TREAT Trial Addresses the Safety and Efficacy of Ticagrelor Use for STEMI Management in the Setting of Fibrinolytic Therapy ACC 2019: Ticagrelor versus Clopidogrel in Patients with STEMI Treated with Fibrinolytic Therapy

According to the results of the TREAT trial, among patients aged under 75 years with STEMI, administration of ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular events in comparison with clopidogrel. The results of the 12-month analysis were recently published in the Journal of the American College of Cardiology.

Management of patients presenting with ST-elevation myocardial infarction (STEMI) has been defined by data from large, high-quality randomized clinical trials that have examined both medical and procedural therapies. Guideline-directed care based on considerable evidence from these trials supports best outcomes with prompt culprit vessel revascularization via percutaneous coronary intervention (PCI). But the realities of the management of STEMI worldwide are characterized by differences in reperfusion therapy and particularly marked variability in PCI use.1 Because lytic therapy remains a standard of care in much of the world, especially in the 10 countries within the Ticagrelor in Patients With ST-Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis (TREAT) trial,2 evaluating best practices associated with improved outcomes becomes important. A prior publication in JAMA had aimed to evaluate the short-term safety of ticagrelor when compared with clopidogrel in patients with ST-elevation myocardial infarction treated with fibrinolytic therapy. The findings of this study had been suggestive of the fact that in patients younger than 75 years with ST-segment elevation myocardial infarction, delayed administration of ticagrelor after fibrinolytic therapy was non-inferior to clopidogrel for TIMI major bleeding at 30 days. Despite that, the efficacy of ticagrelor in the long-term post-ST-elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remained uncertain. Thus, the investigators aimed to evaluate the efficacy of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy and reported these results after a 12-month analysis.

Otavio Berwanger and his colleagues conducted an international, multicenter, randomized, open-label with blinded endpoint adjudication trial that enrolled 3,799 patients (age < 75 years) with STEMI receiving fibrinolytic therapy. The inclusion criteria comprised of those patients aged <75 years, who received fibrinolytic therapy for STEMI and had a presentation within 24 hours from symptom onset. Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300-to-600-mg loading dose, 75 mg daily thereafter The key outcomes were cardiovascular mortality, myocardial infarction, or stroke, and the same composite outcome with the addition of severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events at 12 months. The results of the trial showed that the combined outcome of cardiovascular mortality, myocardial infarction or stroke occurred in 129 of 1,913 patients (6.7%) receiving ticagrelor and in 137 of 1,886 patients (7.3%) receiving clopidogrel (hazard ratio of 0.93; 95% CI, 0.73 to 1.18; P=0.53). The composite of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) treated with ticagrelor and in 171 of 1,886 patients (9.1%) receiving clopidogrel (hazard ratio of 0.88; 95% CI, 0.71 to 1.09; P=0.25). The rates of major, fatal, and intracranial bleeding were similar between the ticagrelor and clopidogrel groups.

Hence, the investigators drew the conclusion that among patients aged under 75 years with STEMI, administration of ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular mortality, myocardial infarction or stroke (hazard ratio of 0.93; 95% CI, 0.73 to 1.18) or of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events (hazard ratio of 0.88; 95% CI, 0.71 to 1.09). Among patients <75 years of age who were treated with fibrinolysis for STEMI, delayed administration of ticagrelor was non-inferior to clopidogrel. There was no excess of major bleeding, fatal bleeding, or intracranial bleeding with ticagrelor vs. clopidogrel. Although the trial was not powered for efficacy, there was no apparent ischemic benefit with ticagrelor. However, there was no denying the fact that Ticagrelor represented a safe treatment option in such patients. In an accompanying editorial, Clyde W. Yancy, MD, MSc and Robert A. Harrington, elaborated on the need for future exploration. “The TREAT trial attempts to address the questions of safety and efficacy of ticagrelor use for STEMI management in the setting of fibrinolytic therapy. This trial answers some questions, but critical others remain. Converting to ticagrelor late after initial exposure to clopidogrel appears safe, as defined by a non-inferior difference in major bleeding (using a wide inferiority margin). But we also await further data addressing short-term and long-term outcomes in this lower-risk population of patients with STEMI. The crucial question that needs to be addressed—concomitant use of ticagrelor with lytic therapy for acute revascularization—remains unanswered in this trial. Given the worldwide burden of acute coronary syndromes and the recognized exigencies which preclude the ubiquitous availability of PCI, we believe this question needs urgent attention. We await future trials.”

To watch the interview with Dr. Otavio Berwanger, click here.

To view the slides, click here.