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New research has shown that the stronger anticlotting medication Ticagrelor ( Brilinta; Brilique in Europe ) reduces death rates without increasing bleeding compared with the current standard treatment of Clopidogrel for myocardial infarction patients.

Clopidogrel ( Plavix ) is an antiplatelet drug that is used in combination with Acetylsalicylic acid ( Aspirin ) in patients with acute coronary syndrome ( non-ST segment myocardial infarction / unstable angina ), in order to prevent clots forming, thus reducing the risk of further myocardial infarctions, stroke, and death.
Ticagrelor is an antiplatelet drug that has a greater and more consistent antiplatelet effect than does Clopidogrel, with a faster onset and offset of action.

In this study, PLATO researchers compared the two drugs in patients with acute coronary syndromes patients who were planned to undergo invasive procedures.

At the beginning of the study, an invasive strategy was planned for 13,408 (72•0%) of 18,624 patients hospitalised for acute coronary syndromes. Patients were randomly assigned in a one-to-one ratio to Ticagrelor and placebo ( 180 mg loading dose followed by 90 mg twice a day ), or to Clopidogrel and placebo ( 300-600 mg loading dose or continuation with maintenance dose followed by 75 mg per day ) for 6-12 months. All patients were given Acetylsalicylic acid.
The primary endpoint was any of cardiovascular death, myocardial infarction, or stroke.

Patients in the Ticagrelor group were 16% less likely to experience the primary endpoint than those in the Clopidogrel group. The endpoint of cardiovascular death, heart attack, or stroke occurred in fewer patients in the Ticagrelor group than in the Clopidogrel group ( event rate at 360 days 9.0% vs 10.7% ). The risk of death was also significantly reduced from 5.0% ( Clopidogrel ) to 3.9% ( Ticagrelor ), a reduction in the risk of dying over one year of around one fifth. Blood clots developing inside heart stents were also significantly reduced. On the other hand, there was no statistically significant difference between Clopidogrel and Ticagrelor groups between Clopidogrel and Ticagrelor groups in the rates of total major bleeding ( 12% each group ), or severe bleeding ( 3% both groups ).

Patients given Ticagrelor had significant and clinically relevant reductions in cardiovascular and total deaths, myocardial infarction, and stent thrombosis, without an increase in risk of major bleeding. The benefits with respect to clinical events and stent thrombosis were consistent whether or not patients were given standard or higher loading doses of Clopidogrel, as advocated for patients undergoing invasive strategies. Thereby, Ticagrelor has important advantages, and improves the early invasive and long-term management of patients with acute coronary syndromes.

In conclusion, the use of Ticagrelor instead of Clopidogrel for 1 year in 1000 patients with acute coronary syndromes and who are planned to undergo an invasive strategy at the start of drug treatment would lead to 11 fewer deaths, 13 fewer myocardial infarctions, and 6 fewer cases of stent thrombosis without an increase in the rates of major bleeding or transfusion.

Gregg W Stone, Columbia University Medical Center, New York, has commented that these compelling results support Ticagrelor as a new standard of care in acute coronary syndromes. However, a personalised approach to drug selection should be used wherein each patient's individualised risk of ischaemia versus bleeding is considered. Clopidogrel might still be appropriate for selected patients who are at relatively low risk of myocardial infarction or stent thrombosis and/or high risk of major bleeding, and/or for whom non-compliance with Ticagrelor because of cost or other considerations ( eg, twice daily dosing ) is a concern. Nonetheless, the introduction of Ticagrelor, a more potent and effective agent which is as safe as its predecessor, is a landmark event that should redefine the care of patients with acute coronary syndromes.

Source: Lancet, 2010


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