Sex Differences among Patients with High Risk Receiving Ticagrelor with or without Aspirin after Percutaneous Coronary Intervention: A Subgroup Analysis of the TWILIGHT Randomized Clinical Trial

Birgit Vogel; Usman Baber; David J. Cohen; Samantha Sartori; Samin K. Sharma; Dominick J. Angiolillo; Serdar Farhan; Ridhima Goel; Zhongjie Zhang; Carlo Briguori; Timothy Collier; George Dangas; Dariusz Dudek; Javier Escaned; Robert Gil; Ya Ling Han; Upendra Kaul; Ran Kornowski; Mitchell W. Krucoff; Vijay Kunadian; Shamir R. Mehta; David Moliterno; E. Magnus Ohman; Gennaro Sardella; Bernhard Witzenbichler; C. Michael Gibson; Stuart Pocock; Kurt Huber; Roxana Mehran

doi:10.1001/jamacardio.2021.1720

Sex Differences among Patients with High Risk Receiving Ticagrelor with or without Aspirin after Percutaneous Coronary Intervention: A Subgroup Analysis of the TWILIGHT Randomized Clinical Trial

Birgit Vogel, Usman Baber, David J. Cohen, Samantha Sartori, Samin K. Sharma, Dominick J. Angiolillo, Serdar Farhan, Ridhima Goel, Zhongjie Zhang, Carlo Briguori, Timothy Collier, George Dangas, Dariusz Dudek, Javier Escaned, Robert Gil, Ya Ling Han, Upendra Kaul, Ran Kornowski, Mitchell W. Krucoff, Vijay KunadianShamir R. Mehta, David Moliterno, E. Magnus Ohman, Gennaro Sardella, Bernhard Witzenbichler, C. Michael Gibson, Stuart Pocock, Kurt Huber, Roxana Mehran

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

24 Scopus citations

Abstract

Importance: Shortened dual antiplatelet therapy followed by potent P2Y12 receptor inhibitor monotherapy reduces bleeding without increasing ischemic events after percutaneous coronary intervention (PCI). Objective: To explore sex differences and evaluate the association of sex with outcomes among patients treated with ticagrelor monotherapy vs ticagrelor plus aspirin. Design, Setting, and Participants: This was a prespecified secondary analysis of TWILIGHT, an investigator-initiated, placebo-controlled randomized clinical trial conducted at 187 sites across 11 countries. Study participants included patients who underwent successful PCI with drug-eluting stents, were planned for discharge with ticagrelor plus aspirin, and who had at least 1 clinical and at least 1 angiographic feature associated with high risk of ischemic or bleeding events. Data were analyzed from May to July 2020. Interventions: At 3 months after PCI, patients adherent to ticagrelor and aspirin without major adverse event were randomized to either aspirin or placebo for an additional 12 months along with ticagrelor. Main Outcomes and Measures: The primary end point was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding at 12 months after randomization. The primary ischemic end point was a composite of death, myocardial infarction, or stroke. Results: Of 9006 enrolled patients, 7119 underwent randomization (mean [SD] age, 63.9 [10.2] years; 5421 [76.1%] men). Women were older (mean [SD] age, 65.5 [9.6] years in women vs 63.4 [10.3] years in men) with higher prevalence of chronic kidney disease (347 women [21.2%] vs 764 men [14.7%]). The primary bleeding end point occurred more often in women than men (hazard ratio [HR], 1.32; 95% CI, 1.06-1.64; P =.01). After multivariate adjustment, incremental bleeding risk associated with female sex was no longer significant (adjusted HR, 1.20; 95% CI, 0.95-1.52; P =.12). Ischemic end points were similar between sexes. Ticagrelor plus placebo vs ticagrelor plus aspirin was associated with lower risk of BARC type 2, 3, or 5 bleeding in women (adjusted HR, 0.62; 95% CI, 0.42-0.92; P =.02) and men (adjusted HR, 0.57; 95% CI, 0.44-0.73; P <.001; P for interaction =.69). Ischemic end points were similar between treatment groups in both sexes. Conclusions and Relevance: These findings suggest that the higher bleeding risk in women compared with men was mostly attributable to baseline differences, whereas ischemic events were similar between sexes. In this high-risk PCI population, the benefits of early aspirin withdrawal with continuation of ticagrelor were generally comparable in women and men. Trial Registration: ClinicalTrials.gov Identifier: NCT02270242.

