Time-Dependent Associations Between Actionable Bleeding, Coronary Thrombotic Events, and Mortality Following Percutaneous Coronary Intervention: Results From the PARIS Registry

Usman Baber; George Dangas; Jaya Chandrasekhar; Samantha Sartori; Philippe Gabriel Steg; David J. Cohen; Gennaro Giustino; Cono Ariti; Bernhard Witzenbichler; Timothy D. Henry; Annapoorna S. Kini; Mitchell W. Krucoff; C. Michael Gibson; Alaide Chieffo; David J. Moliterno; Giora Weisz; Antonio Colombo; Stuart Pocock; Roxana Mehran

doi:10.1016/j.jcin.2016.04.009

Time-Dependent Associations Between Actionable Bleeding, Coronary Thrombotic Events, and Mortality Following Percutaneous Coronary Intervention: Results From the PARIS Registry

Usman Baber, George Dangas, Jaya Chandrasekhar, Samantha Sartori, Philippe Gabriel Steg, David J. Cohen, Gennaro Giustino, Cono Ariti, Bernhard Witzenbichler, Timothy D. Henry, Annapoorna S. Kini, Mitchell W. Krucoff, C. Michael Gibson, Alaide Chieffo, David J. Moliterno, Giora Weisz, Antonio Colombo, Stuart Pocock, Roxana Mehran

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

45 Scopus citations

Abstract

Objectives The aim of this study was to examine the independent associations between actionable bleeding (AB) and coronary thrombotic events (CTE) on mortality risk after percutaneous coronary intervention (PCI). Background The independent impact of AB and CTE on mortality risk after PCI remains poorly characterized. Methods A post hoc analysis was conducted of the PARIS (Patterns of Non-Adherence to Dual Antiplatelet Therapy in Stented Patients) registry, a real-world cohort of 5,018 patients undergoing PCI with stent implantation. CTE included definite or probable stent thrombosis or myocardial infarction. AB was defined as Bleeding Academic Research Consortium type 2 or 3. Associations between CTE and AB, both of which were modeled as time-dependent covariates, and 2-year mortality risk were examined using extended Cox regression. Results Over 2 years, the cumulative incidence of CTE, AB, and all-cause mortality was 5.9% (n = 289), 8.1% (n = 391), and 4.7% (n = 227), respectively. Adjusted hazard ratios for mortality associated with CTE and AB were 3.3 (95% confidence interval: 2.2 to 4.9) and 3.5 (95% confidence interval: 2.3 to 5.4), respectively. Temporal gradients in risk after either event were highest in the first 30 days and declined rapidly thereafter. Thrombotic events occurring while patients were on versus off dual-antiplatelet therapy were associated with a higher mortality risk, whereas risk related to AB was not influenced by dual-antiplatelet therapy status at the time of bleeding. Conclusions Intracoronary thrombosis and AB are associated with mortality risks of comparable magnitude over a 2-year period after PCI, findings that might inform risk/benefit calculations for extension versus discontinuation of dual-antiplatelet therapy.

Original language	English
Pages (from-to)	1349-1357
Number of pages	9
Journal	JACC: Cardiovascular Interventions
Volume	9
Issue number	13
DOIs	https://doi.org/10.1016/j.jcin.2016.04.009
State	Published - Jul 11 2016

