Berwanger O, et al. - In this randomized clinical trial of 3,799 patients with ST-elevation myocardial infarction treated with fibrinolytic therapy, ticagrelor was compared with clopidogrel with respect to short-term safety. Researchers found that, in terms of thrombolysis in myocardial infarction (TIMI) major bleeding at 30 days, delayed administration of ticagrelor after fibrinolytic therapy was noninferior to clopidogrel in patients younger than 75 years with ST-segment elevation myocardial infarction.

Methods

• This multicenter, randomized, open-label with blinded end point adjudication trial included 3,799 patients (younger than 75 years) with ST-segment elevation myocardial infarction receiving fibrinolytic therapy from November 2015 through November 2017 in 152 sites from 10 countries.
• An absolute margin of 1.0% was prespecified upper boundary for noninferiority for bleeding.
• Ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300-mg to 600-mg loading dose, 75 mg daily thereafter) were randomly administered to patients, with randomization done a median of 11.4 hours after fibrinolysis, and 90% were pretreated with clopidogrel.
• TIMI major bleeding through 30 days was considered as primary outcome.

Results

• Data revealed that the mean (SD) age was 58.0 (9.5) years, 2,928 of 3,799 patients (77.1%) were men, and 2,177 of 3,799 patients (57.3%) were white.
• The occurrence of TIMI major bleeding at 30 days was reported in 14 of 1,913 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).
• 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), researchers reported the occurrence of major bleeding defined by the Platelet Inhibition and Patient Outcomes criteria and by the Bleeding Academic Research Consortium types 3 to 5 bleeding.
• Similar rates of fatal (0.16% vs 0.11%; P=.67) and intracranial bleeding (0.42% vs 0.37%; P=.82) were observed between the ticagrelor and clopidogrel groups, respectively.
• With ticagrelor vs clopidogrel, minor and minimal bleeding were more common.
• In 76 patients (4.0%) treated with ticagrelor and in 82 patients (4.3%) treated with clopidogrel (hazard ratio, 0.91; 95% CI, 0.67-1.25; P=.57), the occurrence of the composite of death from vascular causes, myocardial infarction, or stroke was reported.