Author + information
- Received February 12, 2019
- Revision received March 6, 2019
- Accepted March 7, 2019
- Published online March 18, 2019.
- Otavio Berwanger, MD, PhDa,∗ (, )@OtavioBerwanger,
- Renato D. Lopes, MD, MHS, PhDb,c,
- Diogo D.F. Moia, PharmDa,
- Francisco A. Fonseca, MD, PhDc,
- Lixin Jiang, MD, PhDd,
- Shaun G. Goodman, MD, MSce,
- Stephen J. Nicholls, MD, PhDf,
- Alexander Parkhomenko, MD, PhDg,
- Oleg Averkov, MD, PhDh,
- Carlos Tajer, MD, PhDi,
- Germán Malaga, MDj,
- Jose F.K. Saraiva, MD, PhDk,
- Helio P. Guimaraes, MD, PhDa,
- Pedro G.M. de Barros e Silva, MD, MHS, PhDa,
- Lucas P. Damiani, MSca,
- Renato H.N. Santosa,
- Denise M. Paisani, PhDa,
- Tamiris A. Miranda, PharmDa,
- Nanci Valeis, Dra,
- Leopoldo S. Piegas, MD, PhDl,
- Christopher B. Granger, MD, PhDb,
- Harvey D. White, MD, DScm and
- Jose C. Nicolau, MD, PhDn
- aResearch Institute - Heart Hospital (HCor), São Paulo, Brazil
- bDuke Clinical Research Institute, Durham, United States
- cUniversidade Federal de São Paulo, São Paulo, Brazil
- dFuwai Hospital, Beijing, China
- eCanadian Heart Research Centre (CHRC) and Division of Cardiology, St. Michael’s Hospital, University of Toronto, Toronto, Canada
- fMonash Cardiovascular Research Centre, Monash University, Melbourne, Australia
- gInstitute of Cardiology - Emergency Cardiology Department, Kiev, Ukraine
- hPirogov Russian National Research Medical University, Moscow, Russia
- iHospital de Alta Complejidad El Cruce, Buenos Aires, Argentina
- jSchool of Medicine, Universidad Peruana Cayetano Heredia, Lima, Peru
- kHospital e Maternidade Celso Pierro, Campinas, Brazil
- lHeart Hospital (HCor), São Paulo, Brazil
- mAuckland City Hospital - Auckland District Health Board, Auckland, New Zealand
- nInstituto do Coração (InCor) - Hospital das Clinicas HCFMUSP - Faculdade de Medicina - Universidade de São Paulo, São Paulo, Brazil
- ↵∗Corresponding author: Otavio Berwanger, MD, PhD Research Institute – Heart Hospital (HCor) Abílio Soares St 250, 12th floor 04005-000 - São Paulo, SP, Brazil Telephone: +55 (11) 30536611; Ext: 8102 Fax: +55 (11) 3886 4695
Background The efficacy of ticagrelor in the long-term post ST-elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain.
Objectives To evaluate the efficacy of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy.
Methods We 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. 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.
Results 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.
Conclusions Among patients aged under 75 years with STEMI, administration of ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular events when compared with clopidogrel.
Funding: TREAT was an investigator-initiated trial funded by AstraZeneca. The funding sources had no role in the conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The trial was coordinated by the Research Institute - Heart Hospital (HCor).
Disclosures: Dr. Berwanger reports grants and personal fees from Astra Zeneca, grants from Amgen, grants and personal fees from Bayer, personal fees from Novo Nordisk, grants from Boehringer Ingelheim, grants and personal fees from Roche Diagnosis, personal fees from Sanofi, outside the submitted work.
Dr. Lopes reports institutional research grant and consulting fees from Bristol-Myers Squibb; institutional research grant from GlaxoSmithKline; consulting fees from Bayer, Boehringer Ingelheim, Pfizer, Merck, Portola.
Dr. Granger reports research contracts with Apple, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Daiichi Sankyo, Janssen, Novartis, GlaxoSmithKline, Medtronic Foundation, Pfizer, FDA, NIH; consulting relationship with Abbvie, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Boston Scientific, Gilead, Pfizer, Daiichi Sankyo, Novartis, Medtronic, Merck, Novo Nordisk, Roche Diagnostics
SG Goodman – Research grant support (e.g., steering committee or data monitoring committee) and/or speaker/consulting honoraria (e.g., advisory boards) from: Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Daiichi-Sankyo, Eli Lilly, Fenix Group International, Ferring Pharmaceuticals, GlaxoSmithKline, Janssen/Johnson & Johnson, Luitpold Pharmaceuticals, Matrizyme, Merck, Novartis, Novo Nordisk A/C, Pfizer, Regeneron, Sanofi, Servier, Tenax Therapeutics; Heart and Stroke Foundation of Ontario/University of Toronto, Canadian Heart Research Centre and MD Primer, Canadian VIGOUR Centre, Duke Clinical Research Institute, PERFUSE
SJ Nicholls - Research support: AstraZeneca, Amgen, Anthera, Eli Lilly, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron and LipoScience. Consulting and honoraria: Akcea, AstraZeneca, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, Boehringer Ingelheim
JC Nicolau – Research support: Amgen, Bayer, Bristol-Meyers Squibb, Dalcor, Janssen, Sanofi, Astrazeneca, Boheringer Ingelheim, Novartis, Perfuse and Pfizer. Consulting or honoraria: Sanofi, Amgen, Servier.
The remaining authors have nothing to disclose.
Short Tweet: TREAT Trial. In conclusion, among patients aged under 75 years with ST-segment elevation myocardial infarction, administration of ticagrelor after fibrinolytic therapy may not significantly reduce the frequency of major cardiovascular events at 12 months when compared with clopidogrel. Finally, our results suggest the safety of ticagrelor, in comparison to clopidogrel, up to 12 months post fibrinolytic-treated STEMI.
Trial Registration: ClinicalTrials.gov number, NCT02298088.
- Received February 12, 2019.
- Revision received March 6, 2019.
- Accepted March 7, 2019.
- 2019 American College of Cardiology Foundation
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