Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Patients Following Acute Coronary Syndromes: From Lipid Lowering and Plaque Stabilization to Improved Outcomes
Abstract
:1. Introduction
2. Rationale for Post-ACS Lipid Lowering
3. Studies of PCSK9 after ACS
4. PCSK9 Inhibitors Immediately after an Acute Coronary Syndrome
Study | Study Type, Year | PCSK9 Inhibitor | Participants (n) | Setting | Follow-Up | LDL-C Reduction from Baseline | LDL-C Difference at Follow-Up between Groups | Adverse Outcomes | Other Outcomes | |
---|---|---|---|---|---|---|---|---|---|---|
PCSK9i (mg/dL) | Control (mg/dL) | |||||||||
EVOPACS [51] | RCT, 2019 | Evolocumab—420 mg (in-hospital and week 4) | 308 ACS patients (1:1) | ACS, suboptimal LDL-C | 8 weeks | 139.6 to 30.55 | 132.25 to 79.66 | −40.7% (95% CI: −45.2 to −36.2; p < 0.001) | No difference between groups | LDL-C < 70 mg/dL; PCSK9i: 95.7% control: 37.6% |
VCU-AlirocRT [52] | RCT, 2019 | Alirocumab—150 mg (in-hospital) | 20 ACS patients (1:1) | NSTEMI, LDL-C > 70 mg/dL on statin | 14 days | 91 to 28 | 98 to 90 | NR | None related to treatment | No difference in hs-CRP |
EVACS I [53] | RCT, 2020 | Evolocumab—420 mg (in-hospital) | 57 ACS patients | NSTEMI | 30 days | 91.5 to 35.9 | 89.6 to 64.5 | Evolocumab arm LDL-C a mean of 28.6 mg/dL lower than placebo (p < 0.001) | None related to treatment | LDL-C at targets: PCSK9i: 65.4–80.8% control: 23.8–38.1% (p = 0.01) |
Vavuranakis et al. [54] | RCT, 2022 | Evolocumab—420 mg (in-hospital) | 74 ACS patients | NSTEMI | 30 days | NR | NR | NR | None related to treatment | Lp(a): PCSK9i: 49 to 44 nmol/L (p = NS) control: 64 to 82 nmol/L (p < 0.01) |
EPIC-STEMI [56] | RCT, 2022 | Alirocumab—150 mg (pre-PCI, 2 weeks, 4 weeks) | 68 ACS patients | STEMI | 6 weeks | 114.85 to 29 | 110.98 to 50.27 | −22.3% (95% CI: −31.1 to −13.5; p < 0.001). | None related to treatment | LDL-C at targets: PCSK9i: 92.1% control: 56.7% |
Xu et al. [57] | Prospective, 2021 | Evolocumab—140 mg (in-hospital and every 2 weeks) | 334 ACS patients (96 PCSK9i vs. 238 control) | NSTEMI, suboptimal LDL-C | 12 weeks | 143 to 27 | 127.6 to 77.4 | −41.8% (95% CI −45.0 to −38.5%; p < 0.001) | No significant differences | LDL-C <55 mg/dL PCSK9i: 90.6% control: 7.1% |
Zhang et al. [58] | Retrospective, 2022 | Evolocumab—140 mg (in-hospital and every 2 weeks | 1654 ACS patients (414 PCSK9; 1150 Control) | ACS, suboptimal LDL-C | 18 months | 129.2 to 28.6 | 126 to 78.1 | −42.48 (−40.51 to −44.45; p < 0.001) | Composite of ischemic events and mortality: PCSK9i: 8.2% vs. control: 12.4%; HR: 0.65; 95% CI, 0.45–0.95) No safety events | LDL-C < 55 mg/dL PCSK9i: 91.6% control: 10.7% |
Hao et al. [59] | RCT, 2022 | Evolocumab—140 mg (in-hospital and every 2 weeks | 136 ACS patients | High-risk ACS, suboptimal LDL-C | 3 months | 136.9 to 22.4 | 136.2 to 49.1 | −83.9% vs. −63.9% | MACE: PCSK9i: 88% vs. control: 24.6%; p = 0.015 | LDL-C at targets: PCSK9i: 82.4% control: 22% |
5. PCSK9 Inhibitors in Acute Coronary Syndromes: More than Lipid Lowering
5.1. PCSK9 and Plaque Modification
5.2. PCSK9 Inhibition and Microcirculation
5.3. PCSK9 Inhibition and Platelet Function
6. Future Directions
7. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Dimitriadis, K.; Pyrpyris, N.; Iliakis, P.; Beneki, E.; Adamopoulou, E.; Papanikolaou, A.; Konstantinidis, D.; Fragkoulis, C.; Kollias, A.; Aznaouridis, K.; et al. Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Patients Following Acute Coronary Syndromes: From Lipid Lowering and Plaque Stabilization to Improved Outcomes. J. Clin. Med. 2024, 13, 5040. https://doi.org/10.3390/jcm13175040
Dimitriadis K, Pyrpyris N, Iliakis P, Beneki E, Adamopoulou E, Papanikolaou A, Konstantinidis D, Fragkoulis C, Kollias A, Aznaouridis K, et al. Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Patients Following Acute Coronary Syndromes: From Lipid Lowering and Plaque Stabilization to Improved Outcomes. Journal of Clinical Medicine. 2024; 13(17):5040. https://doi.org/10.3390/jcm13175040
Chicago/Turabian StyleDimitriadis, Kyriakos, Nikolaos Pyrpyris, Panagiotis Iliakis, Eirini Beneki, Eleni Adamopoulou, Aggelos Papanikolaou, Dimitrios Konstantinidis, Christos Fragkoulis, Anastasios Kollias, Konstantinos Aznaouridis, and et al. 2024. "Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Patients Following Acute Coronary Syndromes: From Lipid Lowering and Plaque Stabilization to Improved Outcomes" Journal of Clinical Medicine 13, no. 17: 5040. https://doi.org/10.3390/jcm13175040