March 26, 2019
TREAT Trial Evaluates Safety and Efficacy of Ticagrelor After STEMI
March 26, 2019—The TREAT trial demonstrated that ticagrelor's efficacy and safety was equivalent to clopidogrel in data presented at the American College of Cardiology (ACC) 68th Annual Scientific Session, held March 16–18 in New Orleans, Louisiana. The study was simultaneously published by Otavio Berwanger, MD, et al online in Journal of the American College of Cardiology.
According to the ACC's press release, TREAT is the first large, international trial to assess ticagrelor’s safety and efficacy for patients taking fibrinolytic therapy. In data presented in 2018, the trial met its primary endpoint (major bleeding at 30 days) showing comparable safety between ticagrelor and clopidogrel. The trial was funded by AstraZeneca, maker of ticagrelor, as an investigator-initiated trial.
The current prespecified analysis of efficacy and safety at 12 months presented by investigators at the ACC meeting suggests that ticagrelor and clopidogrel have comparable efficacy and offers further confirmation that ticagrelor is safe to use in this patient population.
As noted in the ACC announcement, ticagrelor takes effect more quickly than clopidogrel. A previous study, PLATO, found that ticagrelor was superior to clopidogrel at preventing adverse cardiac events in patients with acute coronary syndromes who were not given fibrinolytic therapy. TREAT was designed to determine whether these benefits extend to patients given fibrinolytic therapy after ST-segment elevated myocardial infarction (STEMI).
Dr. Berwanger, Chair of the Steering Committee for TREAT, commented in the ACC announcement, “In spite of the fact that ticagrelor is more potent than clopidogrel, we found that it is safe to use ticagrelor in this population. In terms of efficacy, it is appropriate to interpret it statistically as a neutral trial, though it should be looked at in the broader context along with PLATO.”
Investigators advised that the trial was conducted in 10 countries on five continents and included a mix of higher- and lower-income countries and thus has worldwide relevance. They noted that the use of fibrinolytic therapy is most common where percutaneous coronary intervention is not available 24 hours a day, which includes most lower- and middle-income countries as well as some higher-income countries.
The trial enrolled 3,800 patients treated for STEMI at more than 180 centers. All patients had received fibrinolytic therapy within 24 hours of their heart attack. Patients, who were randomly assigned 1:1 to ticagrelor or clopidogrel, were given an initial loading dose of their assigned drug, then continued taking the drug for 12 months.
The key endpoint for the 12-month analysis was a composite of death from vascular causes, heart attack, stroke, severe recurrent ischemia, transient ischemic attack, or another arterial thrombotic event. The endpoint rate was 8% for ticagrelor and 9.1% for clopidogrel, but the difference was not statistically significant.
The investigators noted that the TREAT trial was much smaller than the earlier PLATO trial, which had more than 18,000 participants, and had a lower than expected number of adverse events, limiting its statistical power. The risk reductions of ticagrelor as compared with the clopidogrel groups were identical in both studies; however, the gap was considered statistically significant in PLATO because of that trial’s larger size.
When the investigators analyzed pooled data combining PLATO and TREAT, they found that ticagrelor significantly improved outcomes compared to clopidogrel.
Dr. Berwanger stated, “The TREAT patients are exactly the population that was excluded from PLATO. By combining both trials, we can say that ticagrelor is beneficial across the whole spectrum of patients with acute coronary syndromes, regardless of how they are managed in terms of fibrinolytic therapy.”
As summarized further in the ACC announcement, when TREAT data were analyzed alone, investigators found no significant difference in terms of the secondary composite endpoint that included death from vascular causes, heart attack, or stroke, (6.9% with ticagrelor vs 7.3% with clopidogrel). They also found no significant differences in terms of the individual components of the composite endpoint or death from any cause.
Finally, the TREAT investigators assessed the bleeding event rate using criteria defined by the TIMI (thrombolysis in myocardial Infarction) score, as well as the BARC (Bleeding Academic Research Consortium) categories and the definition used in PLATO. Rates of the most important types of bleeding such as major bleeding and major and minor bleeding combined were low (1%–2%) and not significantly different between the two groups, suggesting the safety of ticagrelor. However, rates of minor, nonclinically relevant bleeding (such as from a nosebleed or minor cut) were significantly higher in the ticagrelor group (5.9% vs 2.9%). This difference was expected and in line with previous studies, noted Dr. Berwanger in the ACC announcement.