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

Biomed Res Int. 2021 Jan 23:2021:6661847. doi: 10.1155/2021/6661847. eCollection 2021.

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.

Publication types

  • Review

MeSH terms

  • Aspirin / therapeutic use
  • Blood Platelets / drug effects*
  • CD36 Antigens / genetics
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hyperlipidemias / drug therapy*
  • Organic Anion Transporters / genetics
  • Platelet Activation / drug effects*
  • Platelet Activation / genetics
  • Signal Transduction / drug effects

Substances

  • CD36 Antigens
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Organic Anion Transporters
  • SLCO2B1 protein, human
  • Aspirin