Ticagrelor (Brilinta): An oral P2Y12 platelet inhibitor to reduce rate of thrombotic cardiovascular events in patients with acute coronary syndrome

October 1, 2011

New molecular entity: Ticagrelor tablets were FDA approved to reduce rate of thrombotic cardiovascular events in patients with ACS.

According to the American Heart Association, acute coronary syndrome (ACS) (including unstable angina, ST-segment elevation, and non-ST-segment elevation myocardial infarction) occurs in more than 3% of Americans each year. Antiplatelet medications have become mainstays in the treatment of ACS. On July 20, 2011, FDA approved ticagrelor tablets to reduce the rate of thrombotic cardiovascular events in patients with ACS. Ticagrelor binds to the P2Y12-ADP receptor to inhibit platelet activation.

Efficacy. Ticagrelor's efficacy data come from the PLATO trial, which randomly assigned 9,333 patients experiencing ACS to receive ticagrelor and 9,291 to its competitor clopidogrel. Patients were administered ticagrelor or clopidogrel 24 hours after presenting with chest pain or with symptoms consistent with ACS. After 6 to 12 months of follow-up, ticagrelor use was found to reduce patients' hazard of developing the combined end point of cardiovascular death, non-fatal myocardial infarctions, and non-fatal strokes by 16% (P=.0003). This overall reduction was driven by reductions in cardiovascular death [21% relative risk reduction, P=.0013] and myocardial infarction [16% relative risk reduction, P=.0045], but not stroke. All cause death was reduced by 22% as well (P=.0003).

Safety. Ticagrelor has been evaluated for safety in >10,000 patients including 3,000 patients for over 1 year. As with other antiplatelet agents, one of the most common adverse effects of ticagrelor is bleeding (12%), which at times can be significant or even fatal. However, major bleeding occurred at similar rates between ticagrelor and clopidogrel (HR=1.04, P=.43) in PLATO. It is recommended that bleeding be managed without discontinuation of ticagrelor, if possible, in order to prevent an increased risk of cardiovascular events. A variety of non-bleeding adverse effects were seen in patients using ticagrelor, including self-limiting dyspnea (13.8%), headache (6.5%), cough (4.9%), dizziness (4.5%), and nausea (4.3%). Contraindications to ticagrelor include patients with a history of intracranial hemorrhaging, pathological bleeding, or severe hepatic impairment.