Points
- The results of the PACMAN-AMI clinical trial showed a reduction in both mean PAV and lipid core burden index after 52 weeks of alirocumab therapy compared to a placebo control
- Coronary plaque characteristics for PCSK9i-treated patients also displayed LDL-C levels below current guideline thresholds
- PACMAN-AMI showed the benefits of pairing aggressive lipid-lowering strategies and PCSK9i treatment with statin therapy
Summary
Schwartz et al (2018) reported that previous results under the ODYSSEY OUTCOMES trial showed the risk-reducing effect of alirocumab, a proprotein convertase subtilisin-kexin type 9 inhibitor (PCSK9i), when added to high-intensity statin therapy. Alongside this, it should also be noted that patients with a history of acute myocardial infarction (AMI) remain at risk for recurrent ischemic cardiovascular events despite early starts of statin therapy.
According to studies by Nicholis et al (2016) and Nicholis et al (2021), trials like the GLAGOV and HUYGENS trials delved deeper into the effects of PCSK9i treatment with evolocumab in stable coronary artery disease patients; there, they found favorable changes to coronary plaque characteristics. Of particular interest is alterations in plaque characteristics in patients with early PCSK9i treatment after AMI beacuse high-risk lesions are associated with non-infarct-related arteries (IRA).
Addressing these concerns is the Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction (PACMAN-AMI) clinical trial, a randomized placebo-controlled double-blinded clinical trial. There, 300 patients who went through successful percutaneous coronary intervention (PCI) for AMI enrolled in biweekly subcutaneous alirocumab treatment or a placebo within 24 hours of their PCI paired with high-intensity statin treatment (Raber et al, 2022).
Primary endpoint analysis through intravascular ultrasound (IVUS) showed a greatly reduced mean percent atheroma volume (PAV) after 52 weeks of alirocumab therapy (-2.13% vs. -0.92% in alirocumab vs. placebo, p < 0.001). Secondary endpoints, on the other hand, were assessed by near-infrared spectroscopy (NIRS) and showed a lipid core burden index reduction. Additionally, this was accompanied by a great increase in minimal fibrous cap thickness in the alirocumab arm, which was observed with optical coherence tomography (OCT). The studies between groups all showed similar adverse effects.
Evaluation via invasive imaging techniques allowed for coronary plaque characterization, including composition, phenotype, and evolution in multiple non-IRAs. LDL-C levels for plaque from PCSK9i-treated patients were found to be below current guideline thresholds (mean LDL-C 23.6 mg/dL in the alirocumab group compared with 74.4 mg/dL in the placebo group, mean change in LDL-C from baseline -131.2 vs. -76.5 mg/dL, p < 0.001). Alongside this, the treatment translated to a greater reduction in IVUS-derived PAV.
Overall, PACMAN-AMI showed the benefits of an aggressive combination lipid-lowering strategy together with PCSK9i treatment under the support of high-risk statin therapy. These results suggest that LDL-C lowering may lead to beneficial changes in coronary plaque. However, the effect of plaque volume reduction and characteristics change on clinical outcomes remains yet to be demonstrated.
References Nicholls, S. J., Nissen, S. E., Prati, F., Windecker, S., Kataoka, Y., Puri, R., Hucko, T., Kassahun, H., Liao, J., Somaratne, R., Butters, J., Di Giovanni, G., Jones, S., & Psaltis, P. J. (2021). Assessing the impact of PCSK9 inhibition on coronary plaque phenotype with optical coherence tomography: Rationale and design of the randomized, placebo-controlled HUYGENS study. Cardiovascular Diagnosis and Therapy, 11(1), 120–129. https://doi.org/10.21037/cdt-20-684 Nicholls, S. J., Puri, R., Anderson, T., Ballantyne, C. M., Cho, L., Kastelein, J. J. P., Koenig, W., Somaratne, R., Kassahun, H., Yang, J., Wasserman, S. M., Scott, R., Ungi, I., Podolec, J., Ophuis, A. O., Cornel, J. H., Borgman, M., Brennan, D. M., & Nissen, S. E. (2016). Effect of evolocumab on progression of coronary disease in statin-treated patients: The glagov randomized clinical trial. JAMA, 316(22), 2373–2384. https://doi.org/10.1001/jama.2016.16951 Räber, L., Ueki, Y., Otsuka, T., Losdat, S., Häner, J. D., Lonborg, J., Fahrni, G., Iglesias, J. F., van Geuns, R.-J., Ondracek, A. S., Radu Juul Jensen, M. D., Zanchin, C., Stortecky, S., Spirk, D., Siontis, G. C. M., Saleh, L., Matter, C. M., Daemen, J., Mach, F., … PACMAN-AMI collaborators. (2022). 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, 327(18), 1771–1781. https://doi.org/10.1001/jama.2022.5218 Schwartz, G. G., Steg, P. G., Szarek, M., Bhatt, D. L., Bittner, V. A., Diaz, R., Edelberg, J. M., Goodman, S. G., Hanotin, C., Harrington, R. A., Jukema, J. W., Lecorps, G., Mahaffey, K. W., Moryusef, A., Pordy, R., Quintero, K., Roe, M. T., Sasiela, W. J., Tamby, J.-F., … ODYSSEY OUTCOMES Committees and Investigators. (2018). Alirocumab and cardiovascular outcomes after acute coronary syndrome. The New England Journal of Medicine, 379(22), 2097–2107. https://doi.org/10.1056/NEJMoa1801174
