Association of Chronic Obstructive Pulmonary Disease with Morbidity and Mortality in Patients with Peripheral Artery Disease: Insights from the EUCLID Trial

Abstract

Jemi Galani,1 Hillary Mulder,2 Frank W Rockhold,2 E Hope Weissler,2,3 Iris Baumgartner,4 Jeffrey S Berger,5 Juuso I Blomster,6 F Gerry R Fowkes,7 William R Hiatt,8,9 Brian G Katona,10 Lars Norgren,11 Kenneth W Mahaffey,12 Jennifer K Quint,13 Manesh R Patel,1,2 W Schuyler Jones1,2 1Department of Medicine, Duke University Medical Center, Durham, NC, USA; 2Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA; 3Department of Surgery, Division of Vascular Surgery, Duke University Health System, Durham, NC, USA; 4Department of Medicine, Swiss Cardiovascular Center, University of Bern, Bern, Switzerland; 5Departments of Medicine and Surgery, New York University School of Medicine, New York, NY, USA; 6University of Turku, Turku, Finland; 7Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK; 8Division of Cardiology, University of Colorado School of Medicine, Aurora, CO, USA; 9CPC Clinical Research, Aurora, CO, USA; 10AstraZeneca, Gaithersburg, MD, USA; 11Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 12Stanford Center for Clinical Research, Stanford University School of Medicine, Stanford, CA, USA; 13Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College London, London, UKCorrespondence: W Schuyler JonesDuke University Medical Center, Box 3330, Durham, NC, 27710, USATel [phone]Fax [phone]Email [email protected]: Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of developing lower extremity peripheral artery disease (PAD) and suffering PAD-related morbidity and mortality. However, the effect and burden of COPD on patients with PAD is less well defined. This post hoc analysis from EUCLID aimed to analyze the risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with PAD and concomitant COPD compared with those without COPD, and to describe the adverse events specific to patients with COPD.Methods: EUCLID randomized 13,885 patients with symptomatic PAD to monotherapy with either ticagrelor or clopidogrel for the prevention of MACE. In this analysis, MACE, MALE, mortality, and adverse events were compared between groups with and without COPD using unadjusted and adjusted Cox proportional hazards model.Results: Of the 13,883 patients with COPD status available at baseline, 11% (n=1538) had COPD. Patients with COPD had a higher risk of MACE (6.02 vs 4.29 events/100 patient-years; p< 0.001) due to a significantly higher risk of myocardial infarction (MI) (3.55 vs 1.85 events/100 patient-years; p< 0.001) when compared with patients without COPD. These risks persisted after adjustment (MACE: adjusted hazard ratio (aHR) 1.30, 95% confidence interval [CI] 1.11– 1.52; p< 0.001; MI: aHR 1.45, 95% CI 1.18– 1.77; p< 0.001). However, patients with COPD did not have an increased risk of MALE or major bleeding. Patients with COPD were more frequently hospitalized for dyspnea and pneumonia (2.66 vs 0.9 events/100 patient-years; aHR 2.77, 95% CI 2.12– 3.63; p< 0.001) and more frequently discontinued study drug prematurely (19.36 vs 12.54 events/100 patient-years; p< 0.001; aHR 1.34, 95% CI 1.22– 1.47; p< 0.001).Conclusion: In patients with comorbid PAD and COPD, the risks of MACE, respiratory-related adverse events, and premature study drug discontinuation were higher when compared with patients without COPD.Registration: ClinicalTrials.gov: NCT01732822.Keywords: peripheral artery disease, chronic obstructive pulmonary disease, major adverse cardiovascular events

Keywords

• peripheral artery disease
• chronic obstructive pulmonary disease
• major adverse cardiovascular events