Bibliographical note

Funding Information:
This study was funded by Bristol-Myers Squibb and Sanofi. Dr. Dangas has received consulting fees and honoraria from Johnson & Johnson, Sanofi, Covidien, The Medicines Company, Merck, CSL Behring, AstraZeneca, Medtronic, Abbott Vascular, Bayer, Boston Scientific, Osprey Medical, and GE Healthcare; and research grant support from Sanofi, Bristol-Myers Squibb, and Lilly/Daiichi Sankyo. Dr. Steg has served as an adviser or a consultant for Amarin, AstraZeneca Pharmaceuticals, Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Eli Lilly, Medtronic, Otsuka Pharmaceutical, Pfizer, Roche, Sanofi, Servier, Takeda Pharmaceuticals North America, The Medicines Company, and Vivus; and has received clinical research grants from Sanofi and Servier. Dr. Cohen has received research grant support from Abbott Vascular, AstraZeneca, Biomet, Boston Scientific, Cardiovascular Systems, Daiichi Sankyo, Edwards Lifesciences, Eli Lilly, and Medtronic; and is a consultant for Abbott Vascular, Medtronic, and Merck. Dr. Henry has received research grant support from Eli Lilly and Daiichi Sankyo. Dr. Kini serves on the Speakers Bureau of the American College of Cardiology; and has received consulting fees from WebMD. Dr. Krucoff has received consulting fees from Abbott Vascular, Abbott, OrbusNeich, Angelmed, Volcano, Biosensors, Svelte, Medtronic, and Terumo; and research grant support from Abbott, Terumo, Angelmed, Ikaria, OrbusNeich, Medtronic, CSI, Eli Lilly, and Medtronic. Dr. Gibson has received research grant support from Angel Medical Corporation, Atrium Medical Systems, Bayer, Ikaria, Janssen/Johnson & Johnson, Lantheus Medical Imaging, Merck, Portola Pharmaceuticals, Roche Diagnostics, Sanofi, Stealth Peptides, St. Jude Medical, Volcano, and Walk Vascular; consulting fees from AstraZeneca, Baxter Healthcare, Bayer, CRF, Consensus Medical Communications, CSL Behring, Cytori Therapeutics, Eli Lilly/Daiichi Sankyo, Exeter Group, Genentech, GlaxoSmithKline, Janssen/Johnson & Johnson, Ortho McNeil, St. Jude Medical, The Medicines Company; and royalty fees from UpToDate in Cardiovascular Medicine. Dr. Colombo has received consulting fees and honoraria from CID and other financial benefit from Direct Flow Medical. Dr. Mehran has received institutional grant support from The Medicines Company, Bristol-Myers Squibb/Sanofi, and Eli Lilly/Daiichi Sankyo; and is a consultant to Janssen Pharmaceuticals and Maya Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Publisher Copyright:
© 2016 American College of Cardiology Foundation

Keywords

bleeding
dual-antiplatelet therapy
mortality

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

Access to Document

10.1016/j.jcin.2016.04.009

Cite this

Baber, U., Dangas, G., Chandrasekhar, J., Sartori, S., Steg, P. G., Cohen, D. J., Giustino, G., Ariti, C., Witzenbichler, B., Henry, T. D., Kini, A. S., Krucoff, M. W., Gibson, C. M., Chieffo, A., Moliterno, D. J., Weisz, G., Colombo, A., Pocock, S., & Mehran, R. (2016). Time-Dependent Associations Between Actionable Bleeding, Coronary Thrombotic Events, and Mortality Following Percutaneous Coronary Intervention: Results From the PARIS Registry. JACC: Cardiovascular Interventions, 9(13), 1349-1357. https://doi.org/10.1016/j.jcin.2016.04.009

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title = "Time-Dependent Associations Between Actionable Bleeding, Coronary Thrombotic Events, and Mortality Following Percutaneous Coronary Intervention: Results From the PARIS Registry",

abstract = "Objectives The aim of this study was to examine the independent associations between actionable bleeding (AB) and coronary thrombotic events (CTE) on mortality risk after percutaneous coronary intervention (PCI). Background The independent impact of AB and CTE on mortality risk after PCI remains poorly characterized. Methods A post hoc analysis was conducted of the PARIS (Patterns of Non-Adherence to Dual Antiplatelet Therapy in Stented Patients) registry, a real-world cohort of 5,018 patients undergoing PCI with stent implantation. CTE included definite or probable stent thrombosis or myocardial infarction. AB was defined as Bleeding Academic Research Consortium type 2 or 3. Associations between CTE and AB, both of which were modeled as time-dependent covariates, and 2-year mortality risk were examined using extended Cox regression. Results Over 2 years, the cumulative incidence of CTE, AB, and all-cause mortality was 5.9% (n = 289), 8.1% (n = 391), and 4.7% (n = 227), respectively. Adjusted hazard ratios for mortality associated with CTE and AB were 3.3 (95% confidence interval: 2.2 to 4.9) and 3.5 (95% confidence interval: 2.3 to 5.4), respectively. Temporal gradients in risk after either event were highest in the first 30 days and declined rapidly thereafter. Thrombotic events occurring while patients were on versus off dual-antiplatelet therapy were associated with a higher mortality risk, whereas risk related to AB was not influenced by dual-antiplatelet therapy status at the time of bleeding. Conclusions Intracoronary thrombosis and AB are associated with mortality risks of comparable magnitude over a 2-year period after PCI, findings that might inform risk/benefit calculations for extension versus discontinuation of dual-antiplatelet therapy.",

