title: Subsequent arterial ischemic events in patients receiving anticoagulant therapy for venous thromboembolism.
abstract: OBJECTIVE
  Patients with acute venous thromboembolism (VTE) are at increased risk for the development of subsequent arterial ischemic events unrelated to the diagnosis of VTE. Accurate identification of VTE patients at increased risk for ischemic events during the course of anticoagulation may help to select those who would potentially benefit from concomitant therapy with anticoagulants and antiplatelets.
  
  
  METHODS
  We used the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) Registry to assess the rate and severity of subsequent ischemic events (ie, stroke, myocardial infarction, lower limb amputation, or mesenteric ischemia) appearing during the course of anticoagulant therapy and tried to identify risk factors for these events.
  
  
  RESULTS
  From February 2009 to March 2014, 23,370 patients were recruited: 12,397 initially presenting with pulmonary embolism (PE) and 10,973 with deep venous thrombosis. During the course of anticoagulation (mean, 9.2 months), 597 patients developed recurrent VTE, 652 bled, 162 had ischemic events (stroke, 86; myocardial infarction, 53; limb amputation, 13; mesenteric ischemia, 11), and 2063 died. Of these, 29 patients died of recurrent PE, 83 of bleeding, and 53 of the ischemic events. On multivariable analysis, cancer (hazard ratio [HR], 1.77; 95% confidence interval [CI], 1.21-2.61), chronic lung disease (HR, 1.54; 95% CI, 1.05-2.26), renal insufficiency (HR, 1.72; 95% CI, 1.25-2.36), anemia (HR, 1.54; 95% CI, 1.11-2.14), prior artery disease (HR, 1.84; 95% CI, 1.29-2.64), and diabetes (HR, 1.58; 95% CI, 1.10-2.27) independently predicted the risk for ischemic events. Most of these variables also predicted major bleeding (cancer, chronic lung disease, renal insufficiency, anemia, and prior artery disease) or recurrent PE (cancer, chronic lung disease, anemia, and prior artery disease).
  
  
  CONCLUSIONS
  In patients receiving anticoagulation for VTE, the mortality due to PE recurrences was lower than the mortality due to ischemic events. Most independent predictors for ischemic events were also predictors for major bleeding and for recurrent PE.
authors.affiliation: Department of Internal Medicine, Hospital Universitario Infanta Sofía, San Sebastián de los Reyes, Madrid, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Madridano
authors.affiliation: Department of Internal Medicine, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: del Toro
authors.affiliation: Department of Internal Medicine, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Lorenzo
authors.affiliation: Department of Internal Medicine, Hospital Universitario Infanta Sofía, San Sebastián de los Reyes, Madrid, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Martín
authors.affiliation: Department of Internal Medicine, Hospital Universitario Infanta Sofía, San Sebastián de los Reyes, Madrid, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Gómez Cerezo
authors.affiliation: Department of Pneumonology, Hospital General Universitario de Alicante, Alicante, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Hernández
authors.affiliation: Department of Cardiothoracic and Vascular Sciences, University of Padua, Padua, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Prandoni
authors.affiliation: Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain. Electronic address: mmonreal.germanstrias@gencat.cat.
authors.forename: Manuel
authors.initials: M
authors.lastname: Monreal
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D009203:Myocardial Infarction / Q000139:chemically induced*; D011655:Pulmonary Embolism / Q000150:complications / Q000188:drug therapy; D020521:Stroke / Q000139:chemically induced*; D054556:Venous Thromboembolism / Q000188:drug therapy*
chemical_list: D000925:Anticoagulants