Efficacy and Safety of Ticagrelor Monotherapy in Patients Undergoing Multivessel PCI

Kuniaki Takahashi; Patrick W. Serruys; Ply Chichareon; Chun Chin Chang; Mariusz Tomaniak; Rodrigo Modolo; Norihiro Kogame; Michael Magro; Saqib Chowdhary; Ingo Eitel; Robert Zweiker; Paul Ong; Michael Mundt Ottesen; Jan G.P. Tijssen; Joanna J. Wykrzykowska; Robbert J. de Winter; Scot Garg; Hans Peter Stoll; Christian Hamm; Philippe Gabriel Steg; Yoshinobu Onuma; Marco Valgimigli; Pascal Vranckx; Didier Carrie; Stephan Windecker

doi:10.1016/j.jacc.2019.08.997

Efficacy and Safety of Ticagrelor Monotherapy in Patients Undergoing Multivessel PCI

Kuniaki Takahashi, Patrick W. Serruys^*, Ply Chichareon, Chun Chin Chang, Mariusz Tomaniak, Rodrigo Modolo, Norihiro Kogame, Michael Magro, Saqib Chowdhary, Ingo Eitel, Robert Zweiker, Paul Ong, Michael Mundt Ottesen, Jan G.P. Tijssen, Joanna J. Wykrzykowska, Robbert J. de Winter, Scot Garg, Hans Peter Stoll, Christian Hamm, Philippe Gabriel StegYoshinobu Onuma, Marco Valgimigli, Pascal Vranckx, Didier Carrie, Stephan Windecker

^*Corresponding author for this work

Clinic of Internal Medicine II - Cardiology

25 Citations (Scopus)

Abstract

Background: Data on optimal antiplatelet treatment regimens in patients who undergo multivessel percutaneous coronary intervention (PCI) are sparse. Objectives: This post hoc study investigated the impact of an experimental strategy (1-month dual antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) versus a reference regimen (12-month DAPT followed by 12-month aspirin monotherapy) according to multivessel PCI. Methods: The GLOBAL LEADERS trial is a prospective, multicenter, open-label, randomized controlled trial, allocating all-comer patients in a 1:1 ratio to either the experimental strategy or the reference regimen. The primary endpoint was the composite of all-cause death or new Q-wave myocardial infarction at 2 years. The secondary safety endpoint was Bleeding Academic Research Consortium type 3 or 5 bleeding. Results: Among the overall study population (n=15,845), 3,576 patients (22.4%) having multivessel PCI experienced a significantly higher risk of ischemic and bleeding events at 2 years, compared to those having single-vessel PCI. There was an interaction between the experimental strategy and multivessel PCI on the primary endpoint (hazard ratio: 0.62; 95% confidence interval: 0.44 to 0.88; p_interaction = 0.031). This difference was largely driven by a lower risk of all-cause mortality. In contrast, the risk of Bleeding Academic Research Consortium type 3 or 5 bleeding was statistically similar between the 2 regimens (hazard ratio: 0.92; 95% confidence interval: 0.61 to 1.39; p_interaction = 0.754). Conclusions: Long-term ticagrelor monotherapy following 1-month DAPT can favorably balance ischemic and bleeding risks in patients with multivessel PCI. These findings should be interpreted as hypothesis-generating and need to be replicated in future dedicated randomized trials. (GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation; NCT01813435).

Original language	English
Journal	Journal of the American College of Cardiology
Volume	74
Issue number	16
Pages (from-to)	2015-2027
Number of pages	13
ISSN	0735-1097
DOIs	https://doi.org/10.1016/j.jacc.2019.08.997
Publication status	Published - 22.10.2019

