학술논문
Ticagrelor with or without aspirin following percutaneous coronary intervention in high-risk patients with concomitant peripheral artery disease: A subgroup analysis of the TWILIGHT randomized clinical trial.
Document Type
Academic Journal
Author
Krucoff M; Division of Cardiology, Department of Medicine, Duke University Medical Center, Duke Clinical Research Institute, Durham, NC.; Spirito A; The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Baber U; Department of Cardiology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK.; Sartori S; The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Angiolillo DJ; Division of Cardiology, University of Florida College of Medicine, Jacksonville, FL.; Briguori C; Mediterranea Cardiocentro, Naples, Italy.; Cohen DJ; Cardiovascular Research Foundation, New York, NY; St. Francis Hospital, Roslyn, Roslyn, NY.; Collier T; Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom.; Dangas G; The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Dudek D; Jagiellonian University Medical College, Krakow, Poland.; Escaned J; Hospital Clínico San Carlos IDISCC, Complutense University of Madrid, Madrid, Spain.; Gibson CM; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.; Han YL; General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, China.; Huber K; Third Department Medicine, Cardiology and Intensive Care Medicine, Wilhelminen Hospital, Vienna, Austria; Sigmund Freud University, Medical Faculty, Vienna, Austria.; Kastrati A; Deutsches Herzzentrum München, Munich, Germany.; Kaul U; Batra Hospital and Medical Research Centre, New Delhi, India.; Kornowski R; Rabin Medical Center, Petach Tikva, Israel.; Kunadian V; Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.; Vogel B; The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Mehta SR; Hamilton Health Sciences, Hamilton, Ontario, Canada.; Moliterno D; Division of Cardiovascular Medicine, University of Kentucky, Lexington, KY.; Sardella G; Policlinico Umberto I University, Rome, Italy.; Shlofmitz RA; St. Francis Hospital, Roslyn, Roslyn, NY.; Sharma S; The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Steg PG; Université Paris-Cité, Paris, France.; Pocock S; Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom.; Mehran R; The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: roxana.mehran@mountsinai.org.
Source
Publisher: Mosby Country of Publication: United States NLM ID: 0370465 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-6744 (Electronic) Linking ISSN: 00028703 NLM ISO Abbreviation: Am Heart J Subsets: MEDLINE
Subject
Language
English
Abstract
Background: The optimal antiplatelet regimen after percutaneous coronary intervention (PCI) in patients with peripheral artery disease (PAD) is still debated. This analysis aimed to compare the effect of ticagrelor monotherapy versus ticagrelor plus aspirin in patients with PAD undergoing PCI.
Methods: In the TWILIGHT trial, patients at high ischemic or bleeding risk that underwent PCI were randomized after 3 months of dual antiplatelet therapy (DAPT) to aspirin or matching placebo in addition to open-label ticagrelor for 12 additional months. In this post-hoc analysis, patient cohorts were examined according to the presence or absence of PAD. The primary endpoint was Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. The key secondary endpoint was a composite of all-cause death, myocardial infarction (MI), or stroke. Endpoints were assessed at 12 months after randomization.
Results: Among 7,119 patients, 489 (7%) had PAD and were older, more likely to have comorbidities, and multivessel disease. PAD patients had more bleeding or ischemic complications than no-PAD patients. Ticagrelor monotherapy compared to ticagrelor plus aspirin was associated with less BARC 2, 3, or 5 bleeding in PAD (4.6% vs 8.7%; HR 0.52; 95%CI 0.25-1.07) and no-PAD patients (4.0% vs 7.0%; HR 0.56; 95%CI 0.45-0.69; interaction P-value .830) and a similar risk of death, MI, or stroke in these 2 groups (interaction P-value .446).
Conclusions: Despite their higher ischemic and bleeding risk, patients with PAD undergoing PCI derived a consistent benefit from ticagrelor monotherapy after 3 months of DAPT in terms of bleeding reduction without any relevant increase in ischemic events. CLINICAL TRIAL REGISTRY INFORMATION:: https://www.
