Dr Christopher P Cannon MD a , Prof Robert A Harrington MD b, Stefan James MD c, Diego Ardissino MD d, Prof Richard C Becker MD b, HÃ¥kan Emanuelsson MD e, Steen Husted MD g, Prof Hugo Katus MD h, Prof Matyas Keltai MD i, Nardev S Khurmi MD f, Frederic Kontny MD j, Prof Basil S Lewis MD k, Prof Philippe Gabriel Steg MD l, Robert F Storey MD m, Daniel Wojdyla MSc b, Prof Lars Wallentin MD c, for the PLATelet inhibition and patient Outcomes (PLATO) investigators. The Lancet, Early Online Publication, 14 January 2010

Figure. Structure of Ticagrelor
Background
Variation in and irreversibility of platelet inhibition with clopidogrel has led to controversy about its optimum dose and timing of administration in patients with acute coronary syndromes. We compared ticagrelor, a more potent reversible P2Y12 inhibitor with clopidogrel in such patients.

Methods
At randomisation, an invasive strategy was planned for 13 408 (72·0%) of 18 624 patients hospitalised for acute coronary syndromes (with or without ST elevation). In a double-blind, double-dummy study, 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 aspirin. The primary composite endpoint was cardiovascular death, myocardial infarction, or stroke. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00391872.
Findings
6732 patients were assigned to ticagrelor and 6676 to clopidogrel. The primary composite endpoint occurred in fewer patients in the ticagrelor group than in the clopidogrel group (569 [event rate at 360 days 9·0%] vs 668 [10·7%], hazard ratio 0·84, 95% CI 0·75—0·94; p=0·0025). There was no difference between clopidogrel and ticagrelor groups in the rates of total major bleeding (691 [11·6%] vs 689 [11·5%], 0·99 [0·89—1·10]; p=0·8803) or severe bleeding, as defined according to the Global Use of Strategies To Open occluded coronary arteries, (198 [3·2%] vs 185 [2·9%], 0·91 [0·74—1·12]; p=0·3785).
Interpretation
Ticagrelor seems to be a better option than clopidogrel for patients with acute coronary syndromes for whom an early invasive strategy is planned.
Funding
AstraZeneca

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