PCSK9 inhibitors in peripheral arterial disease: a systematic review
File(s)
Published version
Author(s)
Bandukwala, Lameeya Murtaza
Curley, Daniel
Bontinis, Alkis
Bontinis, Vangelis
Shalhoub, Joseph
Type
Journal Article
Abstract
Background
Dyslipidaemia is a key modifiable risk factor for peripheral arterial disease (PAD), and statin therapy for lipid-lowering is well established in its management. Proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors lower lipids and cardiovascular risk; however, their impact on limb-based outcomes in PAD remains uncertain.
Methods
A systematic review was conducted in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Studies evaluating PCSK9 inhibitor therapy in patients with PAD were eligible for inclusion.
Results
Four studies met the inclusion criteria and were included in the review, comprising three randomized controlled trials (RCTs) and 1 prospective case series, with a total of 3,770 patients. The majority of included participants were derived from a large multicenter RCT, FOURIER, which contributed 3,642 patients from its PAD subgroup. In the FOURIER PAD subgroup, Evolocumab significantly reduced major adverse limb events (MALEs) compared with placebo in patients receiving background statin therapy (Hazard Ratio 0.58; 95% Confidence Interval 0.38–0.88). Smaller studies in patients with PAD and chronic limb-threatening ischemia reported improvements in amputation-free survival, wound healing, walking performance, and markers of endothelial function and atherosclerotic burden.
Conclusion
PCSK9 inhibitors appear to provide limb-related benefits in patients with PAD, without ill-effects. These benefits include decrease in MALEs and improvements in functional and physiological parameters, and may extend beyond lipid lowering alone. However, current evidence is limited, heterogeneous, and exploratory. Dedicated, adequately powered randomized trials focusing on clearly defined limb outcomes are needed to clarify the role of PCSK9 inhibitors in PAD management.
Dyslipidaemia is a key modifiable risk factor for peripheral arterial disease (PAD), and statin therapy for lipid-lowering is well established in its management. Proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors lower lipids and cardiovascular risk; however, their impact on limb-based outcomes in PAD remains uncertain.
Methods
A systematic review was conducted in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Studies evaluating PCSK9 inhibitor therapy in patients with PAD were eligible for inclusion.
Results
Four studies met the inclusion criteria and were included in the review, comprising three randomized controlled trials (RCTs) and 1 prospective case series, with a total of 3,770 patients. The majority of included participants were derived from a large multicenter RCT, FOURIER, which contributed 3,642 patients from its PAD subgroup. In the FOURIER PAD subgroup, Evolocumab significantly reduced major adverse limb events (MALEs) compared with placebo in patients receiving background statin therapy (Hazard Ratio 0.58; 95% Confidence Interval 0.38–0.88). Smaller studies in patients with PAD and chronic limb-threatening ischemia reported improvements in amputation-free survival, wound healing, walking performance, and markers of endothelial function and atherosclerotic burden.
Conclusion
PCSK9 inhibitors appear to provide limb-related benefits in patients with PAD, without ill-effects. These benefits include decrease in MALEs and improvements in functional and physiological parameters, and may extend beyond lipid lowering alone. However, current evidence is limited, heterogeneous, and exploratory. Dedicated, adequately powered randomized trials focusing on clearly defined limb outcomes are needed to clarify the role of PCSK9 inhibitors in PAD management.
Date Issued
2026-07-01
Date Acceptance
2026-03-05
Citation
Annals of Vascular Surgery, 2026, 128, pp.395-401
ISSN
0890-5096
Publisher
Elsevier BV
Start Page
395
End Page
401
Journal / Book Title
Annals of Vascular Surgery
Volume
128
Copyright Statement
© 2026 Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/ 4.0/).
License URL
Identifier
10.1016/j.avsg.2026.03.025
Publication Status
Published
Date Publish Online
2026-03-25