Factors contributing to the lower mortality with ticagrelor compared with clopidogrel in patients undergoing coronary artery bypass surgery

Christoph Varenhorst; Ulrica Alström; Benjamin M. Scirica; Charles W. Hogue; Nils Åsenblad; Robert F. Storey; Ph Gabriel Steg; Jay Horrow; Kenneth W. Mahaffey; Richard C. Becker; Stefan James; Christopher P. Cannon; Gunnar Brandrup-Wognsen; Lars Wallentin; Claes Held

doi:10.1016/j.jacc.2012.07.021

Factors contributing to the lower mortality with ticagrelor compared with clopidogrel in patients undergoing coronary artery bypass surgery

Christoph Varenhorst^*, Ulrica Alström, Benjamin M. Scirica, Charles W. Hogue, Nils Åsenblad, Robert F. Storey, Ph Gabriel Steg, Jay Horrow, Kenneth W. Mahaffey, Richard C. Becker, Stefan James, Christopher P. Cannon, Gunnar Brandrup-Wognsen, Lars Wallentin, Claes Held

^*Corresponding author for this work

Anesthesiology

Research output: Contribution to journal › Article › peer-review

83 Scopus citations

Abstract

Objectives: This study investigated the differences in specific causes of post-coronary artery bypass graft surgery (CABG) deaths in the PLATO (Platelet Inhibition and Patient Outcomes) trial. Background: In the PLATO trial, patients assigned to ticagrelor compared with clopidogrel and who underwent CABG had significantly lower total and cardiovascular mortality. Methods: In the 1,261 patients with CABG performed within 7 days after stopping study drug, reviewers blinded to treatment assignment classified causes of death into subcategories of vascular and nonvascular, and specifically identified bleeding or infection events that either caused or subsequently contributed to death. Results: Numerically more vascular deaths occurred in the clopidogrel versus the ticagrelor group related to myocardial infarction (14 vs. 10), heart failure (9 vs. 6), arrhythmia or sudden death (9 vs. 3), and bleeding, including hemorrhagic stroke (7 vs. 2). Clopidogrel was also associated with an excess of nonvascular deaths related to infection (8 vs. 2). Among factors directly causing or contributing to death, bleeding and infections were more common in the clopidogrel group compared with the ticagrelor group (infections: 16 vs. 6, p < 0.05, and bleeding: 27 vs. 9, p < 0.01, for clopidogrel and ticagrelor, respectively). Conclusions: The mortality reduction with ticagrelor versus clopidogrel following CABG in the PLATO trial was associated with fewer deaths from cardiovascular, bleeding, and infection complications. (Platelet Inhibition and Patient Outcomes [PLATO]; NCT00391872)

Original language	English (US)
Pages (from-to)	1623-1630
Number of pages	8
Journal	Journal of the American College of Cardiology
Volume	60
Issue number	17
DOIs	https://doi.org/10.1016/j.jacc.2012.07.021
State	Published - Oct 23 2012

