Ticagrelor vs clopidogrel after fibrinolytic therapy in patients with st-elevation myocardial infarction a randomized clinical trial

Otavio Berwanger, Jose C. Nicolau, Antonio C. Carvalho, Lixin Jiang, Shaun G. Goodman, Stephen J. Nicholls, Alexander Parkhomenko, Oleg Averkov, Carlos Tajer, Germán Malaga, Jose F.K. Saraiva, Francisco A. Fonseca, Fábio A. De Luca, Helio P. Guimaraes, Pedro G.M. De Barros E Silva, Lucas P. Damiani, Denise M. Paisani, Camila M.R. Lasagno, Carolina T. Candido, Nanci Valeis & 5 others Diogo D.F. Moia, Leopoldo S. Piegas, Christopher B. Granger, Harvey D. White, Renato D. Lopes

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

IMPORTANCE The bleeding safety of ticagrelor in patients with ST-elevationmyocardial infarction treated with fibrinolytic therapy remains uncertain. OBJECTIVE To evaluate the short-Term safety of ticagrelor when compared with clopidogrel in patients with ST-elevationmyocardial infarction treated with fibrinolytic therapy. DESIGN, SETTING AND PARTICIPANTS We conducted a multicenter, randomized, open-label with blinded end point adjudication trial that enrolled 3799 patients (younger than 75 years) with ST-segment elevationmyocardial infarction receiving fibrinolytic therapy in 152 sites from 10 countries from November 2015 through November 2017. The prespecified upper boundary for noninferiority for bleeding was an absolute margin of 1.0%. INTERVENTIONS Patients were randomized to ticagrelor (180-mg loading dose, 90mg twice daily thereafter) or clopidogrel (300-mg to 600-mg loading dose, 75mg daily thereafter). Patients were randomized with a median of 11.4 hours after fibrinolysis, and 90% were pretreated with clopidogrel. MAIN OUTCOMES AND MEASURES The primary outcomewas thrombolysis inmyocardial infarction (TIMI) major bleeding through 30 days. RESULTS The mean (SD) age was 58.0 (9.5) years, 2928 of 3799 patients (77.1%) were men, and 2177 of 3799 patients (57.3%) were white. At 30 days, TIMI major bleeding had occurred in 14 of 1913 patients (0.73%) receiving ticagrelor and in 13 of 1886 patients (0.69%) receiving clopidogrel (absolute difference, 0.04%; 95%CI, -0.49% to 0.58%; P < .001 for noninferiority). Major bleeding defined by the Platelet Inhibition and Patient Outcomes criteria and by the Bleeding Academic Research Consortium types 3 to 5 bleeding occurred in 23 patients (1.20%) in the ticagrelor group and in 26 patients (1.38%) in the clopidogrel group (absolute difference, -0.18%; 95%CI, -0.89% to 0.54; P = .001 for noninferiority). The rates of fatal (0.16%vs 0.11%; P = .67) and intracranial bleeding (0.42%vs 0.37%; P = .82) were similar between the ticagrelor and clopidogrel groups, respectively. Minor and minimal bleeding were more common with ticagrelor than with clopidogrel. The composite of death from vascular causes,myocardial infarction, or stroke occurred in 76 patients (4.0%) treated with ticagrelor and in 82 patients (4.3%) receiving clopidogrel (hazard ratio, 0.91; 95%CI, 0.67-1.25; P = .57). CONCLUSIONS AND RELEVANCE In patients younger than 75 years with ST-segment elevation myocardial infarction, delayed administration of ticagrelor after fibrinolytic therapy was noninferior to clopidogrel for TIMI major bleeding at 30 days.

LanguageEnglish
Pages391-399
Number of pages9
JournalJAMA Cardiology
Volume3
Issue number5
DOIs
Publication statusPublished - 1 May 2018

