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

4 December 2007 | Volume 147 Issue 11 | Pages 766-774

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.

Editors' Notes Context The decision to discontinue anticoagulation for venous thromboembolism (VTE) should depend in part on the subsequent risk for a fatal recurrence. Previous studies have measured fatality rates in patients still receiving anticoagulant drugs. Contribution In a cohort from 2 source studies that had monitored 2052 patients for an average of 4.5 years after discontinuing anticoagulation for a first episode of VTE, the annual risk for any fatal pulmonary embolism (PE) was 0.43 events per 100 patient-years. The risk for definite or probable fatal recurrent PE was 0.17 events per 100 patient-years. Implication Although these rates seem low, decision makers must also take into account the rates of fatal PE recurrence and fatal hemorrhage if anticoagulant therapy is continued. —The Editors

 

Author and Article Information

From McMaster University, Hamilton, Ontario, Canada; Karolinska University Hospital, Stockholm, Sweden; Arcispedale Santa Maria Nuova, Reggio Emilia, Italy; and University of Padua, Padua, Italy.

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.