Funding

This study was supported by AstraZeneca. Dr. Varenhorst has received a research grant from AstraZeneca to perform this research; and is a member of the Speakers' Bureaus for AstraZeneca, Eli Lilly & Company, and The Medicines Company. Dr. Scirica has received research grants from Merck , AstraZeneca , Johnson & Johnson , Bayer , Daiichi Sankyo , Bristol-Myers Squibb , Gilead Sciences , and Novartis ; and is a consultant to Gilead Sciences, Arena, and Lexicon. Dr. Hogue has received research support from Covidien; and is a consultant to Covidien, Merck, and Ornim. Dr. Storey is a consultant to AstraZeneca, Accumetrics, Merck, Novartis, Eli Lilly & Company, Daiichi Sankyo, Eisai, Iroko, The Medicines Company, Sanofi Aventis, Bristol-Myers Squibb, and Medscape. Dr. Steg is a consultant to AstraZeneca, Amarin, Amgen, Astellas, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly & Company, Daiichi Sankyo, Eisai, GlaxoSmithKline, Medtronic, Merck, Novartis, Otsuka, Pfizer, Roche, The Medicines Company, Sanofi Aventis, and Servier; is a member of the Speakers' Bureaus for AstraZeneca, Bayer, Bristol-Myers Squibb, Pfizer, The Medicines Company, Sanofi Aventis, and Servier; and has received Data Safety Monitoring Board support from Ablynx. Dr. Horrow is the executive director of AstraZeneca LP, and has equity ownership in the company. Dr. Mahaffey has received grant support from AstraZeneca , Bayer , Boehringer Ingelheim , Bristol-Myers Squibb , Daiichi Sankyo , Eli Lilly & Company , GlaxoSmithKline , Johnson & Johnson , Merck , Novartis , Pozen , Regado Biotechnologies , Sanofi Aventis , Schering Plough , and The Medicines Company ; and is a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly & Company, GlaxoSmithKline, Johnson & Johnson, Merck, Pfizer, Polymedix, and Sanofi Aventis. Dr. Becker is a consultant to and receives support from AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Johnson & Johnson, The Medicines Company, Merck, and Regado. Dr. James has received institutional grants from AstraZeneca , Eli Lilly & Company , and MSD ; and honoraria from AstraZeneca, Eli Lilly & Company, MSD, Merck, and The Medicines Company. Dr. Cannon has received grant support from Accumetrics , AstraZeneca , Essentialis , GlaxoSmithKline , Merck , Regeneron , Sanofi Aventis , and Takeda ; is a member of the Advisory Boards for Alnylam, Bristol-Myers Squibb, and Pfizer; has received funds from these companies, which have been donated to charity; and is a clinical advisor to Automated Medical Systems with equity in the company. Dr. Wallentin is a consultant to Merck/Schering Plough, Regado Biosciences, Evolva, Portola, C.S.L. Behring, Athera Biotechnologies, Boehringer-Ingelheim, AstraZeneca, GlaxoSmithKline, and Brisol-Myers Squibb/Pfizer; has received research grants from AstraZeneca , Merck/Schering-Plough , Boehringer-Ingelheim , Bristol-Myers Squibb/Pfizer , and GlaxoSmithKline ; and lecture fees from AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb/Pfizer, GlaxoSmithKline, and Schering-Plough/Merck. Dr. Held is on the Advisory Boards for AstraZeneca, Roche, and Pfizer; and has received institutional grants from Schering-Plough/Merck , GlaxoSmithKline , Bristol-Myers Squibb , and Roche . All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Keywords

bypass
clopidogrel
myocardial infarction
surgery
ticagrelor

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

Access to Document

10.1016/j.jacc.2012.07.021

Cite this

Varenhorst, C., Alström, U., Scirica, B. M., Hogue, C. W., Åsenblad, N., Storey, R. F., Steg, P. G., Horrow, J., Mahaffey, K. W., Becker, R. C., James, S., Cannon, C. P., Brandrup-Wognsen, G., Wallentin, L., & Held, C. (2012). Factors contributing to the lower mortality with ticagrelor compared with clopidogrel in patients undergoing coronary artery bypass surgery. Journal of the American College of Cardiology, 60(17), 1623-1630. https://doi.org/10.1016/j.jacc.2012.07.021

@article{bc89b6b4af7241cdba470f05b5ed233a,

title = "Factors contributing to the lower mortality with ticagrelor compared with clopidogrel in patients undergoing coronary artery bypass surgery",

abstract = "Objectives: This study investigated the differences in specific causes of post-coronary artery bypass graft surgery (CABG) deaths in the PLATO (Platelet Inhibition and Patient Outcomes) trial. Background: In the PLATO trial, patients assigned to ticagrelor compared with clopidogrel and who underwent CABG had significantly lower total and cardiovascular mortality. Methods: In the 1,261 patients with CABG performed within 7 days after stopping study drug, reviewers blinded to treatment assignment classified causes of death into subcategories of vascular and nonvascular, and specifically identified bleeding or infection events that either caused or subsequently contributed to death. Results: Numerically more vascular deaths occurred in the clopidogrel versus the ticagrelor group related to myocardial infarction (14 vs. 10), heart failure (9 vs. 6), arrhythmia or sudden death (9 vs. 3), and bleeding, including hemorrhagic stroke (7 vs. 2). Clopidogrel was also associated with an excess of nonvascular deaths related to infection (8 vs. 2). Among factors directly causing or contributing to death, bleeding and infections were more common in the clopidogrel group compared with the ticagrelor group (infections: 16 vs. 6, p < 0.05, and bleeding: 27 vs. 9, p < 0.01, for clopidogrel and ticagrelor, respectively). Conclusions: The mortality reduction with ticagrelor versus clopidogrel following CABG in the PLATO trial was associated with fewer deaths from cardiovascular, bleeding, and infection complications. (Platelet Inhibition and Patient Outcomes [PLATO]; NCT00391872)",

