Author + information
- Received October 24, 2017
- Revision received July 12, 2018
- Accepted July 23, 2018
- Published online September 24, 2018.
- Iris Baumgartner, MDa,
- Lars Norgren, MD, PhDb,
- F. Gerry R. Fowkes, MDc,
- Hillary Mulder, MSd,
- Manesh R. Patel, MDd,
- Jeffrey S. Berger, MDe,
- W. Schuyler Jones, MDd,
- Frank W. Rockhold, PhDd,
- Brian G. Katona, PharmDf,
- Kenneth Mahaffey, MDg,
- William R. Hiatt, MDh,∗ (, )@CUMedicalSchool@TheMahaf,
- on behalf of the Executive Committee and Investigators of the EUCLID Trial
- aSwiss Cardiovascular Centre, Inselspital, Division of Angiology, Bern University Hospital, University of Bern, Bern, Switzerland
- bFaculty of Medicine and Health, Örebro University, Örebro, Sweden
- cUsher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom
- dDuke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
- eDepartments of Medicine and Surgery, New York University School of Medicine, New York, New York
- fAstraZeneca Gaithersburg, Gaithersburg, Maryland
- gStanford Center for Clinical Research, Stanford University, School of Medicine, Stanford, California
- hDivision of Cardiology and CPC Clinical Research, University of Colorado School of Medicine, Aurora, Colorado
- ↵∗Address for correspondence:
Dr. William R. Hiatt, University of Colorado School of Medicine, Division of Cardiology and CPC Clinical Research, Aurora, Colorado 80045.
Background Lower extremity revascularization (LER) is a common treatment in patients with peripheral artery disease (PAD), but long-term outcomes are poorly defined.
Objectives The aim was to analyze LER in the EUCLID (Examining Use of tiCagreLor In paD) trial to determine predictors and cardiovascular outcomes.
Methods Patients were grouped according to whether they received a post-randomization LER (n = 1,738) or not (n = 12,147). All variables were assessed for significance in univariable and parsimonious multivariable models. The primary endpoint was myocardial infarction, ischemic stroke, or cardiovascular death; major adverse limb events (MALE) included acute limb ischemia or major amputation.
Results A post-randomization LER occurred in 12.5% of patients and was an endovascular LER in 74.7%. Endovascular LERs were performed more often in North America, whereas surgical procedures occurred more frequently in Europe. Independent factors predicting LER were prior and type of prior LER, geographic region, limb symptoms, diabetes, and smoking. A post-randomization LER was associated with an increased risk for the primary endpoint (hazard ratio: 1.60; 95% confidence interval: 1.35 to 1.90; p < 0.0001) and MALE (hazard ratio: 12.0; 95% confidence interval: 9.47 to 15.30; p < 0.0001). Event rates for the primary endpoint after LER were numerically higher in the surgical subgroup, but MALE were similar between surgical and endovascular LER.
Conclusions In the EUCLID trial, LER was most often endovascular. Following LER, there was an increased hazard for the primary endpoint (with higher event rates in the surgical group) and a markedly increased risk for MALE events (with similar event rates between surgical and endovascular LER procedures). (A Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease [EUCLID]; NCT01732822)
- acute limb ischemia
- cardiovascular event
- lower extremity revascularization
- peripheral artery disease
The EUCLID trial was funded by AstraZeneca. Dr. Baumgartner has received research grants from Abbott Vascular, Cook, Terumo, Amgen, and Boston Scientific; and has received consulting fees from AstraZeneca, Bayer, and Amgen. Dr. Norgren has received research grants from AnGes and Mitsubishi; and has received consulting fees from AstraZeneca, Bayer, AnGes, Pluristem, CESCA Therapeutics, and Mitsubishi. Dr. Fowkes has served on advisory boards for AstraZeneca, Bayer, and Merck. Dr. Patel has received institutional research grants from AstraZeneca, Bayer, CSL Behring, HeartFlow, and Janssen Research; and has served as a consultant/advisory board member for Bayer and Janssen. Dr. Berger has received institutional research grants from AstraZeneca, the National Heart, Lung, and Blood Institute, and the American Heart Association; and has received consulting fees from Janssen, Merck, and Takeda. Dr. Jones has received an institutional research grant from AstraZeneca; and has served as a consultant for Bayer, Janssen Pharmaceuticals, and Bristol-Myers Squibb. Dr. Rockhold has served as a consultant for GlaxoSmithKline, Merck Serono, UCB, and Abbvie; and has equity interest in GlaxoSmithKline. Dr. Katona is an employee of AstraZeneca. Dr. Mahaffey has received research grants from Afferent, Amgen, Apple, Inc., AstraZeneca, Cardiva Medical, Inc., Daiichi, Ferring, Google (Verily), Johnson & Johnson, Luitpold, Medtronic, Merck, Novartis, Sanofi, St. Jude, and Tenax; has served as a consultant for or provided other services to Ablynx, AstraZeneca, Baim Institute, Boehringer Ingelheim, Bristol-Myers Squibb, Cardiometabolic Health Congress, Elsevier, GlaxoSmithKline, Johnson & Johnson, Medergy, Medscape, Merck, Mitsubishi, Myokardia, Novartis, Oculeve, Portola, Radiometer, Springer Publishing, Theravance, University of California at San Francisco, and WebMD; and has equity in BioPrint Fitness. Dr. Hiatt has received research grant support through CPC Clinical Research from Bayer, Janssen, AstraZeneca, and the National Institutes of Health. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received October 24, 2017.
- Revision received July 12, 2018.
- Accepted July 23, 2018.
- 2018 American College of Cardiology Foundation
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