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

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2025 Mar 12

PMID 40072082

Authors

Tommaso Bucci

Danilo Menichelli

Ilaria Maria Palumbo

Daniele Pastori

Paul R J Ames

Gregory Y H Lip

Pasquale Pignatelli

Affiliations

Soon will be listed here.

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.

References

Ferrara D, Swerlick R, Casper K, Meroni P, Vega-Ostertag M, Harris E . Fluvastatin inhibits up-regulation of tissue factor expression by antiphospholipid antibodies on endothelial cells. J Thromb Haemost. 2004; 2(9):1558-63. DOI: 10.1111/j.1538-7836.2004.00896.x. View

Pastori D, Menichelli D, Cammisotto V, Pignatelli P . Use of Direct Oral Anticoagulants in Patients With Antiphospholipid Syndrome: A Systematic Review and Comparison of the International Guidelines. Front Cardiovasc Med. 2021; 8:715878. PMC: 8368436. DOI: 10.3389/fcvm.2021.715878. View

Hirsh J, Warkentin T, Raschke R, Granger C, Ohman E, Dalen J . Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest. 1998; 114(5 Suppl):489S-510S. DOI: 10.1378/chest.114.5_supplement.489s. View

Kunutsor S, Seidu S, Khunti K . Statins and primary prevention of venous thromboembolism: a systematic review and meta-analysis. Lancet Haematol. 2017; 4(2):e83-e93. DOI: 10.1016/S2352-3026(16)30184-3. View

Ferrara D, Liu X, Espinola R, Meroni P, Abukhalaf I, Harris E . Inhibition of the thrombogenic and inflammatory properties of antiphospholipid antibodies by fluvastatin in an in vivo animal model. Arthritis Rheum. 2003; 48(11):3272-9. DOI: 10.1002/art.11449. View

Hulten E, Jackson J, Douglas K, George S, Villines T . The effect of early, intensive statin therapy on acute coronary syndrome: a meta-analysis of randomized controlled trials. Arch Intern Med. 2006; 166(17):1814-21. DOI: 10.1001/archinte.166.17.1814. View

Korbecki J, Baranowska-Bosiacka I, Gutowska I, Chlubek D . The effect of reactive oxygen species on the synthesis of prostanoids from arachidonic acid. J Physiol Pharmacol. 2013; 64(4):409-21. View

Cervera R, Serrano R, Pons-Estel G, Ceberio-Hualde L, Shoenfeld Y, de Ramon E . Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis. 2014; 74(6):1011-8. DOI: 10.1136/annrheumdis-2013-204838. View

Bertolaccini M, Amengual O, Andreoli L, Atsumi T, Chighizola C, Forastiero R . 14th International Congress on Antiphospholipid Antibodies Task Force. Report on antiphospholipid syndrome laboratory diagnostics and trends. Autoimmun Rev. 2014; 13(9):917-30. DOI: 10.1016/j.autrev.2014.05.001. View

10.

Harm T, Frey M, Dittrich K, Goldschmied A, Rohlfing A, Fu X . Statin Treatment Is Associated with Alterations in the Platelet Lipidome. Thromb Haemost. 2023; 123(6):585-596. DOI: 10.1055/s-0043-1764353. View

11.

Parmar G, Novak Z, Spangler E, Patterson M, Passman M, Beck A . Statin use improves limb salvage after intervention for peripheral arterial disease. J Vasc Surg. 2019; 70(2):539-546. DOI: 10.1016/j.jvs.2018.07.089. View

12.

Kunutsor S, Seidu S, Khunti K . Statins and secondary prevention of venous thromboembolism: pooled analysis of published observational cohort studies. Eur Heart J. 2017; 38(20):1608-1612. PMC: 5837543. DOI: 10.1093/eurheartj/ehx107. View

13.

Yang Y, Chien D, Wu M, FitzGerald J, Grossman J, Hahn B . Novel autoantibodies against the activated coagulation factor IX (FIXa) in the antiphospholipid syndrome that interpose the FIXa regulation by antithrombin. J Immunol. 2009; 182(3):1674-80. DOI: 10.4049/jimmunol.182.3.1674. View

14.

Rice J, Stoll L, Li W, Denning G, Weydert J, Charipar E . Low-level endotoxin induces potent inflammatory activation of human blood vessels: inhibition by statins. Arterioscler Thromb Vasc Biol. 2003; 23(9):1576-82. DOI: 10.1161/01.ATV.0000081741.38087.F9. View

15.

Verro P, Levine S, Tietjen G . Cerebrovascular ischemic events with high positive anticardiolipin antibodies. Stroke. 1998; 29(11):2245-53. DOI: 10.1161/01.str.29.11.2245. View

16.

Jajoria P, Murthy V, Papalardo E, Romay-Penabad Z, Gleason C, Pierangeli S . Statins for the treatment of antiphospholipid syndrome?. Ann N Y Acad Sci. 2009; 1173:736-45. DOI: 10.1111/j.1749-6632.2009.04815.x. View

17.

Bucci T, Ames P, Triggiani M, Parente R, Ciampa A, Pignatelli P . Cardiac and vascular features of arterial and venous primary antiphospholipid syndrome. The multicenter ATHERO-APS study. Thromb Res. 2021; 209:69-74. DOI: 10.1016/j.thromres.2021.12.001. View

18.

Ieko M, Nakabayashi T, Takeda M, Naitoh S, Atsumi T, Koike T . The inhibition of protein C anticoagulant activity by anti-β2-glycoprotein I (β2GPI) antibodies isolated from patients with antiphospholipid syndrome by chromatography methods. Mod Rheumatol. 2014; 12(1):44-9. DOI: 10.3109/s101650200007. View

19.

Ferro D, Basili S, Alessandri C, Mantovani B, Cordova C, Violi F . Simvastatin reduces monocyte-tissue-factor expression type IIa hypercholesterolaemia. Lancet. 1998; 350(9086):1222. DOI: 10.1016/S0140-6736(05)63452-6. View

20.

Bucci T, Merashli M, Pignatelli P, Pastori D, Delgado-Alves J, Lip G . Intima media thickness of the carotid artery in primary antiphospholipid syndrome: A systematic review and meta-analysis. Autoimmun Rev. 2024; 23(11):103657. DOI: 10.1016/j.autrev.2024.103657. View