Dabigatran, rivaroxaban, apixaban, edoxaban, and betrixaban are direct oral anticoagulants (DOACs). Their inter-individual variability in pharmacodynamics and pharmacokinetics (transport and metabolism) is high, and could result from genetic polymorphisms. As recommended by the French Network of Pharmacogenetics (RNPGx), the management of some treatments in cardiovascular diseases (as antiplatelet agents, oral vitamin K antagonists, and statins) can rely on genetic testing in order to improve healthcare by reducing therapeutic resistance or toxicity. This paper is a review of association studies between single nucleotide polymorphisms (SNPs) and systemic exposure variation of DOACs. Most of the results presented here have a lot to do with some SNPs of CES1 (rs2244613, rs8192935, and rs71647871) and ABCB1 (rs1128503, rs2032582, rs1045642, and rs4148738) genes, and dabigatran, rivaroxaban, and apixaban. Regarding edoxaban and betrixaban, as well as SNPs in the CYP3A4 and CYP3A5 genes, literature is scarce, and further studies are needed.

Cardiovascular diseases are a leading cause of death in developed countries. Increasing evidence shows that the alteration in the normal functions of the vascular endothelium plays a major role in the development of cardiovascular diseases. However, specific agents designed to prevent endothelial dysfunction and related cardiovascular complications are still lacking. One emerging strategy is to increase the bioavailability of epoxyeicosatrienoic acids (EETs), synthesized by cytochrome P450 epoxygenases from arachidonic acid. EETs are endothelium-derived hyperpolarising and relaxing factors and display attractive anti-inflammatory and metabolic properties. Genetic polymorphism studies in humans, and experiments in animal models of diseases, have identified soluble epoxide hydrolase (sEH), the major enzyme involved in EET degradation, as a potential pharmacological target. This review presents EET pathway and its functions and summarises the data supporting the development of sEH inhibitors for the treatment of cardiovascular and metabolic diseases. Furthermore, the authors present the different chemical families of sEH inhibitors developed and their effects in animal models of cardiovascular and metabolic diseases. Several generations of sEH inhibitors have now been designed to treat endothelial dysfunction and cardiovascular complications for a variety of diseases. The safety of these drugs remains to be carefully investigated, particularly in relation to carcinogenesis. The increasing knowledge of the biological role of each of the EET isomers and of their metabolites may improve their pharmacological profile. This, in turn, could potentially lead to the identification of new pharmacological agents that achieve the cellular effects needed without the deleterious side effects.