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

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

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