Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicentre, open-label, randomised superiority trial

GLOBAL LEADERS Investigators

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Abstract

Background: We hypothesised that ticagrelor, in combination with aspirin for 1 month, followed by ticagrelor alone, improves outcomes after percutaneous coronary intervention compared with standard antiplatelet regimens. Methods: GLOBAL LEADERS was a randomised, open-label superiority trial at 130 sites in 18 countries. Patients undergoing percutaneous coronary intervention with a biolimus A9-eluting stent for stable coronary artery disease or acute coronary syndromes were randomly assigned (1:1) to 75–100 mg aspirin daily plus 90 mg ticagrelor twice daily for 1 month, followed by 23 months of ticagrelor monotherapy, or standard dual antiplatelet therapy with 75–100 mg aspirin daily plus either 75 mg clopidogrel daily (for patients with stable coronary artery disease) or 90 mg ticagrelor twice daily (for patients with acute coronary syndromes) for 12 months, followed by aspirin monotherapy for 12 months. Randomisation was concealed, stratified by centre and clinical presentation (stable coronary artery disease vs acute coronary syndrome), and blocked, with randomly varied block sizes of two and four. The primary endpoint at 2 years was a composite of all-cause mortality or non-fatal centrally adjudicated new Q-wave myocardial infarction as assessed by a core lab in a blinded manner. The key secondary safety endpoint was site-reported bleeding assessed according to the Bleeding Academic Research Consortium criteria (grade 3 or 5). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01813435, and is closed to new participants, with follow-up completed. Findings: Between July 1, 2013, and Nov 9, 2015, 15 968 participants were randomly assigned, 7980 to the experimental group and 7988 to the control group. At 2 years, 304 (3·81%) participants in the experimental group had died or had a non-fatal centrally adjudicated new Q-wave myocardial infarction, compared with 349 (4·37%) participants in the control group (rate ratio 0·87 [95% CI 0·75–1·01]; p=0·073]). There was no evidence for a difference in treatment effects for the primary endpoint across prespecified subgroups of acute coronary syndromes and stable coronary artery disease (p=0·93). Grade 3 or 5 bleeding occurred in 163 participants in the experimental group and 169 in the control group (2·04% vs 2·12%; rate ratio 0·97 [95% CI 0·78–1·20]; p=0·77). Interpretation: Ticagrelor in combination with aspirin for 1 month followed by ticagrelor alone for 23 months was not superior to 12 months of standard dual antiplatelet therapy followed by 12 months of aspirin alone in the prevention of all-cause mortality or new Q-wave myocardial infarction 2 years after percutaneous coronary intervention. Funding: AstraZeneca, Biosensors, and The Medicines Company.

Original languageEnglish
Pages (from-to)940-949
Number of pages10
JournalThe Lancet
Volume392
Issue number10151
DOIs
Publication statusPublished - Sep 15 2018

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clopidogrel
Drug-Eluting Stents
Aspirin
Acute Coronary Syndrome
Coronary Artery Disease
Percutaneous Coronary Intervention
Myocardial Infarction
Hemorrhage
Control Groups
Intention to Treat Analysis
Mortality
Biosensing Techniques
Random Allocation
Ticagrelor
Stents

