Ticagrelor Monotherapy After PCI in High-Risk Patients With Prior MI: A Prespecified TWILIGHT Substudy

Mauro Chiarito; Usman Baber; Davide Cao; Samin K. Sharma; George Dangas; Dominick J. Angiolillo; Carlo Briguori; David J. Cohen; Dariusz Dudek; Vladimír Džavík; Javier Escaned; Robert Gil; Christian W. Hamm; Timothy Henry; Kurt Huber; Adnan Kastrati; Upendra Kaul; Ran Kornowski; Mitchell Krucoff; Vijay Kunadian; Shamir R. Mehta; David Moliterno; E. Magnus Ohman; Keith Oldroyd; Gennaro Sardella; Zhang Zhongjie; Samantha Sartori; Giulio Stefanini; Richard Shlofmitz; P. Gabriel Steg; Giora Weisz; Bernhard Witzenbichler; Ya ling Han; Stuart Pocock; C. Michael Gibson; Roxana Mehran

doi:10.1016/j.jcin.2021.11.005

Ticagrelor Monotherapy After PCI in High-Risk Patients With Prior MI: A Prespecified TWILIGHT Substudy

Mauro Chiarito, Usman Baber, Davide Cao, Samin K. Sharma, George Dangas, Dominick J. Angiolillo, Carlo Briguori, David J. Cohen, Dariusz Dudek, Vladimír Džavík, Javier Escaned, Robert Gil, Christian W. Hamm, Timothy Henry, Kurt Huber, Adnan Kastrati, Upendra Kaul, Ran Kornowski, Mitchell Krucoff, Vijay KunadianShamir R. Mehta, David Moliterno, E. Magnus Ohman, Keith Oldroyd, Gennaro Sardella, Zhang Zhongjie, Samantha Sartori, Giulio Stefanini, Richard Shlofmitz, P. Gabriel Steg, Giora Weisz, Bernhard Witzenbichler, Ya ling Han, Stuart Pocock, C. Michael Gibson, Roxana Mehran

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

8 Scopus citations

Abstract

Objectives: The aim of this study was to evaluate if patients with prior myocardial infarction (MI) could benefit from ticagrelor monotherapy in terms of bleeding reduction without any compromise in ischemic event prevention. Background: Patients with history of MI who undergo percutaneous coronary intervention (PCI) remain at risk for recurrent ischemic events. The optimal antithrombotic strategy for this cohort remains debated. Methods: In this prespecified analysis of the randomized TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial, the authors evaluated the impact of history of MI on treatment effect of ticagrelor monotherapy versus ticagrelor plus aspirin in patients undergoing PCI with drug-eluting stent with at least 1 clinical and 1 angiographic high-risk feature and free from adverse events at 3 months after index PCI. The primary endpoint was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, and the key secondary endpoint was the composite of all-cause death, MI, or stroke, both at 12 months after randomization. Results: A total of 1,937 patients (29.7%) with and 4,595 patients (70.3%) without prior MI were randomized to ticagrelor and placebo or ticagrelor and aspirin. At 1 year after randomization, patients with prior MI experienced higher rates of death, MI, or stroke (5.7% vs 3.2%; P < 0.001) but similar BARC types 2 to 5 bleeding (5.0% vs 5.5%; P = 0.677) compared with patients without prior MI. Ticagrelor monotherapy consistently reduced the risk for the primary bleeding outcome in patients with (3.4% vs 6.7%; HR: 0.50; 95% CI: 0.33-0.76) and without (4.2% vs 7.0%; HR: 0.58; 95% CI: 0.45-0.76; P_interaction = 0.54) prior MI. Rates of the key secondary ischemic outcome were not significantly different between treatment groups irrespective of history of MI (prior MI, 6.0% vs 5.5% [HR: 1.09; 95% CI: 0.75-1.58]; no prior MI, 3.1% vs 3.3% [HR: 0.92; 95% CI: 0.67-1.28]; P_interaction = 0.52). Conclusions: Ticagrelor monotherapy is associated with significantly lower risk for bleeding events compared with ticagrelor plus aspirin, without any compromise in ischemic prevention, among high-risk patients with history of MI undergoing PCI.

