- •Data on long-term venous thromboembolism (VTE) recurrence risk according to gender in patients < 50 years are conflicting. Men are thought to have a greater risk of recurrent VTE than women, but risk factors at first venous thromboembolic event, and particularly hormonal exposure, have to be carefully considered because they may act as potential confounders.
- •In this cohort of 875 patients (315 men and 560 women), the risk of recurrent VTE was three-fold higher in men than in women in univariable analysis (annual incidence rates of recurrent VTE of 4.8% versus 1.8%-person-years, P<0.001).
- •However, in multivariable analysis, this difference was not found to be associated to gender itself, but to circumstances of the index thromboembolic event.
- •Women with a first episode of hormone-related VTE have a very low risk of recurrence (<2% per year), whatever the duration of hormonal exposure at the time of index event.
Abstract
Background
Data on long-term venous thromboembolism (VTE) recurrence risk according to gender
are conflicting.
Objective
To evaluate long-term VTE recurrence risk after a first VTE in men and women under
50 years old.
Methods
Since May 2000, 875 consecutive patients (315 men, 560 women) with a first symptomatic
VTE under 50 years old were enrolled in a French prospective multicentre cohort study
and were followed up as long as possible. The primary outcome was symptomatic recurrent
VTE during follow-up.
Results
At baseline, men were older and had more comorbidities than women. First VTE was mainly
unprovoked in men (80.6%) and hormone-related in women (84.3%). During a median follow-up
of 7.0 years (inter-quartile range, 5.0–11.0), recurrent VTE occurred in 97 men (30.8%)
and in 72 women (12.9%) (annual incidence rates of recurrent VTE of 4.8% versus 1.8%-person-years, P<0.001). However, there was no difference according to gender in subgroups of patients
with a first unprovoked VTE (5.8% versus 3.8%-person-years, P = 0.09). In women, duration of hormonal treatment before first VTE did not influence
recurrence risk. In multivariable analysis, unprovoked VTE and family history of VTE
were independently associated with recurrence (hazard ratio of 2.50 (95% confidence
interval, 1.61 to 3.85) and 1.52 (1.11 to 2.09) respectively).
Limitations
Number of women with unprovoked VTE was low.
Conclusions
In patients with a first VTE under 50 years old, a first unprovoked episode and a
family history of VTE, but not gender, were associated with a high risk of long-term
recurrence.
Keywords
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References
- ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS).Eur Heart J. 2020; 41: 543-603
- Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report.Chest. 2016; 149: 315-352
- Optimum duration of anticoagulation for deep-vein thrombosis and pulmonary embolism.Lancet. 1992; 340 (Research Committee of the British Thoracic Society): 873-876
- Optimal duration of oral anticoagulant therapy: a randomized trial comparing four weeks with three months of warfarin in patients with proximal deep vein thrombosis.Thromb Haemost. 1995; 74: 606-611
- A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. Duration of anticoagulation trial study group.N Engl J Med. 1995; 332: 1661-1665
- Six months vs extended oral anticoagulation after a first episode of pulmonary embolism: the PADIS-PE randomized clinical trial.JAMA. 2015; 314: 31-40
- Six months versus two years of oral anticoagulation after a first episode of unprovoked deep-vein thrombosis. The PADIS-DVT randomized clinical trial.Haematologica. 2019; 104: 1493-1501
- Sex-specific risk factors for recurrent venous thromboembolism.Thromb Res. 2012; 130: 16-20
- Long-term prospective study of recurrent venous thromboembolism in patients younger than 50 years.Pathophysiol Haemost Thromb. 2005; 34: 6-12
- A lower risk of recurrent venous thrombosis in women compared with men is explained by sex-specific risk factors at time of first venous thrombosis in thrombophilic families.Blood. 2009; 114: 2031-2036
- Effect of patient's sex on risk of recurrent venous thromboembolism: a meta-analysis.Lancet. 2006; 368: 371-378
- The risk of recurrent venous thromboembolism in men and women.N Engl J Med. 2004; 350: 2558-2563