Funding

The Global Leaders trial was supported by unrestricted grants from AstraZeneca, Biosensors, and The Medicines Company. ECRI (European Cardiovascular Research Institute) was formally the sponsor of the study. Dr. Serruys has received personal fees from Abbott Laboratories, AstraZeneca, Biotronik, Cardialysis, GLG Research, Medtronic, Sino Medical Sciences Technology, Soci?t? Europa Digital Publishing, Stentys France, Svelte Medical Systems, Philips/Volcano, St. Jude Medical, Qualimed, and Xeltis. Dr. Chichareon has received a research grant from Biosensors. Dr. Tomaniak has received lecture fees from AstraZeneca. Dr. Modolo has received research grants from the Sao Paulo Research Foundation (FAPESP grant number 2017/22013-8), Biosensors, and SMT. Dr. Eitel has received personal fees from AstraZeneca, Bayer, and Edwards Lifesciences. Dr. de Winter has received an unrestricted educational research grant from AstraZeneca for the Academic Medical Center, University of Amsterdam. Dr. Tijssen has received personal fees from Cardialysis for Data Safety Monitoring Board membership of the ?Global Leaders' trial. Dr. Stoll is a full-time employee of Biosensors International. Dr. Hamm has received personal fees from AstraZeneca. Dr. Steg has received grants and personal fees from Bayer/Janssen, Merck, Sanofi, Amarin, and Servier; and has received personal fees from Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Idorsia, Pfizer, Novartis, Novo Nordisk, Regeneron, Lilly, and AstraZeneca. Dr. Valgimigli has received grants and personal fees from Abbott, Terumo, and AstraZeneca; has received personal fees from Chiesi, Bayer, Daiichi-Sankyo, Amgen, Biosensors, and Idorsia; and has received grants from Medicure. Dr. Vranckx has received personal fees from AstraZeneca and The Medicines Company; and has received personal fees from Bayer Health Care, Daiichi-Sankyo, Terumo, and CLS Behring. Dr. Windecker has received grants from Amgen, Abbott, Biotronik, Bristol-Myers Squibb, Boston Scientific, Medtronic, Edwards Lifesciences, Bayer, St. Jude, and Terumo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Jean-Philippe Collet, MD, served as Guest Associate Editor for this paper.

Research Areas and Centers

Centers: Cardiological Center Luebeck (UHZL)

DFG Research Classification Scheme

2.22-12 Cardiology, Angiology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jacc.2019.08.997

Cite this

Takahashi, K., Serruys, P. W., Chichareon, P., Chang, C. C., Tomaniak, M., Modolo, R., Kogame, N., Magro, M., Chowdhary, S., Eitel, I., Zweiker, R., Ong, P., Ottesen, M. M., Tijssen, J. G. P., Wykrzykowska, J. J., de Winter, R. J., Garg, S., Stoll, H. P., Hamm, C., ... Windecker, S. (2019). Efficacy and Safety of Ticagrelor Monotherapy in Patients Undergoing Multivessel PCI. Journal of the American College of Cardiology, 74(16), 2015-2027. https://doi.org/10.1016/j.jacc.2019.08.997

@article{46e82fa7e7574ce0bb181b639ce2a0c7,

title = "Efficacy and Safety of Ticagrelor Monotherapy in Patients Undergoing Multivessel PCI",

abstract = "Background: Data on optimal antiplatelet treatment regimens in patients who undergo multivessel percutaneous coronary intervention (PCI) are sparse. Objectives: This post hoc study investigated the impact of an experimental strategy (1-month dual antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) versus a reference regimen (12-month DAPT followed by 12-month aspirin monotherapy) according to multivessel PCI. Methods: The GLOBAL LEADERS trial is a prospective, multicenter, open-label, randomized controlled trial, allocating all-comer patients in a 1:1 ratio to either the experimental strategy or the reference regimen. The primary endpoint was the composite of all-cause death or new Q-wave myocardial infarction at 2 years. The secondary safety endpoint was Bleeding Academic Research Consortium type 3 or 5 bleeding. Results: Among the overall study population (n=15,845), 3,576 patients (22.4\%) having multivessel PCI experienced a significantly higher risk of ischemic and bleeding events at 2 years, compared to those having single-vessel PCI. There was an interaction between the experimental strategy and multivessel PCI on the primary endpoint (hazard ratio: 0.62; 95\% confidence interval: 0.44 to 0.88; pinteraction = 0.031). This difference was largely driven by a lower risk of all-cause mortality. In contrast, the risk of Bleeding Academic Research Consortium type 3 or 5 bleeding was statistically similar between the 2 regimens (hazard ratio: 0.92; 95\% confidence interval: 0.61 to 1.39; pinteraction = 0.754). Conclusions: Long-term ticagrelor monotherapy following 1-month DAPT can favorably balance ischemic and bleeding risks in patients with multivessel PCI. These findings should be interpreted as hypothesis-generating and need to be replicated in future dedicated randomized trials. (GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation; NCT01813435).",