Original language	English
Pages (from-to)	282-293
Number of pages	12
Journal	JACC: Cardiovascular Interventions
Volume	15
Issue number	3
DOIs	https://doi.org/10.1016/j.jcin.2021.11.005
State	Published - 14 Feb 2022

Keywords

aspirin
drug-eluting stent(s)
percutaneous coronary intervention
prior myocardial infarction
ticagrelor

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10.1016/j.jcin.2021.11.005

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Chiarito, M., Baber, U., Cao, D., Sharma, S. K., Dangas, G., Angiolillo, D. J., Briguori, C., Cohen, D. J., Dudek, D., Džavík, V., Escaned, J., Gil, R., Hamm, C. W., Henry, T., Huber, K., Kastrati, A., Kaul, U., Kornowski, R., Krucoff, M., ... Mehran, R. (2022). Ticagrelor Monotherapy After PCI in High-Risk Patients With Prior MI: A Prespecified TWILIGHT Substudy. JACC: Cardiovascular Interventions, 15(3), 282-293. https://doi.org/10.1016/j.jcin.2021.11.005

@article{1e89fd0cca4043f7a6ffc928fe444434,

title = "Ticagrelor Monotherapy After PCI in High-Risk Patients With Prior MI: A Prespecified TWILIGHT Substudy",

abstract = "Objectives: The aim of this study was to evaluate if patients with prior myocardial infarction (MI) could benefit from ticagrelor monotherapy in terms of bleeding reduction without any compromise in ischemic event prevention. Background: Patients with history of MI who undergo percutaneous coronary intervention (PCI) remain at risk for recurrent ischemic events. The optimal antithrombotic strategy for this cohort remains debated. Methods: In this prespecified analysis of the randomized TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial, the authors evaluated the impact of history of MI on treatment effect of ticagrelor monotherapy versus ticagrelor plus aspirin in patients undergoing PCI with drug-eluting stent with at least 1 clinical and 1 angiographic high-risk feature and free from adverse events at 3 months after index PCI. The primary endpoint was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, and the key secondary endpoint was the composite of all-cause death, MI, or stroke, both at 12 months after randomization. Results: A total of 1,937 patients (29.7%) with and 4,595 patients (70.3%) without prior MI were randomized to ticagrelor and placebo or ticagrelor and aspirin. At 1 year after randomization, patients with prior MI experienced higher rates of death, MI, or stroke (5.7% vs 3.2%; P < 0.001) but similar BARC types 2 to 5 bleeding (5.0% vs 5.5%; P = 0.677) compared with patients without prior MI. Ticagrelor monotherapy consistently reduced the risk for the primary bleeding outcome in patients with (3.4% vs 6.7%; HR: 0.50; 95% CI: 0.33-0.76) and without (4.2% vs 7.0%; HR: 0.58; 95% CI: 0.45-0.76; Pinteraction = 0.54) prior MI. Rates of the key secondary ischemic outcome were not significantly different between treatment groups irrespective of history of MI (prior MI, 6.0% vs 5.5% [HR: 1.09; 95% CI: 0.75-1.58]; no prior MI, 3.1% vs 3.3% [HR: 0.92; 95% CI: 0.67-1.28]; Pinteraction = 0.52). Conclusions: Ticagrelor monotherapy is associated with significantly lower risk for bleeding events compared with ticagrelor plus aspirin, without any compromise in ischemic prevention, among high-risk patients with history of MI undergoing PCI.",

keywords = "aspirin, drug-eluting stent(s), percutaneous coronary intervention, prior myocardial infarction, ticagrelor",