Clinicaltrials: gov/study/NCT02270242.
Competing Interests: Conflict of interest Dr Spirito received a research grant from the Swiss National Science Foundation (SNSF). Dr Baber has received honoraria from AstraZeneca and Boston Scientific. Dr. Angiolillo declares that he has received consulting fees or honoraria from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, Novartis, PhaseBio, PLx Pharma, Pfizer, Sanofi and Vectura; D.J.A. also declares that his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, and the Scott R. MacKenzie Foundation. Dr Cohen has received grant support, paid to his institution, and consulting fees from AstraZeneca, Medtronic, and Abbott Vascular; and has received grant support, paid to his institution, from Boston Scientific. Dr Dangas has received consulting fees and advisory board fees from AstraZeneca; has received consulting fees from Biosensors; and previously held stock in Medtronic. Dr Escaned has received consulting and lecture fees from Abbott, Philips, Boston Scientific, and Medtronic; and has received lecture fees from Abiomed, Terumo, and Biosensors. Dr. Gibson has received grant support and consulting fees from Angel Medical, Bayer, CSL Behring, Janssen. Pharmaceuticals, Johnson & Johnson, and Portola Pharmaceuticals; has received consulting 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, Boston Scientific, Impact Bio, MedImmume, Medtelligence, MicroPort, the PERT Consortium, and GE Healthcare; holds equity in Inference; serves as chief executive officer of the Baim Institute; and has received grant support, paid to the Baim Institute, from Bristol Myers Squibb and Astra Zeneca. Dr Huber has received lecture fees from AstraZeneca and Bayer. Dr. Kastrati is an inventor in a patent application related to drug-eluting stent technology; he also serves in the Data and Safety Monitoring Board of the TARGET IV trial sponsored by the Cardiovascular Research Foundation in New York, USA. Dr Mehta has received grant support from and has served on an executive committee and as site investigator for AstraZeneca. Dr Steg received research grant from Amarin, Bayer, Sanofi and Servier; speaking or consulting fees from Amarin, Amgen, AstraZeneca, Bayer/Janssen, Bristol Myers Squibb, Idorsia, Myokardia, Novartis, Novo Nordisk, PhaseBio, Pfizer, Regeneron, Sanofi, and Servier. Dr. Mehran reports institutional research payments from Abbott, Abiomed, Alleviant Medical, Amgen, AM-Pharma, Arena, AstraZeneca, Atricure, Bayer, Biosensors, Biotronik, Boston Scientific, Bristol-Myers Squibb, CardiaWave, CeloNova, Chiesi, Concept Medical, CSL Behring, Cytosorbents, Daiichi Sankyo, Element Science, Faraday, Humacyte, Idorsia Pharmaceuticals, Janssen, Medtronic, Novartis, OrbusNeich, PhaseBio, Philips, Pi-Cardia, PLx Pharma, RenalPro, RM Global, Shockwave, Vivasure, Zoll; personal fees from Cine-Med Research, Novartis, WebMD; Equity <1% in Applied Therapeutics, Elixir Medical, Stel, ControlRad (spouse); Scientific Advisory Board for AMA, ACC (BOT Member), SCAI (Women in Innovations Committee Member), JAMA Associate Editor; Faculty CRF (no fee). The remaining authors have nothing to disclose.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Methods: In the TWILIGHT trial, patients at high ischemic or bleeding risk that underwent PCI were randomized after 3 months of dual antiplatelet therapy (DAPT) to aspirin or matching placebo in addition to open-label ticagrelor for 12 additional months. In this post-hoc analysis, patient cohorts were examined according to the presence or absence of PAD. The primary endpoint was Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. The key secondary endpoint was a composite of all-cause death, myocardial infarction (MI), or stroke. Endpoints were assessed at 12 months after randomization.
