title: Incidence of recurrent thromboembolic and bleeding complications among patients with venous thromboembolism in relation to both malignancy and achieved international normalized ratio: a retrospective analysis.
abstract: OBJECTIVE
  Initial heparinization followed by vitamin K antagonists is the treatment of choice for patients with venous thromboembolism. There is controversy whether known malignancy is a risk factor for recurrences and bleeding complications during this treatment. Furthermore, the incidence of such events in these patients is dependent on the achieved International Normalized Ratio (INR). The aim of this study was to assess the incidence of venous thromboembolic recurrence and major bleeding among patients with venous thromboembolism in relation to both malignancy and the achieved INR.
  
  
  METHODS
  In a retrospective analysis, the INR-specific incidence of venous thromboembolic and major bleeding events during oral anticoagulant therapy was calculated separately for patients with and without malignancy. Eligible patients participated in two multicenter, randomized clinical trials on the initial treatment of venous thromboembolism. Patients were initially treated with heparin (standard or low-molecular weight). Treatment with vitamin K antagonists was started within 1 day and continued for 3 months, with a target INR of 2.0 to 3.0.
  
  
  RESULTS
  In 1,303 eligible patients (264 with malignancy), 35 recurrences and 12 bleeds occurred. Patients with malignancy, compared with nonmalignant patients, had a clinically and statistically significantly increased overall incidence of recurrence (27.1 v 9.0, respectively, per 100 patient-years) as well as bleeding (13.3 v 2.1, respectively, per 100 patient-years). In both groups of patients, the incidence of recurrence was lower when the INR was above 2.0 compared with below 2.0.
  
  
  CONCLUSIONS
  Although adequately dosed vitamin K antagonists are effective in patients with malignant disease, the incidence of thrombotic and bleeding complications remains higher than in patients without malignancy.
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, University of Amsterdam, the Netherlands. B.A.Hutten@amc.uva.nl
authors.forename: B A
authors.initials: BA
authors.lastname: Hutten
authors.forename: M H
authors.initials: MH
authors.lastname: Prins
authors.forename: M
authors.initials: M
authors.lastname: Gent
authors.forename: J
authors.initials: J
authors.lastname: Ginsberg
authors.forename: J G
authors.initials: JG
authors.lastname: Tijssen
authors.forename: H R
authors.initials: HR
authors.lastname: Büller
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology*; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D019934:International Normalized Ratio / Q000379:methods; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009369:Neoplasms / Q000150:complications*; D011655:Pulmonary Embolism / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D020246:Venous Thrombosis / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology; D014812:Vitamin K / Q000037:antagonists & inhibitors
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D014812:Vitamin K; D006493:Heparin