keywords = "bypass, clopidogrel, myocardial infarction, surgery, ticagrelor",

author = "Christoph Varenhorst and Ulrica Alstr{\"o}m and Scirica, {Benjamin M.} and Hogue, {Charles W.} and Nils {\AA}senblad and Storey, {Robert F.} and Steg, {Ph Gabriel} and Jay Horrow and Mahaffey, {Kenneth W.} and Becker, {Richard C.} and Stefan James and Cannon, {Christopher P.} and Gunnar Brandrup-Wognsen and Lars Wallentin and Claes Held",

note = "Funding Information: This study was supported by AstraZeneca. Dr. Varenhorst has received a research grant from AstraZeneca to perform this research; and is a member of the Speakers' Bureaus for AstraZeneca, Eli Lilly & Company, and The Medicines Company. Dr. Scirica has received research grants from Merck , AstraZeneca , Johnson & Johnson , Bayer , Daiichi Sankyo , Bristol-Myers Squibb , Gilead Sciences , and Novartis ; and is a consultant to Gilead Sciences, Arena, and Lexicon. Dr. Hogue has received research support from Covidien; and is a consultant to Covidien, Merck, and Ornim. Dr. Storey is a consultant to AstraZeneca, Accumetrics, Merck, Novartis, Eli Lilly & Company, Daiichi Sankyo, Eisai, Iroko, The Medicines Company, Sanofi Aventis, Bristol-Myers Squibb, and Medscape. Dr. Steg is a consultant to AstraZeneca, Amarin, Amgen, Astellas, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly & Company, Daiichi Sankyo, Eisai, GlaxoSmithKline, Medtronic, Merck, Novartis, Otsuka, Pfizer, Roche, The Medicines Company, Sanofi Aventis, and Servier; is a member of the Speakers' Bureaus for AstraZeneca, Bayer, Bristol-Myers Squibb, Pfizer, The Medicines Company, Sanofi Aventis, and Servier; and has received Data Safety Monitoring Board support from Ablynx. Dr. Horrow is the executive director of AstraZeneca LP, and has equity ownership in the company. Dr. Mahaffey has received grant support from AstraZeneca , Bayer , Boehringer Ingelheim , Bristol-Myers Squibb , Daiichi Sankyo , Eli Lilly & Company , GlaxoSmithKline , Johnson & Johnson , Merck , Novartis , Pozen , Regado Biotechnologies , Sanofi Aventis , Schering Plough , and The Medicines Company ; and is a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly & Company, GlaxoSmithKline, Johnson & Johnson, Merck, Pfizer, Polymedix, and Sanofi Aventis. Dr. Becker is a consultant to and receives support from AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Johnson & Johnson, The Medicines Company, Merck, and Regado. Dr. James has received institutional grants from AstraZeneca , Eli Lilly & Company , and MSD ; and honoraria from AstraZeneca, Eli Lilly & Company, MSD, Merck, and The Medicines Company. Dr. Cannon has received grant support from Accumetrics , AstraZeneca , Essentialis , GlaxoSmithKline , Merck , Regeneron , Sanofi Aventis , and Takeda ; is a member of the Advisory Boards for Alnylam, Bristol-Myers Squibb, and Pfizer; has received funds from these companies, which have been donated to charity; and is a clinical advisor to Automated Medical Systems with equity in the company. Dr. Wallentin is a consultant to Merck/Schering Plough, Regado Biosciences, Evolva, Portola, C.S.L. Behring, Athera Biotechnologies, Boehringer-Ingelheim, AstraZeneca, GlaxoSmithKline, and Brisol-Myers Squibb/Pfizer; has received research grants from AstraZeneca , Merck/Schering-Plough , Boehringer-Ingelheim , Bristol-Myers Squibb/Pfizer , and GlaxoSmithKline ; and lecture fees from AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb/Pfizer, GlaxoSmithKline, and Schering-Plough/Merck. Dr. Held is on the Advisory Boards for AstraZeneca, Roche, and Pfizer; and has received institutional grants from Schering-Plough/Merck , GlaxoSmithKline , Bristol-Myers Squibb , and Roche . All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. ",

