Author + information
- Received August 19, 2019
- Revision received November 8, 2019
- Accepted November 26, 2019
- Published online February 10, 2020.
- Axel Haine, MDa,
- Sarah Kavanagh, MPHb,
- Jeffrey S. Berger, MD, MSc,
- Connie N. Hess, MD, MHSb,
- Lars Norgren, MD, PhDd,
- F. Gerry R. Fowkes, MDe,
- Brian G. Katona, PharmDf,
- Kenneth W. Mahaffey, MDg,
- Juuso I. Blomster, MDh,i,
- Manesh R. Patel, MDj,
- W. Schuyler Jones, MDj,
- Frank W. Rockhold, PhDj,
- William R. Hiatt, MDb,∗ (, )@WilliamHiatt18,
- Iris Baumgartner, MDa,
- on behalf of the International Steering Committee and Investigators of the EUCLID Trial
- aSwiss Cardiovascular Centre, Inselspital, Division of Angiology, Bern University Hospital, University of Bern, Bern, Switzerland
- bUniversity of Colorado School of Medicine and CPC Clinical Research, Aurora, Colorado
- cDepartments of Medicine and Surgery, New York University School of Medicine, New York, New York
- dFaculty of Medicine and Health, Örebro University, Örebro, Sweden
- eUsher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom
- fAstraZeneca Gaithersburg, Gaithersburg, Maryland
- gStanford Center for Clinical Research, Stanford University School of Medicine, Stanford, California
- hHeart Centre, Turku University Hospital, Turku, Finland
- iUniversity of Turku, Turku, Finland
- jDuke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
- ↵∗Address for correspondence:
Dr. William R. Hiatt, University of Colorado School of Medicine, Division of Cardiology and CPC Clinical Research, c/o CPC Clinical Research, 13199 E. Montview Boulevard, Suite 200, Aurora, Colorado 80045.
Background Patients with peripheral artery disease (PAD) have a higher risk of major adverse cardiovascular events (MACE) compared with those without PAD.
Objectives The aim of this post hoc analysis was to evaluate sex-specific differences in MACE and limb events in the EUCLID (Examining Use of Ticagrelor in PAD) trial.
Methods Cox proportional hazards models were used to compare time-to-event outcomes stratified by sex. Covariates were introduced after adjusted model selection.
Results EUCLID enrolled 13,885 patients with PAD (28% women [n = 3,888]). PAD severity and medical treatment were comparable between sexes, whereas prior lower extremity revascularization was reported less frequently in women (54.8% vs. 57.3%; p = 0.006). Women were older (mean ± SD age: 67.8 ± 8.9 vs. 66.1 ± 8.2 years; p < 0.001) and more likely to have diabetes mellitus (p = 0.004), hypertension, hyperlipidemia, and chronic kidney disease (all p < 0.001). Over a mean follow-up of 30 months, women had a lower risk of MACE (9.5% vs. 11.2%; adjusted hazard ratio: 0.77; 95% confidence interval: 0.68 to 0.88; p < 0.001) and all-cause-mortality (7.6% vs. 9.7%; adjusted hazard ratio: 0.61; 95% confidence interval: 0.53 to 0.71; p < 0.001). In contrast, risk for major adverse limb events (2.6% vs. 3.0%) and hospitalization for acute limb ischemia (1.6% vs. 1.7%) were not different by sex.
Conclusions Although women with PAD are at lower risk for MACE and all-cause mortality, risk for limb events was similar between sexes over a mean follow-up of 30 months. Understanding sex-specific differences and dissociation between baseline cardiovascular risk and subsequent cardiovascular events requires further investigation. (A Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease [EUCLID]; NCT01732822)
The EUCLID trial was funded by AstraZeneca. Ms. Kavanagh has received consulting fees from Karuna Pharmaceuticals, Tal Medical, ResTORbio, AveXis Pharmaceuticals, DiaMedica Therapeutics, Zosano Pharma, Pure Tech Health, and UCB Pharma. Dr. Berger has received institutional research grants from AstraZeneca, the National Heart, Lung, and Blood Institute, and American Heart Association; and has received consulting fees from Janssen, Merck, Takeda, and Amgen. Dr. Hess has received research grants to CPC Clinical Research from Amgen, Merck, and Bayer. Dr. Norgren has received research grants from AnGEs and Mitsubishi; has served on the steering committee for Pluristem and Bayer; has served as a consultant for AnGEs and Cesca; and has received consultation fees from Pluristem, AnGEs, and Bayer. Dr. Fowkes has been a member of advisory boards for AstraZeneca, Bayer, and Merck. Dr. Katona is an employee of AstraZeneca. Dr. Mahaffey has received research grants from Afferent, Amgen, Apple, AstraZeneca, Cardiva Medical, Daiichi-Sankyo, Ferring, Google (Verily), Johnson & Johnson, Luitpold, Medtronic, Merck, National Institutes of Health, Novartis, Sanofi, St. Jude, and Tenax; and has received consulting fees from Abbott, Ablynx, AstraZeneca, Baim Institute, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Medscape, Mitsubishi, Myokardia, National Institutes of Health, Novartis, Novo Nordisk, Portola, Radiometer, Regeneron, SmartMedics, Springer Publishing, and UCSF. Dr. Blomster has provided consultation for and had prior employment by AstraZeneca. Dr. Patel has received institutional research grants from and served on the advisory board for AstraZeneca, Bayer, CSL, HeartFlow, and Janssen Research. Dr. Jones has received an institutional research grant from AstraZeneca. Dr. Rockhold has served on the advisory board for Athira, Spencer Healthcare, and DataVant; has received research funding from the National Institutes of Health, PCORI, Duke Clinical Research Institute, Alzheimer’s Drug Discovery Foundation, AstraZeneca, Bristol-Myers Squibb, American Regent, ReNeuron, Eidos, Luitpold, and Janssen; has received consulting/honoraria from California Institute for Regenerative Medicine, PCORI, BARDA, Merck Serono, Janssen, ResTORbio, Eidos Therapeutics, Sarepta, Phathom, FuturaMedical, AbbVie, Amgen, Complexa, Novo Nordisk, Adverum Biotechnologies, AstraZeneca, Aldeyra, KLSMC, Tolerion, Rhythm, Apple, Merck Research Laboratories, and Chimerix; and holds equity interest in GlaxoSmithKline, DataVant, and M3 Biotechnology. Dr. Hiatt has received research grant support to CPC Clinical Research from Bayer, Janssen, AstraZeneca, and the National Institutes of Health. Dr. Baumgartner has received institutional research grants from Abbott Vascular, Cook, and Boston Scientific. Dr. Haine has reported that he has no relationships relevant to the contents of this paper to disclose.
- Received August 19, 2019.
- Revision received November 8, 2019.
- Accepted November 26, 2019.
- 2020 American College of Cardiology Foundation
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