author = "Kuniaki Takahashi and Serruys, \{Patrick W.\} and Ply Chichareon and Chang, \{Chun Chin\} and Mariusz Tomaniak and Rodrigo Modolo and Norihiro Kogame and Michael Magro and Saqib Chowdhary and Ingo Eitel and Robert Zweiker and Paul Ong and Ottesen, \{Michael Mundt\} and Tijssen, \{Jan G.P.\} and Wykrzykowska, \{Joanna J.\} and \{de Winter\}, \{Robbert J.\} and Scot Garg and Stoll, \{Hans Peter\} and Christian Hamm and Steg, \{Philippe Gabriel\} and Yoshinobu Onuma and Marco Valgimigli and Pascal Vranckx and Didier Carrie and Stephan Windecker",

note = "Funding Information: The Global Leaders trial was supported by unrestricted grants from AstraZeneca, Biosensors, and The Medicines Company. ECRI (European Cardiovascular Research Institute) was formally the sponsor of the study. Dr. Serruys has received personal fees from Abbott Laboratories, AstraZeneca, Biotronik, Cardialysis, GLG Research, Medtronic, Sino Medical Sciences Technology, Soci?t? Europa Digital Publishing, Stentys France, Svelte Medical Systems, Philips/Volcano, St. Jude Medical, Qualimed, and Xeltis. Dr. Chichareon has received a research grant from Biosensors. Dr. Tomaniak has received lecture fees from AstraZeneca. Dr. Modolo has received research grants from the Sao Paulo Research Foundation (FAPESP grant number 2017/22013-8), Biosensors, and SMT. Dr. Eitel has received personal fees from AstraZeneca, Bayer, and Edwards Lifesciences. Dr. de Winter has received an unrestricted educational research grant from AstraZeneca for the Academic Medical Center, University of Amsterdam. Dr. Tijssen has received personal fees from Cardialysis for Data Safety Monitoring Board membership of the ?Global Leaders' trial. Dr. Stoll is a full-time employee of Biosensors International. Dr. Hamm has received personal fees from AstraZeneca. Dr. Steg has received grants and personal fees from Bayer/Janssen, Merck, Sanofi, Amarin, and Servier; and has received personal fees from Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Idorsia, Pfizer, Novartis, Novo Nordisk, Regeneron, Lilly, and AstraZeneca. Dr. Valgimigli has received grants and personal fees from Abbott, Terumo, and AstraZeneca; has received personal fees from Chiesi, Bayer, Daiichi-Sankyo, Amgen, Biosensors, and Idorsia; and has received grants from Medicure. Dr. Vranckx has received personal fees from AstraZeneca and The Medicines Company; and has received personal fees from Bayer Health Care, Daiichi-Sankyo, Terumo, and CLS Behring. Dr. Windecker has received grants from Amgen, Abbott, Biotronik, Bristol-Myers Squibb, Boston Scientific, Medtronic, Edwards Lifesciences, Bayer, St. Jude, and Terumo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Jean-Philippe Collet, MD, served as Guest Associate Editor for this paper. Publisher Copyright: {\textcopyright} 2019 American College of Cardiology Foundation Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",

year = "2019",

month = oct,

day = "22",

doi = "10.1016/j.jacc.2019.08.997",

language = "English",

volume = "74",

pages = "2015--2027",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier Inc.",