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{061cca86db814fa680f56960d0ec4327,
title = "Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicentre, open-label, randomised superiority trial",
abstract = "Background: We hypothesised that ticagrelor, in combination with aspirin for 1 month, followed by ticagrelor alone, improves outcomes after percutaneous coronary intervention compared with standard antiplatelet regimens. Methods: GLOBAL LEADERS was a randomised, open-label superiority trial at 130 sites in 18 countries. Patients undergoing percutaneous coronary intervention with a biolimus A9-eluting stent for stable coronary artery disease or acute coronary syndromes were randomly assigned (1:1) to 75–100 mg aspirin daily plus 90 mg ticagrelor twice daily for 1 month, followed by 23 months of ticagrelor monotherapy, or standard dual antiplatelet therapy with 75–100 mg aspirin daily plus either 75 mg clopidogrel daily (for patients with stable coronary artery disease) or 90 mg ticagrelor twice daily (for patients with acute coronary syndromes) for 12 months, followed by aspirin monotherapy for 12 months. Randomisation was concealed, stratified by centre and clinical presentation (stable coronary artery disease vs acute coronary syndrome), and blocked, with randomly varied block sizes of two and four. The primary endpoint at 2 years was a composite of all-cause mortality or non-fatal centrally adjudicated new Q-wave myocardial infarction as assessed by a core lab in a blinded manner. The key secondary safety endpoint was site-reported bleeding assessed according to the Bleeding Academic Research Consortium criteria (grade 3 or 5). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01813435, and is closed to new participants, with follow-up completed. Findings: Between July 1, 2013, and Nov 9, 2015, 15 968 participants were randomly assigned, 7980 to the experimental group and 7988 to the control group. At 2 years, 304 (3·81{\%}) participants in the experimental group had died or had a non-fatal centrally adjudicated new Q-wave myocardial infarction, compared with 349 (4·37{\%}) participants in the control group (rate ratio 0·87 [95{\%} CI 0·75–1·01]; p=0·073]). There was no evidence for a difference in treatment effects for the primary endpoint across prespecified subgroups of acute coronary syndromes and stable coronary artery disease (p=0·93). Grade 3 or 5 bleeding occurred in 163 participants in the experimental group and 169 in the control group (2·04{\%} vs 2·12{\%}; rate ratio 0·97 [95{\%} CI 0·78–1·20]; p=0·77). Interpretation: Ticagrelor in combination with aspirin for 1 month followed by ticagrelor alone for 23 months was not superior to 12 months of standard dual antiplatelet therapy followed by 12 months of aspirin alone in the prevention of all-cause mortality or new Q-wave myocardial infarction 2 years after percutaneous coronary intervention. Funding: AstraZeneca, Biosensors, and The Medicines Company.",
author = "{GLOBAL LEADERS Investigators} and Pascal Vranckx and Marco Valgimigli and Peter J{\"u}ni and Christian Hamm and Steg, {Philippe Gabriel} and Dik Heg and {van Es}, {Gerrit Anne} and McFadden, {Eugene P.} and Yoshinobu Onuma and {van Meijeren}, Cokky and Ply Chichareon and Edouard Benit and Helge M{\"o}llmann and Luc Janssens and Maurizio Ferrario and Aris Moschovitis and Aleksander Zurakowski and Marcello Dominici and {Van Geuns}, {Robert Jan} and Kurt Huber and Ton Slagboom and Serruys, {Patrick W.} and Stephan Windecker and Mohamed Abdellaoui and David Adlam and Ibrahim Akin and {Albarran Gonzalez-Trevilla}, Agustin and Manuel Almeida and {Alves Lemos Neto}, Pedro and Adel Aminian and Richard Anderson and Rick Andreae and Michael Angioi and Taku Asano and Emanuele Barbato and Peter Barlis and Pascal Barraud and Edouard Benit and Olivier Bertrand and Farzin Beygui and Leonardo Bolognese and Roberto Botelho and Coby Bouwman and Marco Bressers and Philippe Brunel and Pawel Buszman and Ian Buysschaert and {Canas da Silva}, Pedro and Antonio Colombo and Maurizio Ferrario",
year = "2018",
month = "9",
day = "15",
doi = "10.1016/S0140-6736(18)31858-0",
language = "English",
volume = "392",
pages = "940--949",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Lancet Publishing Group",
number = "10151",

}

TY - JOUR

T1 - Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent

T2 - a multicentre, open-label, randomised superiority trial

AU - GLOBAL LEADERS Investigators

AU - Vranckx, Pascal

AU - Valgimigli, Marco

AU - Jüni, Peter

AU - Hamm, Christian

AU - Steg, Philippe Gabriel

AU - Heg, Dik

AU - van Es, Gerrit Anne

AU - McFadden, Eugene P.

AU - Onuma, Yoshinobu

AU - van Meijeren, Cokky

AU - Chichareon, Ply

AU - Benit, Edouard

AU - Möllmann, Helge

AU - Janssens, Luc

AU - Ferrario, Maurizio

AU - Moschovitis, Aris

AU - Zurakowski, Aleksander

AU - Dominici, Marcello

AU - Van Geuns, Robert Jan

AU - Huber, Kurt

AU - Slagboom, Ton

AU - Serruys, Patrick W.

