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Review
. 2025 Feb 28;14(5):353.
doi: 10.3390/cells14050353.

Statins as an Adjunctive Antithrombotic Agent in Thrombotic Antiphospholipid Syndrome: Mechanisms and Clinical Implications

Tommaso Bucci  1   2 , Danilo Menichelli  2   3 , Ilaria Maria Palumbo  2   3 , Daniele Pastori  1   2   4 , Paul R J Ames  5   6 , Gregory Y H Lip  1   7   8 , Pasquale Pignatelli  2
Affiliations
Review

Statins as an Adjunctive Antithrombotic Agent in Thrombotic Antiphospholipid Syndrome: Mechanisms and Clinical Implications

Tommaso Bucci et al. Cells. .

Abstract

The thrombotic physiopathology of antiphospholipid syndrome (APS) is complex, heterogeneous, and dynamic. While venous thromboembolism (VTE) is the most common initial presentation, arterial thrombotic events (ATE) become more frequent in advanced stages and are associated with high morbidity and mortality. Despite the use of oral anticoagulants (OACs), thrombotic APS remains associated with a high risk of recurrent thrombosis. Given their potential antithrombotic effects capable of reducing the risk of both VTE and ATE, statins have been proposed as an adjunctive therapy to OACs for patients with APS and recurrent thrombosis. However, this recommendation is primarily based on studies not specifically conducted in APS populations, with only preclinical data or evidence from retrospective observational studies available from APS patients cohorts. For these reasons, this narrative review aims to synthesise the studies evaluating the potential antithrombotic effects of statins in patients with APS, highlighting the progress made and identifying areas for future research.

Keywords: antiphospholipid syndrome; mechanism; statins; thrombosis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Mechanisms of thrombogenesis in antiphospholipid syndrome. aB2GPI Ab: anti-beta2glycoprotein I antibodies, eNOS: endothelial nitric oxide synthase, FIX/FX/FV/PAI-I: anticoagulation factor IX/X/V/plasminogen activator inhibitor -I, FVII/FVIIa: anticoagulation factor VII/VII activated, FXII: anticoagulation factor XII, NETs: neutrophil extracellular traps, NF-kB: nuclear factor k B, NO: nitric oxide, ox-LDL: oxidised low-density lipoprotein, ROS: reactive oxygen species, TF: tissue factor, tPA: tissue plasminogen activator TXA2: thromboxane A2, vWF: Von Willebrand factor, WBC: white blood cells.
Figure 2
Figure 2
Summary of mechanisms involved in the antithrombotic property of statins. COX-1: cyclooxygenase-1, eNOS: endothelial nitric oxide synthase, FV: factor V, KLF2: Kruppel-like factor 2, NF-kB: nuclear factor k B, NO: nitric oxide, ox-LDL: oxidised low-density lipoprotein, PAI-1: plasminogen activator inhibitor-1, PLA2: phospholipase A2, TF: tissue factor, TM: thrombomodulin, TXA2: thromboxane A2.
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