number = "16",

}

Takahashi, K, Serruys, PW, Chichareon, P, Chang, CC, Tomaniak, M, Modolo, R, Kogame, N, Magro, M, Chowdhary, S, Eitel, I, Zweiker, R, Ong, P, Ottesen, MM, Tijssen, JGP, Wykrzykowska, JJ, de Winter, RJ, Garg, S, Stoll, HP, Hamm, C, Steg, PG, Onuma, Y, Valgimigli, M, Vranckx, P, Carrie, D & Windecker, S 2019, 'Efficacy and Safety of Ticagrelor Monotherapy in Patients Undergoing Multivessel PCI', Journal of the American College of Cardiology, vol. 74, no. 16, pp. 2015-2027. https://doi.org/10.1016/j.jacc.2019.08.997

TY - JOUR

T1 - Efficacy and Safety of Ticagrelor Monotherapy in Patients Undergoing Multivessel PCI

AU - Takahashi, Kuniaki

AU - Serruys, Patrick W.

AU - Chichareon, Ply

AU - Chang, Chun Chin

AU - Tomaniak, Mariusz

AU - Modolo, Rodrigo

AU - Kogame, Norihiro

AU - Magro, Michael

AU - Chowdhary, Saqib

AU - Eitel, Ingo

AU - Zweiker, Robert

AU - Ong, Paul

AU - Ottesen, Michael Mundt

AU - Tijssen, Jan G.P.

AU - Wykrzykowska, Joanna J.

AU - de Winter, Robbert J.

AU - Garg, Scot

AU - Stoll, Hans Peter

AU - Hamm, Christian

AU - Steg, Philippe Gabriel

AU - Onuma, Yoshinobu

AU - Valgimigli, Marco

AU - Vranckx, Pascal

AU - Carrie, Didier

AU - Windecker, Stephan

N1 - Funding Information: The Global Leaders trial was supported by unrestricted grants from AstraZeneca, Biosensors, and The Medicines Company. ECRI (European Cardiovascular Research Institute) was formally the sponsor of the study. Dr. Serruys has received personal fees from Abbott Laboratories, AstraZeneca, Biotronik, Cardialysis, GLG Research, Medtronic, Sino Medical Sciences Technology, Soci?t? Europa Digital Publishing, Stentys France, Svelte Medical Systems, Philips/Volcano, St. Jude Medical, Qualimed, and Xeltis. Dr. Chichareon has received a research grant from Biosensors. Dr. Tomaniak has received lecture fees from AstraZeneca. Dr. Modolo has received research grants from the Sao Paulo Research Foundation (FAPESP grant number 2017/22013-8), Biosensors, and SMT. Dr. Eitel has received personal fees from AstraZeneca, Bayer, and Edwards Lifesciences. Dr. de Winter has received an unrestricted educational research grant from AstraZeneca for the Academic Medical Center, University of Amsterdam. Dr. Tijssen has received personal fees from Cardialysis for Data Safety Monitoring Board membership of the ?Global Leaders' trial. Dr. Stoll is a full-time employee of Biosensors International. Dr. Hamm has received personal fees from AstraZeneca. Dr. Steg has received grants and personal fees from Bayer/Janssen, Merck, Sanofi, Amarin, and Servier; and has received personal fees from Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Idorsia, Pfizer, Novartis, Novo Nordisk, Regeneron, Lilly, and AstraZeneca. Dr. Valgimigli has received grants and personal fees from Abbott, Terumo, and AstraZeneca; has received personal fees from Chiesi, Bayer, Daiichi-Sankyo, Amgen, Biosensors, and Idorsia; and has received grants from Medicure. Dr. Vranckx has received personal fees from AstraZeneca and The Medicines Company; and has received personal fees from Bayer Health Care, Daiichi-Sankyo, Terumo, and CLS Behring. Dr. Windecker has received grants from Amgen, Abbott, Biotronik, Bristol-Myers Squibb, Boston Scientific, Medtronic, Edwards Lifesciences, Bayer, St. Jude, and Terumo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Jean-Philippe Collet, MD, served as Guest Associate Editor for this paper. Publisher Copyright: © 2019 American College of Cardiology Foundation Copyright: Copyright 2019 Elsevier B.V., All rights reserved.

