ArticlesEffect of patient's sex on risk of recurrent venous thromboembolism: a meta-analysis
Introduction
Venous thromboembolism, consisting of deep-vein thrombosis and pulmonary embolism, is a potentially fatal disorder with an estimated annual incidence of 0·1% in white populations.1 After stopping anticoagulant treatment, individuals who have had a first episode of venous thromboembolism are at long-term increased risk of further events. In two prospective cohort studies of consecutive patients with deep-vein thrombosis who stopped taking anticoagulants after a minimum of 3 months of treatment, the cumulative incidence of recurrent venous thromboembolism was approximately 25% after 5 years.2, 3 About 5% of recurrent episodes are fatal,4 recurrent deep-vein thrombosis substantially increases the risk of the post-thrombotic syndrome,5 and recurrent pulmonary embolism predisposes to chronic pulmonary hypertension.6
Oral anticoagulant treatment with a vitamin K antagonist is highly effective at preventing recurrent venous thromboembolism.7, 8, 9 However, oral anticoagulant treatment is associated with an increased risk of bleeding, which can be fatal10 and is inconvenient. The decision to continue treatment is affected by the balance between the heightened risk of recurrent venous thromboembolism if treatment is stopped and the raised risk of bleeding if treatment is continued. Identification of risk factors for recurrent venous thromboembolism in individual patients can help to identify those who will benefit from long-term anticoagulation. The presence of a temporary risk factor, such as recent surgery, is associated with a lower risk of recurrence than is unprovoked thrombosis or a continuing risk factor.8, 11, 12, 13, 14, 15 Patients with proximal deep-vein thrombosis or pulmonary embolism have a two-fold increase in recurrence compared with patients with isolated distal deep-vein thrombosis,12 as do individuals with more than one previous thrombotic episode compared with those with only a single event.16, 17 Malignancy increases the risk of recurrence by about three-fold,2, 16, 18 as does the presence of antiphospholipid antibodies.12
Two studies suggested that after stopping anticoagulant treatment men have a significantly higher risk of recurrent venous thromboembolism than do women,19, 20 whereas analysis of data from two randomised trials did not show such an association.21 To establish if there is a higher risk of recurrent venous thromboembolism in men than in women we did a meta-analysis of all relevant available evidence. A secondary objective of this analysis was to look for potential explanations for any observed difference in risk between men and women.
Section snippets
Methods
We prospectively developed a protocol that defined specific objectives, the strategy for study identification, criteria for study selection, methods to be used for assessing study quality, how data would be extracted, study outcomes, and statistical methodology.
Results
Using the predefined search strategy we identified 1733 potentially eligible articles (figure 1). 15 studies were eligible for inclusion in the meta-analysis.7, 8, 12, 13, 17, 19, 20, 21, 24, 25, 26, 27, 28, 29, 30 Initial agreement between the two reviewers on whether a study was eligible for inclusion occurred in 84/89 manuscripts (94%; κ=0·88); initial disagreement was resolved by discussion in the other five studies (three were included8, 24, 25 and two were excluded3, 31). Details of the
Discussion
Our analysis showed that men have about a 50% higher risk than women of recurrent thrombosis and that this increase is consistent across different subgroups of patients with venous thromboembolism. The cause of this heightened risk in male patients is unclear. The lower risk of recurrent venous thromboembolism in women has been suggested to be associated with a higher prevalence in women than in men of distal deep-vein thrombosis, which is associated with a lower risk of recurrent venous
References (34)
- et al.
The post-thrombotic syndrome: current knowledge, controversies, and directions for future research
Blood Rev
(2002) - et al.
Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study
Lancet
(2003) - et al.
Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis
Blood
(2002) - et al.
High risk of recurrent venous thromboembolism in men
J Thromb Haemost
(2004) - et al.
Meta-analysis in clinical trials
Control Clin Trials
(1986) - et al.
A prospective controlled study of the efficacy of short-term anticoagulation therapy in patients with deep vein thrombosis of the lower extremity
J Vasc Surg
(1998) - et al.
Comparison of 1 month with 3 months of anticoagulation for a first episode of venous thromboembolism associated with a transient risk factor
J Thromb Haemost
(2004) - et al.
Need for long-term anticoagulant treatment in symptomatic calf-vein thrombosis
Lancet
(1985) - et al.
Poor anticoagulation quality in the first 3 months after unprovoked venous thromboembolism is a risk factor for long-term recurrence
J Thromb Haemost
(2005) The epidemiology of venous thromboembolism
Circulation
(2003)