Original language	English
Pages (from-to)	1032-1041
Number of pages	10
Journal	JAMA Cardiology
Volume	6
Issue number	9
DOIs	https://doi.org/10.1001/jamacardio.2021.1720
State	Published - Sep 2021

Bibliographical note

Funding Information:
The TWILIGHT trial was a placebo-controlled randomized clinical trial conducted in 187 sites across 11 countries. The trial rationale, design, and main findings have been reported previously.2,5 The Icahn School of Medicine at Mount Sinai designed and sponsored the trial supported by an investigator-initiated grant from AstraZeneca. National regulatory agencies and institutional review boards or ethics committees of participating centers approved the trial protocol (Supplement 1). An independent data safety monitoring board provided external oversight to ensure safety of all trial participants. All patients provided written informed consent prior to participation. The TWILIGHT trial was conducted from July 2015 to July 2019.

Funding Information:
receiving personal fees from Amgen, AstraZeneca, and Boston Scientific during the conduct of the study. Dr Cohen reported receiving grants and personal fees from AstraZeneca, Medtronic, and Abbott Vascular and grants from Boston Scientific outside the submitted work. Dr Sharma reported receiving personal fees from Abbott Vascular, Boston Scientific, and Cardiovascular Systems and serving on an advisory board for Boston Scientific outside the submitted work. Dr Angiolillo reported receiving grants and personal fees from Abbott, Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, CeloNova, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi, and The Medicines Company; personal fees from St Jude Medical; and grants (paid to his institution) from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry, Merck, Novartis, Osprey Medical, Renal Guard Solutions, and the Scott R. MacKenzie Foundation. Dr Briguori reported receiving grants from Mount Sinai during the conduct of the study. Dr Collier reported serving on data monitoring committees sponsored by AstraZeneca, Boston Scientific, Daiichi-Sankyo, Devax, Infraredx, Medtronic, Pfizer, and Zoll. Dr Dangas reported receiving grants from AstraZeneca, personal fees from AstraZeneca and Biosensors, and owning stock in Medtronic outside the submitted work. Dr Escaned reported receiving personal fees from Abbott, Philips, Boston Scientific, Medtronic, Abiomed, Terumo, and Biosensors. Dr Krucoff reported receiving grants and personal fees from Abbott Vascular, Biosensors, Boston Scientific, Celonova, Medtronic, OrbusNeich. Dr Kunadian reports receiving personal fees/ honoraria from Bayer, AstraZeneca, Abbott, Amgen, Daichii Sankyo. Dr Mehta reported receiving grants from AstraZeneca during the conduct of the study. Dr Moliterno reported receiving grants from AstraZeneca during the conduct of the study. Dr Ohman reported receiving grants from Chiesi and Portola and personal fees from Cytokinetics, Abiomed, Pfizer, 3D Communications, ACI Clinical, Biotie, Cara Therapeutics, Cardinal Health, Faculty Connection, Imbria, Impulse Medical, Janssen Pharmaceuticals, Medscape, Milestone Pharmaceuticals, XyloCor, and Otsuka outside the submitted work. Dr Witzenbichler reported personal fees from Mount Sinai Hospital during the conduct of the study. Dr Gibson reported receiving grants and personal fees from Angel Medical, Bayer, CSL Behring, Johnson & Johnson, Janssen, AstraZeneca, Portola Pharmaceuticals, personal fees from the Medicines Company, Eli Lilly, Gilead Sciences, Novo Nordisk, WebMD, UpToDate Cardiovascular Medicine, Amarin Pharma, Amgen, Boehringer Ingelheim, Chiesi, Merck, PharmaMar, Sanofi, Somahlution, Verreseon Corporation, Boston Scientific, Impact Bio, MedImmume, Medtelligence, MicroPort, PERT Consortium, and GE Healthcare; owning stock in nference; serving as chief executive officer of Baim Institute, and receiving grants (paid to

Publisher Copyright:
© 2021 American Medical Association. All rights reserved.

