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.
|Number of pages||10|
|State||Published - Sep 2021|
Bibliographical noteFunding 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.
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
© 2021 American Medical Association. All rights reserved.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine