Brilique is licensed for use in combination with aspirin to prevent atherothrombotic events in patients with acute coronary syndromes (ACS), including those managed medically, with percutaneous coronary intervention and with CABG.
Ticagrelor is a selective adenosine diphosphate (ADP) receptor antagonist, which reversibly interacts with the platelet P2Y12 ADP receptor to prevent ADP-mediated platelet activation and aggregation.1
The efficacy of ticagrelor and clopidogrel was compared in a double-blind trial involving 18,624 patients hospitalised for ACS with or without ST-segment elevation, with symptom onset during the previous 24 hours; clopidogrel in combination with aspirin is currently the treatment of choice in this patient group.2
Patients were randomised to receive ticagrelor (loading dose of 180mg followed by 90mg twice daily) or clopidogrel (loading dose of 300-600mg followed by 75mg daily) in combination with aspirin (75-100mg daily) if tolerated.2
After 12 months, significantly fewer patients in the ticagrelor group reached the primary efficacy endpoint (death from vascular causes, MI or stroke) than in the clopidogrel group (9.8% versus 11.7%, p<0.001).2
The incidence of several of the major secondary endpoints was also significantly lower with ticagrelor than with clopidogrel: death from any cause, MI or stroke (10.2% versus 12.3%, p<0.001); death from vascular causes, MI, stroke, recurrent ischaemia [including severe], TIA or other arterial thrombotic event (14.6% versus 16.7%, p<0.001); MI (5.8% versus 6.9%, p=0.005); and death from vascular causes (4.0% versus 5.1%, p=0.001).
In addition, ticagrelor was associated with a reduction in the rate of death from any cause compared with clopidogrel (4.5% versus 5.9%, p<0.001).2
The incidence of stroke did not differ significantly between the two treatment groups (1.5% versus 1.3%, p=0.22) nor did the rate of major bleeding (primary safety endpoint; 11.6% versus 11.2%, p=0.43). However, the rate of bleeding not related to CABG was significantly higher for ticagrelor than for clopidogrel (4.5% versus 3.8%, p=0.03).2
Dyspnoea was also significantly more common in the ticagrelor group, occurring in 13.8% of patients compared with 7.8% of patients in the clopidogrel group (p<0.001).2
In addition, a greater incidence of ventricular pauses ≥3 seconds was observed in the ticagrelor group in week one but not at day 30, and this group also had a greater increase in creatinine and uric acid levels during the treatment period than the clopidogrel group.2 The other most commonly reported adverse effects for ticagrelor include contusion and epistaxis.1
Similar results were observed in a secondary analysis involving a subset of patients with a planned early invasive strategy (n=13,408).3 In this subgroup, the rate of the primary efficacy endpoint was 9% in the ticagrelor group compared with 10.7% in the clopidogrel group (p=0.0025). In addition, the rate of all-cause mortality was significantly lower with ticagrelor than with clopidogrel (3.9% versus 5%, p=0.01) with no increase in the risk of major bleeding.3
Premature discontinuation of any antiplatelets, including ticagrelor, could result in an increased risk of cardiovascular death or MI as a result of the patient’s underlying disease and should therefore be avoided.1 Any lapses in therapy should be avoided and a patient who misses a dose should take only one 90mg tablet at the next scheduled time.1
- Brilique Summary of Product Characteristics, December 2010.
- Wallentin L et al. N Engl J Med 2009; 361: 1045-57.
- Cannon C et al. Lancet 2010; 375: 283-93.
Further information: AstraZeneca
Updated 7 January 2011
In the original and print versions of this article, the third paragraph of the ‘Clinical studies’ section began with the words "After 12 weeks…". We would like to point out that it should have read "After 12 months…", as this was the time point at which the primary end point was assessed in the pivotal study of ticagrelor and the period for which treatment with ticagrelor is recommended. The error has been corrected above.