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

Access to Document

10.1001/jamacardio.2021.1720

Cite this

Vogel, B., Baber, U., Cohen, D. J., Sartori, S., Sharma, S. K., Angiolillo, D. J., Farhan, S., Goel, R., Zhang, Z., Briguori, C., Collier, T., Dangas, G., Dudek, D., Escaned, J., Gil, R., Han, Y. L., Kaul, U., Kornowski, R., Krucoff, M. W., ... Mehran, R. (2021). Sex Differences among Patients with High Risk Receiving Ticagrelor with or without Aspirin after Percutaneous Coronary Intervention: A Subgroup Analysis of the TWILIGHT Randomized Clinical Trial. JAMA Cardiology, 6(9), 1032-1041. https://doi.org/10.1001/jamacardio.2021.1720

@article{3e6fa00e1b6f44ca81ee441ceea8fb81,

title = "Sex Differences among Patients with High Risk Receiving Ticagrelor with or without Aspirin after Percutaneous Coronary Intervention: A Subgroup Analysis of the TWILIGHT Randomized Clinical Trial",

abstract = "Importance: Shortened dual antiplatelet therapy followed by potent P2Y12 receptor inhibitor monotherapy reduces bleeding without increasing ischemic events after percutaneous coronary intervention (PCI). Objective: To explore sex differences and evaluate the association of sex with outcomes among patients treated with ticagrelor monotherapy vs ticagrelor plus aspirin. Design, Setting, and Participants: This was a prespecified secondary analysis of TWILIGHT, an investigator-initiated, placebo-controlled randomized clinical trial conducted at 187 sites across 11 countries. Study participants included patients who underwent successful PCI with drug-eluting stents, were planned for discharge with ticagrelor plus aspirin, and who had at least 1 clinical and at least 1 angiographic feature associated with high risk of ischemic or bleeding events. Data were analyzed from May to July 2020. Interventions: At 3 months after PCI, patients adherent to ticagrelor and aspirin without major adverse event were randomized to either aspirin or placebo for an additional 12 months along with ticagrelor. Main Outcomes and Measures: The primary end point was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding at 12 months after randomization. The primary ischemic end point was a composite of death, myocardial infarction, or stroke. Results: Of 9006 enrolled patients, 7119 underwent randomization (mean [SD] age, 63.9 [10.2] years; 5421 [76.1%] men). Women were older (mean [SD] age, 65.5 [9.6] years in women vs 63.4 [10.3] years in men) with higher prevalence of chronic kidney disease (347 women [21.2%] vs 764 men [14.7%]). The primary bleeding end point occurred more often in women than men (hazard ratio [HR], 1.32; 95% CI, 1.06-1.64; P =.01). After multivariate adjustment, incremental bleeding risk associated with female sex was no longer significant (adjusted HR, 1.20; 95% CI, 0.95-1.52; P =.12). Ischemic end points were similar between sexes. Ticagrelor plus placebo vs ticagrelor plus aspirin was associated with lower risk of BARC type 2, 3, or 5 bleeding in women (adjusted HR, 0.62; 95% CI, 0.42-0.92; P =.02) and men (adjusted HR, 0.57; 95% CI, 0.44-0.73; P <.001; P for interaction =.69). Ischemic end points were similar between treatment groups in both sexes. Conclusions and Relevance: These findings suggest that the higher bleeding risk in women compared with men was mostly attributable to baseline differences, whereas ischemic events were similar between sexes. In this high-risk PCI population, the benefits of early aspirin withdrawal with continuation of ticagrelor were generally comparable in women and men. Trial Registration: ClinicalTrials.gov Identifier: NCT02270242.",