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Berwanger, O., Nicolau, J. C., Carvalho, A. C., Jiang, L., Goodman, S. G., Nicholls, S. J., ... Lopes, R. D. (2018). Ticagrelor vs clopidogrel after fibrinolytic therapy in patients with st-elevation myocardial infarction a randomized clinical trial. JAMA Cardiology, 3(5), 391-399. https://doi.org/10.1001/jamacardio.2018.0612
Berwanger, Otavio ; Nicolau, Jose C. ; Carvalho, Antonio C. ; Jiang, Lixin ; Goodman, Shaun G. ; Nicholls, Stephen J. ; Parkhomenko, Alexander ; Averkov, Oleg ; Tajer, Carlos ; Malaga, Germán ; Saraiva, Jose F.K. ; Fonseca, Francisco A. ; De Luca, Fábio A. ; Guimaraes, Helio P. ; De Barros E Silva, Pedro G.M. ; Damiani, Lucas P. ; Paisani, Denise M. ; Lasagno, Camila M.R. ; Candido, Carolina T. ; Valeis, Nanci ; Moia, Diogo D.F. ; Piegas, Leopoldo S. ; Granger, Christopher B. ; White, Harvey D. ; Lopes, Renato D. / Ticagrelor vs clopidogrel after fibrinolytic therapy in patients with st-elevation myocardial infarction a randomized clinical trial. In: JAMA Cardiology. 2018 ; Vol. 3, No. 5. pp. 391-399.
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abstract = "IMPORTANCE The bleeding safety of ticagrelor in patients with ST-elevationmyocardial infarction treated with fibrinolytic therapy remains uncertain. OBJECTIVE To evaluate the short-Term safety of ticagrelor when compared with clopidogrel in patients with ST-elevationmyocardial infarction treated with fibrinolytic therapy. DESIGN, SETTING AND PARTICIPANTS We conducted a multicenter, randomized, open-label with blinded end point adjudication trial that enrolled 3799 patients (younger than 75 years) with ST-segment elevationmyocardial infarction receiving fibrinolytic therapy in 152 sites from 10 countries from November 2015 through November 2017. The prespecified upper boundary for noninferiority for bleeding was an absolute margin of 1.0{\%}. INTERVENTIONS Patients were randomized to ticagrelor (180-mg loading dose, 90mg twice daily thereafter) or clopidogrel (300-mg to 600-mg loading dose, 75mg daily thereafter). Patients were randomized with a median of 11.4 hours after fibrinolysis, and 90{\%} were pretreated with clopidogrel. MAIN OUTCOMES AND MEASURES The primary outcomewas thrombolysis inmyocardial infarction (TIMI) major bleeding through 30 days. RESULTS The mean (SD) age was 58.0 (9.5) years, 2928 of 3799 patients (77.1{\%}) were men, and 2177 of 3799 patients (57.3{\%}) were white. At 30 days, TIMI major bleeding had occurred in 14 of 1913 patients (0.73{\%}) receiving ticagrelor and in 13 of 1886 patients (0.69{\%}) receiving clopidogrel (absolute difference, 0.04{\%}; 95{\%}CI, -0.49{\%} to 0.58{\%}; P < .001 for noninferiority). Major bleeding defined by the Platelet Inhibition and Patient Outcomes criteria and by the Bleeding Academic Research Consortium types 3 to 5 bleeding occurred in 23 patients (1.20{\%}) in the ticagrelor group and in 26 patients (1.38{\%}) in the clopidogrel group (absolute difference, -0.18{\%}; 95{\%}CI, -0.89{\%} to 0.54; P = .001 for noninferiority). The rates of fatal (0.16{\%}vs 0.11{\%}; P = .67) and intracranial bleeding (0.42{\%}vs 0.37{\%}; P = .82) were similar between the ticagrelor and clopidogrel groups, respectively. Minor and minimal bleeding were more common with ticagrelor than with clopidogrel. The composite of death from vascular causes,myocardial infarction, or stroke occurred in 76 patients (4.0{\%}) treated with ticagrelor and in 82 patients (4.3{\%}) receiving clopidogrel (hazard ratio, 0.91; 95{\%}CI, 0.67-1.25; P = .57). CONCLUSIONS AND RELEVANCE In patients younger than 75 years with ST-segment elevation myocardial infarction, delayed administration of ticagrelor after fibrinolytic therapy was noninferior to clopidogrel for TIMI major bleeding at 30 days.",
author = "Otavio Berwanger and Nicolau, {Jose C.} and Carvalho, {Antonio C.} and Lixin Jiang and Goodman, {Shaun G.} and Nicholls, {Stephen J.} and Alexander Parkhomenko and Oleg Averkov and Carlos Tajer and Germ{\'a}n Malaga and Saraiva, {Jose F.K.} and Fonseca, {Francisco A.} and {De Luca}, {F{\'a}bio A.} and Guimaraes, {Helio P.} and {De Barros E Silva}, {Pedro G.M.} and Damiani, {Lucas P.} and Paisani, {Denise M.} and Lasagno, {Camila M.R.} and Candido, {Carolina T.} and Nanci Valeis and Moia, {Diogo D.F.} and Piegas, {Leopoldo S.} and Granger, {Christopher B.} and White, {Harvey D.} and Lopes, {Renato D.}",
year = "2018",
month = "5",
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doi = "10.1001/jamacardio.2018.0612",
language = "English",
volume = "3",
pages = "391--399",
journal = "JAMA Cardiology",
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Berwanger, O, Nicolau, JC, Carvalho, AC, Jiang, L, Goodman, SG, Nicholls, SJ, Parkhomenko, A, Averkov, O, Tajer, C, Malaga, G, Saraiva, JFK, Fonseca, FA, De Luca, FA, Guimaraes, HP, De Barros E Silva, PGM, Damiani, LP, Paisani, DM, Lasagno, CMR, Candido, CT, Valeis, N, Moia, DDF, Piegas, LS, Granger, CB, White, HD & Lopes, RD 2018, 'Ticagrelor vs clopidogrel after fibrinolytic therapy in patients with st-elevation myocardial infarction a randomized clinical trial', JAMA Cardiology, vol. 3, no. 5, pp. 391-399. https://doi.org/10.1001/jamacardio.2018.0612

