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Elaborately Engineering a Self-Indicating Dual-Drug Nanoassembly for Site-Specific Photothermal-Potentiated Thrombus Penetration and Thrombolysis Comparison of 1-month Versus 12-month Dual Antiplatelet Therapy after Implantation of Drug-eluting Stents Guided by either Intravascular Ultrasound or Angiography in Patients with Acute Coronary Syndrome: Rationale and Design of Prospective, Multicenter, Randomized, Controlled IVUS-ACS & ULTIMATE-DAPT trial 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines Dual Antiplatelet Therapy Duration in Medically Managed Acute Coronary Syndrome Patients: Sub-Analysis of the OPT-CAD Study Antibody-Based Ticagrelor Reversal Agent in Healthy Volunteers 6-month versus 12-month or longer dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (SMART-DATE): a randomised, open-label, non-inferiority trial Patient-oriented composite endpoints and net adverse clinical events with ticagrelor monotherapy following percutaneous coronary intervention: Insights from the randomized GLOBAL LEADERS trial Dual Antiplatelet TherapyIs It Time to Cut the Cord With Aspirin? Dual Antiplatelet Therapy Duration: Reconciling the Inconsistencies Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI

Clinical Trial2018 Mar 11.[Epub ahead of print]

JOURNAL:JAMA Cardiol. Article Link

Ticagrelor vs Clopidogrel After Fibrinolytic Therapy in Patients With ST-Elevation Myocardial Infarction: A Randomized Clinical Trial

Writing Committee for the TREAT Study Group, Berwanger O, Nicolau JC et al. Keywords: ticagrelor; clopidogrel; fibrinolytic therapy; STEMI, TIMI major bleeding

ABSTRACT


IMPORTANCE - The bleeding safety of ticagrelor in patients with ST-elevation myocardial infarction treated with fibrinolytic therapy remains uncertain.


OBJECTIVE - To evaluate the short-term safety of ticagrelor when compared with clopidogrel in patients with ST-elevation myocardial infarction treated with fibrinolytic therapy.

DESIGN, SETTING AND PARTICIPANTS - We conducted a multicenter, randomized, open-label with blinded end point adjudication trial that enrolled 3799 patients (younger than 75 years) with ST-segment elevation myocardial infarction receiving fibrinolytic therapy in 152 sites from 10 countries from November 2015 through November 2017. The prespecified upper boundary for noninferiority for bleeding was an absolute margin of 1.0%.

INTERVENTIONS - Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300-mg to 600-mg loading dose, 75 mg daily thereafter). Patients were randomized with a median of 11.4 hours after fibrinolysis, and 90% were pretreated with clopidogrel.

MAIN OUTCOMES AND MEASURES - The primary outcome was thrombolysis in myocardial infarction (TIMI) major bleeding through 30 days.

RESULTS - The mean (SD) age was 58.0 (9.5) years, 2928 of 3799 patients (77.1%) were men, and 2177 of 3799 patients (57.3%) were white. At 30 days, TIMI major bleeding had occurred in 14 of 1913 patients (0.73%) receiving ticagrelor and in 13 of 1886 patients (0.69%) receiving clopidogrel (absolute difference, 0.04%; 95% CI, -0.49% to 0.58%; P < .001 for noninferiority). Major bleeding defined by the Platelet Inhibition and Patient Outcomes criteria and by the Bleeding Academic Research Consortium types 3 to 5 bleeding occurred in 23 patients (1.20%) in the ticagrelor group and in 26 patients (1.38%) in the clopidogrel group (absolute difference, -0.18%; 95% CI, -0.89% to 0.54; P = .001 for noninferiority). The rates of fatal (0.16% vs 0.11%; P = .67) and intracranial bleeding (0.42% vs 0.37%; P = .82) were similar between the ticagrelor and clopidogrel groups, respectively. Minor and minimal bleeding were more common with ticagrelor than with clopidogrel. The composite of death from vascular causes, myocardial infarction, or stroke occurred in 76 patients (4.0%) treated with ticagrelor and in 82 patients (4.3%) receiving clopidogrel (hazard ratio, 0.91; 95% CI, 0.67-1.25; P = .57).

CONCLUSIONS AND RELEVANCE - In patients younger than 75 years with ST-segment elevation myocardial infarction, delayed administration of ticagrelor after fibrinolytic therapy was noninferior to clopidogrel for TIMI major bleeding at 30 days.


TRIAL REGISTRATION - clinicaltrials.gov Identifier: NCT02298088.