author = "Birgit Vogel and Usman Baber and Cohen, {David J.} and Samantha Sartori and Sharma, {Samin K.} and Angiolillo, {Dominick J.} and Serdar Farhan and Ridhima Goel and Zhongjie Zhang and Carlo Briguori and Timothy Collier and George Dangas and Dariusz Dudek and Javier Escaned and Robert Gil and Han, {Ya Ling} and Upendra Kaul and Ran Kornowski and Krucoff, {Mitchell W.} and Vijay Kunadian and Mehta, {Shamir R.} and David Moliterno and Ohman, {E. Magnus} and Gennaro Sardella and Bernhard Witzenbichler and Gibson, {C. Michael} and Stuart Pocock and Kurt Huber and Roxana Mehran",

note = "Funding Information: The TWILIGHT trial was a placebo-controlled randomized clinical trial conducted in 187 sites across 11 countries. The trial rationale, design, and main findings have been reported previously.2,5 The Icahn School of Medicine at Mount Sinai designed and sponsored the trial supported by an investigator-initiated grant from AstraZeneca. National regulatory agencies and institutional review boards or ethics committees of participating centers approved the trial protocol (Supplement 1). An independent data safety monitoring board provided external oversight to ensure safety of all trial participants. All patients provided written informed consent prior to participation. The TWILIGHT trial was conducted from July 2015 to July 2019. Funding Information: receiving personal fees from Amgen, AstraZeneca, and Boston Scientific during the conduct of the study. Dr Cohen reported receiving grants and personal fees from AstraZeneca, Medtronic, and Abbott Vascular and grants from Boston Scientific outside the submitted work. Dr Sharma reported receiving personal fees from Abbott Vascular, Boston Scientific, and Cardiovascular Systems and serving on an advisory board for Boston Scientific outside the submitted work. Dr Angiolillo reported receiving grants and personal fees from Abbott, Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, CeloNova, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi, and The Medicines Company; personal fees from St Jude Medical; and grants (paid to his institution) from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry, Merck, Novartis, Osprey Medical, Renal Guard Solutions, and the Scott R. MacKenzie Foundation. Dr Briguori reported receiving grants from Mount Sinai during the conduct of the study. Dr Collier reported serving on data monitoring committees sponsored by AstraZeneca, Boston Scientific, Daiichi-Sankyo, Devax, Infraredx, Medtronic, Pfizer, and Zoll. Dr Dangas reported receiving grants from AstraZeneca, personal fees from AstraZeneca and Biosensors, and owning stock in Medtronic outside the submitted work. Dr Escaned reported receiving personal fees from Abbott, Philips, Boston Scientific, Medtronic, Abiomed, Terumo, and Biosensors. Dr Krucoff reported receiving grants and personal fees from Abbott Vascular, Biosensors, Boston Scientific, Celonova, Medtronic, OrbusNeich. Dr Kunadian reports receiving personal fees/ honoraria from Bayer, AstraZeneca, Abbott, Amgen, Daichii Sankyo. Dr Mehta reported receiving grants from AstraZeneca during the conduct of the study. Dr Moliterno reported receiving grants from AstraZeneca during the conduct of the study. Dr Ohman reported receiving grants from Chiesi and Portola and personal fees from Cytokinetics, Abiomed, Pfizer, 3D Communications, ACI Clinical, Biotie, Cara Therapeutics, Cardinal Health, Faculty Connection, Imbria, Impulse Medical, Janssen Pharmaceuticals, Medscape, Milestone Pharmaceuticals, XyloCor, and Otsuka outside the submitted work. Dr Witzenbichler reported personal fees from Mount Sinai Hospital during the conduct of the study. Dr Gibson reported receiving grants and personal fees from Angel Medical, Bayer, CSL Behring, Johnson & Johnson, Janssen, AstraZeneca, Portola Pharmaceuticals, personal fees from the Medicines Company, Eli Lilly, Gilead Sciences, Novo Nordisk, WebMD, UpToDate Cardiovascular Medicine, Amarin Pharma, Amgen, Boehringer Ingelheim, Chiesi, Merck, PharmaMar, Sanofi, Somahlution, Verreseon Corporation, Boston Scientific, Impact Bio, MedImmume, Medtelligence, MicroPort, PERT Consortium, and GE Healthcare; owning stock in nference; serving as chief executive officer of Baim Institute, and receiving grants (paid to Publisher Copyright: {\textcopyright} 2021 American Medical Association. All rights reserved.",

