Major Adverse Limb Events and Mortality in Patients With Peripheral Artery Disease

ISS Fro Ha Ha He pa ve of pa AG Eth Eik Yu BACKGROUND Patients with lower extremity peripheral artery disease (PAD) are at increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). There is limited information on the prognosis of patients who experience MALE. OBJECTIVES Among participants with lower extremity PAD, this study investigated: 1) if hospitalizations, MACE, amputations, and deaths are higher after the first episode of MALE compared with patients with PAD who do not experience MALE; and 2) the impact of treatment with low-dose rivaroxaban and aspirin compared with aspirin alone on the incidence of MALE, peripheral vascular interventions, and all peripheral vascular outcomes over a median follow-up of 21 months. METHODS We analyzed outcomes in 6,391 patients with lower extremity PAD who were enrolled in the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial. COMPASS was a randomized, double-blind placebo-controlled study of low-dose rivaroxaban and aspirin combination or rivaroxaban alone compared with aspirin alone. MALE was defined as severe limb ischemia leading to an intervention or major vascular amputation. RESULTS A total of 128 patients experienced an incident of MALE. After MALE, the 1-year cumulative risk of a subsequent hospitalization was 61.5%; for vascular amputations, it was 20.5%; for death, it was 8.3%; and for MACE, it was 3.7%. The MALE index event significantly increased the risk of experiencing subsequent hospitalizations (hazard ratio [HR]: 7.21; p < 0.0001), subsequent amputations (HR: 197.5; p < 0.0001), and death (HR: 3.23; p < 0.001). Compared with aspirin alone, the combination of rivaroxaban 2.5 mg twice daily and aspirin lowered the incidence of MALE by 43% (p 1⁄4 0.01), total vascular amputations by 58% (p 1⁄4 0.01), peripheral vascular interventions by 24% (p 1⁄4 0.03), and all peripheral vascular outcomes by 24% (p 1⁄4 0.02). CONCLUSIONS Among individuals with lower extremity PAD, the development of MALE is associated with a poor prognosis, making prevention of this condition of utmost importance. The combination of rivaroxaban 2.5 mg twice daily and aspirin significantly lowered the incidence of MALE and the related complications, and this combination should be considered as an important therapy for patients with PAD. (Cardiovascular Outcomes for People Using Anticoagulation Strategies [COMPASS]; NCT01776424) (J Am Coll Cardiol 2018;71:2306–15) © 2018 by the American College of Cardiology Foundation. N 0735-1097/$36.00 https://doi.org/10.1016/j.jacc. 2018.03. 008 m the Department of Medicine, Population Health Research Institute, McMaster University, Hamilton Health Sciences, milton, Ontario, Canada; CISSS du Bas-St-Laurent, Quebec, Canada; School of Rehabilitation Science, McMaster University, milton Health Sciences, Hamilton, Ontario, Canada; Population Health Research Institute, McMaster University, Hamilton alth Sciences, Hamilton, Ontario, Canada; Department of Cardiology, Dupuytren University Hospital, Limoges, France; Dertment of Medicine, University of Philippines/Philippine Heart Centre, Manila, Philippines; Department of Medicine, Unirsity of Washington, Seattle, Washington; Department of Medicine, Semmelweis University, Budapest, Hungary; Department Medicine, Brigham and Women’s Hospital Heart and Vascular Center, Harvard Medical School, Boston, Massachusetts; Dertment of Medicine, University of Leuven, Leuven, Belgium; University of Edinburgh, Edinburgh, United Kingdom; and Bayer , Wuppertal, Germany. This study was funded by Bayer AG. Dr. Anand is supported by a Tier 1 Canada Research Chair in nicity and Cardiovascular Disease and the Michael G. DeGroote Heart and Stroke Foundation Chair in Population Health. Dr. elboom is supported by the Jack Hirsh Population Health Research Institute Chair in Thrombosis Research. Dr. suf is supported by the Heart & Stroke Foundation/Marion W. Burke Chair in Cardiovascular Disease. Dr. Anand has received AB BR E V I A T I O N S