The PLATO trial: Ticagrelor vs clopidogrel for ACS [Classics Series]
1. Treatment with ticagrelor significantly reduces mortality in patients with acute coronary syndrome when compared to clopidogrel.
2. Ticagrelor does not significantly increase the incidence of major bleeding.
Original Date of Publication: September 2009
Study Rundown: Clopidogrel is a commonly used medication in the management of acute coronary syndromes (ACS). A previous study comparing prasugrel, another oral antiplatelet agent, with clopidogrel demonstrated a significant reduction in the risk of coronary thrombotic events, but no improvement in mortality. The Platelet Inhibition and Patient Outcomes (PLATO) trial compared the use of ticagrelor, a newer and more potent oral platelet inhibitor, with clopidogrel in treating patients with ACS. In summary, patients treated with ticagrelor experienced significantly lower rates of death from vascular causes, myocardial infarction, or stroke at 12 months when compared to patients on clopidogrel (HR 0.84; 95%CI 0.77-0.92). This was driven by both significant reductions in the rate of death from vascular causes and myocardial infarction. Moreover, there was no significant difference between the two groups in the rate of major bleeding (HR1.04; 95%CI 0.95-1.13).
In-Depth [randomized, controlled study]: Originally published in 2009 in NEJM, this study was a multicenter trial, which randomized patients to treatment with clopidogrel or ticagrelor in addition to aspirin after ACS. Patients were eligible for the study if they were hospitalized for ACS with or without ST-segment elevation, with symptom onset in the previous 24 hours. Patients were excluded if they had contraindications to clopidogrel, they received fibrinolytic therapy in the 24 hours prior to randomization, they needed oral anticoagulation, they had an increased risk of bradycardia, or they were being treated with a strong cytochrome P-450 3A inhibitor or inducer. The primary endpoint was a composite of death from vascular causes, myocardial infarction, or stroke. Major life-threatening bleeding was defined as fatal bleeding, intracranial bleeding, intrapericardial bleeding with cardiac tamponade, shock/hypotension as a result of bleeding, hemoglobin decrease ≥5.0 g/dL, or need for transfusion of ≥4 units of packed red blood cells.
A total of 18,624 patients were recruited from 862 centres in 43 countries. At 12 months, the primary endpoint occurred significantly less in the ticagrelor group as compared with the clopidogrel group (HR 0.84; 95%CI 0.77-0.92). This difference was driven by significant reductions in rates of myocardial infarction (HR 0.84; 95%CI 0.75-0.95) and death from vascular causes (HR 0.79; 95%CI 0.69-0.91) in the ticagrelor group. The rates of major bleeding were not significantly different between the two groups (HR 1.04; 95%CI 0.95-1.13). Notably, the rate of fatal intracranial bleeding was significantly higher in the ticagrelor group compared to the clopidogrel group (p=0.02).
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