The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients

Abstract

While it has long been recognized that patients with acute unprovoked deep vein thrombosis (DVT) or pulmonary embolism (PE) have a higher risk of recurrent venous thromboembolism (VTE) than that of patients with secondary thrombosis, whether other clinical parameters can help predict the development of recurrent events is controversial. The aim of this investigation was to assess the rate of recurrent VTE after withdrawal of vitamin K antagonists, and to identify clinical parameters associated with a higher likelihood of recurrence. Design and MethodsWe followed, up to a maximum of 10 years, 1626 consecutive patients who had discontinued anticoagulation after a first episode of clinically symptomatic proximal DVT and/or PE. All patients with clinically suspected recurrent VTE underwent objective tests to confirm or rule out the clinical suspicion. ResultsAfter a median follow-up of 50 months, 373 patients (22.9%) had had recurrent episodes of VTE. The cumulative incidence of recurrent VTE was 11.0% (95% CI, 9.5-12.5) after 1 year, 19.6% (17.5-21.7) after 3 years, 29.1% (26.3-31.9) after 5 years, and 39.9% (35.4-44.4) after 10 years. The adjusted hazard ratio for recurrent VTE was 2.30 (95% CI, 1.82-2.90) in patients whose first VTE was unprovoked, 2.02 (1.52-2.69) in those with thrombophilia, 1.44 (1.03-2.03) in those presenting with primary DVT, 1.39 (1.08-1.80) for patients who received a shorter (up to 6 months) duration of anticoagulation, and 1.14 (1.06-1.12) for every 10-year increase of age. When the analysis was confined to patients with unprovoked VTE the results did not change. Interpretation and ConclusionsBesides unprovoked presentation, other factors independently associated with a statistically significant increased risk of recurrent VTE are thrombophilia, clinical presentation with primary DVT, shorter duration of anticoagulation, and increasing age. 1-6 While it is generally accepted that patients with thromboembolic events of unknown origin have a more than two-fold higher rate of recurrent VTE in comparison to patients whose thrombosis is associated with acquired, transient risk factors, 1-6 whether other of the patients' baseline features can help to identify those subjects who might benefit from prolonged anticoagulation is unclear. For example, it is virtually unknown whether aging, an important risk factor for VTE, 4 is also associated with an increased risk of recurrence. The role of thrombophilic abnormalities, especially those that are highly prevalent in western countries (i.e., factor V Leiden and prothrombin G20210A mutation), is controversial.5-14 Although recent data suggest that clinical presentation with primary PE 15 and male sex 16-18 increase the risk of recurrent VTE, these findings still await confirmation. Finally, whether the duration of anticoagulation following the initial thrombotic episode has any influence on the subsequent rate of recurrent VTE is uncertain. 2,19-22Here we report on the prospective long-term followup of a large series of patients with proximal DVT and...

Duration of Anticoagulation Therapy for Venous Thromboembolism

“…The annual risk of recurrent VTE after a first idiopathic VTE is about 10% during the first 2 years, and then about 3%, which gives a cumulative recurrence rate of 20% at 3 years and 40% at 5 years. 18 Recently, a case-fatality rate for VTE after treatment discontinuation of 8% (idiopathic DVT) to 12% (idiopathic PE) could be established by Douketis et al 22 in a pooled analysis of the DURAC I study 9 and an Italian study 18 in more than 2000 patients who were followed for several years. On the other hand, annual risks of major bleeding have been reported in 2% to 12% in controlled studies, 24 or even 29% 25 in the RIETE Registry with a case-fatality rate of 10% 26 to 33%.…”

“…Moreover, in this series, the recurrence rate was lower (5.5 per 100 patient-years, 95%CI: 3.7-7.8) than in the PROLONG study. In a similar attempt to better evaluate the risk of recurrence after a first DVT, Prandoni et al 18 showed that the presence of residual DVT is a risk factor for recurrent thromboembolism in patients with acute DVT. However, the exact instructions for use of either D-dimer or residual DVT remain to be established.…”

Cost-effectiveness of edoxaban compared to warfarin for the treatment and secondary prevention of venous thromboembolism in the UK

“…Whenever the model required data that could not be retrieved from the Hokusai-VTE trial, transition probabilities were derived from publications; these data included the probability of developing CTEPH [10] and PTS [11] after a VTE event, the probability of disability following ICH [12], some disease-specific mortality rates (due to a PE recurrence [13], the probability of dying when disabled from ICH [14], and short-term [15] and long-term mortality [16] from CTEPH), and the probability of developing rVTE while off treatment [17] (Table 2). The general mortality of the cohort depended on the gender distribution and mean age across the time horizon.…”

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“…Blacks also had a higher proportion of idiopathic DVT and idiopathic PE compared with Whites, who more often had secondary, provoked VTE. This finding is ominous for Blacks because after discontinuing anticoagulation, those with idiopathic VTE have a much higher rate of recurrent events than those with provoked VTE [10].…”