Clinical pharmacology of antiplatelet drugs: implications for personalized therapy

Abstract

Purpose: This review describes the pharmacodynamics and pharmacokinetics of currently available antiplatelet drugs, with an emphasis on implications for personalized therapy. Methods: Scientific literature published between January 1985 and December 2025 was collected from electronic databases. Primary research papers, reviews, and clinical practice guideline articles were included for discussion. Results: Aspirin and thienopyridine-type adenosine diphosphate (ADP) receptor antagonists (clopidogrel and ticlopidine) irreversibly inhibit their targets throughout the platelet lifespan, but daily dosing is required to inhibit newly formed platelets. In addition, clopidogrel bioactivity is affected by polymorphisms and interactions with cytochrome P450 2C19; while ticlopidine is rarely used due to serious side effects, such as blood dyscrasia. Newer ADP receptor antagonists (prasugrel, ticagrelor, and cangrelor) are more potent than clopidogrel and ticlopidine. Both high-dose aspirin and ADP receptor antagonists are recommended in acute settings, such as acute coronary syndrome (ACS) with percutaneous coronary intervention (PCI) and acute ischemic stroke, because they are associated with more rapid and potent antiplatelet activity. Moreover, recent evidence based on clinical and pharmacological data suggests that optimization of dual antiplatelet therapy (DAPT) with aspirin and ADP receptor antagonists can enable more effective management of thrombosis. Phosphodiesterase inhibitors (cilostazol and dipyridamole) are weaker antiplatelets that are used in combination with aspirin or clopidogrel in secondary stroke prevention. Glycoprotein IIb/IIIa inhibitors might be considered as adjunct therapy in ACS patients undergoing PCI who present with large thrombus burden. Vorapaxar is a thrombin receptor antagonist; and its slow receptor dissociation rate, coupled with a very long plasma half-life, might increase bleeding risk and limit its clinical use. Conclusion: Overall, the pharmacodynamics and pharmacokinetics of antiplatelets strongly support development of personalized antiplatelet therapy to achieve therapeutic outcomes and minimize the risks of unwanted effects.