year = "2012",

month = oct,

day = "23",

doi = "10.1016/j.jacc.2012.07.021",

language = "English (US)",

volume = "60",

pages = "1623--1630",

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

issn = "0735-1097",

publisher = "Elsevier Inc.",

number = "17",

}

Varenhorst, C, Alström, U, Scirica, BM, Hogue, CW, Åsenblad, N, Storey, RF, Steg, PG, Horrow, J, Mahaffey, KW, Becker, RC, James, S, Cannon, CP, Brandrup-Wognsen, G, Wallentin, L & Held, C 2012, 'Factors contributing to the lower mortality with ticagrelor compared with clopidogrel in patients undergoing coronary artery bypass surgery', Journal of the American College of Cardiology, vol. 60, no. 17, pp. 1623-1630. https://doi.org/10.1016/j.jacc.2012.07.021

Factors contributing to the lower mortality with ticagrelor compared with clopidogrel in patients undergoing coronary artery bypass surgery. / Varenhorst, Christoph; Alström, Ulrica; Scirica, Benjamin M. et al.
In: Journal of the American College of Cardiology, Vol. 60, No. 17, 23.10.2012, p. 1623-1630.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Factors contributing to the lower mortality with ticagrelor compared with clopidogrel in patients undergoing coronary artery bypass surgery

AU - Varenhorst, Christoph

AU - Alström, Ulrica

AU - Scirica, Benjamin M.

AU - Hogue, Charles W.

AU - Åsenblad, Nils

AU - Storey, Robert F.

AU - Steg, Ph Gabriel

AU - Horrow, Jay

AU - Mahaffey, Kenneth W.

AU - Becker, Richard C.

AU - James, Stefan

AU - Cannon, Christopher P.

AU - Brandrup-Wognsen, Gunnar

AU - Wallentin, Lars

AU - Held, Claes

N1 - Funding Information: This study was supported by AstraZeneca. Dr. Varenhorst has received a research grant from AstraZeneca to perform this research; and is a member of the Speakers' Bureaus for AstraZeneca, Eli Lilly & Company, and The Medicines Company. Dr. Scirica has received research grants from Merck , AstraZeneca , Johnson & Johnson , Bayer , Daiichi Sankyo , Bristol-Myers Squibb , Gilead Sciences , and Novartis ; and is a consultant to Gilead Sciences, Arena, and Lexicon. Dr. Hogue has received research support from Covidien; and is a consultant to Covidien, Merck, and Ornim. Dr. Storey is a consultant to AstraZeneca, Accumetrics, Merck, Novartis, Eli Lilly & Company, Daiichi Sankyo, Eisai, Iroko, The Medicines Company, Sanofi Aventis, Bristol-Myers Squibb, and Medscape. Dr. Steg is a consultant to AstraZeneca, Amarin, Amgen, Astellas, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly & Company, Daiichi Sankyo, Eisai, GlaxoSmithKline, Medtronic, Merck, Novartis, Otsuka, Pfizer, Roche, The Medicines Company, Sanofi Aventis, and Servier; is a member of the Speakers' Bureaus for AstraZeneca, Bayer, Bristol-Myers Squibb, Pfizer, The Medicines Company, Sanofi Aventis, and Servier; and has received Data Safety Monitoring Board support from Ablynx. Dr. Horrow is the executive director of AstraZeneca LP, and has equity ownership in the company. Dr. Mahaffey has received grant support from AstraZeneca , Bayer , Boehringer Ingelheim , Bristol-Myers Squibb , Daiichi Sankyo , Eli Lilly & Company , GlaxoSmithKline , Johnson & Johnson , Merck , Novartis , Pozen , Regado Biotechnologies , Sanofi Aventis , Schering Plough , and The Medicines Company ; and is a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly & Company, GlaxoSmithKline, Johnson & Johnson, Merck, Pfizer, Polymedix, and Sanofi Aventis. Dr. Becker is a consultant to and receives support from AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Johnson & Johnson, The Medicines Company, Merck, and Regado. Dr. James has received institutional grants from AstraZeneca , Eli Lilly & Company , and MSD ; and honoraria from AstraZeneca, Eli Lilly & Company, MSD, Merck, and The Medicines Company. Dr. Cannon has received grant support from Accumetrics , AstraZeneca , Essentialis , GlaxoSmithKline , Merck , Regeneron , Sanofi Aventis , and Takeda ; is a member of the Advisory Boards for Alnylam, Bristol-Myers Squibb, and Pfizer; has received funds from these companies, which have been donated to charity; and is a clinical advisor to Automated Medical Systems with equity in the company. Dr. Wallentin is a consultant to Merck/Schering Plough, Regado Biosciences, Evolva, Portola, C.S.L. Behring, Athera Biotechnologies, Boehringer-Ingelheim, AstraZeneca, GlaxoSmithKline, and Brisol-Myers Squibb/Pfizer; has received research grants from AstraZeneca , Merck/Schering-Plough , Boehringer-Ingelheim , Bristol-Myers Squibb/Pfizer , and GlaxoSmithKline ; and lecture fees from AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb/Pfizer, GlaxoSmithKline, and Schering-Plough/Merck. Dr. Held is on the Advisory Boards for AstraZeneca, Roche, and Pfizer; and has received institutional grants from Schering-Plough/Merck , GlaxoSmithKline , Bristol-Myers Squibb , and Roche . All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