Results: Among 7,119 patients, 489 (7%) had PAD and were older, more likely to have comorbidities, and multivessel disease. PAD patients had more bleeding or ischemic complications than no-PAD patients. Ticagrelor monotherapy compared to ticagrelor plus aspirin was associated with less BARC 2, 3, or 5 bleeding in PAD (4.6% vs 8.7%; HR 0.52; 95%CI 0.25-1.07) and no-PAD patients (4.0% vs 7.0%; HR 0.56; 95%CI 0.45-0.69; interaction P-value .830) and a similar risk of death, MI, or stroke in these 2 groups (interaction P-value .446).
Conclusions: Despite their higher ischemic and bleeding risk, patients with PAD undergoing PCI derived a consistent benefit from ticagrelor monotherapy after 3 months of DAPT in terms of bleeding reduction without any relevant increase in ischemic events. CLINICAL TRIAL REGISTRY INFORMATION:: https://www.
Clinicaltrials: gov/study/NCT02270242.
Competing Interests: Conflict of interest Dr Spirito received a research grant from the Swiss National Science Foundation (SNSF). Dr Baber has received honoraria from AstraZeneca and Boston Scientific. Dr. Angiolillo declares that he has received consulting fees or honoraria from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, Novartis, PhaseBio, PLx Pharma, Pfizer, Sanofi and Vectura; D.J.A. also declares that his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, and the Scott R. MacKenzie Foundation. Dr Cohen has received grant support, paid to his institution, and consulting fees from AstraZeneca, Medtronic, and Abbott Vascular; and has received grant support, paid to his institution, from Boston Scientific. Dr Dangas has received consulting fees and advisory board fees from AstraZeneca; has received consulting fees from Biosensors; and previously held stock in Medtronic. Dr Escaned has received consulting and lecture fees from Abbott, Philips, Boston Scientific, and Medtronic; and has received lecture fees from Abiomed, Terumo, and Biosensors. Dr. Gibson has received grant support and consulting fees from Angel Medical, Bayer, CSL Behring, Janssen. Pharmaceuticals, Johnson & Johnson, and Portola Pharmaceuticals; has received consulting 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, Boston Scientific, Impact Bio, MedImmume, Medtelligence, MicroPort, the PERT Consortium, and GE Healthcare; holds equity in Inference; serves as chief executive officer of the Baim Institute; and has received grant support, paid to the Baim Institute, from Bristol Myers Squibb and Astra Zeneca. Dr Huber has received lecture fees from AstraZeneca and Bayer. Dr. Kastrati is an inventor in a patent application related to drug-eluting stent technology; he also serves in the Data and Safety Monitoring Board of the TARGET IV trial sponsored by the Cardiovascular Research Foundation in New York, USA. Dr Mehta has received grant support from and has served on an executive committee and as site investigator for AstraZeneca. Dr Steg received research grant from Amarin, Bayer, Sanofi and Servier; speaking or consulting fees from Amarin, Amgen, AstraZeneca, Bayer/Janssen, Bristol Myers Squibb, Idorsia, Myokardia, Novartis, Novo Nordisk, PhaseBio, Pfizer, Regeneron, Sanofi, and Servier. Dr. Mehran reports institutional research payments from Abbott, Abiomed, Alleviant Medical, Amgen, AM-Pharma, Arena, AstraZeneca, Atricure, Bayer, Biosensors, Biotronik, Boston Scientific, Bristol-Myers Squibb, CardiaWave, CeloNova, Chiesi, Concept Medical, CSL Behring, Cytosorbents, Daiichi Sankyo, Element Science, Faraday, Humacyte, Idorsia Pharmaceuticals, Janssen, Medtronic, Novartis, OrbusNeich, PhaseBio, Philips, Pi-Cardia, PLx Pharma, RenalPro, RM Global, Shockwave, Vivasure, Zoll; personal fees from Cine-Med Research, Novartis, WebMD; Equity <1% in Applied Therapeutics, Elixir Medical, Stel, ControlRad (spouse); Scientific Advisory Board for AMA, ACC (BOT Member), SCAI (Women in Innovations Committee Member), JAMA Associate Editor; Faculty CRF (no fee). The remaining authors have nothing to disclose.
(Copyright © 2024 Elsevier Inc. All rights reserved.)