author = "Mauro Chiarito and Usman Baber and Davide Cao and Sharma, {Samin K.} and George Dangas and Angiolillo, {Dominick J.} and Carlo Briguori and Cohen, {David J.} and Dariusz Dudek and Vladim{\'i}r D{\v z}av{\'i}k and Javier Escaned and Robert Gil and Hamm, {Christian W.} and Timothy Henry and Kurt Huber and Adnan Kastrati and Upendra Kaul and Ran Kornowski and Mitchell Krucoff and Vijay Kunadian and Mehta, {Shamir R.} and David Moliterno and Ohman, {E. Magnus} and Keith Oldroyd and Gennaro Sardella and Zhang Zhongjie and Samantha Sartori and Giulio Stefanini and Richard Shlofmitz and Steg, {P. Gabriel} and Giora Weisz and Bernhard Witzenbichler and Han, {Ya ling} and Stuart Pocock and Gibson, {C. Michael} and Roxana Mehran",

note = "Funding Information: This research was conducted with support from AstraZeneca Pharmaceuticals LP. Dr Baber has received honoraria from AstraZeneca and Boston Scientific. Dr Sharma has received Speakers Bureau fees from Abbott Vascular, Boston Scientific, and Cardiovascular Systems. Dr Dangas has received personal fees from Biosensors and Philips. Dr Angiolillo has received consulting fees or honoraria from Abbott, Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi, and The Medicines Company; has received payments for participation in review activities from CeloNova and St Jude Medical, outside the present work; and has received research grants to his institution from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Matsutani Chemical Industry, Merck, Novartis, Osprey Medical, Renal Guard Solutions, and the Scott R. MacKenzie Foundation. Dr Stefanini has received a research grant from Boston Scientific; and has received speaker and consulting fees from Bayer, Braun, Biosensors, Boston Scientific, Daiichi-Sankyo and GADA, outside the submitted work. Dr Gibson has received grants and personal fees from Johnson & Johnson, Janssen, and CSL Behring; has received personal fees from Bayer, AstraZeneca (during the conduct of the study), Angel Medical Corporation, The Medicines Company, the Boston Clinical Research Institute, the Cardiovascular Research Foundation, Gilead Sciences, WebMD, UpToDate in Cardiovascular Medicine, Boehringer Ingelheim, Somahlution, Vereseon, Boston Scientific, the Duke Clinical Research Institute, Medtelligence, Microport, PERT Consortium, Caladrius Biosciences, CeleCor Therapeutics, Thrombolytic Science, Eidos Therapeutics, Kiniksa Pharmaceuticals, Microdrop, MD Magazine, MJ Health, Samsung, the Society for Cardiovascular Angiography and Interventions, Revance Therapeutics, Pfizer, GenTech, CytoSorbents, AMAG Pharmaceuticals, Bristol Myers Squibb, Intercept Pharmaceuticals, Novartis, Syneos Health, and Amarin; has received other compensation from nference, Dyad Medical, and Absolutys, and PhaseBio; has received nonfinancial support from the Baim Institute; and has received grants from the SCAD Alliance, outside the submitted work. Dr Mehran has received institutional grants from Abbott Laboratories, AstraZeneca, Bayer, Beth Israel Deaconess, Bristol Myers Squibb, Chiesi, CSL Behring, Daiichi-Sankyo Inc, Medtronic, Novartis Pharmaceuticals, and OrbusNeich; has received personal fees from Boston Scientific, Janssen, Scientific Affairs, Sanofi, and Siemens Medical Solutions; has received consulting fees paid to the institution from Abbott Laboratories and Bristol Myers Squibb; and is an advisory board member (funding paid to the institution) for Spectranetics/Philips/Volcano. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Funding Information: The TWILIGHT study design has been previously described ( 11 , 12 ). TWILIGHT was a randomized, double-blind, placebo-controlled trial conducted at 187 hospitals in 11 countries. The trial was designed and sponsored by the Icahn School of Medicine at Mount Sinai and was supported by an investigator-initiated grant from AstraZeneca Pharmaceuticals, which provided support with study medications but had no role in the design of the study, data collection and analysis, results interpretation, preparation of the manuscript, or decision to submit the manuscript for publication. Both the executive and steering committees supervised trial conduct, integrity of data analysis, and reporting of results. The study protocol was reviewed and approved by national regulatory agencies and Institutional Review Boards or ethics committees of each participating center. Publisher Copyright: {\textcopyright} 2022 American College of Cardiology Foundation",