year = "2021",

month = sep,

doi = "10.1001/jamacardio.2021.1720",

language = "English",

volume = "6",

pages = "1032--1041",

number = "9",

}

Vogel, B, Baber, U, Cohen, DJ, Sartori, S, Sharma, SK, Angiolillo, DJ, Farhan, S, Goel, R, Zhang, Z, Briguori, C, Collier, T, Dangas, G, Dudek, D, Escaned, J, Gil, R, Han, YL, Kaul, U, Kornowski, R, Krucoff, MW, Kunadian, V, Mehta, SR, Moliterno, D, Ohman, EM, Sardella, G, Witzenbichler, B, Gibson, CM, Pocock, S, Huber, K & Mehran, R 2021, 'Sex Differences among Patients with High Risk Receiving Ticagrelor with or without Aspirin after Percutaneous Coronary Intervention: A Subgroup Analysis of the TWILIGHT Randomized Clinical Trial', JAMA Cardiology, vol. 6, no. 9, pp. 1032-1041. https://doi.org/10.1001/jamacardio.2021.1720

Sex Differences among Patients with High Risk Receiving Ticagrelor with or without Aspirin after Percutaneous Coronary Intervention: A Subgroup Analysis of the TWILIGHT Randomized Clinical Trial. / Vogel, Birgit; Baber, Usman; Cohen, David J. et al.
In: JAMA Cardiology, Vol. 6, No. 9, 09.2021, p. 1032-1041.

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

TY - JOUR

T1 - Sex Differences among Patients with High Risk Receiving Ticagrelor with or without Aspirin after Percutaneous Coronary Intervention

T2 - A Subgroup Analysis of the TWILIGHT Randomized Clinical Trial

AU - Vogel, Birgit

AU - Baber, Usman

AU - Cohen, David J.

AU - Sartori, Samantha

AU - Sharma, Samin K.

AU - Angiolillo, Dominick J.

AU - Farhan, Serdar

AU - Goel, Ridhima

AU - Zhang, Zhongjie

AU - Briguori, Carlo

AU - Collier, Timothy

AU - Dangas, George

AU - Dudek, Dariusz

AU - Escaned, Javier

AU - Gil, Robert

AU - Han, Ya Ling

AU - Kaul, Upendra

AU - Kornowski, Ran

AU - Krucoff, Mitchell W.

AU - Kunadian, Vijay

AU - Mehta, Shamir R.

