The University of Southampton
University of Southampton Institutional Repository

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

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
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

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.

Adenosine/administration & dosage, Aged, Aspirin/administration & dosage, Clopidogrel, Coronary Angiography, Coronary Artery Disease/drug therapy, Drug Therapy, Combination, Drug-Eluting Stents/adverse effects, Female, Humans, Intention to Treat Analysis, Male, Middle Aged, Myocardial Infarction/mortality, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors/administration & dosage, Purinergic P2Y Receptor Antagonists/administration & dosage, Ticagrelor, Ticlopidine/administration & dosage
0140-6736
940-949
Vranckx, Pascal
ae1689bd-bcd7-403b-ae43-a24cd61d905d
Valgimigli, Marco
2097fa94-7c8f-4aa8-8834-0d70940546d9
Jüni, Peter
1448ad34-a0d4-4faa-962b-abf202246167
Hamm, Christian
d6b04c5b-2831-4adb-8be5-6f7874ee5c05
Steg, Philippe Gabriel
1cebb409-f5f0-46a0-8682-34fd905aec17
Heg, Dik
5c602c49-aef0-4a14-aa46-6f660e334e7e
van Es, Gerrit Anne
3f0dd784-1ef0-47a4-9de3-03a17e5c46d8
McFadden, Eugene P
1b00e428-6d5f-45a2-af26-abdd4a80d8bc
Onuma, Yoshinobu
3bae88ea-1afa-43b2-bbd0-a68d72d78662
van Meijeren, Cokky
fe9b10aa-d5b2-48ef-b008-644c4936946f
Chichareon, Ply
8ea6d41d-b7a6-4421-abca-943b23adffb5
Benit, Edouard
8df377c5-4b71-437d-b2b5-d933ce0fe4a8
Möllmann, Helge
700011f1-5ae4-41ec-b662-90d4b6f49e08
Janssens, Luc
43a3def3-9012-420d-b5d7-367b7d94e9d6
Ferrario, Maurizio
84eac6eb-4d23-4697-ac3b-9f25bbb146ef
Moschovitis, Aris
4068a8f1-0017-4968-9bd4-a5d82e872c56
Zurakowski, Aleksander
0acb1c00-dd6c-45a5-9eeb-80bd14b41424
Dominici, Marcello
6fbb26bb-9fff-450f-a74d-af2614047209
Van Geuns, Robert Jan
e136194d-997b-4646-84c6-728fe177eb8a
Huber, Kurt
910d9bc4-35eb-4625-99f8-b0c8d66a78a3
Slagboom, Ton
e2935cbe-f965-453f-ba68-5ba195c7bac8
Serruys, Patrick W
98dfd61b-78fb-4f77-9995-7d9959332961
Windecker, Stephan
70cd1533-13ce-40d1-9181-180196de2e8f
Curzen, Nicholas
70f3ea49-51b1-418f-8e56-8210aef1abf4
GLOBAL LEADERS Investigators
Vranckx, Pascal
ae1689bd-bcd7-403b-ae43-a24cd61d905d
Valgimigli, Marco
2097fa94-7c8f-4aa8-8834-0d70940546d9
Jüni, Peter
1448ad34-a0d4-4faa-962b-abf202246167
Hamm, Christian
d6b04c5b-2831-4adb-8be5-6f7874ee5c05
Steg, Philippe Gabriel
1cebb409-f5f0-46a0-8682-34fd905aec17
Heg, Dik
5c602c49-aef0-4a14-aa46-6f660e334e7e
van Es, Gerrit Anne
3f0dd784-1ef0-47a4-9de3-03a17e5c46d8
McFadden, Eugene P
1b00e428-6d5f-45a2-af26-abdd4a80d8bc
Onuma, Yoshinobu
3bae88ea-1afa-43b2-bbd0-a68d72d78662
van Meijeren, Cokky
fe9b10aa-d5b2-48ef-b008-644c4936946f
Chichareon, Ply
8ea6d41d-b7a6-4421-abca-943b23adffb5
Benit, Edouard
8df377c5-4b71-437d-b2b5-d933ce0fe4a8
Möllmann, Helge
700011f1-5ae4-41ec-b662-90d4b6f49e08
Janssens, Luc
43a3def3-9012-420d-b5d7-367b7d94e9d6
Ferrario, Maurizio
84eac6eb-4d23-4697-ac3b-9f25bbb146ef
Moschovitis, Aris
4068a8f1-0017-4968-9bd4-a5d82e872c56
Zurakowski, Aleksander
0acb1c00-dd6c-45a5-9eeb-80bd14b41424
Dominici, Marcello
6fbb26bb-9fff-450f-a74d-af2614047209
Van Geuns, Robert Jan
e136194d-997b-4646-84c6-728fe177eb8a
Huber, Kurt
910d9bc4-35eb-4625-99f8-b0c8d66a78a3
Slagboom, Ton
e2935cbe-f965-453f-ba68-5ba195c7bac8
Serruys, Patrick W
98dfd61b-78fb-4f77-9995-7d9959332961
Windecker, Stephan
70cd1533-13ce-40d1-9181-180196de2e8f
Curzen, Nicholas
70f3ea49-51b1-418f-8e56-8210aef1abf4

GLOBAL LEADERS Investigators (2018) 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. The Lancet, 392 (10151), 940-949. (doi:10.1016/S0140-6736(18)31858-0).

Record type: Article

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.

This record has no associated files available for download.

More information

e-pub ahead of print date: 27 August 2018
Published date: 15 September 2018
Keywords: Adenosine/administration & dosage, Aged, Aspirin/administration & dosage, Clopidogrel, Coronary Angiography, Coronary Artery Disease/drug therapy, Drug Therapy, Combination, Drug-Eluting Stents/adverse effects, Female, Humans, Intention to Treat Analysis, Male, Middle Aged, Myocardial Infarction/mortality, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors/administration & dosage, Purinergic P2Y Receptor Antagonists/administration & dosage, Ticagrelor, Ticlopidine/administration & dosage

Identifiers

Local EPrints ID: 443208
URI: http://eprints.soton.ac.uk/id/eprint/443208
ISSN: 0140-6736
PURE UUID: f4492c58-2b32-41d2-be1f-741be320653e
ORCID for Nicholas Curzen: ORCID iD orcid.org/0000-0001-9651-7829

Catalogue record

Date deposited: 14 Aug 2020 16:34
Last modified: 16 Aug 2024 01:40

Export record

Altmetrics

Contributors

Author: Pascal Vranckx
Author: Marco Valgimigli
Author: Peter Jüni
Author: Christian Hamm
Author: Philippe Gabriel Steg
Author: Dik Heg
Author: Gerrit Anne van Es
Author: Eugene P McFadden
Author: Yoshinobu Onuma
Author: Cokky van Meijeren
Author: Ply Chichareon
Author: Edouard Benit
Author: Helge Möllmann
Author: Luc Janssens
Author: Maurizio Ferrario
Author: Aris Moschovitis
Author: Aleksander Zurakowski
Author: Marcello Dominici
Author: Robert Jan Van Geuns
Author: Kurt Huber
Author: Ton Slagboom
Author: Patrick W Serruys
Author: Stephan Windecker
Author: Nicholas Curzen ORCID iD
Corporate Author: GLOBAL LEADERS Investigators

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×