year = "2022",

month = feb,

day = "14",

doi = "10.1016/j.jcin.2021.11.005",

language = "English",

volume = "15",

pages = "282--293",

journal = "JACC: Cardiovascular Interventions",

issn = "1936-8798",

publisher = "Elsevier Inc.",

number = "3",

}

Chiarito, M, Baber, U, Cao, D, Sharma, SK , Dangas, G, Angiolillo, DJ, Briguori, C, Cohen, DJ, Dudek, D, Džavík, V, Escaned, J, Gil, R, Hamm, CW, Henry, T, Huber, K, Kastrati, A, Kaul, U, Kornowski, R, Krucoff, M, Kunadian, V, Mehta, SR, Moliterno, D, Ohman, EM, Oldroyd, K, Sardella, G, Zhongjie, Z, Sartori, S, Stefanini, G, Shlofmitz, R, Steg, PG, Weisz, G, Witzenbichler, B, Han, YL, Pocock, S, Gibson, CM & Mehran, R 2022, 'Ticagrelor Monotherapy After PCI in High-Risk Patients With Prior MI: A Prespecified TWILIGHT Substudy', JACC: Cardiovascular Interventions, vol. 15, no. 3, pp. 282-293. https://doi.org/10.1016/j.jcin.2021.11.005

TY - JOUR

T1 - Ticagrelor Monotherapy After PCI in High-Risk Patients With Prior MI

T2 - A Prespecified TWILIGHT Substudy

AU - Chiarito, Mauro

AU - Baber, Usman

AU - Cao, Davide

AU - Sharma, Samin K.

AU - Dangas, George

AU - Angiolillo, Dominick J.

AU - Briguori, Carlo

AU - Cohen, David J.

AU - Dudek, Dariusz

AU - Džavík, Vladimír

AU - Escaned, Javier

AU - Gil, Robert

AU - Hamm, Christian W.

AU - Henry, Timothy

AU - Huber, Kurt

AU - Kastrati, Adnan

AU - Kaul, Upendra

AU - Kornowski, Ran

AU - Krucoff, Mitchell

AU - Kunadian, Vijay

AU - Mehta, Shamir R.