AU - Moliterno, David

AU - Ohman, E. Magnus

AU - Sardella, Gennaro

AU - Witzenbichler, Bernhard

AU - Gibson, C. Michael

AU - Pocock, Stuart

AU - Huber, Kurt

AU - Mehran, Roxana

N1 - Funding Information: The TWILIGHT trial was a placebo-controlled randomized clinical trial conducted in 187 sites across 11 countries. The trial rationale, design, and main findings have been reported previously.2,5 The Icahn School of Medicine at Mount Sinai designed and sponsored the trial supported by an investigator-initiated grant from AstraZeneca. National regulatory agencies and institutional review boards or ethics committees of participating centers approved the trial protocol (Supplement 1). An independent data safety monitoring board provided external oversight to ensure safety of all trial participants. All patients provided written informed consent prior to participation. The TWILIGHT trial was conducted from July 2015 to July 2019. Funding Information: receiving personal fees from Amgen, AstraZeneca, and Boston Scientific during the conduct of the study. Dr Cohen reported receiving grants and personal fees from AstraZeneca, Medtronic, and Abbott Vascular and grants from Boston Scientific outside the submitted work. Dr Sharma reported receiving personal fees from Abbott Vascular, Boston Scientific, and Cardiovascular Systems and serving on an advisory board for Boston Scientific outside the submitted work. Dr Angiolillo reported receiving grants and personal fees from Abbott, Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, CeloNova, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi, and The Medicines Company; personal fees from St Jude Medical; and grants (paid to his institution) from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry, Merck, Novartis, Osprey Medical, Renal Guard Solutions, and the Scott R. MacKenzie Foundation. Dr Briguori reported receiving grants from Mount Sinai during the conduct of the study. Dr Collier reported serving on data monitoring committees sponsored by AstraZeneca, Boston Scientific, Daiichi-Sankyo, Devax, Infraredx, Medtronic, Pfizer, and Zoll. Dr Dangas reported receiving grants from AstraZeneca, personal fees from AstraZeneca and Biosensors, and owning stock in Medtronic outside the submitted work. Dr Escaned reported receiving personal fees from Abbott, Philips, Boston Scientific, Medtronic, Abiomed, Terumo, and Biosensors. Dr Krucoff reported receiving grants and personal fees from Abbott Vascular, Biosensors, Boston Scientific, Celonova, Medtronic, OrbusNeich. Dr Kunadian reports receiving personal fees/ honoraria from Bayer, AstraZeneca, Abbott, Amgen, Daichii Sankyo. Dr Mehta reported receiving grants from AstraZeneca during the conduct of the study. Dr Moliterno reported receiving grants from AstraZeneca during the conduct of the study. Dr Ohman reported receiving grants from Chiesi and Portola and personal fees from Cytokinetics, Abiomed, Pfizer, 3D Communications, ACI Clinical, Biotie, Cara Therapeutics, Cardinal Health, Faculty Connection, Imbria, Impulse Medical, Janssen Pharmaceuticals, Medscape, Milestone Pharmaceuticals, XyloCor, and Otsuka outside the submitted work. Dr Witzenbichler reported personal fees from Mount Sinai Hospital during the conduct of the study. Dr Gibson reported receiving grants and personal fees from Angel Medical, Bayer, CSL Behring, Johnson & Johnson, Janssen, AstraZeneca, Portola Pharmaceuticals, personal fees from the Medicines Company, Eli Lilly, Gilead Sciences, Novo Nordisk, WebMD, UpToDate Cardiovascular Medicine, Amarin Pharma, Amgen, Boehringer Ingelheim, Chiesi, Merck, PharmaMar, Sanofi, Somahlution, Verreseon Corporation, Boston Scientific, Impact Bio, MedImmume, Medtelligence, MicroPort, PERT Consortium, and GE Healthcare; owning stock in nference; serving as chief executive officer of Baim Institute, and receiving grants (paid to Publisher Copyright: © 2021 American Medical Association. All rights reserved.

PY - 2021/9

Y1 - 2021/9

N2 - Importance: Shortened dual antiplatelet therapy followed by potent P2Y12 receptor inhibitor monotherapy reduces bleeding without increasing ischemic events after percutaneous coronary intervention (PCI). Objective: To explore sex differences and evaluate the association of sex with outcomes among patients treated with ticagrelor monotherapy vs ticagrelor plus aspirin. Design, Setting, and Participants: This was a prespecified secondary analysis of TWILIGHT, an investigator-initiated, placebo-controlled randomized clinical trial conducted at 187 sites across 11 countries. Study participants included patients who underwent successful PCI with drug-eluting stents, were planned for discharge with ticagrelor plus aspirin, and who had at least 1 clinical and at least 1 angiographic feature associated with high risk of ischemic or bleeding events. Data were analyzed from May to July 2020. Interventions: At 3 months after PCI, patients adherent to ticagrelor and aspirin without major adverse event were randomized to either aspirin or placebo for an additional 12 months along with ticagrelor. Main Outcomes and Measures: The primary end point was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding at 12 months after randomization. The primary ischemic end point was a composite of death, myocardial infarction, or stroke. Results: Of 9006 enrolled patients, 7119 underwent randomization (mean [SD] age, 63.9 [10.2] years; 5421 [76.1%] men). Women were older (mean [SD] age, 65.5 [9.6] years in women vs 63.4 [10.3] years in men) with higher prevalence of chronic kidney disease (347 women [21.2%] vs 764 men [14.7%]). The primary bleeding end point occurred more often in women than men (hazard ratio [HR], 1.32; 95% CI, 1.06-1.64; P =.01). After multivariate adjustment, incremental bleeding risk associated with female sex was no longer significant (adjusted HR, 1.20; 95% CI, 0.95-1.52; P =.12). Ischemic end points were similar between sexes. Ticagrelor plus placebo vs ticagrelor plus aspirin was associated with lower risk of BARC type 2, 3, or 5 bleeding in women (adjusted HR, 0.62; 95% CI, 0.42-0.92; P =.02) and men (adjusted HR, 0.57; 95% CI, 0.44-0.73; P <.001; P for interaction =.69). Ischemic end points were similar between treatment groups in both sexes. Conclusions and Relevance: These findings suggest that the higher bleeding risk in women compared with men was mostly attributable to baseline differences, whereas ischemic events were similar between sexes. In this high-risk PCI population, the benefits of early aspirin withdrawal with continuation of ticagrelor were generally comparable in women and men. Trial Registration: ClinicalTrials.gov Identifier: NCT02270242.

