
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).
Study Design
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%
Inclusion criteria:
- 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
Exclusion criteria:
- 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%
Principal Findings:
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%
Triple regression: Defined as combined presence of percent atheroma volume (PAV) reduction, maximum lipid core burden index within 4 mm (maxLCBI4mm) reduction, and minimal fibrous cap thickness (FCT) increase on serial multimodality intracoronary imaging. Data available for 265 patients; 31.7% had evidence of triple regression at 52 weeks. Overall, 75.1% of patients showed PAV reduction, 64.1% reduction in maxLCBI4mm, and 64.9% increase in minimal FCT. Multivariable analysis identified maxLCBI4mm (odds ratio [OR] 1.03, 1.01 to 1.06, p = 0.013) and alirocumab treatment (OR 2.83, 1.57 to 5.16, p = 0.001) as independent predictors of triple regression. The incidence of the composite endpoint was lower in patients with triple regression as compared with patients without (8.3% vs. 18.2%, p = 0.042). This result was primarily driven by a trend for lower risk of ischemia-driven revascularization (8.3% vs. 17.7%, p = 0.06).
Lesion-level analysis: In a post hoc lesion-level analysis, nonculprit lesions were identified as segments with plaque burden ≥40% defined by IVUS. 591 lesions were included for this analysis: 287 lesions (118 patients, 214 vessels) in the alirocumab group and 304 lesions (127 patients, 239 vessels) in the placebo group. Lesion-level mean change in percent atheroma volume (PAV) was −4.86% with alirocumab vs. −2.78% with placebo (difference, −2.02; 95% CI, −3.00 to −1.05; p < 0.001). At the minimum lumen area site, mean change in PAV was −10.14% with alirocumab vs. −6.70% with placebo (difference, −3.36; 95% CI, −4.98 to −1.75; p < 0.001). Among 122 lipid-rich lesions, 61.8% in the alirocumab arm and 41.8% in the placebo arm showed a less lipid-rich plaque phenotype at follow-up (p = 0.03). Among 63 lesions with thin-cap fibroatheroma at baseline, 30.8% in the alirocumab arm and 8.1% in the placebo arm showed a fibrous/fibrocalcific plaque phenotype at follow-up (p = 0.02).
Interpretation:
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. Clinical events were low. About one-third of patients achieved so-called “triple regression” of plaque, and this was higher among patients on alirocumab and those with higher baseline lipid accumulation. Patients who achieved triple regression had better clinical outcomes compared with those who did not. Lesion analysis confirmed PAV regression and conversion of presumed high-risk plaque to more stable, less lipid-rich plaque, although this latter aspect needs to be further validated.
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.
References:
Biccirè FG, Kakizaki R, Koskinas KC, et al. Lesion-Level Effects of LDL-C–Lowering Therapy in Patients With Acute Myocardial Infarction: A Post Hoc Analysis of the PACMAN-AMI Trial. JAMA Cardiol 2024;Sep 2:[Epublished].
Biccirè FG, Häner J, Losdat S, et al. Concomitant Coronary Atheroma Regression and Stabilization in Response to Lipid-Lowering Therapy: A PACMAN-AMI Trial Subanalysis. J Am Coll Cardiol 2023;82:1737-47.
Presented by Dr. Flavio G. Biccirè at the European Society of Cardiology Congress, Amsterdam, Netherlands, August 26, 2023.
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;327:1771-81.
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, Cardiovascular Care Team, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, Vascular Medicine, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Interventions and ACS, Interventions and Vascular Medicine, Chronic Angina
Keywords: ACC22, ACC Annual Scientific Session, Acute Coronary Syndrome, ESC Congress, ESC23, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Non-ST Elevated Myocardial Infarction, PCSK9 protein, human, Percutaneous Coronary Intervention, Plaque, Atherosclerotic, Proprotein Convertase 9, ST Elevation Myocardial Infarction
< Back to Listings