- The long-term recurrence risk of patients with unprovoked venous thromboembolism: an observational cohort study.J Thromb Haemost. 2016; 14: 2402-2409
- Sex, age and normal post-anticoagulation d-dimer as risk factors for recurrence after idiopathic venous thromboembolism in the Prolong study extension.J Thromb Haemost. 2010; 8: 1933-1942
- High risk of recurrent venous thromboembolism in men.J Thromb Haemost. 2004; 2: 2152-2155
- Sex difference in risk of recurrent venous thrombosis and the risk profile for a second event.J Thromb Haemost. 2010; 8: 2159-2168
- Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study.Arch Intern Med. 2000; 160: 761-768
- Hormonal factors and risk of recurrent venous thrombosis: the prevention of recurrent venous thromboembolism trial.J Thromb Haemost. 2006; 4: 2199-2203
- Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: multinational prospective cohort management study.BMJ. 2017; 356: j1065
- A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT study.Arch Intern Med. 1991; 151: 933-938
- 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.Haematologica. 2007; 92: 199-205
- Mortality and recurrence after treatment of VTE: long term follow-up of patients with good life-expectancy.Thromb Res. 2011; 127: 540-546
- Recurrent venous thromboembolism after deep vein thrombosis: incidence and risk factors.Arch Intern Med. 2000; 160: 769-774
- Risk factors for recurrent venous thromboembolism after unprovoked pulmonary embolism: the PADIS-PE randomised trial.Eur Respir J. 2018; 511701202
- Risk of recurrent venous thromboembolism in COPD patients: results from a prospective cohort study.Eur Respir J. 2017; 501700094
- Antipsychotic drugs and the risk of recurrent venous thromboembolism: a prospective cohort study.Eur J Intern Med. 2018; 52: 22-27
- Body mass index, a major confounder to insulin resistance association with unprovoked venous thromboembolism. Results from the EDITH case-control study.Thromb Haemost. 2013; 110: 593-597
- Factors that predict risk of thrombosis in relatives of patients with unprovoked venous thromboembolism.Chest. 2009; 136: 1537-1545
- Factors that predict thrombosis in relatives of patients with venous thromboembolism.Blood. 2014; 124: 2124-2130
- Personalized thromboprophylaxis using a risk score for the management of pregnancies with high risk of thrombosis: a prospective clinical study.J Thromb Haemost. 2017; 15: 897-906
- Recurrent venous thromboembolism after pregnancy-associated versus unprovoked thromboembolism.Thromb Haemost. 2008; 100: 246-252
- Family history for venous thromboembolism and the risk for recurrence.Am J Med. 2006; 119: 50-53
- Family history of venous thromboembolism (VTE) as a predictor for recurrent VTE in unprovoked VTE patients.J Thromb Haemost. 2013; 11: 200-203
- Role of family history of venous thromboembolism and thrombophilia as predictors of recurrence: a prospective follow-up study.J Thromb Haemost. 2015; 13: 2180-2186
- VTE, thrombophilia, antithrombotic therapy, and pregnancy: antithrombotic therapy and prevention of thrombosis, 9th ed: american College of Chest Physicians evidence-based clinical practice guidelines.Chest. 2012; 141 (e691S-e736S)
- Definition of post-thrombotic syndrome of the leg for use in clinical investigations: a recommendation for standardization.J Thromb Haemost. 2009; 7: 879-883
Article info
Publication history
Published online: November 16, 2020
Accepted:
October 15,
2020
Received in revised form:
September 23,
2020
Received:
July 23,
2020
Identification
Copyright
© 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
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- Sex, age and venous thrombosis—Are men and women indeed from different planets?European Journal of Internal MedicineVol. 84
- Preview“Mars or Venus” titled Elliot and Rubin their editorial that accompanied the landmark study which described for the first time the strikingly higher risk of recurrent venous thromboembolism (VTE) in men compared with women [1,2]. This finding was unexpected, as - if at all - many people regarded women and not men at a higher risk of venous thrombosis. Indeed, large epidemiologic studies indicate slightly higher incidence rates of a first VTE in women, particularly in those at a younger age [3]. Using the data set of the MEGA study, Roach et al.
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