keywords = "bleeding, dual-antiplatelet therapy, mortality",

author = "Usman Baber and George Dangas and Jaya Chandrasekhar and Samantha Sartori and Steg, {Philippe Gabriel} and Cohen, {David J.} and Gennaro Giustino and Cono Ariti and Bernhard Witzenbichler and Henry, {Timothy D.} and Kini, {Annapoorna S.} and Krucoff, {Mitchell W.} and Gibson, {C. Michael} and Alaide Chieffo and Moliterno, {David J.} and Giora Weisz and Antonio Colombo and Stuart Pocock and Roxana Mehran",

note = "Funding Information: This study was funded by Bristol-Myers Squibb and Sanofi. Dr. Dangas has received consulting fees and honoraria from Johnson & Johnson, Sanofi, Covidien, The Medicines Company, Merck, CSL Behring, AstraZeneca, Medtronic, Abbott Vascular, Bayer, Boston Scientific, Osprey Medical, and GE Healthcare; and research grant support from Sanofi, Bristol-Myers Squibb, and Lilly/Daiichi Sankyo. Dr. Steg has served as an adviser or a consultant for Amarin, AstraZeneca Pharmaceuticals, Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Eli Lilly, Medtronic, Otsuka Pharmaceutical, Pfizer, Roche, Sanofi, Servier, Takeda Pharmaceuticals North America, The Medicines Company, and Vivus; and has received clinical research grants from Sanofi and Servier. Dr. Cohen has received research grant support from Abbott Vascular, AstraZeneca, Biomet, Boston Scientific, Cardiovascular Systems, Daiichi Sankyo, Edwards Lifesciences, Eli Lilly, and Medtronic; and is a consultant for Abbott Vascular, Medtronic, and Merck. Dr. Henry has received research grant support from Eli Lilly and Daiichi Sankyo. Dr. Kini serves on the Speakers Bureau of the American College of Cardiology; and has received consulting fees from WebMD. Dr. Krucoff has received consulting fees from Abbott Vascular, Abbott, OrbusNeich, Angelmed, Volcano, Biosensors, Svelte, Medtronic, and Terumo; and research grant support from Abbott, Terumo, Angelmed, Ikaria, OrbusNeich, Medtronic, CSI, Eli Lilly, and Medtronic. Dr. Gibson has received research grant support from Angel Medical Corporation, Atrium Medical Systems, Bayer, Ikaria, Janssen/Johnson & Johnson, Lantheus Medical Imaging, Merck, Portola Pharmaceuticals, Roche Diagnostics, Sanofi, Stealth Peptides, St. Jude Medical, Volcano, and Walk Vascular; consulting fees from AstraZeneca, Baxter Healthcare, Bayer, CRF, Consensus Medical Communications, CSL Behring, Cytori Therapeutics, Eli Lilly/Daiichi Sankyo, Exeter Group, Genentech, GlaxoSmithKline, Janssen/Johnson & Johnson, Ortho McNeil, St. Jude Medical, The Medicines Company; and royalty fees from UpToDate in Cardiovascular Medicine. Dr. Colombo has received consulting fees and honoraria from CID and other financial benefit from Direct Flow Medical. Dr. Mehran has received institutional grant support from The Medicines Company, Bristol-Myers Squibb/Sanofi, and Eli Lilly/Daiichi Sankyo; and is a consultant to Janssen Pharmaceuticals and Maya Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: {\textcopyright} 2016 American College of Cardiology Foundation",

year = "2016",

month = jul,

day = "11",

doi = "10.1016/j.jcin.2016.04.009",

language = "English",

volume = "9",

pages = "1349--1357",

number = "13",

}

Baber, U, Dangas, G, Chandrasekhar, J, Sartori, S, Steg, PG, Cohen, DJ, Giustino, G, Ariti, C, Witzenbichler, B, Henry, TD, Kini, AS, Krucoff, MW, Gibson, CM, Chieffo, A, Moliterno, DJ, Weisz, G, Colombo, A, Pocock, S & Mehran, R 2016, 'Time-Dependent Associations Between Actionable Bleeding, Coronary Thrombotic Events, and Mortality Following Percutaneous Coronary Intervention: Results From the PARIS Registry', JACC: Cardiovascular Interventions, vol. 9, no. 13, pp. 1349-1357. https://doi.org/10.1016/j.jcin.2016.04.009

