Effect of Statins on Platelet Activation and Function: From Molecular Pathways to Clinical Effects

Abstract

Purpose. Statins are a class of drugs widely used in clinical practice for their lipid-lowering and pleiotropic effects. In recent years, a correlation between statins and platelet function has been unveiled in the literature that might introduce new therapeutic indications for this class of drugs. This review is aimed at summarizing the mechanisms underlying statin-platelet interaction in the cardiologic scenario and building the basis for future in-depth studies. Methods. We conducted a literature search through PubMed, Embase, EBSCO, Cochrane Database of Systematic Reviews, and Web of Science from their inception to June 2020. Results. Many pathways could explain the interaction between statins and platelets, but the specific effect depends on the specific compound. Some could be mediated by enzymes that allow the entry of drugs into the cell (OATP2B1) and others by enzymes that mediate their activation (PLA2, MAPK, TAX2, PPARs, AKT, and COX-1), recruitment and adhesion (LOX-1, CD36, and CD40L), or apoptosis (BCL2). Statins also appear to have a synergistic effect with aspirin and low molecular weight heparins. Surprisingly, they seem to have an antagonistic effect with clopidogrel. Conclusion. There are many pathways potentially responsible for the interactions between statins and platelets. Their effect appears to be closely related, and each single effect can be barely measured. Also, the same compound might have complex downstream signaling with potentially opposite effects, i.e., beneficial or deleterious. The multiple clinical implications that can be derived as a result of this interaction, however, represent an excellent reason to develop future in-depth studies.

Recent advances in biopolymer-based hemostatic materials

“…Besides, the nanoparticles created by cholic-acid-mediated self-assembly of polyethyleneimine release various soluble biomolecules, including growth factors, coagulant factors and extracellular vesicles. Platelets can also evade the immune system, adhere to the subendothelial layer and interact with pathogens [ 42 , 43 ]. Due to these properties, numerous platelet membrane-coated nanostructures have been developed as drug delivery methods.…”

Effect of Low-Dose Statins in Addition to Standard Therapy on Brain Perfusion and Neurocognitive Performance in Patients with Major Depressive Disorder

“…Another predictor variable was biomarkers related with platelet activation, which is observed with the use of statins [72][73][74]. Platelet activation has been associated also with depression and even suicide and has been proposed as a depression marker although the findings are rather controversial [75][76][77][78].…”

Pleiotropic Effects of PCSK9: Focus on Thrombosis and Haemostasis

“…As previously mentioned, hypercholesterolemia is associated with a higher risk for thrombus formation and lowering the LDL-C levels reduces this risk [ 97 ]. When evaluating the effect of other lipid-lowering therapies on thrombogenesis, there are numerous studies that suggest that statins have an effect on platelet function [ 98 , 99 , 100 ] and on thrombin formation [ 101 ], thereby reducing the risk of venous thrombosis [ 41 ]. Patients under a high intensity treatment with a statin display reduced platelet reactivity compared to patients on treatment with a statin on lower doses [ 102 ].…”