TREAT: Ticagrelor after fibrinolytic therapy may reduce bleeding events after STEMI
NEW ORLEANS — Ticagrelor after fibrinolytic therapy in patients younger than 75 years with STEMI may not reduce the frequency of major CV events at 12 months compared with patients treated with clopidogrel, but it may be safe with regard to major bleeding, according to data from the TREAT trial presented at the American College of Cardiology Scientific Session.
These findings have also been published in the Journal of the American College of Cardiology.
Thirty-day results of this trial were previously presented. As Cardiology Today’s Intervention previously reported, delayed administration of ticagrelor (Brilinta, AstraZeneca) after fibrinolytic therapy was noninferior to clopidogrel for major bleeding at 30 days among patients younger than 75 years with STEMI.
Otavio Berwanger, MD, PhD, cardiologist, clinical trialist and director of the Academic Research Organization at Albert Einstein Hospital in São Paulo, and colleagues analyzed data from 3,799 patients with the onset of STEMI within 24 hours who were treated with fibrinolytic therapy. Patients were assigned to ticagrelor (n = 1,913; median age, 59 years; 77% men) or clopidogrel (n = 1,886; median age, 59 years; 77% men).
Those assigned ticagrelor received a loading dose of 180 mg followed by 90 mg twice per day for 12 months. The clopidogrel group received a loading dose of 300 mg then 75 mg per day for 12 months.
Patients were followed up at hospital discharge or 7 days, 30 days, 6 months and 12 months.
The primary safety outcome of interest was TIMI major bleeding. Secondary safety outcomes of interest included all bleeding events. The study also included secondary efficacy outcomes of interest, which were death from MI, CV, stroke, severe recurrent ischemia, transient ischemic attack or other arterial thrombotic events.
Of the patients in the study, 60.4% of patients in the ticagrelor group and 58.7% of those in the clopidogrel group underwent PCI.
At 12 months, there were similar rates of bleeding in the ticagrelor and clopidogrel groups for TIMI major bleeding (1.05% vs. 1.22%, respectively; HR = 0.86; 95% CI, 0.47-1.56), PLATO major bleeding (1.57% vs. 2.12%, respectively; HR = 0.74; 95% CI, 0.47-1.18) and BARC types 3 to 5 bleeding (1.62% vs. 1.96%, respectively; HR = 0.82; 95% CI, 0.51-1.33). This was a similar trend to what was seen at 30 days, Berwanger said during the presentation. Rates in the ticagrelor and clopidogrel groups were also similar for intracranial bleeding (0.52% vs. 0.48%, respectively; HR = 1.1; 95% CI, 0.45-2.7) and fatal bleeding (0.31% vs. 0.21%, respectively; HR = 1.47; 95% CI, 0.42-5.22).
Patients assigned ticagrelor had more total bleeding events compared with those assigned clopidogrel (10.25% vs. 6.15%; HR = 1.69; 95% CI, 1.34-2.13). This was also seen for TIMI minimal bleeding (5.85% vs. 2.86%; HR = 2.06; 95% CI, 1.49-2.85) and clinically significant TIMI (5.28% vs. 3.76%; HR = 1.41; 95% CI, 1.04-1.91).
The ticagrelor group had a lower cumulative incidence of secondary efficacy outcomes at 1 year compared with the clopidogrel group, although it was not statistically significant (HR = 0.88; 95% CI, 0.71-1.09). There was also no difference between both groups in 3-point major adverse CV events at 12 months (HR = 0.93; 95% CI, 0.73-1.18).
A pooled analysis of the TREAT and PLATO trials found that there were no inconsistencies in the findings for a composite outcome of death from MI, vascular causes or stroke or a composite outcome of MI, CV death, severe recurrent ischemia, stroke, TIA or other arterial thrombotic events. There were similar results from the pooled analysis of subgroups from both trials.
“Results suggest the safety of ticagrelor with regard to major bleeding in comparison to clopidogrel up to 12 months in fibrinolytic-treated STEMI patients,” Berwanger said during the presentation.
“TREAT is closing the knowledge gap, showing that [ticagrelor] can be used in conjunction with thrombolytic therapy,” Elisabeth Björk, senior vice president and head of late cardiovascular, renal and metabolism in biopharmaceutical R&D at AstraZeneca, said in a press release. “This is particularly important for those patients who are not able to receive surgical intervention in the immediate hours after a heart attack.” – by Darlene Dobkowski
Berwanger O. Late-Breaking Clinical Trials: Interventional. Presented at: American College of Cardiology Scientific Session; March 16-18, 2019; New Orleans.
Disclosures: The study was funded by AstraZeneca. Berwanger reports he received research support from Amgen, AstraZeneca, Bayer Healthcare, Boehringer Ingelheim, Novartis, Novo Nordisk, Roche Diagnosis and Sanofi-Aventis. Björk is an employee of AstraZeneca. Please see the study for all other authors’ relevant financial disclosures.