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. 2025 Jan 30;87(2):891-899.
doi: 10.1097/MS9.0000000000002927. eCollection 2025 Feb.

Evaluating the role of PCSK9 inhibitors in reducing cardiovascular events among statin-intolerant patients: a systematic review and meta-analysis

Muhammad Farhan  1 , Gumana Ashraf Hussein  2 , Thuraya Alom  2 , Arghadip Das  3 , Tooba Ahmed Durrani  2 , Zahraa Mohamed Hayani  2 , Abdulrahman Alkassar  1 , Hala Ashraf Oweis  2 , Muhammad Hashir Nazir  4 , Damandeep Kaur Dhillon  5 , Ernst Servil  5 , Tirath Patel  6
Affiliations

Evaluating the role of PCSK9 inhibitors in reducing cardiovascular events among statin-intolerant patients: a systematic review and meta-analysis

Muhammad Farhan et al. Ann Med Surg (Lond). .

Abstract

Objective: To assess the efficacy and safety of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors in reducing major adverse cardiovascular events (MACE) in statin-intolerant patients, focusing on low-density lipoprotein cholesterol (LDL-C) reduction and cardiovascular outcomes.

Methods: A systematic review and meta-analysis were conducted according to the PRISMA guidelines. Randomised control trails (RCTs) and observational studies from PubMed, Cochrane Library, and Web of Science databases were included. Independent reviewers extracted the data, and the analyses were performed using fixed- and random-effects models. Heterogeneity was evaluated using the I2 statistic and publication bias was assessed using Egger's test.

Results: Fifteen studies involving 69-18 924 participants were included. PCSK9 inhibitors reduced LDL-C levels by 50-70% and lowered the risk of MACE by 12% (OR 0.88). Minimal heterogeneity (I2 = 0%) indicated consistency across studies. Subgroup analysis showed greater efficacy in high-risk populations (e.g., acute coronary syndrome and familial hypercholesterolemia). Adverse events were mild, with minimal muscle-related side effects.

Conclusion: PCSK9 inhibitors are effective and safe alternatives for LDL-C reduction and cardiovascular risk mitigation in patients with statin intolerance. Their efficacy, favorable safety profile, and consistency across studies highlight their potential for managing dyslipidemia, particularly in high-risk groups. Further research on long-term outcomes is required.

Keywords: LDL-C reduction; PCSK9 inhibitors; cardiovascular risk; lipid-lowering therapy; major adverse cardiovascular events (MACE); statin intolerance.

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Conflict of interest statement

All the authors declare to have no conflicts of interest relevant to this study.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
PRISMA framework for analysis.
Figure 2.
Figure 2.
Forest plot of MACE reduction.
Figure 3.
Figure 3.
Funnel plot for publication bias.
See this image and copyright information in PMC

References

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