Brilinta (ticagrelor) is a reversibly binding oral adenosine diphosphate (ADP) receptor antagonist. It selectively inhibits P2Y12, a key target receptor for ADP. ADP receptor blockade inhibits the action of platelets in the blood, reducing recurrent thrombotic events.
Brilinta is specifically indicated to reduce the rate of thrombotic cardiovascular events in patients with acute coronary syndrome (unstable angina, non-ST elevation myocardial infarction, or ST elevation myocardial infarction).
Brilinta is supplied as a tablet for oral administration. The recommended initial dose is 180 mg (two 90 mg tablets) loading dose and continue treatment with 90 mg twice daily. After the initial loading dose of aspirin (usually 325 mg), use Brilinta with a daily maintenance dose of aspirin of 75-100 mg.
The FDA approval of Brilinta was based on a randomized double-blind study, PLATO. This study compared Brilinta (n=9333) to clopidogrel (n=9291), both given in combination with aspirin and other standard therapy, in subjects with acute coronary syndromes. The treatment duration was at least six months and for up to 12 months. Subjects who presented within 24 hours of onset of the most recent episode of chest pain or symptoms were randomized to receive Brilinta or clopidogrel. Brilinta was administered at a loading dose of 180 mg followed by a maintenance dose of 90 mg twice daily. Clopidogrel was administered at an initial loading dose of 300 mg, if previous clopidogrel therapy had not been given prior to randomization. Subjects undergoing PCI could receive an additional 300 mg of clopidogrel at investigator discretion. Concomitant aspirin was recommended at a loading dose of 160-500 mg. The study’s primary endpoint was the composite of first occurrence of cardiovascular death, non-fatal MI (excluding silent MI), or non-fatal stroke. Brilinta achieved greater efficacy over clopidogrel (9.8% vs. 11.7% at 12 months; p<0.001), without an increase in major bleeding (11.6% vs. 11.2%, p=0.43). A statistically significant reduction in both CV death (4.0% vs. 5.1%, p=0.001) and heart attacks was also observed (5.8% vs. 6.9%, p=0.005) with no difference in stroke (1.5% vs. 1.3%, p=0.22). Brilinta also demonstrated significant results across multiple secondary efficacy endpoints including CV death (4.0% vs. 5.1%, p=0.001); all-cause mortality (4.5% vs. 5.9%, p<0.001); myocardial infarction (5.8% vs. 6.9%, p=0.005); the composite of myocardial infarction, stroke, and all-cause mortality (10.2% vs. 12.3%, p<0.001) and a composite of cardiovascular death, myocardial infarction, stroke, transient ischemic attack, recurrent cardiac ischemia, severe recurrent cardiac ischemia, and other arterial thrombotic events (14.6% vs. 16.7%, p<0.001). When PLATO minor bleeding was added to the major bleeding results, Brilinta showed an increase versus clopidogrel (16.1% vs. 14.6%, p=0.008). There was also an increase in non-procedural related bleeding with Brilinta.
Adverse events associated with the use of Brilinta may include, but are not limited to, the following:
Brilinta (ticagrelor) is a cyclopentyltriazolopyrimidine and inhibits platelet activation and aggregation mediated by the P2Y12 ADP-receptor.
Held C, Asenblad N, Bassand JP, Becker RC, Cannon CP, Claeys MJ, Harrington RA, Horrow J, Husted S, James SK, Mahaffey KW, Nicolau JC, Scirica BM, Storey RF, Vintila M, Ycas J, Wallentin L Ticagrelor versus clopidogrel in patients with acute coronary syndromes undergoing coronary artery bypass surgery: results from the PLATO (Platelet Inhibition and Patient Outcomes) trial. Journal of the American College of Cardiology 2011 Feb 8;57(6):672-84
Steg PG, James S, Harrington RA, Ardissino D, Becker RC, Cannon CP, Emanuelsson H, Finkelstein A, Husted S, Katus H, Kilhamn J, Olofsson S, Storey RF, Weaver WD, Wallentin L; PLATO Study Group Ticagrelor versus clopidogrel in patients with ST-elevation acute coronary syndromes intended for reperfusion with primary percutaneous coronary intervention: A Platelet Inhibition and Patient Outcomes (PLATO) trial subgroup analysis. Circulation 2010 Nov 23;122(21):2131-41
Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA; PLATO Investigators, Freij A, Thorsén M Ticagrelor versus clopidogrel in patients with acute coronary syndromes. New England Journal of Medicine 2009 Sep 10;361(11):1045-57
For additional information regarding Brilinta or thrombotic events relating to acute coronary syndrome, please visit the AstraZeneca web page.