The Risk for Fatal Pulmonary Embolism after Discontinuing Anticoagulant Therapy for Venous Thromboembolism

  1. James D. Douketis, MD;
  2. Chu Shu Gu, MSc;
  3. Sam Schulman, MD, PhD;
  4. Angelo Ghirarduzzi, MD;
  5. Vittorio Pengo, MD; and
  6. Paolo Prandoni, MD, PhD
  1. From McMaster University, Hamilton, Ontario, Canada; Karolinska University Hospital, Stockholm, Sweden; Arcispedale Santa Maria Nuova, Reggio Emilia, Italy; and University of Padua, Padua, Italy.

    Abstract

    Background: The long-term risk for fatal pulmonary embolism (PE) after treatment of venous thromboembolism (VTE) may be an important factor in the decision to discontinue this treatment.

    Objective: To provide reliable and precise estimates of the annual risk for fatal PE and the case-fatality rate of disease recurrence and to assess these outcomes according to the initial presentation of VTE (deep venous thrombosis [DVT], PE, or both) and its etiology (secondary or idiopathic) in patients who have discontinued anticoagulant therapy.

    Design: Prospective cohort study.

    Setting: Academic medical centers.

    Patients: Inception cohort of patients with a first episode of symptomatic VTE who discontinued anticoagulant therapy.

    Measurements: Incidence rates of any fatal PE (which included sudden death from possible fatal PE) and definite or probable PE per 100 person-years of follow-up and case-fatality rate of recurrent VTE.

    Results: Of 2052 patients studied, 1450 had DVT, 310 had PE, and 292 had DVT and PE. The mean duration of previous anticoagulant therapy was 6 months (range, 3 to 39 months), and the mean duration of follow-up after discontinuation of treatment was 54 months (range, 1 to 120 months). The annual risk for any fatal PE and definite or probable fatal PE after discontinuation of anticoagulation was 0.49 events (95% CI, 0.36 to 0.64 events) per 100 person-years and 0.19 events (CI, 0.12 to 0.30 events) per 100 person-years, respectively. The case-fatality rate of recurrent disease was 9.0% (CI, 6.8% to 11.8%) for any fatal PE and 3.8% (CI, 2.4% to 5.9%) for definite or probable fatal PE.

    Limitation: The findings are less pertinent to patients with active cancer, permanent immobility, or high-risk thrombophilia.

    Conclusion: The risk for fatal PE is 0.19 to 0.49 events per 100 person-years for patients who have finished a course of anticoagulant therapy for a first episode of symptomatic VTE. The case-fatality rate for death from recurrent PE is 4% to 9%. This information helps to inform patient prognosis and may assist clinicians in deciding whether to discontinue anticoagulant therapy for VTE.

    Article and Author Information

    • Acknowledgment: The authors thank Drs. Jeffrey S. Ginsberg, Frederick A. Spencer, and Richard H. White for their helpful reviews of this manuscript.

    • Potential Financial Conflicts of Interest: None disclosed.

    • Requests for Single Reprints: James D. Douketis, MD, St. Joseph's Healthcare, Room F-544, 50 Charlton Avenue East, Hamilton, Ontario, Canada, L8N 4A6; e-mail, jdouket{at}mcmaster.ca.

    • Current Author Addresses: Dr. Douketis: St. Joseph's Healthcare, Room F-544, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada.

    • Mr. Gu: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario L8V 1C3, Canada.

    • Dr. Schulman: Department of Hematology, Karolinska University Hospital, Stockholm, Sweden.

    • Dr. Ghirarduzzi: Department of Internal Medicine, Angiology Unit, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.

    • Dr. Pengo: Department of Cardiothoracic and Vascular Sciences, University of Padua, Padua, Italy.

    • Dr. Prandoni: Department of Medical and Surgical Sciences, Thromboembolism Unit, University of Padua, Padua, Italy.

    • Author Contributions: Conception and design: J.D. Douketis, S. Schulman, P. Prandoni.

    • Analysis and interpretation of the data: J.D. Douketis, C.S. Gu, S. Schulman, A. Ghirarduzzi, V. Pengo, P. Prandoni.

    • Drafting of the article: J.D. Douketis, C.S. Gu.

    • Critical revision of the article for important intellectual content: J.D. Douketis, S. Schulman, P. Prandoni.

    • Final approval of the article: J.D. Douketis, C.S. Gu, S. Schulman, A. Ghirarduzzi, V. Pengo, P. Prandoni.

    • Provision of study materials or patients: S. Schulman, A. Ghirarduzzi, V. Pengo, P. Prandoni.

    • Statistical expertise: C.S. Gu.

    • Collection and assembly of data: S. Schulman, A. Ghirarduzzi, V. Pengo, P. Prandoni.

    Summary for Patients

    • Summaries for Patients:Risk for Fatal Pulmonary Embolism after Discontinuing Anticoagulation Ann Intern Med December 4, 2007 147:I-38
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    1. Ann Intern Med December 4, 2007 vol. 147 no. 11 766-774
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