AU - Windecker, Stephan

AU - Abdellaoui, Mohamed

AU - Adlam, David

AU - Akin, Ibrahim

AU - Albarran Gonzalez-Trevilla, Agustin

AU - Almeida, Manuel

AU - Alves Lemos Neto, Pedro

AU - Aminian, Adel

AU - Anderson, Richard

AU - Andreae, Rick

AU - Angioi, Michael

AU - Asano, Taku

AU - Barbato, Emanuele

AU - Barlis, Peter

AU - Barraud, Pascal

AU - Benit, Edouard

AU - Bertrand, Olivier

AU - Beygui, Farzin

AU - Bolognese, Leonardo

AU - Botelho, Roberto

AU - Bouwman, Coby

AU - Bressers, Marco

AU - Brunel, Philippe

AU - Buszman, Pawel

AU - Buysschaert, Ian

AU - Canas da Silva, Pedro

AU - Colombo, Antonio

AU - Ferrario, Maurizio

PY - 2018/9/15

Y1 - 2018/9/15

N2 - Background: We hypothesised that ticagrelor, in combination with aspirin for 1 month, followed by ticagrelor alone, improves outcomes after percutaneous coronary intervention compared with standard antiplatelet regimens. Methods: GLOBAL LEADERS was a randomised, open-label superiority trial at 130 sites in 18 countries. Patients undergoing percutaneous coronary intervention with a biolimus A9-eluting stent for stable coronary artery disease or acute coronary syndromes were randomly assigned (1:1) to 75–100 mg aspirin daily plus 90 mg ticagrelor twice daily for 1 month, followed by 23 months of ticagrelor monotherapy, or standard dual antiplatelet therapy with 75–100 mg aspirin daily plus either 75 mg clopidogrel daily (for patients with stable coronary artery disease) or 90 mg ticagrelor twice daily (for patients with acute coronary syndromes) for 12 months, followed by aspirin monotherapy for 12 months. Randomisation was concealed, stratified by centre and clinical presentation (stable coronary artery disease vs acute coronary syndrome), and blocked, with randomly varied block sizes of two and four. The primary endpoint at 2 years was a composite of all-cause mortality or non-fatal centrally adjudicated new Q-wave myocardial infarction as assessed by a core lab in a blinded manner. The key secondary safety endpoint was site-reported bleeding assessed according to the Bleeding Academic Research Consortium criteria (grade 3 or 5). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01813435, and is closed to new participants, with follow-up completed. Findings: Between July 1, 2013, and Nov 9, 2015, 15 968 participants were randomly assigned, 7980 to the experimental group and 7988 to the control group. At 2 years, 304 (3·81%) participants in the experimental group had died or had a non-fatal centrally adjudicated new Q-wave myocardial infarction, compared with 349 (4·37%) participants in the control group (rate ratio 0·87 [95% CI 0·75–1·01]; p=0·073]). There was no evidence for a difference in treatment effects for the primary endpoint across prespecified subgroups of acute coronary syndromes and stable coronary artery disease (p=0·93). Grade 3 or 5 bleeding occurred in 163 participants in the experimental group and 169 in the control group (2·04% vs 2·12%; rate ratio 0·97 [95% CI 0·78–1·20]; p=0·77). Interpretation: Ticagrelor in combination with aspirin for 1 month followed by ticagrelor alone for 23 months was not superior to 12 months of standard dual antiplatelet therapy followed by 12 months of aspirin alone in the prevention of all-cause mortality or new Q-wave myocardial infarction 2 years after percutaneous coronary intervention. Funding: AstraZeneca, Biosensors, and The Medicines Company.

AB - Background: We hypothesised that ticagrelor, in combination with aspirin for 1 month, followed by ticagrelor alone, improves outcomes after percutaneous coronary intervention compared with standard antiplatelet regimens. Methods: GLOBAL LEADERS was a randomised, open-label superiority trial at 130 sites in 18 countries. Patients undergoing percutaneous coronary intervention with a biolimus A9-eluting stent for stable coronary artery disease or acute coronary syndromes were randomly assigned (1:1) to 75–100 mg aspirin daily plus 90 mg ticagrelor twice daily for 1 month, followed by 23 months of ticagrelor monotherapy, or standard dual antiplatelet therapy with 75–100 mg aspirin daily plus either 75 mg clopidogrel daily (for patients with stable coronary artery disease) or 90 mg ticagrelor twice daily (for patients with acute coronary syndromes) for 12 months, followed by aspirin monotherapy for 12 months. Randomisation was concealed, stratified by centre and clinical presentation (stable coronary artery disease vs acute coronary syndrome), and blocked, with randomly varied block sizes of two and four. The primary endpoint at 2 years was a composite of all-cause mortality or non-fatal centrally adjudicated new Q-wave myocardial infarction as assessed by a core lab in a blinded manner. The key secondary safety endpoint was site-reported bleeding assessed according to the Bleeding Academic Research Consortium criteria (grade 3 or 5). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01813435, and is closed to new participants, with follow-up completed. Findings: Between July 1, 2013, and Nov 9, 2015, 15 968 participants were randomly assigned, 7980 to the experimental group and 7988 to the control group. At 2 years, 304 (3·81%) participants in the experimental group had died or had a non-fatal centrally adjudicated new Q-wave myocardial infarction, compared with 349 (4·37%) participants in the control group (rate ratio 0·87 [95% CI 0·75–1·01]; p=0·073]). There was no evidence for a difference in treatment effects for the primary endpoint across prespecified subgroups of acute coronary syndromes and stable coronary artery disease (p=0·93). Grade 3 or 5 bleeding occurred in 163 participants in the experimental group and 169 in the control group (2·04% vs 2·12%; rate ratio 0·97 [95% CI 0·78–1·20]; p=0·77). Interpretation: Ticagrelor in combination with aspirin for 1 month followed by ticagrelor alone for 23 months was not superior to 12 months of standard dual antiplatelet therapy followed by 12 months of aspirin alone in the prevention of all-cause mortality or new Q-wave myocardial infarction 2 years after percutaneous coronary intervention. Funding: AstraZeneca, Biosensors, and The Medicines Company.

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U2 - 10.1016/S0140-6736(18)31858-0

DO - 10.1016/S0140-6736(18)31858-0

M3 - Article

C2 - 30166073

AN - SCOPUS:85054275514

VL - 392

SP - 940

EP - 949

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 10151

ER -