PY - 2019/10/22

Y1 - 2019/10/22

N2 - Background: Data on optimal antiplatelet treatment regimens in patients who undergo multivessel percutaneous coronary intervention (PCI) are sparse. Objectives: This post hoc study investigated the impact of an experimental strategy (1-month dual antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) versus a reference regimen (12-month DAPT followed by 12-month aspirin monotherapy) according to multivessel PCI. Methods: The GLOBAL LEADERS trial is a prospective, multicenter, open-label, randomized controlled trial, allocating all-comer patients in a 1:1 ratio to either the experimental strategy or the reference regimen. The primary endpoint was the composite of all-cause death or new Q-wave myocardial infarction at 2 years. The secondary safety endpoint was Bleeding Academic Research Consortium type 3 or 5 bleeding. Results: Among the overall study population (n=15,845), 3,576 patients (22.4%) having multivessel PCI experienced a significantly higher risk of ischemic and bleeding events at 2 years, compared to those having single-vessel PCI. There was an interaction between the experimental strategy and multivessel PCI on the primary endpoint (hazard ratio: 0.62; 95% confidence interval: 0.44 to 0.88; pinteraction = 0.031). This difference was largely driven by a lower risk of all-cause mortality. In contrast, the risk of Bleeding Academic Research Consortium type 3 or 5 bleeding was statistically similar between the 2 regimens (hazard ratio: 0.92; 95% confidence interval: 0.61 to 1.39; pinteraction = 0.754). Conclusions: Long-term ticagrelor monotherapy following 1-month DAPT can favorably balance ischemic and bleeding risks in patients with multivessel PCI. These findings should be interpreted as hypothesis-generating and need to be replicated in future dedicated randomized trials. (GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation; NCT01813435).

AB - Background: Data on optimal antiplatelet treatment regimens in patients who undergo multivessel percutaneous coronary intervention (PCI) are sparse. Objectives: This post hoc study investigated the impact of an experimental strategy (1-month dual antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) versus a reference regimen (12-month DAPT followed by 12-month aspirin monotherapy) according to multivessel PCI. Methods: The GLOBAL LEADERS trial is a prospective, multicenter, open-label, randomized controlled trial, allocating all-comer patients in a 1:1 ratio to either the experimental strategy or the reference regimen. The primary endpoint was the composite of all-cause death or new Q-wave myocardial infarction at 2 years. The secondary safety endpoint was Bleeding Academic Research Consortium type 3 or 5 bleeding. Results: Among the overall study population (n=15,845), 3,576 patients (22.4%) having multivessel PCI experienced a significantly higher risk of ischemic and bleeding events at 2 years, compared to those having single-vessel PCI. There was an interaction between the experimental strategy and multivessel PCI on the primary endpoint (hazard ratio: 0.62; 95% confidence interval: 0.44 to 0.88; pinteraction = 0.031). This difference was largely driven by a lower risk of all-cause mortality. In contrast, the risk of Bleeding Academic Research Consortium type 3 or 5 bleeding was statistically similar between the 2 regimens (hazard ratio: 0.92; 95% confidence interval: 0.61 to 1.39; pinteraction = 0.754). Conclusions: Long-term ticagrelor monotherapy following 1-month DAPT can favorably balance ischemic and bleeding risks in patients with multivessel PCI. These findings should be interpreted as hypothesis-generating and need to be replicated in future dedicated randomized trials. (GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation; NCT01813435).

UR - https://www.scopus.com/pages/publications/85072864021

U2 - 10.1016/j.jacc.2019.08.997

DO - 10.1016/j.jacc.2019.08.997

M3 - Journal articles

C2 - 31623758

AN - SCOPUS:85072864021

SN - 0735-1097

VL - 74

SP - 2015

EP - 2027

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

IS - 16

ER -

Efficacy and Safety of Ticagrelor Monotherapy in Patients Undergoing Multivessel PCI

Abstract

Funding

Research Areas and Centers

DFG Research Classification Scheme

UN SDGs

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