BACKGROUND: Guidelines suggest that "upstream" P2Y12 receptor antagonists should be considered in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). HYPOTHESIS: Early use of ticagrelor in patients managed with an invasive strategy would be more effective than clopidogrel because of its more rapid onset of action and greater potency. METHODS: In the PLATO trial, 6792 NSTE-ACS patients were randomized to ticagrelor or clopidogrel (started prior to angiography) and underwent angiography within 72 hours of randomization. We compared efficacy and safety outcomes of ticagrelor vs clopidogrel as a function of "early" (<3h) vs "late" (≥3h) time to angiography. Adjusted Cox proportional hazards models evaluated interaction between randomized treatment and time from randomization to angiography on subsequent outcomes. RESULTS: Overall, a benefit of ticagrelor vs clopidogrel for cardiovascular death/myocardial infarction/stroke was seen at day 7 (hazard ratio [HR]: 0.67, P = 0.002), day 30 (HR: 0.81, P = 0.042), and 1 year (HR: 0.80, P = 0.0045). There were no significant interactions in the <3h vs ≥3h groups at any timepoint. For major bleeding, overall there was no significant increase (HR: 1.04, 95% confidence interval: 0.85-1.27); but there was a significant interaction with no difference between ticagrelor and clopidogrel in the early group (HR: 0.79), but higher bleeding risk with ticagrelor in the late angiography group, at 7 days (HR: 1.51, Pint = 0.002). Patterns were similar at 30 days and 1 year. CONCLUSIONS: The benefit of ticagrelor over clopidogrel was consistent in those undergoing early and late angiography, supporting upstream use of ticagrelor.

AstraZeneca Research and Development Gothenburg Sweden

Baim Institute for Clinical Research and Cardiovascular Division Brigham and Women's Hospital Boston Massachusetts

Département Hospitalo Universitaire FIRE AP HP Hôpital Bichat Paris France; Paris Diderot University Sorbonne Paris Cité Paris France; NHLI Imperial College ICMS Royal Brompton Hospital London UK; FACT an F CRIN network INSERM U1148 Paris France

Department of Cardiology National Heart Centre Singapore

Department of Emergency Medicine Thomas Jefferson University Philadelphia Pennsylvania

Department of Emergency Medicine University of Texas Southwestern Dallas

Department of Health Sciences Research Mayo Clinic Rochester Minnesota; former employee at Duke Clinical Research Institute Duke University Medical Center North Carolina

Department of Infection Immunity and Cardiovascular Disease University of Sheffield United Kingdom

Department of Internal Medicine Cardiology Masaryk University Brno Czech Republic

Department of Medical Sciences Cardiology and Uppsala Clinical Research Center Uppsala University Sweden

Department of Medical Sciences Cardiology Uppsala University Sweden

Department of Medicine Brigham and Women's Hospital Boston Massachusetts

Division of Cardiovascular Health and Disease Heart Lung and Vascular Institute University of Cincinnati College of Medicine Ohio

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