Ticagrelor Sample Clauses

Ticagrelor. Ticagrelor (AZD6140) belongs to a new class of antiplatelet agents, the cyclopentyltriazo- lopyrimidines. Although its mechanism of action is also exerted through P2Y12 platelet receptor inhibition, in contrast to clopidogrel and prasugrel, this inhibition is reversible. It’s an active metabolite (no metabolism of a pro-drug is required) with a rapid onset of action and greater degree of platelet inhibition compared to clopidogrel. The efficacy and safety of ticagrelor were evaluated in the Platelet Inhibition and Patient Outcomes (PLATO) trial where 18624 ACS patients (38% of them with STEMI) were randomly assigned to either ticagrelor (180 mg loading dose followed by 90 mg twice daily) or clopidogrel (300 to 600 mg load- ing dose followed by 75 mg daily) for one year. All patients were also receiving aspirin. At the end of the follow up period, patients on ticagrelor presented significantly lower rates of the composite primary end point (cardiovascular death, myocardial infarction or stroke) compared to clopidogrel (9.8 vs 11.7%) without any significant difference in the rates of major bleeding among the two groups219. Despite the encouraging results, ticagrelor is not clinically available yet, while some have serious concerns regarding the effects of a possible poor compliance to medication; given the reversible nature and the not yet fully explained side-effect of dyspnea. Pending in official registration, ticagrelor is already, like prasugrel, announced in the new ESC guidelines for myocardial revascularization as class I indication for the treatment of NSTE-ACS and STEMI220.

Ticagrelor. Unlike clopidogrel and prasugrel, ticagrelor is a cyclo-pentyltriazolo-pyrimidine ADP antagonist that has distinct pharmacokinetic and pharmacodynamic properties. Ticagrelor binds directly to the P2Y12 receptor and alters its conformation, resulting in reversible inhibition. The drug does not require metabolic activation and thus exhibits a comparatively rapid onset and offset of effect, necessitating comparatively frequent dosing to achieve steady ADP inhibition 120. Plasma levels of ticagrelor peak at 1.5 – 3 hours post-ingestion and reach steady state after 2 – 3 days 121. Although metabolic activation is not required for initiation of its anti-platelet effects, the drug does have an active metabolite, AR-C124910XX, which is produced following the interaction of the parent drug with cytochrome P450 120 121. Ticagrelor is administered as a loading dose of 180 mg, followed by maintenance dosing of either 60 or 90 mg twice daily. The ‘PLATelet inhibition and patient Outcomes’ (PLATO) study showed that ticagrelor was superior to clopidogrel in reducing mortality and further cardiovascular events in patients presenting with ACS, regardless of the presence or absence of CYP2C19 and CYP2C9 polymorphisms 122. The DISPERSE-2 trial showed that there was no increase in major bleeding events in patients with non-ST segment ACS taking ticagrelor compared with clopidogrel, however there were significantly more minor bleeding events 123. Ticagrelor achieves higher levels of platelet inhibition than clopidogrel 124, likely due to a combination of factors, including the aforementioned genetic variations in absorption and metabolism of clopidogrel. Dyspnoea is a well-documented adverse effect of ticagrelor use, although to date the mechanism of this physiological response is unclear, particularly as this is not a prominent feature of other drugs in this class. Adenosine activates pulmonary vagal C nerve fibres, inducing dyspnoea 125. It has been postulated that ADP receptor inhibition results in higher levels of extracellular adenosine, due to drug-induced inhibition of a sodium-independent equilibrative nucleoside transporter and subsequent reduced adenosine clearance 126 127. Although other ADP-receptor inhibitors, such as clopidogrel, bind irreversibly to P2Y12 receptors, they have a comparatively short half-life and thus when they inhibit receptors on cells other than platelets, such as neurons, their effects are transient as the presence of a cell nucleus allows syn...