Time-Dependent Associations Between Actionable Bleeding, Coronary Thrombotic Events, and Mortality Following Percutaneous Coronary Intervention: Results From the PARIS Registry. / Baber, Usman; Dangas, George; Chandrasekhar, Jaya et al.
In: JACC: Cardiovascular Interventions, Vol. 9, No. 13, 11.07.2016, p. 1349-1357.

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

TY - JOUR

T1 - Time-Dependent Associations Between Actionable Bleeding, Coronary Thrombotic Events, and Mortality Following Percutaneous Coronary Intervention

T2 - Results From the PARIS Registry

AU - Baber, Usman

AU - Dangas, George

AU - Chandrasekhar, Jaya

AU - Sartori, Samantha

AU - Steg, Philippe Gabriel

AU - Cohen, David J.

AU - Giustino, Gennaro

AU - Ariti, Cono

AU - Witzenbichler, Bernhard

AU - Henry, Timothy D.

AU - Kini, Annapoorna S.

AU - Krucoff, Mitchell W.

AU - Gibson, C. Michael

AU - Chieffo, Alaide

AU - Moliterno, David J.

AU - Weisz, Giora

AU - Colombo, Antonio

AU - Pocock, Stuart

AU - Mehran, Roxana

N1 - Funding Information: This study was funded by Bristol-Myers Squibb and Sanofi. Dr. Dangas has received consulting fees and honoraria from Johnson & Johnson, Sanofi, Covidien, The Medicines Company, Merck, CSL Behring, AstraZeneca, Medtronic, Abbott Vascular, Bayer, Boston Scientific, Osprey Medical, and GE Healthcare; and research grant support from Sanofi, Bristol-Myers Squibb, and Lilly/Daiichi Sankyo. Dr. Steg has served as an adviser or a consultant for Amarin, AstraZeneca Pharmaceuticals, Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Eli Lilly, Medtronic, Otsuka Pharmaceutical, Pfizer, Roche, Sanofi, Servier, Takeda Pharmaceuticals North America, The Medicines Company, and Vivus; and has received clinical research grants from Sanofi and Servier. Dr. Cohen has received research grant support from Abbott Vascular, AstraZeneca, Biomet, Boston Scientific, Cardiovascular Systems, Daiichi Sankyo, Edwards Lifesciences, Eli Lilly, and Medtronic; and is a consultant for Abbott Vascular, Medtronic, and Merck. Dr. Henry has received research grant support from Eli Lilly and Daiichi Sankyo. Dr. Kini serves on the Speakers Bureau of the American College of Cardiology; and has received consulting fees from WebMD. Dr. Krucoff has received consulting fees from Abbott Vascular, Abbott, OrbusNeich, Angelmed, Volcano, Biosensors, Svelte, Medtronic, and Terumo; and research grant support from Abbott, Terumo, Angelmed, Ikaria, OrbusNeich, Medtronic, CSI, Eli Lilly, and Medtronic. Dr. Gibson has received research grant support from Angel Medical Corporation, Atrium Medical Systems, Bayer, Ikaria, Janssen/Johnson & Johnson, Lantheus Medical Imaging, Merck, Portola Pharmaceuticals, Roche Diagnostics, Sanofi, Stealth Peptides, St. Jude Medical, Volcano, and Walk Vascular; consulting fees from AstraZeneca, Baxter Healthcare, Bayer, CRF, Consensus Medical Communications, CSL Behring, Cytori Therapeutics, Eli Lilly/Daiichi Sankyo, Exeter Group, Genentech, GlaxoSmithKline, Janssen/Johnson & Johnson, Ortho McNeil, St. Jude Medical, The Medicines Company; and royalty fees from UpToDate in Cardiovascular Medicine. Dr. Colombo has received consulting fees and honoraria from CID and other financial benefit from Direct Flow Medical. Dr. Mehran has received institutional grant support from The Medicines Company, Bristol-Myers Squibb/Sanofi, and Eli Lilly/Daiichi Sankyo; and is a consultant to Janssen Pharmaceuticals and Maya Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: © 2016 American College of Cardiology Foundation