AU - Moliterno, David

AU - Ohman, E. Magnus

AU - Oldroyd, Keith

AU - Sardella, Gennaro

AU - Zhongjie, Zhang

AU - Sartori, Samantha

AU - Stefanini, Giulio

AU - Shlofmitz, Richard

AU - Steg, P. Gabriel

AU - Weisz, Giora

AU - Witzenbichler, Bernhard

AU - Han, Ya ling

AU - Pocock, Stuart

AU - Gibson, C. Michael

AU - Mehran, Roxana

N1 - Funding Information: This research was conducted with support from AstraZeneca Pharmaceuticals LP. Dr Baber has received honoraria from AstraZeneca and Boston Scientific. Dr Sharma has received Speakers Bureau fees from Abbott Vascular, Boston Scientific, and Cardiovascular Systems. Dr Dangas has received personal fees from Biosensors and Philips. Dr Angiolillo has received consulting fees or honoraria from Abbott, Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi, and The Medicines Company; has received payments for participation in review activities from CeloNova and St Jude Medical, outside the present work; and has received research grants to his institution from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Matsutani Chemical Industry, Merck, Novartis, Osprey Medical, Renal Guard Solutions, and the Scott R. MacKenzie Foundation. Dr Stefanini has received a research grant from Boston Scientific; and has received speaker and consulting fees from Bayer, Braun, Biosensors, Boston Scientific, Daiichi-Sankyo and GADA, outside the submitted work. Dr Gibson has received grants and personal fees from Johnson & Johnson, Janssen, and CSL Behring; has received personal fees from Bayer, AstraZeneca (during the conduct of the study), Angel Medical Corporation, The Medicines Company, the Boston Clinical Research Institute, the Cardiovascular Research Foundation, Gilead Sciences, WebMD, UpToDate in Cardiovascular Medicine, Boehringer Ingelheim, Somahlution, Vereseon, Boston Scientific, the Duke Clinical Research Institute, Medtelligence, Microport, PERT Consortium, Caladrius Biosciences, CeleCor Therapeutics, Thrombolytic Science, Eidos Therapeutics, Kiniksa Pharmaceuticals, Microdrop, MD Magazine, MJ Health, Samsung, the Society for Cardiovascular Angiography and Interventions, Revance Therapeutics, Pfizer, GenTech, CytoSorbents, AMAG Pharmaceuticals, Bristol Myers Squibb, Intercept Pharmaceuticals, Novartis, Syneos Health, and Amarin; has received other compensation from nference, Dyad Medical, and Absolutys, and PhaseBio; has received nonfinancial support from the Baim Institute; and has received grants from the SCAD Alliance, outside the submitted work. Dr Mehran has received institutional grants from Abbott Laboratories, AstraZeneca, Bayer, Beth Israel Deaconess, Bristol Myers Squibb, Chiesi, CSL Behring, Daiichi-Sankyo Inc, Medtronic, Novartis Pharmaceuticals, and OrbusNeich; has received personal fees from Boston Scientific, Janssen, Scientific Affairs, Sanofi, and Siemens Medical Solutions; has received consulting fees paid to the institution from Abbott Laboratories and Bristol Myers Squibb; and is an advisory board member (funding paid to the institution) for Spectranetics/Philips/Volcano. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Funding Information: The TWILIGHT study design has been previously described ( 11 , 12 ). TWILIGHT was a randomized, double-blind, placebo-controlled trial conducted at 187 hospitals in 11 countries. The trial was designed and sponsored by the Icahn School of Medicine at Mount Sinai and was supported by an investigator-initiated grant from AstraZeneca Pharmaceuticals, which provided support with study medications but had no role in the design of the study, data collection and analysis, results interpretation, preparation of the manuscript, or decision to submit the manuscript for publication. Both the executive and steering committees supervised trial conduct, integrity of data analysis, and reporting of results. The study protocol was reviewed and approved by national regulatory agencies and Institutional Review Boards or ethics committees of each participating center. Publisher Copyright: © 2022 American College of Cardiology Foundation

PY - 2022/2/14

Y1 - 2022/2/14

N2 - Objectives: The aim of this study was to evaluate if patients with prior myocardial infarction (MI) could benefit from ticagrelor monotherapy in terms of bleeding reduction without any compromise in ischemic event prevention. Background: Patients with history of MI who undergo percutaneous coronary intervention (PCI) remain at risk for recurrent ischemic events. The optimal antithrombotic strategy for this cohort remains debated. Methods: In this prespecified analysis of the randomized TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial, the authors evaluated the impact of history of MI on treatment effect of ticagrelor monotherapy versus ticagrelor plus aspirin in patients undergoing PCI with drug-eluting stent with at least 1 clinical and 1 angiographic high-risk feature and free from adverse events at 3 months after index PCI. The primary endpoint was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, and the key secondary endpoint was the composite of all-cause death, MI, or stroke, both at 12 months after randomization. Results: A total of 1,937 patients (29.7%) with and 4,595 patients (70.3%) without prior MI were randomized to ticagrelor and placebo or ticagrelor and aspirin. At 1 year after randomization, patients with prior MI experienced higher rates of death, MI, or stroke (5.7% vs 3.2%; P < 0.001) but similar BARC types 2 to 5 bleeding (5.0% vs 5.5%; P = 0.677) compared with patients without prior MI. Ticagrelor monotherapy consistently reduced the risk for the primary bleeding outcome in patients with (3.4% vs 6.7%; HR: 0.50; 95% CI: 0.33-0.76) and without (4.2% vs 7.0%; HR: 0.58; 95% CI: 0.45-0.76; Pinteraction = 0.54) prior MI. Rates of the key secondary ischemic outcome were not significantly different between treatment groups irrespective of history of MI (prior MI, 6.0% vs 5.5% [HR: 1.09; 95% CI: 0.75-1.58]; no prior MI, 3.1% vs 3.3% [HR: 0.92; 95% CI: 0.67-1.28]; Pinteraction = 0.52). Conclusions: Ticagrelor monotherapy is associated with significantly lower risk for bleeding events compared with ticagrelor plus aspirin, without any compromise in ischemic prevention, among high-risk patients with history of MI undergoing PCI.

