TREAT Trial: No Difference in Recurrent Cardiovascular Events by 1 Year Between Ticagrelor and Clopidogrel in Patients with a STEMI Who Receive Fibrinolysis

Fahad Alkhalfan, M.D.
By Fahad Alkhalfan, M.D. on

A randomized controlled trial led by Dr. Otavio Berwanger published in JACC showed that in patients less than 75 with an ST-elevation myocardial infarction, administering ticagrelor as opposed to clopidogrel does not offer a reduced rate of recurrent cardiovascular events.

Randomized controlled trials have already demonstrated that dual antiplatelet therapy with aspirin and clopidogrel, a P2Y12 inhibitor, reduces the risk of recurrent cardiovascular events in patients with ST-elevation myocardial infarction (STEMI). However, ticagrelor, a reversible and direct oral antagonist P2Y12 inhibitor, provides a more reliable degree of consistent P2Y12 inhibition as compared to clopidogrel. When compared to clopidogrel, ticagrelor has already been shown to improve outcomes in patients undergoing percutaneous coronary outcome. However, whether this benefit applies to patients received fibrinolytic therapy is not known. The investigators aimed to assess whether ticagrelor is more effective than clopidogrel in improving outcomes in patients with STEMI by 12 months.

“According to our findings, in patients under 75 years of age with STEMI who received fibrinolytic therapy as their initial reperfusion strategy, administration of ticagrelor did not reduce the rates of major cardiovascular events compared with clopidogrel at 12 months. Results were consistent in the intention-to-treat, as-treated, and per-protocol analyses. The more intense platelet inhibition with ticagrelor is suggested by the observation of higher rates of minimal bleeding among patients receiving ticagrelor, although there was no significant increase in the rate of severe, major, or life-threatening bleeding.” – Dr. Otavio Berwanger, M.D., Ph.D.

The TREAT trial was an international, randomized, open-label, multi-center trial that randomized 3,799 patients to either ticagrelor (1,913) or clopidogrel (1,886). Patients were eligible for enrollment if they presented within 24 hours of symptoms, had a STEMI, were less than 75 years of age and received a fibrinolytic. The efficacy outcome in this paper included a composite of death from vascular causes, myocardial infarction or stroke by 12 months. Additionally, the composite outcome, as well as the occurrence of severe recurrent ischemia, transient ischemic attack or arterial thrombotic event at 12 months, was assessed. Additionally, bleeding between the two groups was assessed. This was a time-to-event analysis and outcomes were assessed using a cox-proportional hazards model.

A total of 3,700 patients were included in the analysis (1,913 on ticagrelor and 1,886 on clopidogrel). There were no significant differences in the baseline characteristics between the two groups. The efficacy outcome of cardiovascular death, myocardial infarction or stroke by 12 months occurred in 129 of 1,913 patients receiving ticagrelor (6.7%) and 137 of 1,886 of patients on clopidogrel (7.3%) (HR 0.93, 95% CI 0.73-1.18, p = 0.53). Additionally, the second composite ischemic endpoint of cardiovascular death, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) on ticagrelor and 171 of 1,886 patients (9.1%) on clopidogrel (HR 0.88, 95% CI 0.71-1.09, p = 0.25). Finally, the results of major (1.0% vs 1.2% in ticagrelor and clopidogrel groups, p = 0.61), fatal (0.3% vs 0.2% for ticagrelor and clopidogrel, p = 0.55) and intracranial bleeding (0.3% vs 0.2% for ticagrelor and clopidogrel, p=0.76) was similar between the two groups. The evidence suggests that there is no difference in outcomes between the two groups.

The findings of this study suggest that there is no difference between ticagrelor and clopidogrel in terms of preventing recurrent ischemic events by 1 year. Although primary percutaneous coronary intervention is considered the preferred method of reperfusion, it may not always be possible. Fibrinolytic therapy is still commonly used worldwide, and, in these patients, it is not known whether ticagrelor is better. Currently, while guidelines do recommend using dual antiplatelet therapy in patients with STEMI who receive fibrinolytic therapy, ticagrelor is not recommended due to a lack of evidence. The evidence here is in contrast to the PLATO trial that was previously published which showed that ticagrelor was more effective. However, there were fewer patients in the TREAT trial and this difference, in conclusion, may be attributed to an issue with power. Additionally, it is important to recognize that the results here do not apply to patients over the age of 75. While the results of the TREAT trial do show that ticagrelor is a potentially safe alternative to clopidogrel, it does not support the theory that ticagrelor is better at preventing a recurrent ischemic event.

Leave a Reply