Precision antiplatelet therapy

Res Pract Thromb Haemost. 2023 Mar 28;7(3):100138. doi: 10.1016/j.rpth.2023.100138. eCollection 2023 Mar.

Abstract

A State of the Art lecture titled "Personalizing Antiplatelet Therapy Based on Platelet Turnover and Metabolic Phenotype" was presented by Bianca Rocca at the International Society on Thrombosis and Haemostasis (ISTH) Congress in 2022. Increased variability in drug response may be associated with serious, mechanism-based and off-target side effects, especially in the case of drugs that do not routinely undergo therapeutic drug monitoring, such as antiplatelet drugs or direct oral anticoagulants. Precision pharmacology can be defined as the identification of a drug regimen that maximizes the benefit/risk balance at the level of an individual patient. Key tools for identifying relevant sources of variability and developing precision drug dosing are represented by genetic, biochemical, and pharmacological biomarkers recognized as a valid surrogate or strong predictor of major clinical complications. Pharmacodynamic, pharmacokinetic, and/or disease-related biomarkers are central to identifying the right population to be targeted, characterizing the sources of variability in drug response, guiding precision treatments that maximize benefits and minimize risks, and designing precision dosing trials. Another valuable tool for guiding precision pharmacology is represented by in silico pharmacokinetic/pharmacodynamic models and simulations instructed by real-world data of validated biomarkers. This review critically analyzes the tools for precision dosing and exemplifies conditions in which precision dosing can considerably optimize the efficacy and safety of antiplatelet drugs, namely aspirin and P2Y12 receptor blockers, used alone and in combination. Finally, we summarize relevant new data on this topic presented during the 2022 ISTH Congress.

Keywords: arterial occlusive diseases; aspirin; platelet aggregation inhibitors; precision medicine; purinergic P2Y receptor antagonists.