Thromb Haemost 2023; 123(06): 573-575
DOI: 10.1055/a-2052-9650
Invited Editorial Focus

Statin Treatment and the Alterations in the Platelet Lipidome: What Is the Impact of Lipid Profile on Thrombosis?

1   Division of General Internal Medicine & Family Medicine, Department of General and Acute Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan
2   Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States
3   Department of Medicine (Cardiology), Tokai University School of Medicine, Isehara, Kanagawa, Japan
› Author Affiliations

The Association of Lipid and Thrombosis: Current Evidence

It is well known that low-density lipoprotein (LDL) plays important roles in thrombosis[1] such as major adverse cardiovascular events (MACEs) including cardiovascular death, myocardial infarction, and ischemic stroke. A large body of clinical evidence has clearly shown that statin treatments lower the risk of thrombosis-related MACE, especially in arterial diseases.[2] Recent clinical studies testing the efficacy of nonstatin lipid-lowering agents have also shown that these medications further reduce the risk of thrombosis-related MACE and have supported the idea of the so-called “lower the better” strategy for LDL.[3] [4] However, there is still an ongoing debate on whether statin has a pleiotropic effect over simple LDL reduction.

In contrast to the success in targeting LDL, clinical trials targeting lipids other than LDL have largely failed to show efficacy in preventing thrombosis. These results suggested that simple lowering/increasing of a lipid family other than LDL have limited effect for thrombosis-related MACE. However, lipids are an important component in the cell membrane and have complex biological functions. It could have complex associations with the progression of atherosclerosis and thrombosis-related MACE that are not reflected in simple lowering/increasing. There may also be functionally synergistic actions between antiplatelet and lipid-lowering drugs, which may reduce the incidence of atherothrombotic vascular events, as recently reviewed.[5]

Publication History

Received: 06 March 2023

Accepted: 07 March 2023

Accepted Manuscript online:
13 March 2023

Article published online:
03 April 2023

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  • Reference

  • 1 Arnett DK, Blumenthal RS, Albert MA. et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019; 140 (11) e596-e646
  • 2 Pastori D, Farcomeni A, Milanese A. et al. Statins and major adverse limb events in patients with peripheral artery disease: a systematic review and meta-analysis. Thromb Haemost 2020; 120 (05) 866-875
  • 3 Cannon CP, Blazing MA, Giugliano RP. et al; IMPROVE-IT Investigators. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015; 372 (25) 2387-2397
  • 4 Sabatine MS, Giugliano RP, Keech AC. et al; FOURIER Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017; 376 (18) 1713-1722
  • 5 Schrör K, Verheugt FWA, Trenk D. Drug-drug interaction between antiplatelet therapy and lipid-lowering agents (statins and PCSK9 inhibitors). Thromb Haemost 2023; 123 (02) 166-176
  • 6 Harm T, Frey M, Dittrich K. et al. Statin treatment is associated with alterations in the platelet lipidome. Thromb Haemost 2023; 123 (06) 585-596
  • 7 Stellos K, Sauter R, Fahrleitner M. et al. Binding of oxidized low-density lipoprotein on circulating platelets is increased in patients with acute coronary syndromes and induces platelet adhesion to vascular wall in vivo–brief report. Arterioscler Thromb Vasc Biol 2012; 32 (08) 2017-2020
  • 8 Faber J, Hvas AM, Kristensen SD, Grove EL, Adelborg K. Immature platelets and risk of cardiovascular events among patients with ischemic heart disease: a systematic review. Thromb Haemost 2021; 121 (05) 659-675
  • 9 Maly M, Riedel T, Stikarova J. et al. Incorporation of fibrin, platelets, and red blood cells into a coronary thrombus in time and space. Thromb Haemost 2022; 122 (03) 434-444
  • 10 Goto S, Goto S. Selection of a suitable patient population for new antiplatelet therapy from the large clinical trial database of the thrombin receptor antagonist in secondary prevention of atherothrombotic ischemic events-thrombolysis in myocardial infarction 50 (TRA-2P-TIMI50) trial. Circulation 2015; 131 (12) 1041-1043
  • 11 Komatsuya K, Kaneko K, Kasahara K. Function of platelet glycosphingolipid microdomains/lipid rafts. Int J Mol Sci 2020; 21 (15) 21
  • 12 Wei H, Malcor JM, Harper MT. Lipid rafts are essential for release of phosphatidylserine-exposing extracellular vesicles from platelets. Sci Rep 2018; 8 (01) 9987
  • 13 Goto S, Tamura N, Handa S, Arai M, Kodama K, Takayama H. Involvement of glycoprotein VI in platelet thrombus formation on both collagen and von Willebrand factor surfaces under flow conditions. Circulation 2002; 106 (02) 266-272
  • 14 Huang M, Rigby AC, Morelli X. et al. Structural basis of membrane binding by Gla domains of vitamin K-dependent proteins. Nat Struct Biol 2003; 10 (09) 751-756
  • 15 Suzuki J, Umeda M, Sims PJ, Nagata S. Calcium-dependent phospholipid scrambling by TMEM16F. Nature 2010; 468 (7325): 834-838
  • 16 Hoshiba Y, Hatakeyama K, Tanabe T, Asada Y, Goto S. Co-localization of von Willebrand factor with platelet thrombi, tissue factor and platelets with fibrin, and consistent presence of inflammatory cells in coronary thrombi obtained by an aspiration device from patients with acute myocardial infarction. J Thromb Haemost 2006; 4 (01) 114-120
  • 17 Goto S, Tamura N, Eto K, Ikeda Y, Handa S. Functional significance of adenosine 5′-diphosphate receptor (P2Y(12)) in platelet activation initiated by binding of von Willebrand factor to platelet GP Ibalpha induced by conditions of high shear rate. Circulation 2002; 105 (21) 2531-2536