From the Guidelines
Ticagrelor is an oral antiplatelet medication that works by reversibly inhibiting the P2Y12 receptor on platelets, preventing ADP (adenosine diphosphate) from activating platelets and reducing platelet aggregation and clot formation. Ticagrelor directly and reversibly binds to the P2Y12 receptor, unlike clopidogrel, which requires metabolic activation to exert its antiplatelet effect, leading to a faster onset of action and more consistent platelet inhibition 1. The mechanism of action of ticagrelor is distinct from other antiplatelet agents, as it binds to the receptor at a location distinct from the ADP binding site and blocks ADP-mediated receptor activation in a noncompetitive fashion, likely through an allosteric mechanism 1. The standard dosing for ticagrelor is a 180 mg loading dose followed by 90 mg twice daily for maintenance, and it is typically used in combination with low-dose aspirin for acute coronary syndromes or after percutaneous coronary intervention 1. Some key benefits of ticagrelor include its rapid onset of action, with a level of inhibition of ADP-induced platelet aggregation exceeding that obtained with a 300- or 600-mg loading dose of clopidogrel within 30 minutes 1. Additionally, ticagrelor has been shown to reduce vascular mortality and MI in patients with acute coronary syndrome, as demonstrated in the PLATO trial 1. However, patients should be aware that ticagrelor can increase the risk of bleeding, and it should be discontinued at least 5 days prior to major surgery, and it can also cause dyspnea in some patients, which is typically self-limiting but may require dose adjustment or discontinuation in severe cases. Key points to consider when prescribing ticagrelor include:
- Rapid onset of action and consistent platelet inhibition
- Reduced risk of vascular mortality and MI in patients with acute coronary syndrome
- Increased risk of bleeding and potential for dyspnea
- Standard dosing of 180 mg loading dose followed by 90 mg twice daily for maintenance.
From the Research
Mechanism of Action of Ticagrelor
The mechanism of action of Ticagrelor, a P2Y12 inhibitor, involves the reversible binding to the P2Y12 receptor, blocking ADP-induced platelet aggregation 2. This is in contrast to thienopyridines, which irreversibly bind to the P2Y12 receptor for the lifetime of the platelet.
Key Features of Ticagrelor
- Ticagrelor binds reversibly to the P2Y12 receptor, allowing for rapid onset and offset of effect 2
- It does not require metabolic activation, unlike thienopyridines 2, 3
- Ticagrelor exhibits a rapid antiplatelet effect, with higher and more consistent levels of inhibition of platelet aggregation (IPA) being maintained across the dosing interval than with clopidogrel 2
- IPA levels decline with plasma drug levels after discontinuation of dosing 2
Additional Mechanisms of Action
- Ticagrelor also inhibits the equilibrative nucleoside transporter 1 (ENT1) on platelets, leading to accumulation of extracellular adenosine and activation of Gs-coupled adenosine A2A receptors 4
- It has been shown to increase platelet cAMP and VASP-P in the absence of ADP in an adenosine receptor-independent manner, suggesting inverse agonism at the P2Y12 receptor 4
- Ticagrelor's inhibition of platelet aggregation is also mediated by the induced increase of adenosine levels, in addition to P2Y12 antagonism 5
Comparison to Other P2Y12 Inhibitors
- Ticagrelor has been compared to clopidogrel in several studies, with results showing a significantly greater reduction in the death rate from vascular causes, myocardial infarction, or stroke without major bleeding 3, 6
- However, ticagrelor has been associated with an increased risk of non-procedure related bleeding, dyspnea, and ventricular pauses 2, 3, 6