PY - 2012/10/23

Y1 - 2012/10/23

N2 - Objectives: This study investigated the differences in specific causes of post-coronary artery bypass graft surgery (CABG) deaths in the PLATO (Platelet Inhibition and Patient Outcomes) trial. Background: In the PLATO trial, patients assigned to ticagrelor compared with clopidogrel and who underwent CABG had significantly lower total and cardiovascular mortality. Methods: In the 1,261 patients with CABG performed within 7 days after stopping study drug, reviewers blinded to treatment assignment classified causes of death into subcategories of vascular and nonvascular, and specifically identified bleeding or infection events that either caused or subsequently contributed to death. Results: Numerically more vascular deaths occurred in the clopidogrel versus the ticagrelor group related to myocardial infarction (14 vs. 10), heart failure (9 vs. 6), arrhythmia or sudden death (9 vs. 3), and bleeding, including hemorrhagic stroke (7 vs. 2). Clopidogrel was also associated with an excess of nonvascular deaths related to infection (8 vs. 2). Among factors directly causing or contributing to death, bleeding and infections were more common in the clopidogrel group compared with the ticagrelor group (infections: 16 vs. 6, p < 0.05, and bleeding: 27 vs. 9, p < 0.01, for clopidogrel and ticagrelor, respectively). Conclusions: The mortality reduction with ticagrelor versus clopidogrel following CABG in the PLATO trial was associated with fewer deaths from cardiovascular, bleeding, and infection complications. (Platelet Inhibition and Patient Outcomes [PLATO]; NCT00391872)

AB - Objectives: This study investigated the differences in specific causes of post-coronary artery bypass graft surgery (CABG) deaths in the PLATO (Platelet Inhibition and Patient Outcomes) trial. Background: In the PLATO trial, patients assigned to ticagrelor compared with clopidogrel and who underwent CABG had significantly lower total and cardiovascular mortality. Methods: In the 1,261 patients with CABG performed within 7 days after stopping study drug, reviewers blinded to treatment assignment classified causes of death into subcategories of vascular and nonvascular, and specifically identified bleeding or infection events that either caused or subsequently contributed to death. Results: Numerically more vascular deaths occurred in the clopidogrel versus the ticagrelor group related to myocardial infarction (14 vs. 10), heart failure (9 vs. 6), arrhythmia or sudden death (9 vs. 3), and bleeding, including hemorrhagic stroke (7 vs. 2). Clopidogrel was also associated with an excess of nonvascular deaths related to infection (8 vs. 2). Among factors directly causing or contributing to death, bleeding and infections were more common in the clopidogrel group compared with the ticagrelor group (infections: 16 vs. 6, p < 0.05, and bleeding: 27 vs. 9, p < 0.01, for clopidogrel and ticagrelor, respectively). Conclusions: The mortality reduction with ticagrelor versus clopidogrel following CABG in the PLATO trial was associated with fewer deaths from cardiovascular, bleeding, and infection complications. (Platelet Inhibition and Patient Outcomes [PLATO]; NCT00391872)

KW - bypass

KW - clopidogrel

KW - myocardial infarction

KW - surgery

KW - ticagrelor

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JO - Journal of the American College of Cardiology

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ER -

Factors contributing to the lower mortality with ticagrelor compared with clopidogrel in patients undergoing coronary artery bypass surgery

Abstract

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