PY - 2016/7/11

Y1 - 2016/7/11

N2 - Objectives The aim of this study was to examine the independent associations between actionable bleeding (AB) and coronary thrombotic events (CTE) on mortality risk after percutaneous coronary intervention (PCI). Background The independent impact of AB and CTE on mortality risk after PCI remains poorly characterized. Methods A post hoc analysis was conducted of the PARIS (Patterns of Non-Adherence to Dual Antiplatelet Therapy in Stented Patients) registry, a real-world cohort of 5,018 patients undergoing PCI with stent implantation. CTE included definite or probable stent thrombosis or myocardial infarction. AB was defined as Bleeding Academic Research Consortium type 2 or 3. Associations between CTE and AB, both of which were modeled as time-dependent covariates, and 2-year mortality risk were examined using extended Cox regression. Results Over 2 years, the cumulative incidence of CTE, AB, and all-cause mortality was 5.9% (n = 289), 8.1% (n = 391), and 4.7% (n = 227), respectively. Adjusted hazard ratios for mortality associated with CTE and AB were 3.3 (95% confidence interval: 2.2 to 4.9) and 3.5 (95% confidence interval: 2.3 to 5.4), respectively. Temporal gradients in risk after either event were highest in the first 30 days and declined rapidly thereafter. Thrombotic events occurring while patients were on versus off dual-antiplatelet therapy were associated with a higher mortality risk, whereas risk related to AB was not influenced by dual-antiplatelet therapy status at the time of bleeding. Conclusions Intracoronary thrombosis and AB are associated with mortality risks of comparable magnitude over a 2-year period after PCI, findings that might inform risk/benefit calculations for extension versus discontinuation of dual-antiplatelet therapy.

AB - Objectives The aim of this study was to examine the independent associations between actionable bleeding (AB) and coronary thrombotic events (CTE) on mortality risk after percutaneous coronary intervention (PCI). Background The independent impact of AB and CTE on mortality risk after PCI remains poorly characterized. Methods A post hoc analysis was conducted of the PARIS (Patterns of Non-Adherence to Dual Antiplatelet Therapy in Stented Patients) registry, a real-world cohort of 5,018 patients undergoing PCI with stent implantation. CTE included definite or probable stent thrombosis or myocardial infarction. AB was defined as Bleeding Academic Research Consortium type 2 or 3. Associations between CTE and AB, both of which were modeled as time-dependent covariates, and 2-year mortality risk were examined using extended Cox regression. Results Over 2 years, the cumulative incidence of CTE, AB, and all-cause mortality was 5.9% (n = 289), 8.1% (n = 391), and 4.7% (n = 227), respectively. Adjusted hazard ratios for mortality associated with CTE and AB were 3.3 (95% confidence interval: 2.2 to 4.9) and 3.5 (95% confidence interval: 2.3 to 5.4), respectively. Temporal gradients in risk after either event were highest in the first 30 days and declined rapidly thereafter. Thrombotic events occurring while patients were on versus off dual-antiplatelet therapy were associated with a higher mortality risk, whereas risk related to AB was not influenced by dual-antiplatelet therapy status at the time of bleeding. Conclusions Intracoronary thrombosis and AB are associated with mortality risks of comparable magnitude over a 2-year period after PCI, findings that might inform risk/benefit calculations for extension versus discontinuation of dual-antiplatelet therapy.

KW - bleeding

KW - dual-antiplatelet therapy

KW - mortality

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Time-Dependent Associations Between Actionable Bleeding, Coronary Thrombotic Events, and Mortality Following Percutaneous Coronary Intervention: Results From the PARIS Registry

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Bibliographical note

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ASJC Scopus subject areas

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