Ticagrelor: oral reversible P2Y(12) receptor antagonist for the management of acute coronary syndromes

Background: The clinical benefits of dual antiplatelet treatment (aspirin + clopidogrel) in the management of acute coronary syndromes (ACS) are well established. However, clopidogrel is a prodrug that requires hepatic activation. Concerns regarding its delayed onset of action, variability in antiplatelet effects, and prolonged recovery of platelet function after discontinuation have prompted the development of P2Y(12) receptor antagonists. Ticagrelor is the most recently developed P2Y(12) receptor antagonist available in the United States. Ticagrelor is a nonthienopyridine antiplatelet agent and is the first reversible oral antagonist of the P2Y(12) receptors.

Objective: This article reviews the pharmacology, clinical efficacy, and tolerability of ticagrelor use in management of ACS.

Methods: Peer-reviewed clinical trials, review articles, and relevant treatment guidelines published from 1966 to March 15, 2012, were identified from the MEDLINE and Current Content databases using the search terms ticagrelor, ACS, pharmacokinetics, pharmacodynamics, pharmacoeconomics, and cost-effectiveness. Citations from available articles were also reviewed for additional references.

Results: Nine pharmacokinetics/pharmacodynamics studies in humans and 1 clinical study were identified. In addition, the findings from 6 subanalyses based on the clinical study were included. Compared with clopidogrel, ticagrelor was associated with a significantly reduced composite rate of death from cardiovascular causes, myocardial infarction, or stroke (ticagrelor, 9.8%; clopidogrel, 11.7%; hazard ratio [HR] = 0.84; 95% CI, 0.77-0.92; P < 0.001). The difference in the rates of major bleeding was not significant (ticagrelor, 11.6%; clopidogrel, 11.2%). Ticagrelor was associated with a higher rate of non-coronary artery bypass graft surgery related major bleeding (4.5% vs 3.8%; P = 0.03), including fatal intracranial bleeding (0.1% vs 0.01%; P = 0.02), and fewer cases of other types of fatal bleeding (0.1% vs 0.3%; P = 0.03). Other adverse events reported with ticagrelor use included dyspnea (13.8%), headache (6.5%), and bradyarrhythmia (5.8%). The effects of ticagrelor have not been compared to those of other antiplatelet agents, including prasugrel.

Conclusions: Based on the findings from the present review, ticagrelor provides reversible inhibition of adenosine diphosphate-induced platelet aggregation, with a faster onset of action than clopidogrel, and is effective in the treatment of patients with ACS. More data are required to definitively position ticagrelor with respect to other antiplatelet agents, including prasugrel.