Emerging antiplatelet agents, differential pharmacology, and clinical utility

Pranab Das¹, Carrie S Oliphant², Elizabeth Beach³, Rashmi Thapa⁴

¹Assistant Professor, Division of Cardiology, Department of Internal Medicine, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA; ²Cardiology Clinical Pharmacy Specialist, Department of Pharmacy, Methodist University Hospital, and Assistant Professor University of Tennessee College of Pharmacy, Memphis, Tennessee, USA; ³PGY-1 Pharmacy Practice Resident, Department of Pharmacy, Methodist University Hospital, Memphis, Tennessee, USA; ⁴Resident, Department of Internal Medicine, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA

Abstract: The aspirin–clopidogrel combination is the current gold standard antiplatelet regimen following percutaneous coronary intervention and for the treatment of acute coronary syndrome. Despite the clinical benefit of this combination, patients continue to have vascular events. Another purinergic (P2Y₁₂) receptor antagonist, prasugrel, became available last year. Although prasugrel is superior to clopidogrel in reducing clinical endpoints, a higher bleeding rate has been identified particularly in high-risk patients. Ticagrelor, a reversible P2Y₁₂ receptor antagonist currently being evaluated for approval, is also more potent than clopidogrel but has a similar bleeding risk. Two additional P2Y₁₂ antagonists are being investigated that will be available as an intravenous formulation. Apart from the P2Y₁₂ receptor antagonists, multiple other agents are being developed with unique mechanisms of platelet inhibition. These agents are being studied as an alternative to or in combination with clopidogrel. The antiplatelet agents currently under development include: thrombin receptor antagonists, phosphodiesterase inhibitors, a thromboxane–prostaglandin receptor antagonist, a serotonin receptor blocker, a platelet adhesion antagonist, nitric oxide-releasing aspirin, a glycoprotein VI antagonist, and a cyclooxygenase inhibitor. The purpose of this review is to describe the efficacy and safety profiles of the emerging antiplatelet agents and their role in the treatment of atherosclerotic cardiovascular diseases.

Keywords: antiplatelet agents, safety, efficacy, clinical pharmacology, clinical trials