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PLATO (Platelet Inhibition and Patient Outcomes)

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- Background:
Ticagrelor, a new antiplatet agent and not a thienopyridine, has a unique mechanism of action in that it is reversible

- Population and treatment:
18 624 ACS patient, with or without ST-segment elevation, randomized in a double-blind, double-dummy fashion to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose, 75 mg thereafter) for one year
Patients also received aspirin 75 mg to 100 mg day, unless they could not tolerate the drug

- Primary outcome:
A composite of death from vascular causes, MI, or stroke

See the article at http://www.theheart.org/article/995621.do

Published in: Health & Medicine, Sports
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PLATO (Platelet Inhibition and Patient Outcomes)

  1. 1. PLATO (Platelet Inhibition and Patient Outcomes) <ul><li>Background: </li></ul><ul><ul><li>Ticagrelor, a new antiplatet agent and not a thienopyridine, has a unique mechanism of action in that it is reversible </li></ul></ul><ul><li>Population and treatment: </li></ul><ul><ul><li>18 624 ACS patient, with or without ST-segment elevation, randomized in a double-blind, double-dummy fashion to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose, 75 mg thereafter) for one year </li></ul></ul><ul><ul><li>Patients also received aspirin 75 mg to 100 mg day, unless they could not tolerate the drug </li></ul></ul><ul><li>Primary outcome: </li></ul><ul><ul><li>A composite of death from vascular causes, MI, or stroke </li></ul></ul>L Wallentin (Uppsala Clinical Research Center, Sweden) European Society of Cardiology 2009 Congress
  2. 2. Major efficacy end points at 12 months a PLATO: Results a. The percentages are Kaplan-Meier estimates of the rate of the end point at 12 months. Patients could have had more than one type of end point. Death from vascular causes included fatal bleeding. Only traumatic fatal bleeding was excluded from the category of death from vascular causes. b. p values were calculated by means of Cox regression analysis. End point Ticagrelor (%) Clopidogrel (%) HR for ticagrelor p b Primary end point 9.8 11.7 0.84 <0.001 Secondary end points Death from any cause/MI/stroke 10.2 12.3 0.84 <0.001 Death from vascular causes/MI/severe recurrent ischemia/recurrent ischemia/transient ischemic attack/other arterial thrombotic event 14.6 16.7 0.88 <0.001 MI 5.8 6.9 0.84 0.005 Death from vascular causes 4.0 5.1 0.79 0.001 Stroke 1.5 1.3 1.17 0.22 – Ischemic 1.1 1.1 0.74 – Hemorrhagic 0.2 0.1 0.10 – Unknown 0.1 0.02 0.04
  3. 3. <ul><li>Bleeding </li></ul><ul><ul><li>No significant difference in the rates of major bleeding between the two agents (11.6% and 11.2%, respectively; p=0.43) </li></ul></ul><ul><ul><li>Ticagrelor was associated with a higher rate of major bleeding not related to CABG than clopidogrel (4.5% vs 3.8%; p=0.03) by the PLATO definition of bleeding, including more instances of fatal intracranial bleeding but fewer of fatal bleeding of other types </li></ul></ul>PLATO: Results
  4. 4. PLATO: Commentary* *All comments from PLATO shows benefits of ticagrelor over clopidogrel (http://www.theheart.org/article/995621.do) &quot;I think it's the best result we've seen since aspirin, which was the last time we saw an antiplatelet drug with a mortality benefit. It could not have come out better.&quot; - Dr Doug Weaver &quot;I see ticagrelor as the antiplatelet agent of choice in situations where surgical procedures cannot be deferred, because of its reversible platelet inhibition.&quot; - Dr Sanjay Kaul &quot;The overall results are clearly impressive, and I think it's going to have a major impact.&quot; - Dr Shamir R Mehta

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