AB - Importance: Shortened dual antiplatelet therapy followed by potent P2Y12 receptor inhibitor monotherapy reduces bleeding without increasing ischemic events after percutaneous coronary intervention (PCI). Objective: To explore sex differences and evaluate the association of sex with outcomes among patients treated with ticagrelor monotherapy vs ticagrelor plus aspirin. Design, Setting, and Participants: This was a prespecified secondary analysis of TWILIGHT, an investigator-initiated, placebo-controlled randomized clinical trial conducted at 187 sites across 11 countries. Study participants included patients who underwent successful PCI with drug-eluting stents, were planned for discharge with ticagrelor plus aspirin, and who had at least 1 clinical and at least 1 angiographic feature associated with high risk of ischemic or bleeding events. Data were analyzed from May to July 2020. Interventions: At 3 months after PCI, patients adherent to ticagrelor and aspirin without major adverse event were randomized to either aspirin or placebo for an additional 12 months along with ticagrelor. Main Outcomes and Measures: The primary end point was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding at 12 months after randomization. The primary ischemic end point was a composite of death, myocardial infarction, or stroke. Results: Of 9006 enrolled patients, 7119 underwent randomization (mean [SD] age, 63.9 [10.2] years; 5421 [76.1%] men). Women were older (mean [SD] age, 65.5 [9.6] years in women vs 63.4 [10.3] years in men) with higher prevalence of chronic kidney disease (347 women [21.2%] vs 764 men [14.7%]). The primary bleeding end point occurred more often in women than men (hazard ratio [HR], 1.32; 95% CI, 1.06-1.64; P =.01). After multivariate adjustment, incremental bleeding risk associated with female sex was no longer significant (adjusted HR, 1.20; 95% CI, 0.95-1.52; P =.12). Ischemic end points were similar between sexes. Ticagrelor plus placebo vs ticagrelor plus aspirin was associated with lower risk of BARC type 2, 3, or 5 bleeding in women (adjusted HR, 0.62; 95% CI, 0.42-0.92; P =.02) and men (adjusted HR, 0.57; 95% CI, 0.44-0.73; P <.001; P for interaction =.69). Ischemic end points were similar between treatment groups in both sexes. Conclusions and Relevance: These findings suggest that the higher bleeding risk in women compared with men was mostly attributable to baseline differences, whereas ischemic events were similar between sexes. In this high-risk PCI population, the benefits of early aspirin withdrawal with continuation of ticagrelor were generally comparable in women and men. Trial Registration: ClinicalTrials.gov Identifier: NCT02270242.

UR - http://www.scopus.com/inward/record.url?scp=85106419474&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85106419474&partnerID=8YFLogxK

U2 - 10.1001/jamacardio.2021.1720

DO - 10.1001/jamacardio.2021.1720

M3 - Article

C2 - 33991416

AN - SCOPUS:85106419474

SN - 2380-6583

VL - 6

SP - 1032

EP - 1041

JO - JAMA Cardiology

JF - JAMA Cardiology

IS - 9

ER -

Sex Differences among Patients with High Risk Receiving Ticagrelor with or without Aspirin after Percutaneous Coronary Intervention: A Subgroup Analysis of the TWILIGHT Randomized Clinical Trial

Abstract

Bibliographical note

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this