Author + information
- Received February 12, 2019
- Revision received March 6, 2019
- Accepted March 7, 2019
- Published online June 3, 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. Santos, Stata,
- 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, BrazilResearch Institute, Heart Hospital (HCor), Sao Paulo, Brazil
- bDuke Clinical Research Institute, Durham, North CarolinaDuke Clinical Research Institute, Durham, North Carolina
- cUniversidade Federal de São Paulo, São Paulo, BrazilUniversidade Federal de Sao Paulo, Sao Paulo, Brazil
- dFuwai Hospital, Beijing, ChinadFuwai Hospital, Beijing, China
- eCanadian Heart Research Centre (CHRC) and Division of Cardiology, St. Michael’s Hospital, University of Toronto, Toronto, Ontario, CanadaCanadian Heart Research Centre (CHRC) and Division of Cardiology, St. Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada
- fMonash Cardiovascular Research Centre, Monash University, Melbourne, Victoria, AustraliaMonash Cardiovascular Research Centre, Monash University, Melbourne, Victoria, Australia
- gInstitute of Cardiology, Emergency Cardiology Department, Kiev, UkraineInstitute of Cardiology, Emergency Cardiology Department, Kiev, Ukraine
- hPirogov Russian National Research Medical University, Moscow, RussiaPirogov Russian National Research Medical University, Moscow, Russia
- iHospital de Alta Complejidad El Cruce, Buenos Aires, ArgentinaHospital de Alta Complejidad El Cruce, Buenos Aires, Argentina
- jSchool of Medicine, Universidad Peruana Cayetano Heredia, Lima, PeruSchool of Medicine, Universidad Peruana Cayetano Heredia, Lima, Peru
- kHospital e Maternidade Celso Pierro, Campinas, BrazilHospital e Maternidade Celso Pierro, Campinas, Brazil
- lHeart Hospital (HCor), São Paulo, BrazilHeart Hospital (HCor), Sao Paulo, Brazil
- mAuckland City Hospital, Auckland District Health Board, Auckland, New ZealandmAuckland 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, BrazilInstituto do Coraçao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
- ↵∗Address for correspondence:
Dr. Otavio Berwanger, Research Institute–Heart Hospital (HCor), Abílio Soares St 250, 12th Floor, 04005-000, São Paulo, SP, Brazil.
Background The efficacy of ticagrelor in the long-term post–ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain.
Objectives The purpose of this study was to evaluate the efficacy of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy.
Methods This international, multicenter, randomized, open-label with blinded endpoint adjudication trial 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: 0.93; 95% confidence interval: 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: 0.88; 95% confidence interval: 0.71 to 1.09; p = 0.25). The rates of major, fatal, and intracranial bleeding were similar between the ticagrelor and clopidogrel groups.
Conclusion Among patients age <75 years with STEMI, administration of ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular events when compared with clopidogrel. (Ticagrelor in Patients With ST Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis [TREAT]; NCT02298088)
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). Dr. Berwanger has received grants from AstraZeneca, Amgen, Bayer, Boehringer Ingelheim, and Roche Diagnostics; and has received personal fees from AstraZeneca, Bayer, Novo Nordisk, Roche Diagnostics, and Sanofi. Dr. Lopes has received institutional research grant and consulting fees from Bristol-Myers Squibb; institutional research grants from GlaxoSmithKline; and consulting fees from Bayer, Boehringer Ingelheim, Pfizer, Merck, and Portola. Dr. Fonseca has served as a consultant for AstraZeneca, Sanofi, Takeda, Abbott, Biolab, Amgen, EMS, Torrent, Novartis, Aché, and Bayer; has served on the Steering Committee of the JUPITER study; and initiated the BATTLE-AMI investigator trial. Dr. Goodman has received 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, and Tenax Therapeutics, as well as the Heart and Stroke Foundation of Ontario/University of Toronto, Canadian Heart Research Centre and MD Primer, Canadian VIGOUR Centre, Duke Clinical Research Institute, and PERFUSE study. Dr. Nicholls has received research support from AstraZeneca, Amgen, Anthera, Eli Lilly, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, and LipoScience; and has served as a consultant for and received honoraria from Akcea, AstraZeneca, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, and Boehringer Ingelheim. Dr. Averkov has received lecturer and adviser fees from AstraZeneca. Dr. de Barros e Silva has received grants and personal fees from Pfizer. Dr. Granger has research contracts with Apple, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi-Sankyo, Janssen, Novartis, GlaxoSmithKline, Medtronic Foundation, Pfizer, the U.S. Food and Drug Administration, and the National Institutes of Health; and has served as a consultant for Abbvie, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Boston Scientific, Gilead, Pfizer, Daiichi-Sankyo, Novartis, Medtronic, Merck, Novo Nordisk, and Roche Diagnostics. Dr. White has served as Executive Committee member and National Coordinator for and received consulting fees for the ODYSSEY Trial (Sanofi) and ACCELERATE Study (Eli Lilly); has received research grant support from the National Institute of Health; has received Advisory Board fees, lecture fees, support towards travel and accommodation, and nonfinancial support from AstraZeneca; has served as a Steering Committee member and National Leader and received consulting fees for the STRENGTH Trial (Omthera Pharmaceuticals); has served on the Steering Committee and received consulting fees for the SPIRE Trial (Pfizer New Zealand); has served as National Lead Investigator and Steering Committee member and received consulting fees for the CAMELIA Trial (Elsai Inc.) and DalGenE Study (DalCor Pharma UK Inc.); has received Advisory Board fees from Sirtex and Actelion; has served on the Executive/Steering Committee, as National Country Lead, and received consulting fees for the AEGIS-II study (CSL Behring LLC); and has received Steering Committee member consulting fees from the HEART-FID study (Luitpold Pharmaceuticals). Dr. Nicolau has received research support from Amgen, Bayer, Bristol-Myers Squibb, Dalcor, Janssen, Sanofi, AstraZeneca, Boehringer Ingelheim, Novartis, Perfuse, and Pfizer; and has received consulting fees or honoraria from Sanofi, Amgen, and Servier. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received February 12, 2019.
- Revision received March 6, 2019.
- Accepted March 7, 2019.
- 2019 American College of Cardiology Foundation
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