AB - Objectives: The aim of this study was to evaluate if patients with prior myocardial infarction (MI) could benefit from ticagrelor monotherapy in terms of bleeding reduction without any compromise in ischemic event prevention. Background: Patients with history of MI who undergo percutaneous coronary intervention (PCI) remain at risk for recurrent ischemic events. The optimal antithrombotic strategy for this cohort remains debated. Methods: In this prespecified analysis of the randomized TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial, the authors evaluated the impact of history of MI on treatment effect of ticagrelor monotherapy versus ticagrelor plus aspirin in patients undergoing PCI with drug-eluting stent with at least 1 clinical and 1 angiographic high-risk feature and free from adverse events at 3 months after index PCI. The primary endpoint was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, and the key secondary endpoint was the composite of all-cause death, MI, or stroke, both at 12 months after randomization. Results: A total of 1,937 patients (29.7%) with and 4,595 patients (70.3%) without prior MI were randomized to ticagrelor and placebo or ticagrelor and aspirin. At 1 year after randomization, patients with prior MI experienced higher rates of death, MI, or stroke (5.7% vs 3.2%; P < 0.001) but similar BARC types 2 to 5 bleeding (5.0% vs 5.5%; P = 0.677) compared with patients without prior MI. Ticagrelor monotherapy consistently reduced the risk for the primary bleeding outcome in patients with (3.4% vs 6.7%; HR: 0.50; 95% CI: 0.33-0.76) and without (4.2% vs 7.0%; HR: 0.58; 95% CI: 0.45-0.76; Pinteraction = 0.54) prior MI. Rates of the key secondary ischemic outcome were not significantly different between treatment groups irrespective of history of MI (prior MI, 6.0% vs 5.5% [HR: 1.09; 95% CI: 0.75-1.58]; no prior MI, 3.1% vs 3.3% [HR: 0.92; 95% CI: 0.67-1.28]; Pinteraction = 0.52). Conclusions: Ticagrelor monotherapy is associated with significantly lower risk for bleeding events compared with ticagrelor plus aspirin, without any compromise in ischemic prevention, among high-risk patients with history of MI undergoing PCI.

KW - aspirin

KW - drug-eluting stent(s)

KW - percutaneous coronary intervention

KW - prior myocardial infarction

KW - ticagrelor

UR - http://www.scopus.com/inward/record.url?scp=85123732996&partnerID=8YFLogxK

U2 - 10.1016/j.jcin.2021.11.005

DO - 10.1016/j.jcin.2021.11.005

M3 - Article

C2 - 35033468

AN - SCOPUS:85123732996

SN - 1936-8798

VL - 15

SP - 282

EP - 293

JO - JACC: Cardiovascular Interventions

JF - JACC: Cardiovascular Interventions

IS - 3

ER -

Ticagrelor Monotherapy After PCI in High-Risk Patients With Prior MI: A Prespecified TWILIGHT Substudy

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