Ticagrelor vs clopidogrel after fibrinolytic therapy in patients with st-elevation myocardial infarction a randomized clinical trial. / Berwanger, Otavio; Nicolau, Jose C.; Carvalho, Antonio C.; Jiang, Lixin; Goodman, Shaun G.; Nicholls, Stephen J.; Parkhomenko, Alexander; Averkov, Oleg; Tajer, Carlos; Malaga, Germán; Saraiva, Jose F.K.; Fonseca, Francisco A.; De Luca, Fábio A.; Guimaraes, Helio P.; De Barros E Silva, Pedro G.M.; Damiani, Lucas P.; Paisani, Denise M.; Lasagno, Camila M.R.; Candido, Carolina T.; Valeis, Nanci; Moia, Diogo D.F.; Piegas, Leopoldo S.; Granger, Christopher B.; White, Harvey D.; Lopes, Renato D.

In: JAMA Cardiology, Vol. 3, No. 5, 01.05.2018, p. 391-399.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Ticagrelor vs clopidogrel after fibrinolytic therapy in patients with st-elevation myocardial infarction a randomized clinical trial

AU - Berwanger, Otavio

AU - Nicolau, Jose C.

AU - Carvalho, Antonio C.

AU - Jiang, Lixin

AU - Goodman, Shaun G.

AU - Nicholls, Stephen J.

AU - Parkhomenko, Alexander

AU - Averkov, Oleg

AU - Tajer, Carlos

AU - Malaga, Germán

AU - Saraiva, Jose F.K.

AU - Fonseca, Francisco A.

AU - De Luca, Fábio A.

AU - Guimaraes, Helio P.

AU - De Barros E Silva, Pedro G.M.

AU - Damiani, Lucas P.

AU - Paisani, Denise M.

AU - Lasagno, Camila M.R.

AU - Candido, Carolina T.

AU - Valeis, Nanci

AU - Moia, Diogo D.F.

AU - Piegas, Leopoldo S.

AU - Granger, Christopher B.

AU - White, Harvey D.

