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Evidence summaries

Fatal Pulmonary Embolism after Discontinuing Anticoagulant Therapy for First Episode of Venous Thromboembolism Vs Fatal Bleeding during Continued Anticoagulation

In patients who discontinue anticoagulant therapy after a first episode of venous thromboembolism (VTE), the risk of fatal pulmonary embolism may be under 1 per 100 person-years, and slightly larger for fatal PE than for fatal bleeding. The risk of fatal pulmonary embolism increases with age and if the initial VTE is idiopathic. Level of evidence: "C"

An inception cohort of patients (n=2052) 1 who completed at least 3 (mean 6) months of anticoagulant therapy after a first episode of symptomatic VTE was followed-up (mean follow-up 54 months, range 1 to 120 months). The inception cohort included 1623 patients from a cohort study and 424 patients from a randomized trial (mean age 62 years). Patients with active cancer, permanent immobility, or high-risk thrombophilia were excluded. The annual risk for any fatal pulmonary embolism (PE), after discontinuation of anticoagulation, was 0.49 events (95% CI 0.36 to 0.64 events) per 100 person-years and definite or probable fatal PE 0.19 events (CI 0.12 to 0.30 events) per 100 person-years. During the first year after anticoagulant therapy was discontinued, the incidence of any fatal PE and definite or probable fatal PE was 0.81% and 0.35%, respectively. After the first year, the annual risk for any fatal PE and definite or probable fatal PE was 0.40 and 0.15 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. In the regression analysis, increasing age (HR 2.12, 95% CI 1.58 to 2.81) and idiopathic VTE (HR 2.42, 95% CI 1.20 to 4.90) were associated with an increased risk for any fatal PE. Disease presentation (DVT or PE) did not affect the risk for fatal PE.

In a prospective cohort 2 of 2745 anticoagulated patients (main indication for treatment was venous thrombolism, 33%, followed by non-ischaemic heart disease, 17%) 153 bleeding complications occurred (7.6 per 100 patient-years) of which 5 were fatal (all cerebral haemorrhages, 0.25 per 100 patient-years). The risk of bleeding was higher in older patients.

A meta-analysis 3 included 33 studies with a total of 4 374 subjects with venous thromboembolism receiving oral anticoagulant therapy (target international normalized ratio, 2.0 to 3.0) for at least 3 months. For patients who received anticoagulant therapy for more than 3 months, the rate of intracranial bleeding was 0.65 per 100 patient-years (CI 0.63 to 0.68 per 100 patient-years) after the initial 3 months of anticoagulation.

    References

    • Douketis JD, Gu CS, Schulman S, Ghirarduzzi A, Pengo V, Prandoni P. The risk for fatal pulmonary embolism after discontinuing anticoagulant therapy for venous thromboembolism. Ann Intern Med 2007 Dec 4;147(11):766-74. [PubMed]
    • Palareti G, Leali N, Coccheri S, Poggi M, Manotti C, D'Angelo A, Pengo V, Erba N, Moia M, Ciavarella N, Devoto G, Berrettini M, Musolesi S. Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT). Italian Study on Complications of Oral Anticoagulant Therapy. Lancet 1996 Aug 17;348(9025):423-8. [PubMed]
    • Linkins LA, Choi PT, Douketis JD. Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. Ann Intern Med 2003 Dec 2;139(11):893-900. [PubMed]

Primary/Secondary Keywords