IMPORTANCE: Prior studies have observed an association between the burden of atherosclerotic vascular disease and the risk of venous thromboembolism (VTE). The association is not well described in peripheral artery disease (PAD) after lower extremity revascularization (LER). OBJECTIVE: To describe the risk of, factors associated with, and outcomes after VTE, as well as the association of low-dose rivaroxaban plus antiplatelet therapy with VTE after LER. DESIGN, SETTING, AND PARTICIPANTS: This global, multicenter cohort study used data from the Vascular Outcomes Study of ASA (acetylsalicylic acid) Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD (VOYAGER PAD) randomized clinical trial, which enrolled patients from 2015 to 2018 with median follow-up of 28 months. Participants included patients with PAD undergoing LER. Patients with an indication for therapeutic anticoagulation were excluded. Data were analyzed from September 2020 to September 2021. EXPOSURE: Randomization to rivaroxaban 2.5 mg twice daily or placebo on a background of aspirin 100 mg daily; short-term clopidogrel was used at the discretion of the treating physician. MAIN OUTCOMES AND MEASURES: Symptomatic VTE was a prespecified secondary outcome and prospectively collected. RESULTS: Among 6564 patients (median [IQR] age, 67 [61-73] years; 4860 [74.0%] men), 66 patients had at least 1 VTE. The 3-year rate of VTE in patients receiving placebo was 1.7%, and the pattern of risk was linear (year 1: 0.5%; year 2: 1.1%). After multivariable modeling, weight (hazard ratio [HR], 3.04; 95% CI, 1.09-8.43), hypertension (HR, 2.11; 95% CI, 0.91-4.89), prior amputation (HR, 2.07; 95% CI, 0.95-4.53), and older age (HR, 1.81; 95% CI, 1.06-3.11) were associated with increased risk of VTE. VTE was associated with risk of subsequent mortality (HR, 7.22; 95% CI, 4.66-11.19). Compared with aspirin alone, rivaroxaban plus aspirin was associated with lower VTE risk (HR, 0.61; 95% CI, 0.37-0.998; P = .047), with benefit apparent early and sustained over time. This association was not modified by use of clopidogrel at randomization (without clopidogrel: HR, 0.55; 95% CI, 0.29-1.07; with clopidogrel: HR, 0.69; 95% CI, 0.32-1.48; P for interaction = .67). CONCLUSIONS AND RELEVANCE: In this cohort study, there was continuous risk for VTE after LER in patients with PAD, with greater risk in patients who were older and had obesity and those with more severe PAD, as reflected by prior amputation. Low-dose rivaroxaban plus aspirin was associated with lower VTE risk compared with aspirin alone, with benefits apparent early and continued over time. The spectrum of venous and arterial thrombotic events and overall benefits of more potent antithrombotic strategies for prevention should be considered after LER for PAD.

Bayer Research and Development Wuppertal Germany

Cardiovascular Division Vanderbilt University Medical Center Nashville Tennessee

CPC Clinical Research Aurora Colorado

Department of Transplantational Surgery Institute of Clinical and Experimental Medicine Prague Czech Republic

Department of Vascular Medicine Klinikum Darmstadt Darmstadt and Center for Thrombosis and Hemostasis University of Mainz Mainz Germany

Department of Vascular Medicine Vascular Surgery Angiology Endovascular Therapy University of Hamburg Eppendorf Hamburg Germany

Division of Cardiology Department of Medicine University of Colorado School of Medicine Aurora

Division of Cardiovascular Medicine Brigham and Women's Hospital Harvard Medical School Boston Massachusetts

Division of Endocrinology Department of Medicine University of Colorado Anschutz Medical Campus Aurora

Division of Hematology Department of Medicine University of Colorado School of Medicine Aurora

Duke Clinical Research Institute Division of Cardiology Duke University Medical Center Durham North Carolina

Heart and Vascular Center Dartmouth Hitchcock Medical Center Lebanon New Hampshire

Janssen Research and Development Raritan New Jersey

Population Health Research Institute Hamilton Health Sciences McMaster University Hamilton Canada

Praxis für Herzkreislaufkrankheiten und Akademie für Gefäßkrankheiten Ettlingen Germany

The State University of New York Downstate Health Sciences University Brooklyn

Toulouse University Hospital Toulouse France

University of Colorado School of Medicine Department of Surgery Aurora

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