AU - Lopes, Renato D.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - IMPORTANCE The bleeding safety of ticagrelor in patients with ST-elevationmyocardial infarction treated with fibrinolytic therapy remains uncertain. OBJECTIVE To evaluate the short-Term safety of ticagrelor when compared with clopidogrel in patients with ST-elevationmyocardial infarction treated with fibrinolytic therapy. DESIGN, SETTING AND PARTICIPANTS We conducted a multicenter, randomized, open-label with blinded end point adjudication trial that enrolled 3799 patients (younger than 75 years) with ST-segment elevationmyocardial infarction receiving fibrinolytic therapy in 152 sites from 10 countries from November 2015 through November 2017. The prespecified upper boundary for noninferiority for bleeding was an absolute margin of 1.0%. INTERVENTIONS Patients were randomized to ticagrelor (180-mg loading dose, 90mg twice daily thereafter) or clopidogrel (300-mg to 600-mg loading dose, 75mg daily thereafter). Patients were randomized with a median of 11.4 hours after fibrinolysis, and 90% were pretreated with clopidogrel. MAIN OUTCOMES AND MEASURES The primary outcomewas thrombolysis inmyocardial infarction (TIMI) major bleeding through 30 days. RESULTS The mean (SD) age was 58.0 (9.5) years, 2928 of 3799 patients (77.1%) were men, and 2177 of 3799 patients (57.3%) were white. At 30 days, TIMI major bleeding had occurred in 14 of 1913 patients (0.73%) receiving ticagrelor and in 13 of 1886 patients (0.69%) receiving clopidogrel (absolute difference, 0.04%; 95%CI, -0.49% to 0.58%; P < .001 for noninferiority). Major bleeding defined by the Platelet Inhibition and Patient Outcomes criteria and by the Bleeding Academic Research Consortium types 3 to 5 bleeding occurred in 23 patients (1.20%) in the ticagrelor group and in 26 patients (1.38%) in the clopidogrel group (absolute difference, -0.18%; 95%CI, -0.89% to 0.54; P = .001 for noninferiority). The rates of fatal (0.16%vs 0.11%; P = .67) and intracranial bleeding (0.42%vs 0.37%; P = .82) were similar between the ticagrelor and clopidogrel groups, respectively. Minor and minimal bleeding were more common with ticagrelor than with clopidogrel. The composite of death from vascular causes,myocardial infarction, or stroke occurred in 76 patients (4.0%) treated with ticagrelor and in 82 patients (4.3%) receiving clopidogrel (hazard ratio, 0.91; 95%CI, 0.67-1.25; P = .57). CONCLUSIONS AND RELEVANCE In patients younger than 75 years with ST-segment elevation myocardial infarction, delayed administration of ticagrelor after fibrinolytic therapy was noninferior to clopidogrel for TIMI major bleeding at 30 days.

AB - IMPORTANCE The bleeding safety of ticagrelor in patients with ST-elevationmyocardial infarction treated with fibrinolytic therapy remains uncertain. OBJECTIVE To evaluate the short-Term safety of ticagrelor when compared with clopidogrel in patients with ST-elevationmyocardial infarction treated with fibrinolytic therapy. DESIGN, SETTING AND PARTICIPANTS We conducted a multicenter, randomized, open-label with blinded end point adjudication trial that enrolled 3799 patients (younger than 75 years) with ST-segment elevationmyocardial infarction receiving fibrinolytic therapy in 152 sites from 10 countries from November 2015 through November 2017. The prespecified upper boundary for noninferiority for bleeding was an absolute margin of 1.0%. INTERVENTIONS Patients were randomized to ticagrelor (180-mg loading dose, 90mg twice daily thereafter) or clopidogrel (300-mg to 600-mg loading dose, 75mg daily thereafter). Patients were randomized with a median of 11.4 hours after fibrinolysis, and 90% were pretreated with clopidogrel. MAIN OUTCOMES AND MEASURES The primary outcomewas thrombolysis inmyocardial infarction (TIMI) major bleeding through 30 days. RESULTS The mean (SD) age was 58.0 (9.5) years, 2928 of 3799 patients (77.1%) were men, and 2177 of 3799 patients (57.3%) were white. At 30 days, TIMI major bleeding had occurred in 14 of 1913 patients (0.73%) receiving ticagrelor and in 13 of 1886 patients (0.69%) receiving clopidogrel (absolute difference, 0.04%; 95%CI, -0.49% to 0.58%; P < .001 for noninferiority). Major bleeding defined by the Platelet Inhibition and Patient Outcomes criteria and by the Bleeding Academic Research Consortium types 3 to 5 bleeding occurred in 23 patients (1.20%) in the ticagrelor group and in 26 patients (1.38%) in the clopidogrel group (absolute difference, -0.18%; 95%CI, -0.89% to 0.54; P = .001 for noninferiority). The rates of fatal (0.16%vs 0.11%; P = .67) and intracranial bleeding (0.42%vs 0.37%; P = .82) were similar between the ticagrelor and clopidogrel groups, respectively. Minor and minimal bleeding were more common with ticagrelor than with clopidogrel. The composite of death from vascular causes,myocardial infarction, or stroke occurred in 76 patients (4.0%) treated with ticagrelor and in 82 patients (4.3%) receiving clopidogrel (hazard ratio, 0.91; 95%CI, 0.67-1.25; P = .57). CONCLUSIONS AND RELEVANCE In patients younger than 75 years with ST-segment elevation myocardial infarction, delayed administration of ticagrelor after fibrinolytic therapy was noninferior to clopidogrel for TIMI major bleeding at 30 days.

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U2 - 10.1001/jamacardio.2018.0612

DO - 10.1001/jamacardio.2018.0612

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JO - JAMA Cardiology

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